zoledronic acid profile

Zoledronic Acid: An imidobisphosphonate inhibitor of BONE RESORPTION that is used for the treatment of malignancy-related HYPERCALCEMIA; OSTEITIS DEFORMANS; and OSTEOPOROSIS. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

zoledronic acid : An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (1)

zoledronic acid is involved in 1 pathway(s), involving a total of 21 unique proteins and 43 unique compounds

ID Source	ID
PubMed CID	68740
CHEMBL ID	924
CHEBI ID	46557
SCHEMBL ID	19054
MeSH ID	M0234600

Synonym
AC-1092
BIDD:PXR0134
BIDD:GT0292
AB01273947-03
AB01273947-02
AB01273947-01
gtpl3177
reclast
zometa
cgp 42446
phosphonic acid, (1-hydroxy-2-(1h-imidazol-1-yl)ethylidene)bis-
zoledronic acid
(1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid
nsc721517
zometa (novartis)
118072-93-8
nsc-721517
phosphonic acid, [1-hydroxy-2-(1h-imidazol-1-yl)ethylidene]bis-
S00092
zol ,
zoledronate ,
zoledronic acid anhydrous
NCGC00159521-02
NCGC00159521-03
zoledronic acid, anhydrous
DB00399
anhydrous zoledronic acid
(1-hydroxy-2-(1h-imidazol-1-yl)ethylidene)bisphosphonic acid
[1-hydroxy-2-(1h-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid)
CHEBI:46557 ,
bisphosphonate 3
chembl924 ,
bdbm12578
[1-hydroxy-2-(1h-imidazol-1-yl)-1-phosphonoethyl]phosphonic acid
jmc515594 compound 55
HMS2089O09
(1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid
AKOS005145739
D08689
zoledronic acid (inn)
A803876
[1-hydroxy-2-(1h-imidazol-1-yl)-ethylidene]bisphosphonic acid
nsc 721517
70hz18ph24 ,
zol 446
bph 91
unii-70hz18ph24
dtxcid8022668
tox21_111739
cas-118072-93-8
dtxsid0042668 ,
zomera
aclasta and reclast
(1-hydroxy-2-(1h-imidazol-1-yl)ethane-1,1-diyl)diphosphonic acid
FT-0601384
NCGC00159521-05
AB07564
S1314
zoledronic acid [who-dd]
zoledronic acid [inn]
zoledronic acid [mi]
HY-13777
CS-1829
SCHEMBL19054
HS-0091
zoledronic acid, zoledronate
XRASPMIURGNCCH-UHFFFAOYSA-N
1-hydroxy-2-(1h-imidazol-1-yl)ethane-1,1-diyldiphosphonic acid
NCGC00159521-04
Q-201946
HB0674
Z0031
c5h10n2o7p2
1-hydroxy-2-(1-imidazolyl)ethane-1,1-diphosphonic acid
AB01273947_04
STL452893
zoledronic-d3 acid
[1-hydroxy-2-(1h-imidazol-1-yl)ethylidene]bisphosphonic acid
mfcd00867791
sr-05000001436
SR-05000001436-1
cgp-4244
cgp42446a
H11422
BCP22750
Z1501485360
zoledronic acid (zoledronate)
Q218507
(1-hydroxy-2-(1h-imidazol-1-yl)ethane-1,1-diyl)diphosphonicacid
EN300-117269
NCGC00159521-18
zoledronic-acid
NCGC00159521-09

Excerpt	Reference
"Zoledronic acid (ZA) is an antiosteoporotic drug that has been proven to reduce mortality after a hip fracture (HF). "	( Arnaud, M; Bioteau, C; Blain, H; Boudissa, M; Drevet, S; Gavazzi, G; Jalbert, R; Parent, T; Tonetti, J, 2022)
"Zoledronic acid (ZA) is an antiresorptive agent typically used for fracture prevention in postmenopausal osteoporosis, malignancy-associated metastatic bone lesions, and as a treatment for hypercalcemia. "	( Gupta, S; Mount, DB; Nigwekar, SU; Portales-Castillo, I; Rennke, HG; Yu, EW, 2022)
"Zoledronic acid is an intravenous, highly potent aminobisphosphonate for use in patients with primary or secondary osteoporosis. "	( Lüthje, P; Nurmi-Lüthje, I, 2022)
"Zoledronic acid (ZA) is an FDA-approved drug and a third-generation bisphosphonate (BPs). "	( Li, G; Li, R; Liang, XZ; Liu, GB; Luo, D; Peng, J; Xu, B, 2019)
"Zoledronic acid (ZA) is a commonly used bisphosphonate due to its effectiveness in increasing bone density and reducing skeletal events, with evidence that it alters angiogenesis."	( E Coates, D; J Seymour, G; K Drummond, B; P Cullinan, M; Zafar, S, 2020)
"Zoledronic acid (ZOL) is a third generation bisphosphonate which can be used as a drug for the treatment of osteoporosis and metastasis. "	( Boran, G; Dierking, I; Ege, D; Kamali, AR; Tavakoli, S, 2020)
"Zoledronic acid (ZA) is a bisphosphonate (BP) drug that has been widely used in clinical treatments as a potent bone resorption inhibitor. "	( Chen, X; Cui, W; Lin, Y; Qin, X; Xiao, D; Zhang, M; Zhang, T; Zhu, J, 2020)
"Zoledronic acid (ZA) is a potent bisphosphonate that inhibits osteoclastic resorption."	( Battaglino, RA; Fang, Y; Goldstein, RF; Morse, LR; Nguyen, N; Troy, KL, 2021)
"Zoledronic acid (ZA) is an effective agent in osteoporosis and malignancy-related bone disease but may be associated with increased risk of atrial fibrillation (AF), although current studies disagree on this risk. "	( Cromer, SJ; D'Silva, KM; Fischer, M; Kim, SC; Yu, EW, 2021)
"Zoledronic acid (ZA) is an intravenous bisphosphonate used to treat pediatric osteoporosis. "	( Diaz, MCG; Louis, S; Rackovsky, N; Rahmani, R; Stauber, SD; Weber, DR, 2021)
"Zoledronic acid is an established agent used in the management of metastatic bone disease. "	( Higashino, M; Hozumi, T; Kogo, M; Kokubu, F; Matsui, M; Nagatani, A; Nakamura, S; Sasaki, T; Shimamoto, K; Sunaga, T; Takahashi, N, 2017)
"Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction."	( Fujiwara, T; Hasei, J; Kagawa, S; Komatsubara, T; Kunisada, T; Omori, T; Osaki, S; Ozaki, T; Sugiu, K; Tazawa, H; Uotani, K; Urata, Y; Yamakawa, Y; Yoshida, A, 2017)
"Zoledronic acid is a potent new generation bisphosphonate increasingly used in oncologic patients and it is usually well tolerated. "	( Gálvez, MIL; Lavado, FM; Leal, LM; Osorio, MRR; Prieto, MP, 2017)
"Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate used for the treatment of bone diseases and calcium metabolism. "	( Desai, D; Grönroos, T; Lehtimäki, J; Rosenholm, JM; Sandholm, J; Tuomela, J; Zhang, J, 2017)
"Zoledronic acid is a nitrogen-containing bisphosphonate that is frequently used in the treatment of osteoporosis. "	( Beelen, KJ; Bornebroek, M; Geijteman, ECT; Loef, M; Schweitzer, DH, 2017)
"Zoledronic acid (zoledronate) is a bisphosphonate used predominantly as a second-line treatment for post-menopausal osteoporosis. "	( Kennedy, T; Ng, J; Sellar, PW; Vaideanu-Collins, D, 2018)
"Zoledronic acid is a long-lasting antiresorptive agent, which is known to reduce short-term periprosthetic bone loss."	( Aro, E; Aro, HT; Mattila, K; Moritz, N, 2018)
"Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect."	( Clézardin, P; Lelièvre, L; Magaud, L; Mathevet, P; Mouret-Reynier, MA; Raban, N; Roche, L; Tigaud, JD; Topart, D; Tubiana-Mathieu, N, 2018)
"Zoledronic acid is a class III drug with poor oral bioavailability due to its poor permeability and low aqueous solubility; hence an attempt has been made to improve its solubility by co-crystallization technology."	( Badamane Sathyanarayana, M; Laxmi, P; Pai, A; Pai, G; Sg, V; Varma, A, 2019)
"Zoledronic Acid is a bisphosphonate used in a 4-week schedule for the treatment of bone metastases. "	( Badalamenti, G; Bazan, V; Castellana, L; Galvano, A; Giuliana, G; Guadagni, F; Incorvaia, L; Pantano, F; Rizzo, S; Russo, A; Santini, D; Toia, F; Tonini, G; Vincenzi, B, 2019)
"Zoledronic acid (Zol) is a potent inhibitor of farnesyl-pyrophosphate synthase with broad clinical use in the treatment of osteoporosis, and bone metastases. "	( Amitay, Y; Gabizon, A; Gorin, J; Shmeeda, H; Tzemach, D, 2013)
"Zoledronic acid (Z) is a bisphosphonate used in hypercalcaemia-related cancer, in complications for bone metastasis and in postmenopausal osteoporosis and it has been related to osteoradionecrosis, especially when associated with radiation to the head and neck structures."	( Achel, D; Alcaraz, M; Alcaraz-Saura, M; Armero, D; Olivares, A, 2013)
"Zoledronic acid is a bisphosphonate that has been shown to delay or prevent the development of skeletal complications in patients with bone metastases and reduce bone pain in these patients."	( Anido, U; Climent, MA; Méndez-Vidal, MJ; Puente, J, 2013)
"Zoledronic acid (ZA) is a third-generation bisphosphonate that reduces skeletal-related events in many adult cancers, and pre-clinical data suggest a possible benefit in OS."	( Bernstein, M; Fan, TM; Goldsby, RE; Gorlick, R; Isakoff, MS; Kim, G; Krailo, M; Lee, S; Marina, N; Meyer, J; Randall, RL; Villaluna, D; Wagner, LM, 2013)
"Zoledronic acid is a third-generation nitrogen-containing BP."	( Magremanne, M; Reychler, H, 2014)
"Zoledronic acid is a bisphosphonate that has been shown to delay or prevent the development of skeletal-related events in patients with bone metastases."	( Cueva, J; Lluch, A; Pérez-Fidalgo, JA; Ponce, J; Ruiz-Borrego, M, 2014)
"Zoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption and has been widely used in bone metastasis malignancies and postmenopausal osteoporosis as a preventive therapy against skeletal-related events. "	( Fan, W; He, M; Zhang, X, 2013)
"Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis."	( Amiaud, J; Battaglia, S; Charrier, C; Gouin, F; Heymann, D; Kim, PP; Lamoureux, F; Odri, G; Redini, F, 2014)
"Zoledronic acid (ZOL) is an intravenous once-yearly bisphosphonate that has been shown to be effective and safe in improving BMD and reducing fracture risk in controlled clinical trials."	( Chen, X; Fan, L; Huang, S; Lin, H; Liu, C; Zhu, X, 2014)
"Zoledronic acid (ZA) is a potential immunotherapy for cancer because it can induce potent γδ T-cell-mediated anti-tumour responses. "	( Bodman-Smith, MD; Copier, J; Dalgleish, AG; Fowler, DW, 2014)
"Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate and is used to reduce cancer-induced osteolysis. "	( Abe, H; Aikata, H; Chayama, K; Hiraga, N; Honda, Y; Imamura, M; Kawaoka, T; Miki, D; Murakami, E; Ochi, H; Ono, A; Shi, N; Takahashi, S; Tsuge, M; Zhang, Y, 2015)
"Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications."	( Cohen, PR, 2015)
"Zoledronic acid (ZA) is a bisphosphonate given intravenously, most commonly for the treatment of postmenopausal osteoporosis. "	( Collier, M; Mahalingam, M; Succaria, F, 2015)
"Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. "	( Akazawa, K; Hasegawa, Y; Hayashi, M; Horiguchi, J; Ishikawa, T; Kim, SJ; Kohno, N; Konishi, M; Kubota, T; Miura, D; Miyashita, M; Shigeoka, Y; Suzuki, M; Taguchi, T; Takao, S; Tanino, H; Yamagami, K, 2015)
"Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate that exhibited anticancer activity in different cancers."	( Biray Avci, C; Dodurga, Y; Elmas, L; Goker, B; Gunduz, C; Kurt, CC; Mutlu, Z; Ozalp, O; Tepedelen, BE, 2016)
"Zoledronic acid is an intravenous bisphosphonate used to increase bone mineral density and reduce the risk of fractures. "	( Al-Nofal, A; Kahoud, RJ; Kumar, S; Tebben, PJ; Tripathi, S; Trivedi, S, 2016)
"Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. "	( Chiarugi, P; Comito, G; Giannoni, E; Lanciotti, M; Morandi, A; Pons Segura, C; Serni, S; Taddei, ML, 2017)
"Zoledronic acid (ZA) is a long-acting bisphosphonate that has been successfully used in children with secondary osteoporosis and osteogenesis imperfecta."	( Alcántara-Montiel, JC; Arce-Cano, M; García-Campos, J; Lugo Reyes, SO; Sánchez-Sánchez, LM; Staines Boone, AT, 2016)
"Zoledronic acid is a option in the management of BMES, since 75% of patients treated with it presented with a complete response."	( Andréu Sánchez, JL; Barbadillo Mateos, C; Blanco, R; Campos Esteban, J; Espinosa-Malpartida, M; Flores-Robles, BJ; Godoy-Tundidor, H; Huntley-Pascual, D; Isasi, CM; Jiménez-Palop, MM; Merino-Argumanez, C; Mulero, JB; Ramos-Giráldez, MC; Sanabria-Sanchinel, AA; Sanz-Sanz, J; Villa-Alcázar, LF, 2017)
"Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. "	( Galapi, F; Lambrinoudaki, I; Papadias, K; Papadimitriou, D; Vlachou, S, 2008)
"Zoledronic acid (ZOL) is a potential inhibitor of osteoclast-mediated bone resorption and basic fibroblast growth factor (bFGF) is a growth factor that stimulates osteoblast-mediated bone formation, and these drugs could enhance fixation of implants under osteoporotic conditions."	( Gao, Y; Hu, J; Li, J; Luo, E; Xue, J; Zhu, S, 2009)
"Zoledronic acid (ZA) is a new generation potent intravenous bisphosphonate that has been approved for the treatment and prevention of bone lesions, and/or hypercalcemia associated with MM."	( Aki, SZ; Cetiner, M; Cetiner, S; Gultekin, SE; Haznedar, R; Kahraman, SA; Kocakahyaoglu, B; Sucak, GT, 2009)
"Zoledronic acid is a cost-effective treatment strategy regardless of fracture type or effectiveness comparability assumptions."	( Beresniak, A; Bisot-Locard, S; Bresse, X; Cortet, B; Fardellone, P; Legrand, E; Vigneron, AM, 2010)
"Zoledronic acid is a potent bisphosphonate that can prevent osteoporosis in patients with nonmetastatic (M0), prostate cancer (CaP) who are initiating ADT."	( Bhoopalam, N; Campbell, SC; Ellis, NK; Friedman, N; Garewal, H; Iyer, P; Moritz, TE; Pandya, M; Reda, DJ; Thottapurathu, L; Vanveldhuizen, P; Warren, SR, 2010)
"IV zoledronic acid is an effective and well-tolerated treatment to prevent bone mineral density loss at the total hip and trochanter for up to 12 months following SCI."	( Bubbear, JS; Ferguson-Pell, M; Gall, A; Keen, RW; Middleton, FR; Swaminathan, R, 2011)
"Zoledronic acid is a third-generation bisphosphonate that is administered as an annual infusion, and it has some interesting features. "	( Reid, DM, 2010)
"Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease."	( Atmaca, H; Cakar, B; Karabulut, B; Karaca, B; Kisim, A; Muslu, U; Uslu, R; Uzunoglu, S; Varol, U, 2010)
"Zoledronic acid is a widely used intravenous bisphosphonate that reduces this skeletal morbidity in both benign and malignant conditions."	( Brown, J; Burkinshaw, R; Coleman, R; Lester, J; Neville-Webbe, H; Winter, M; Woodward, E, 2011)
"Zoledronic acid (ZOL) is a potent amino-bisphosphonate used for the treatment of bone metastases with recently reported antitumor activity. "	( Abbruzzese, A; Ascani, R; Calimeri, T; Caraglia, M; Cigliana, G; De Rosa, G; Franco, R; La Rotonda, MI; Leonetti, C; Liguori, G; Marra, M; Salzano, G; Scarsella, M; Tagliaferri, P; Tassone, P; Zappavigna, S, 2011)
"Zoledronic acid is an iv aminobisphosphonate that is administered annually against osteoporosis."	( Gruber, M; Hamann, C; Hofbauer, LC; Rachner, TD; Tsourdi, E; Ziemssen, T, 2011)
"Zoledronic acid is an intravenous once yearly bisphosphonate that has been shown to be effective and safe in improving BMD (bone mineral density) and reducing fracture risk in controlled clinical trials. "	( Adachi, JD; Brown, JP; Deutsch, G; Kendler, DL; Leclerc, JM; Rigal, R, 2011)
"Zoledronic acid is an effective treatment in preventing SREs in solid tumors and multiple myeloma."	( Culver, KW; Diener, M; Guo, A; Namjoshi, M; Parikh, K; Wu, EQ; Xie, J; Yu, AP, 2011)
"Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. "	( Adinolfi, B; Consolini, R; Failli, A; Legitimo, A; Orsini, G; Romanini, A, 2011)
"Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). "	( Eastham, J; Saad, F; Segal, S, 2014)
"Zoledronic acid (ZOL) is a bisphosphonate with higher potency and faster intravenous infusion, but its efficacy and safety has not been established for OI patients."	( Barros, ER; de Oliveira, TP; Lazaretti-Castro, M; Saraiva, GL, 2012)
"Zoledronic acid (ZA) is an intravenous bisphosphonate approved for the prevention and treatment of cancer skeletal-related events."	( Anglada-Martínez, H; Creus-Baró, N; do Pazo-Oubiña, F; Estefanell-Tejero, A; Molas-Ferrer, G; Ribas-Sala, J; Riu-Viladoms, G, 2012)
"Zoledronic acid (ZA) is a bisphosphonate known to upregulate the expression of TRAIL on human γδ T cells."	( D'Arcy, P; Hu, J; Lidén, M; Lundqvist, A; Rolny, C; Sarhan, D; Wennerberg, E; Winqvist, O, 2013)
"Zoledronic acid (ZA) is an imidazole-containing bisphosphonate that has been extensively studied as an osteoclast inhibitor. "	( Brufsky, AM; Oesterreich, S; Steinman, RA, 2012)
"Zoledronic acid is a first-line option for the treatment of Paget's disease, yet there can be complications in particular clinical scenarios such as pagetic hydrocephalus, as seen in this case."	( Correa, PH; Ferraz-de-Souza, B; Martin, RM, 2013)
"Zoledronic acid (ZOL) is a potent inhibitor of the latter pathway, but its activity in neurological diseases is hampered by its biodistribution that is almost exclusively limited to the bone."	( Abbruzzese Saccardi, A; Caraglia, M; De Novellis, V; De Rosa, G; Giordano, C; Guida, F; Luongo, L; Lusa, S; Maione, S; Marra, M; Rossi, F; Salzano, G; Zappavigna, S, 2013)
"Zoledronic acid is a new, highly potent bisphosphonate drug under clinical evaluation. "	( Deckert, F; Gauron, S; Gosset, G; Legay, F; Pfaar, U; Ravera, C; Schran, H; Wiegand, H, 2002)
"Zoledronic acid is a new-generation, heterocyclic nitrogen-containing bisphosphonate and the most potent inhibitor of bone resorption identified to date."	( Major, P, 2002)
"Zoledronic acid (Zoledronate) is a new, potent third-generation bisphosphonate that has recently been approved by the U.S. "	( Lipton, A, 2003)
"Zoledronic acid (Zometa) is an effective inhibitor of osteoclast-mediated bone resorption. "	( Goa, KL; Wellington, K, 2003)
"Zoledronic acid (ZOL) is a highly potent heterocyclic bisphosphonate which has been shown to inhibit bone resorption in short-term experiments in young growing animals. "	( Evans, GP; Glatt, M; Green, JR; Hornby, SB; Hornby, SL; Pataki, A, 2003)
"Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate and its use in reducing osteoporosis and cancer-induced osteolysis is increasing. "	( Denoyelle, C; Hong, L; Soria, C; Soria, J; Vannier, JP, 2003)
"Zoledronic acid is a potent, third generation, nitrogen-containing bisphosphonate, licensed for the management of skeletal metastases and hypercalcaemia of malignancy, both of which cause considerable morbidity. "	( Coleman, RE; Neville-Webbe, Hl, 2003)
"Zoledronic acid is a nitrogen-containing bisphosphonate that has demonstrated potent anti-tumor activity in vitro and in vivo."	( Coleman, R; Croucher, P; Jagdev, S, 2003)
"Zoledronic acid is a nitrogen-containing bisphosphonate that inhibits bone resorption. "	( Davis, LE; Li, EC, 2003)
"Zoledronic acid is an effective and generally well-tolerated treatment for hypercalcemia of malignancy and skeletal complications of metastatic bone disease."	( Davis, LE; Li, EC, 2003)
"Zoledronic acid is a potent inhibitor of PEC invasion across bone marrow endothelium and colony formation with the bone marrow stroma, affecting the MMP: TIMP-2 balance to favour MMP inhibition."	( Brown, MD; Clarke, NW; George, NJ; Hart, CA; Montague, R; Ramani, VA, 2004)
"Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis."	( Borges, CT; Jorgetti, V; Pereira, RM; Souza, SC, 2004)
"Zoledronic acid is a highly potent N-BP that has been particularly well investigated, preclinically and in clinical practice."	( Clézardin, P, 2005)
"Zoledronic acid is a bisphosphonate that is effective in the treatment of complications of metastatic bone disease. "	( Arcara, C; Badalamenti, G; Casuccio, A; Cicero, G; Di Fede, G; Fulfaro, F; Gebbia, N; Intrivici, C; Leto, G; Rini, GB; Russo, A; Valerio, MR; Vitale, A, 2005)
"Zoledronic acid (ZA) is a potent i.v."	( D'Souza, AB; Ebeling, PR; Grigg, AP; Szer, J, 2006)
"Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. "	( Brown, JP; Curiel, MD; Devogelaer, JP; Eriksen, EF; Fashola, T; Fraser, WD; Hooper, M; Hosking, D; Lyles, K; Miller, P; Pak, J; Reid, IR; Saidi, Y; Su, G; Zelenakas, K, 2007)
"Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate with antitumor activity used to treat patients with malignant diseases. "	( Brauer, KM; Bringmann, A; Brossart, P; Grünebach, F; Schmidt, SM; von Schwarzenberg, K; Weck, MM; Werth, D, 2007)
"Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications."	( Amanat, N; Bilston, L; Godfrey, C; Little, D; McDonald, M, 2007)
"Zoledronic acid is a highly potent bisphosphonate that has been shown to reduce skeletal-related events in patients with androgen-independent prostate cancer metastatic to bone. "	( Arlen, PM; Dahut, WL; Gulley, JL; Wu, S, 2007)
"Zoledronic acid is an effective therapy for the prevention of AI-associated bone loss and, when combined with AI therapy, may provide the greatest clinical benefit without increasing fracture risk."	( Hadji, P, 2007)
"Zoledronic acid (Zometa is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). "	( McKeage, K; Plosker, GL, 2008)
"Zoledronic acid is a new-generation, highly potent, nitrogen-containing bisphosphonate that to the authors knowledge is the most potent inhibitor of bone resorption currently in clinical trials."	( Berenson, JR; Conde, F; Henick, K; Nishikubo, C; Rettig, M; Swift, RA; Vescio, R; Von Teichert, JM, 2001)
"Zoledronic acid is a highly potent, nitrogen-containing bisphosphonate."	( Berenson, JR; Givant, E; Harvey, H; Hupkes, M; Lipton, A; Rosen, LS; Savage, A; Swift, R; Vescio, RA; VonTeichert, JM; Woo, M, 2001)
"Zoledronic acid (zoledronate) is a new generation bisphosphonate that inhibits osteoclast bone resorption. "	( Cheer, SM; Noble, S, 2001)

Excerpt	Reference
"Zoledronic acid has an anti-angiogenic effect on HUVECs attached to titanium implants, while the SLA surface might stimulate HUVECs to express angiogenic and adhesive factor genes despite ZA treatment."	( Deng, F; Liang, C; Wang, T; Xu, R; Yu, X; Yu, Y, 2022)
"Zoledronic acid has a well-established tolerability profile and can be administered safely as long-term therapy, although preventive measures are needed to avoid some severe side effects (nephrotoxicity and osteonecrosis of the jaw) found in a small number of patients receiving long-term therapy."	( Afonso, R; Bosch-Barrera, J; Isla, D; Martínez, N, 2013)
"Zoledronic acid (ZOL) has a suppressive effect on marrow adiposity in ovariectomized rats. "	( Fang, C; Jiang, Z; Li, Y; Luo, X; Shen, J; Yan, F; Yang, Y, 2015)
"Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer."	( Fehm, T; Neubauer, H; Seeger, H; Wallwiener, D; Zwirner, M, 2012)
"Zoledronic acid has a higher response rate, faster onset, and longer duration of action, and is more convenient to administer."	( Berenson, JR, 2001)
"Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa."	( Bachmann, R; Bisping, M; Born, AR; Cortesi, R; Glatt, M; Green, JR; Guiglia, G; Jaeggi, KA; Jeker, H; Klein, R; Müller, K; Ramseier, U; Schmid, J; Schreiber, G; Seltenmeyer, Y; Widler, L, 2002)
"Zoledronic acid has also gained a place in cancer treatment due to its cytotoxic and antiproliferative effects in many cancer cells."	( Boran, T; Jannuzzi, AT; Kara, M; Özden, S; Özhan, G; Öztaş, E, 2022)
"Zoledronic acid (ZA) has been used as a first-line treatment in patients with osteoporosis (OP) who receive an annual injection of 5 mg. "	( Du, G; Fan, D; Han, G; Li, H; Li, R; Liu, D; Liu, Q; Song, C; Tao, L; Zhang, M, 2022)
"Zoledronic Acid (ZA) has been shown to inhibit Osteosarcoma (OSA) progression in preclinical studies. "	( Christou, A; Ferreira, N; Sophocleous, A, 2023)
"Zoledronic acid has demonstrated efficacy to attenuate bone loss at the hip after SCI, but previous studies relied on measurements from dual-energy X-ray absorptiometry."	( Barroso, J; Crack, LE; Edwards, WB; Gabel, L; Haider, IT; Schnitzer, TJ; Simonian, N, 2023)
"Zoledronic acid has an anti-angiogenic effect on HUVECs attached to titanium implants, while the SLA surface might stimulate HUVECs to express angiogenic and adhesive factor genes despite ZA treatment."	( Deng, F; Liang, C; Wang, T; Xu, R; Yu, X; Yu, Y, 2022)
"Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. "	( Gamper, J; Grunt, TW; Gschwantler-Kaulich, D; Mairhofer, M; Singer, CF; Tan, Y; Weingartshofer, S, 2017)
"Zoledronic acid (ZA) has been proven to inhibit angiogenesis, invasion, and adhesion of tumor cells."	( Du, Y; Jin, Z; Li, Y; Sun, T; Tian, J; Xue, H, 2018)
"Zoledronic acid (ZOL) has been indicated to play an essential role in regulating bone mineral density and has already been used in large clinical trials."	( Cheng, YT; Guan, ZZ; Hong, W; Huang, LY; Huang, XL; Li, F; Liao, J; Shi, QH; Wu, C; Zhou, Q, 2019)
"Both zoledronic acid and Dmab have been proven to be superior to oral bisphosphonates like risedronate in improvement of bone mineral density."	( Bultink, IEM; Lems, WF; Raterman, HG, 2019)
"Zoledronic acid has 100 times relative potency that of pamidronate."	( Aihara, T; Furukawa, R; Kikkawa, I; Morimoto, A; Watanabe, H, 2013)
"Zoledronic acid has a well-established tolerability profile and can be administered safely as long-term therapy, although preventive measures are needed to avoid some severe side effects (nephrotoxicity and osteonecrosis of the jaw) found in a small number of patients receiving long-term therapy."	( Afonso, R; Bosch-Barrera, J; Isla, D; Martínez, N, 2013)
"Zoledronic acid has been used for prevention of osteolytic and osteoblastic bone metastasis. "	( Ngarmukos, S; Tanavalee, A; Tantavisut, S; Thanakit, V; Wangroongsub, Y; Wilairatana, V, 2014)
"Zoledronic acid has shown indirect anticancer effects on angiogenesis, the tumor microenvironment and immune responses. "	( Consolini, R; Failli, A; Legitimo, A; Orsini, G; Romanini, A, 2014)
"Zoledronic acid has robust antitumor and antiangiogenic activity and merits further clinical development as ovarian cancer treatment."	( Aslan, B; Calin, G; Dalton, HJ; Del C Monroig, P; Fernandez-de Thomas, RJ; Fuentes-Mattei, E; Gonzalez-Villasana, V; Ivan, C; Kahraman, N; Kanlikilicer, P; Lopez-Berestein, G; Ozpolat, B; Pradeep, S; Previs, RA; Rodriguez-Aguayo, C; Sood, AK; Velazquez-Torres, G; Wang, H, 2015)
"Zoledronic acid (ZOL) has a suppressive effect on marrow adiposity in ovariectomized rats. "	( Fang, C; Jiang, Z; Li, Y; Luo, X; Shen, J; Yan, F; Yang, Y, 2015)
"Zoledronic acid (ZA) has been tested in clinical trials as an additive therapy for early-stage breast cancer. "	( Ding, D; Du, Y; He, ZQ; Jia, XH; Ma, XB; Mao, D; Qiu, JD; Shang, WT; Tian, J; Wang, ZL, 2015)
"Zoledronic acid has infrequently been associated with mucocutaneous adverse reactions. "	( Cohen, PR, 2015)
"Zoledronic acid (ZL) has been used widely for treating skeletal diseases because of its high potency in inhibiting bone resorption. "	( Lin, J; Liu, G; Liu, Q; Lv, G; Qiu, L; Wang, S; Wang, Y, 2016)
"Zoledronic acid (ZOL) has been shown in vitro and in vivo to inhibit osteoclastic activity and to regulate osteoblasts. "	( Alidoust, M; Back, DA; Greiner, SH; Haas, NP; Schmidmaier, G; Schwabe, P; Wildemann, B, 2008)
"Zoledronic acid has undergone international multicentric clinical trials to examine efficiency and long-term side effects including osteonecrosis of the jaw."	( Yamashita, S, 2009)
"Zoledronic acid (ZOL) has shown beneficial effects on bone turnover and bone mineral density (BMD) in postmenopausal osteoporosis. "	( Adachi, JD; Adler, RA; Brown, J; Bucci-Rechtweg, C; Kendler, D; Mesenbrink, P; Miller, PD; Orwoll, ES; Readie, A; Weinstein, RS, 2010)
"Zoledronic acid has direct and indirect antitumor effects. "	( Chen, J; Guo, H; Guo, L; Guo, X; Hu, X; Ragaz, J; Shao, Z; Wang, Z; Wu, J; Xu, X; Zhao, X; Zhu, B; Zhu, J, 2010)
"Zoledronic acid has demonstrated clinical benefits beyond those of pamidronate in a head-to-head trial that included patients with breast cancer or multiple myeloma."	( Aapro, M; Costa, L; Saad, F, 2010)
"Zoledronic acid has positive effects on bone formation in the sagittal suture in response to expansion and decreases the relapse ratio after expansion in rats."	( Babacan, H; Gümüş, C; Inan, S; Oztürk, F, 2011)
"Zoledronic acid (ZOL) has proven efficacy for reducing the risk of skeletal-related events in patients with bone metastases from a broad range of solid tumors and bone lesions from multiple myeloma. "	( Lipton, A, 2011)
"Zoledronic acid has demonstrated the broadest activity in this setting, and is approved for the prevention of skeletal-related events from bone metastases from a variety of solid tumors in addition to breast cancer and multiple myeloma."	( Hirsh, V, 2012)
"Zoledronic acid has been the standard of care for the prevention of skeletal-related events in patients with bone metastases from prostate cancer for the past 10 years. "	( Culine, S; Pouessel, D, 2012)
"Zoledronic acid (ZOL) has been shown to significantly increase bone mineral density and to decrease the incidence of osteoporotic fractures. "	( Dong, J; Li, C; Li, XL; Wang, HR; Zhou, XG, 2012)
"Zoledronic acid (ZA) has been used as the standard treatment for patients with solid cancer or myeloma that has metastasized into bone. "	( Sun, L; Yu, S, 2013)
"Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer."	( Fehm, T; Neubauer, H; Seeger, H; Wallwiener, D; Zwirner, M, 2012)
"Zoledronic acid has demonstrated efficacy in the reduction and delay of SREs in patients with bone metastases."	( Gomez-Veiga, F; Martinez-Breijo, S; Morote, J; Planas, J; Ponce-Reixa, J, 2013)
"Both zoledronic acid and denosumab have been demonstrated to reduce skeletal related events."	( Datta, HK; Hanusch, B; Tuck, SP; Walker, J, 2013)
"Zoledronic acid (4 mg) has been compared to placebo in a randomized Phase III trial involving 422 men with hormone-refractory prostate cancer metastatic to bone."	( Gleason, D; Gordon, D; Kowalski, MO; Lipton, A; Reitsma, D; Rosen, L; Saad, F; Seaman, J; Small, E; Smith, M, 2002)
"Zoledronic acid has the potential to change the treatment of osteoporosis dramatically."	( Body, JJ, 2003)
"Zoledronic acid has been evaluated in randomized, double-blind clinical trials of osteoporosis, Paget's disease of bone, and metastatic, osteolytic and osteoblastic bone disease."	( Theriault, RL, 2003)
"Zoledronic acid has also demonstrated direct anti-tumour activity both in vitro and in animal models, suggesting it may be of benefit in preventing the formation of bone metastases."	( Coleman, RE; Neville-Webbe, Hl, 2003)
"Zoledronic acid has demonstrated efficacy in the management of hypercalcemia and metastatic bone disease."	( Cameron, D, 2003)
"Zoledronic acid has now become an additional option that can provide benefits to patients with prostate cancer throughout the course of their disease."	( Saad, F; Schulman, CC, 2004)
"Zoledronic acid has also received the broadest regulatory approval of any bisphosphonate and can be used to treat HCM or bone lesions secondary to multiple myeloma and a wide variety of solid tumors, including breast, prostate, and lung cancers."	( Berenson, J; Hirschberg, R, 2004)
"Zoledronic acid has also demonstrated efficacy in the treatment of bone metastases in patients with prostate cancer, lung cancer, and other solid tumors."	( Berenson, JR, 2005)
"Zoledronic acid has also demonstrated significant long-term benefits in randomized trials in prostate cancer and other solid tumors, whereas other bisphosphonates have failed."	( Lipton, A, 2005)
"Zoledronic acid has also been compared with another active bisphosphonate (i.e."	( Coleman, RE, 2005)
"Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration."	( Barrett-Lee, P; Cameron, D; Davidson, N; Dodwell, D; Hong, A; Mansi, J; Mason, T; Murphy, R; Wardley, A, 2005)
"Zoledronic acid (ZA) has been shown to inhibit prostate tumor growth in vitro and have beneficial effects in patients with advanced prostate cancer (CaP). "	( Brown, LG; Corey, E; Keller, ET; Quinn, JE; Vessella, RL; Zhang, J, 2005)
"Zoledronic acid has been shown to be effective in the treatment of osteoporosis, hypercalcemia, and metastatic bone tumors. "	( Duan, X; Guan, H; Kleinerman, ES; Zhou, Z, 2005)
"Zoledronic acid (ZOL) has proved activity in bone metastases from prostate cancer through inhibition of mevalonate pathway and of prenylation of intracellular proteins. "	( Abbruzzese, A; Baldi, A; Bertieri, R; Budillon, A; Caraglia, M; D'Alessandro, AM; Leonetti, C; Marra, M; Meo, G; Santini, D; Tonini, G; Zupi, G, 2007)
"Zoledronic acid has been marketed for the past 5 years for the treatment of hypercalcemia of malignancy and malignant bone disease in patients with multiple myeloma or a broad range of solid tumors. "	( Lipton, A, 2007)
"Zoledronic acid has also shown significant reductions in skeletal morbidity in patients with lung cancer or other solid tumors compared with placebo."	( Lipton, A, 2007)
"Zoledronic acid has demonstrated significant long-term benefits for prevention of SREs and palliative effects for bone pain."	( Major, P, 2007)
"Zoledronic acid has demonstrated the greatest SRE risk reduction of all bisphosphonates and significantly improves pain scores in patients with breast cancer."	( Major, P, 2007)
"Zoledronic acid has proven efficacy for reducing risk of SREs, and ongoing studies are under way to evaluate customized treatment schedules."	( Costa, L, 2007)
"Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. "	( Choong, PF; Dass, CR, 2007)
"Zoledronic acid has the potential to improve clinical outcomes by reducing the risk of fracture in patients with osteoporosis."	( Lewiecki, EM, 2008)
"Zoledronic acid has a higher response rate, faster onset, and longer duration of action, and is more convenient to administer."	( Berenson, JR, 2001)

Excerpt	Reference
"Zoledronic acid (ZOL) plays a pivotal role in regulating bone mineral density."	( Cheng, YT; Huang, XL; Li, JP; Liao, J; Liu, C; Shi, XM; Zhou, Q, 2022)
"Zoledronic acid appeared to enhance the subperiosteal diameter, endocortical diameter, and cross-sectional moment of inertia (CSMI) at the narrow neck in comparison with placebo (P < 0.05); however, no difference in TBS was observed between both groups (P > 0.05)."	( Bakhshayeshkaram, M; Dabbaghmanesh, A; Dabbaghmanesh, MH; Dabbaghmanesh, MM; Heydari, ST; Jahromi, SE; Naseri, A; Roshanzamir, S; Talehzadeh, P, 2023)
"Zoledronic acid (ZOL) plays a key role in treating osteosarcoma (OS) and improving the prognosis of patients with OS; however, its mechanism remains unclear."	( Li, JJ; Li, S, 2019)
"Zoledronic acid does not produce dysrhythmia or prodysrhythmic effects in the short term."	( Biamonte, F; Castro, C; Cipriani, C; Clementelli, C; Curione, M; De Lucia, F; Minisola, S; Nieddu, L; Pepe, J; Piemonte, S; Savoriti, C, 2015)
"Zoledronic acid can inhibit HGF proliferation and promote its apoptosis."	( Cui, C; Fu, Q; Guo, Y; Liu, C; Xuan, B; Zhang, J, 2015)
"Zoledronic acid can inhibit the vascular endothelial cell activities of proliferation and migration, and can up-regulate cellular apoptosis, which suggests that direct inhibition of angiogenesis together with vascular impairment might contribute to the development of osteonecrosis of the jaw."	( Chen, Z; Lang, M; Lin, W; Niu, J; Shi, L; Wang, Y; Xu, S; Zhou, Z, 2016)
"Zoledronic acid did not produce an appreciable change in scans."	( Dickow, B; Dobson, K; Heilbrun, LK; Lawhorn-Crews, JM; Shields, AF; Smith, D; Tehrani, OS; Vaishampayan, UN, 2017)
"Zoledronic acid did not produce evidence of MG-63 cell death when administered at 100 mM for 48 hours, but only after exposure of 96 hours."	( Alexis, MN; Consoulas, C; Katopodis, H; Kletsas, D; Konstantinidou, E; Koutsilieris, M; Manoussakis, M; Pitulis, N; Poyatzi, A; Tenta, R; Tiblalexi, D, 2008)
"Zoledronic acid promotes osteoblast proliferation and maturation and modulates osteoprotegerin production."	( Sun, H; Zhang, J; Zhang, WY, 2010)
"Zoledronic acid can inhibit the in vitro proliferation and invasion of HNE1 cell through suppressing the secretion of VEGF, the activities of MMP2 and MMP9 and the expressions of VEGF, MMP2 and MMP9."	( Chen, JY; Hong, CQ; Huang, WL; Li, XY; Lin, W; Lin, YC; Wang, HB, 2011)
"Zoledronic acid can enhance the in vitro effects of anti-proliferation and apoptosis-inducing for paclitaxel on HNE1 cell. "	( Huang, WL; Li, XY; Lin, SL; Lin, W; Lin, WZ; Lin, YC; Wang, HB, 2012)

Excerpt	Reference
"Zoledronic acid (ZA) treatment of in vitro cultured osteoblasts (OB) results in reduction in viability, proliferation and differentiation. "	( Hakim, SG; Rose, D; Scheibert, A; Steller, D; Sturmheit, T, 2022)
"Zoledronic acid treatment significantly up-regulated the levels of ALP, RUNX2, and Bglap. "	( Jin, ZH; Liao, W; Wang, SF, 2020)
"Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders."	( Abate, V; Buonaiuto, A; De Filippo, G; Di Minno, MND; Evangelista, M; Gennari, L; Gentile, M; Giaquinto, A; Iannuzzo, G; Merlotti, D; Picchioni, T; Rendina, D; Strazzullo, P, 2021)
"Zoledronic acid or saline treatment continued after surgery for 4 weeks (short-term subgroup) or 8 weeks (long-term subgroup) until sacrifice."	( Huo, L; Rao, NJ; Wang, JY; Yu, RQ; Zheng, LW, 2021)
"Zoledronic acid treatment could significantly increase the Z-score of BMD and reshape the compressed vertebral bodies."	( Jiang, Y; Li, L; Li, M; Liu, W; Lv, F; Ma, M; Qiu, Z; Song, Y; Wang, O; Xia, W; Xing, X; Xu, X, 2017)
"Zoledronic acid treatment of HOKs and HUVECs had no significant effects on apoptosis (P>0.05), but significantly reduced expression levels of p-EGFR, p-Akt, p-PI3K, p-mTOR), and p-eNOS (P<0.05); EGF partially reversed these effects and increased the expression levels (P<0.05)."	( Guo, T; Liu, D; Liu, J; Pan, J; Wang, Q, 2019)
"Zoledronic acid treatment is potentially important for patients with osteoporosis after THA."	( Geng, D; Guo, X; Liu, Y; Xu, Y; Yang, H; Zhou, W, 2019)
"Home zoledronic acid treatment was well tolerated. "	( Bastit, L; Guérif, S; Khemaies, S; Kouri, CE; Ktiouet, M; Lebret, T; Lortholary, A; Mouysset, JL; Murraciole, X, 2013)
"Zoledronic acid treatment decreased the expression of mesenchymal markers, N-cadherin, Twist, and Snail, and subsequently upregulated expression of E-cadherin."	( Brodie, AH; Gilani, RA; Kazi, AA; Schech, AJ, 2013)
"Zoledronic acid-treated groups showed variable degrees of osteosclerosis and trabecular disorganization on X-ray study."	( Barba-Recreo, P; Burgueño, M; Del Castillo Pardo de Vera, JL; García-Arranz, M; Yébenes, L, 2014)
"Zoledronic acid treatment significantly decreased the number of corticosteroid-induced apoptotic chondrocytes in the joint cartilage (p<0.05)."	( Acar, N; Aslan, T; Ozbey, O; Ozenci, AM; Sahin, Z; Ustünel, I, 2013)
"Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B."	( Fu, J; Ge, XY; Jiang, Y; Li, SL; Yang, LQ; Yang, WW, 2014)
"Zoledronic acid treatment combined with docetaxel-based chemotherapy could have a better bone pain control and improve BPFS and OS for prostate cancer patients with bone metastases. "	( Chen, W; Jin, H; Pan, Y; Wang, F; Weng, Z; Ye, T; Yu, Z; Zheng, Y, 2014)
"Zoledronic acid treatment did not affect the number of osteoclasts in vivo."	( Bakker, LF; de Vries, TJ; Everts, V; Jansen, I; Kroon, SA; Renders, G; van Duin, MA; Vermeer, J, 2017)
"Zoledronic acid treatment increased the relative risk (RR) and the incidence rate (IR) of renal impairment by approximately 1.5-fold in all assessed patients (all tumors) compared with ibandronate."	( Antràs, L; Diel, IJ; Duh, MS; Green, J; Köppler, H; Neary, M; Smith, M; Weide, R; Wintfeld, N, 2009)
"Zoledronic acid treatment in patients with malignant solid tumors causing bone metastases prolongs their survival."	( Tamási, L, 2009)
"Zoledronic acid treatment reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from breast, lung, and urologic cancers including prostate and renal cancer. "	( Boutrus, R; El-Attar, I; El-Hossieny, H; Kader, YA; Nazmy, M; Zaghloul, MS, 2010)
"Zoledronic acid treatment promoted effective osseous protection against the natural demineralization process in patients with prostate cancer recurrence submitted to ADT."	( Hering, F; Meler, A; Rodrigues, P, 2010)
"Zoledronic acid treatment resulted in the formation of more microcracks."	( Brennan, O; Kennedy, OD; Lee, TC; O'Brien, FJ; Rackard, SM, 2011)
"A zoledronic acid treated group was also included in which animals were estrogen deficient for 20 months prior to receiving treatment (Zol, n=4)."	( Brennan, O; Kennedy, OD; Lee, TC; McNamara, LM; O'Brien, FJ; Rackard, SM, 2011)
"Zoledronic acid treatment (4 mg per month) was initiated, and both the tumor and the metastases regressed."	( Brountzos, E; Gouliamos, A; Kouloulias, V; Mystakidou, K; Panagiotou, I, 2011)
"Zoledronic acid (ZOL) treatment has reduced DTCs in the bone marrow of patients with EBC in several studies."	( Becker, S; Fehm, T; Gebauer, G; Hirnle, P; Huober, J; Janni, W; Krämer, B; Lück, HJ; Solomayer, EF; Wackwitz, B; Wallwiener, D, 2012)
"Zoledronic acid treatment decreased bone nodule formation at all concentrations tested (0.01-100 μM). "	( Chanruangvanit, C; Lavanrattanakul, K; Patntirapong, S; Satravaha, Y; Singhatanadgit, W, 2012)
"Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. "	( Antunez, O; Boonen, S; Brixen, K; Bucci-Rechtweg, C; Claessens, F; Dimai, HP; Eriksen, E; Hruska, J; Incera, E; Kaufman, JM; Langdahl, B; Lippuner, K; Lipschitz, S; Orwoll, E; Papanastasiou, P; Reginster, JY; Rizzoli, R; Russo, L; Su, G; Vanderschueren, D; Witvrouw, R; Zanchetta, J, 2012)
"Zoledronic acid treatment and prophylaxis preserved femoral head architecture after traumatic ON in this rat model at 6 weeks. "	( Baldock, PA; Little, DG; Mcevoy, A; Peat, RA; Smith, EJ; Williams, PR, 2003)
"Zoledronic acid treatment does not influence (153)Sm-EDTMP skeletal uptake. "	( Dahmane, A; de Klerk, JM; Lam, MG; Stevens, WH; van Rijk, PP; Zonnenberg, BA, 2008)
"Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants)."	( Adams, A; Heidenreich, A; Jakob, T; Kuhr, K; Macherey, S; Monsef, I; Skoetz, N; Tesfamariam, YM, 2020)
"Treatment with zoledronic acid was beneficial for increasing BMD and reshaping the vertebral bodies of this patient."	( Jiang, Y; Li, L; Li, M; Liu, W; Lv, F; Ma, M; Qiu, Z; Song, Y; Wang, O; Xia, W; Xing, X; Xu, X, 2017)
"Treatment with zoledronic acid 5 mg maintained bone turnover markers in the premenopausal range, increased lumbar spine bone mineral density, and maintained hip bone mineral density in women previously treated with odanacatib 50 mg weekly."	( Harsløf, T; Koldkjær Sølling, AS; Langdahl, B, 2019)
"Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96)."	( Aft, R; Brufsky, AM; Coleman, RE; Eidtmann, H; Gnant, M; Lind, P; Mauri, D; Polyzos, NP; Swenson, K; Tevaarwerk, AJ; Valachis, A, 2013)
"Treatment with zoledronic acid led to a statistically significant increase in hip BMD compared to placebo."	( Kähönen, M; Lahtela, J; Laine, HJ; Mäenpää, H; Mattila, P; Pakarinen, TK, 2013)
"Treatment with zoledronic acid decreased expression of self-renewal proteins, BMI-1 and Oct-4, and both prevented and eliminated mammosphere formation."	( Brodie, AH; Gilani, RA; Kazi, AA; Schech, AJ, 2013)
"Pre-treatment with zoledronic acid caused accumulation of an extra-cellular matrix in the growth plate associated with a trend towards preferential [1] homing of tumour cells to osteoblast-rich areas of bone, but without affecting the total number of tumour cells."	( Brown, HK; Dear, TN; Haider, MT; Holen, I; Hunter, K, 2014)
"Mice treated with zoledronic acid in combination with everolimus had more apoptotic lung cancer cells and more cells were arrested in the G1/G0 phase."	( Lu, S; Song, Z; Yang, S; Yang, X; Yu, Y; Zhang, J, 2014)
"Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. "	( Aglan, MS; El Banna, RA; Elnashar, M; Ibrahim, MM; Otaify, GA; Temtamy, SA, 2016)
"Treatment with zoledronic acid led to a significant increase in trabecular bone volume within the callus, as well as in callus resistance, compared to those in the saline control rats; delayed administration (ZOLW2) reduced intrinsic material properties, including ultimate stress and elastic modulus, and microarchitecture parameters, including bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), and connectivity density (Conn.D), compared with ZOLD1 at 12 weeks after surgery. "	( Dai, K; Ge, S; Hao, Y; Lu, Y; Mao, Z; Wang, L; Wang, X, 2015)
"Treatment with zoledronic acid in osteoporotic patients with spinal fusion shortens the duration of time to fusion, improves the fusion rate, prevents the subsequent adjacent vertebral compression fractures, improves the clinical outcomes, and prevents immobilization-induced bone loss in the hip."	( Chen, F; Dai, Z; Jiang, Y; Kang, Y; Keller, ET; Lv, G, 2016)
"Treatment with zoledronic acid in osteoporotic patients with spinal fusion shortens the time to fusion, improves the fusion rate, prevents subsequent aVCFs, and improves clinical outcomes."	( Chen, F; Dai, Z; Jiang, Y; Kang, Y; Keller, ET; Lv, G, 2016)
"Treatment with zoledronic acid was immediately discontinued."	( Bismuth, H; Brin, YS; Coughlin, R; Heler, Z; Kish, BJ; Nyska, M; Palmanovich, E; Rotman, P; Zehavi, T, 2015)
"Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected."	( Aigner, R; Friedl, G; Radl, R; Rehak, P; Stihsen, C; Windhager, R, 2009)
"Treatment with zoledronic acid amend partially this fault."	( Ajarim, D; Al-Hussein, K; Al-Sayed, A; Al-Sulaiman, A; Aljurf, MD; Alsharif, F; Alzahrani, H; Gaafar, A; Iqniebi, A; Manogaran, PS; Mohamed, GE; Mohareb, F; Tabakhi, A, 2009)
"Treatment with zoledronic acid as late as 2 weeks after ovariectomy still facilitates the full reversal of cancellous bone loss in the rat tibia."	( Fazzalari, NL; Le, V; Ma, B; Perilli, E; Reynolds, K; Salmon, P, 2010)
"Treatment with zoledronic acid increased the mineral content and tissue modulus relative to both the ovariectomised and control groups."	( Brennan, O; Kennedy, OD; Lee, TC; McNamara, LM; O'Brien, FJ; Rackard, SM, 2011)
"Treatment with zoledronic acid achieved the best response with only 2.9% failing to respond adequately."	( de Magalhães Souza Fialho, SC; Heiden, GI; Morato, EF; Neves, FS; Pereira, IA; Toscano, MA; Werner de Castro, GR; Zimmermann, AF, 2012)
"Treatment with Zoledronic acid (ZA) not only mitigated bone pain, but also rapidly improved of PSA and hematological findings."	( Hirata, H; Kanamaru, H; Kato, K; Nagahama, K; Yagibashi, Y; Yamamoto, M, 2011)
"Treatment with zoledronic acid impaired intratumoral MDSC accumulation resulting in delayed tumor growth rate, prolonged median survival, and increased recruitment of T cells to the tumor."	( Belt, BA; Gillanders, WE; Goedegebuure, P; Herndon, J; Hsieh, CS; Lee, HM; Linehan, DC; Mitchem, JB; Porembka, MR, 2012)
"The treatment of zoledronic acid followed by paclitaxel was superior to the other regimens (P < 0.05)."	( Huang, WL; Li, XY; Lin, SL; Lin, W; Lin, WZ; Lin, YC; Wang, HB, 2012)
"The treatment of zoledronic acid followed by paclitaxel may be the optimal regimen."	( Huang, WL; Li, XY; Lin, SL; Lin, W; Lin, WZ; Lin, YC; Wang, HB, 2012)
"Treatment with zoledronic acid had a clear effect on fracture events, and it might contribute an important role for overall survival."	( Huang, C; Huang, WW; Lin, L; Liu, J; Zheng, HY, 2012)
"Cotreatment with zoledronic acid, a potent osteoclast inhibitor, reduced IAP antagonist-enhanced tumor growth in bone and osteolysis."	( Collins, LI; Davis, JL; Faccio, R; Mach, RH; Novack, DV; Piwnica-Worms, D; Su, X; Vangveravong, S; Vora, P; Weilbaecher, KN; Yang, C; Zeng, R, 2013)
"Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial."	( Chen, BL; Coleman, RE; Dugan, W; Eisenberg, PD; Gordon, DH; Kaminski, M; Major, P; Provencher, L; Rosen, LS; Seaman, J; Simeone, J, 2004)
"Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo."	( Angus, PW; Byth, K; Crawford, BA; Handelsman, DJ; Kam, C; McCaughan, GW; Pavlovic, J, 2006)
"Treatment with zoledronic acid can prevent bone loss within the first year after liver transplantation."	( Angus, PW; Byth, K; Crawford, BA; Handelsman, DJ; Kam, C; McCaughan, GW; Pavlovic, J, 2006)
"Treatment with zoledronic acid in combination with doxycycline may be very beneficial for breast cancer patients at risk for osteolytic bone metastasis."	( Duivenvoorden, WC; Kalina, M; Seidlitz, E; Singh, G; Vukmirović-Popović, S, 2007)
"Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. "	( Black, DM; Boonen, S; Caminis, J; Cauley, JA; Cosman, F; Cummings, SR; Delmas, PD; Eastell, R; Eriksen, EF; Hu, H; Hue, TF; Krasnow, J; Lakatos, P; Leung, PC; Man, Z; Mautalen, C; Mesenbrink, P; Reid, IR; Rosario-Jansen, T; Sellmeyer, D; Tong, K, 2007)
"Treatment with zoledronic acid every 3 months preserved bone density and suppressed markers of bone turnover in patients with androgen-deprived prostate cancer, both with and without bone metastases."	( Bylow, K; Demers, LM; Henderson, TO; Huo, D; Ryan, CW; Stadler, WM; Vogelzang, NJ, 2007)
"Treatment with zoledronic acid (ZA) (100 ng/g) or placebo was started at the age of 10 weeks and administered every 2 weeks."	( Derese, I; Lories, RJ; Luyten, FP, 2008)
"Treatment with zoledronic acid and clinically achievable concentrations of paclitaxel resulted in a 4-5-fold increase in tumour cell apoptosis (P< 0.02)."	( Coleman, RE; Croucher, PI; Jagdev, SP; Rostami-H, A; Shipman, CM, 2001)

Role	Description
bone density conservation agent	An agent that inhibits bone resorption and/or favor bone mineralization and bone regeneration. Used to heal bone fractures and to treat bone diseases such as osteopenia and osteoporosis.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Class	Description
imidazoles	A five-membered organic heterocycle containing two nitrogen atoms at positions 1 and 3, or any of its derivatives; compounds containing an imidazole skeleton.
1,1-bis(phosphonic acid)	Any member of the class of phosphonic acids in which a carbon atom is directly attached to two phosphonic acid groups. They are analogues of pyrophosphates (with the central oxygen atom replaced by a carbon atom) and like pyrophosphates they tend to have a strong affinity for bone, so are frequently used for their antiresorptive and hypocalcaemic properties.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathway	Proteins	Compounds
Zoledronate Action Pathway	21	43

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Fumarate hydratase	Homo sapiens (human)	Potency	18.1796	0.0030	8.7949	48.0869	AID1347053
EWS/FLI fusion protein	Homo sapiens (human)	Potency	0.0400	0.0013	10.1577	42.8575	AID1259253; AID1259256
polyprotein	Zika virus	Potency	18.1796	0.0030	8.7949	48.0869	AID1347053
lamin isoform A-delta10	Homo sapiens (human)	Potency	0.6310	0.8913	12.0676	28.1838	AID1487
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
ATP-binding cassette sub-family C member 3	Homo sapiens (human)	IC50 (µMol)	133.0000	0.6315	4.4531	9.3000	AID1473740
Multidrug resistance-associated protein 4	Homo sapiens (human)	IC50 (µMol)	133.0000	0.2000	5.6774	10.0000	AID1473741
Carbonic anhydrase 12	Homo sapiens (human)	IC50 (µMol)	0.3160	0.0057	1.3990	8.5700	AID1125517; AID1152902
Bile salt export pump	Homo sapiens (human)	IC50 (µMol)	134.0000	0.1100	7.1903	10.0000	AID1443980; AID1473738
Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)	IC50 (µMol)	72.5413	0.0040	1.0276	4.5000	AID1638631; AID1798541; AID1801915; AID326141; AID326571; AID391371; AID669079
Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)	Ki	2.7000	1.8000	2.2500	2.7000	AID326142
Carbonic anhydrase 1	Homo sapiens (human)	IC50 (µMol)	10.0000	0.0058	2.1410	7.9000	AID1125514; AID1152899
Carbonic anhydrase 2	Homo sapiens (human)	IC50 (µMol)	0.0620	0.0002	1.1060	8.3000	AID1125515; AID1152900
72 kDa type IV collagenase	Homo sapiens (human)	IC50 (µMol)	7.0000	0.0000	1.2848	10.0000	AID1152905; AID779764
Farnesyl pyrophosphate synthase	Homo sapiens (human)	IC50 (µMol)	3.9102	0.0002	0.7109	9.3600	AID1197852; AID1205918; AID1224396; AID1421103; AID1519530; AID1540919; AID1617550; AID1617551; AID1617552; AID1617553; AID1617557; AID1617560; AID1617561; AID1638632; AID1801915; AID197532; AID318593; AID318594; AID390282; AID669073; AID669077; AID689987; AID734801; AID734803
Farnesyl pyrophosphate synthase	Homo sapiens (human)	Ki	0.0430	0.0001	0.2165	1.9000	AID318593; AID318594
Matrix metalloproteinase-9	Homo sapiens (human)	IC50 (µMol)	52.0000	0.0000	0.7053	10.0000	AID779762
Neutrophil collagenase	Homo sapiens (human)	IC50 (µMol)	17.6000	0.0000	0.9272	10.0000	AID779763
Farnesyl diphosphate synthase	Escherichia coli K-12	IC50 (µMol)	1.1000	1.1000	1.1000	1.1000	AID275060
Matrix metalloproteinase-14	Homo sapiens (human)	IC50 (µMol)	12.6000	0.0003	0.7182	10.0000	AID779761
Farnesyl pyrophosphate synthase	Leishmania donovani	IC50 (µMol)	0.1100	0.1100	0.1560	0.1700	AID72651
Farnesyl pyrophosphate synthase	Leishmania donovani	Ki	0.0110	0.0110	0.0782	0.1900	AID238531
Geranylgeranyl pyrophosphate synthase	Saccharomyces cerevisiae S288C	IC50 (µMol)	14.6491	0.0040	0.4120	0.7100	AID1801914; AID1801915; AID326139
Geranylgeranyl pyrophosphate synthase	Saccharomyces cerevisiae S288C	Ki	0.2600	0.1300	0.1950	0.2600	AID326140
Carbonic anhydrase 9	Homo sapiens (human)	IC50 (µMol)	5.3230	0.0003	0.6302	9.3900	AID1125516; AID1152901
Farnesyl pyrophosphate synthase	Leishmania major	Ki	0.0100	0.0100	0.0390	0.0910	AID1697964
H	Trypanosoma brucei	IC50 (µMol)	226.7000	2.1000	2.1000	2.1000	AID254970
Canalicular multispecific organic anion transporter 1	Homo sapiens (human)	IC50 (µMol)	133.0000	2.4100	6.3433	10.0000	AID1473739
Carbonic anhydrase 14	Homo sapiens (human)	IC50 (µMol)	0.0920	0.0200	0.5329	2.0000	AID1125518; AID1152903
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Butyrophilin subfamily 3 member A1	Homo sapiens (human)	EC50 (µMol)	41.1093	0.0001	0.4719	3.0600	AID1494447; AID1511946; AID1511947; AID1511948; AID1676481
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
positive regulation of cytokine production	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
adaptive immune response	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
positive regulation of type II interferon production	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
activated T cell proliferation	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
T cell receptor signaling pathway	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
regulation of cytokine production	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
xenobiotic metabolic process	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
bile acid and bile salt transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
glucuronoside transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
leukotriene transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
monoatomic anion transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
transport across blood-brain barrier	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
prostaglandin secretion	Multidrug resistance-associated protein 4	Homo sapiens (human)
cilium assembly	Multidrug resistance-associated protein 4	Homo sapiens (human)
platelet degranulation	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic metabolic process	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
bile acid and bile salt transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
prostaglandin transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
urate transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
glutathione transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
cAMP transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
leukotriene transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
monoatomic anion transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
export across plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
transport across blood-brain barrier	Multidrug resistance-associated protein 4	Homo sapiens (human)
guanine nucleotide transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
estrous cycle	Carbonic anhydrase 12	Homo sapiens (human)
chloride ion homeostasis	Carbonic anhydrase 12	Homo sapiens (human)
one-carbon metabolic process	Carbonic anhydrase 12	Homo sapiens (human)
fatty acid metabolic process	Bile salt export pump	Homo sapiens (human)
bile acid biosynthetic process	Bile salt export pump	Homo sapiens (human)
xenobiotic metabolic process	Bile salt export pump	Homo sapiens (human)
xenobiotic transmembrane transport	Bile salt export pump	Homo sapiens (human)
response to oxidative stress	Bile salt export pump	Homo sapiens (human)
bile acid metabolic process	Bile salt export pump	Homo sapiens (human)
response to organic cyclic compound	Bile salt export pump	Homo sapiens (human)
bile acid and bile salt transport	Bile salt export pump	Homo sapiens (human)
canalicular bile acid transport	Bile salt export pump	Homo sapiens (human)
protein ubiquitination	Bile salt export pump	Homo sapiens (human)
regulation of fatty acid beta-oxidation	Bile salt export pump	Homo sapiens (human)
carbohydrate transmembrane transport	Bile salt export pump	Homo sapiens (human)
bile acid signaling pathway	Bile salt export pump	Homo sapiens (human)
cholesterol homeostasis	Bile salt export pump	Homo sapiens (human)
response to estrogen	Bile salt export pump	Homo sapiens (human)
response to ethanol	Bile salt export pump	Homo sapiens (human)
xenobiotic export from cell	Bile salt export pump	Homo sapiens (human)
lipid homeostasis	Bile salt export pump	Homo sapiens (human)
phospholipid homeostasis	Bile salt export pump	Homo sapiens (human)
positive regulation of bile acid secretion	Bile salt export pump	Homo sapiens (human)
regulation of bile acid metabolic process	Bile salt export pump	Homo sapiens (human)
transmembrane transport	Bile salt export pump	Homo sapiens (human)
isoprenoid metabolic process	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
geranyl diphosphate biosynthetic process	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
geranylgeranyl diphosphate biosynthetic process	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
farnesyl diphosphate biosynthetic process	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
isoprenoid biosynthetic process	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
one-carbon metabolic process	Carbonic anhydrase 1	Homo sapiens (human)
morphogenesis of an epithelium	Carbonic anhydrase 2	Homo sapiens (human)
positive regulation of synaptic transmission, GABAergic	Carbonic anhydrase 2	Homo sapiens (human)
positive regulation of cellular pH reduction	Carbonic anhydrase 2	Homo sapiens (human)
angiotensin-activated signaling pathway	Carbonic anhydrase 2	Homo sapiens (human)
regulation of monoatomic anion transport	Carbonic anhydrase 2	Homo sapiens (human)
secretion	Carbonic anhydrase 2	Homo sapiens (human)
regulation of intracellular pH	Carbonic anhydrase 2	Homo sapiens (human)
neuron cellular homeostasis	Carbonic anhydrase 2	Homo sapiens (human)
positive regulation of dipeptide transmembrane transport	Carbonic anhydrase 2	Homo sapiens (human)
regulation of chloride transport	Carbonic anhydrase 2	Homo sapiens (human)
carbon dioxide transport	Carbonic anhydrase 2	Homo sapiens (human)
one-carbon metabolic process	Carbonic anhydrase 2	Homo sapiens (human)
angiogenesis	72 kDa type IV collagenase	Homo sapiens (human)
ovarian follicle development	72 kDa type IV collagenase	Homo sapiens (human)
ovulation from ovarian follicle	72 kDa type IV collagenase	Homo sapiens (human)
luteinization	72 kDa type IV collagenase	Homo sapiens (human)
blood vessel maturation	72 kDa type IV collagenase	Homo sapiens (human)
intramembranous ossification	72 kDa type IV collagenase	Homo sapiens (human)
proteolysis	72 kDa type IV collagenase	Homo sapiens (human)
negative regulation of cell adhesion	72 kDa type IV collagenase	Homo sapiens (human)
heart development	72 kDa type IV collagenase	Homo sapiens (human)
embryo implantation	72 kDa type IV collagenase	Homo sapiens (human)
parturition	72 kDa type IV collagenase	Homo sapiens (human)
response to xenobiotic stimulus	72 kDa type IV collagenase	Homo sapiens (human)
response to mechanical stimulus	72 kDa type IV collagenase	Homo sapiens (human)
peripheral nervous system axon regeneration	72 kDa type IV collagenase	Homo sapiens (human)
response to activity	72 kDa type IV collagenase	Homo sapiens (human)
protein metabolic process	72 kDa type IV collagenase	Homo sapiens (human)
extracellular matrix disassembly	72 kDa type IV collagenase	Homo sapiens (human)
protein catabolic process	72 kDa type IV collagenase	Homo sapiens (human)
positive regulation of cell migration	72 kDa type IV collagenase	Homo sapiens (human)
collagen catabolic process	72 kDa type IV collagenase	Homo sapiens (human)
response to retinoic acid	72 kDa type IV collagenase	Homo sapiens (human)
cellular response to reactive oxygen species	72 kDa type IV collagenase	Homo sapiens (human)
response to nicotine	72 kDa type IV collagenase	Homo sapiens (human)
endodermal cell differentiation	72 kDa type IV collagenase	Homo sapiens (human)
response to hydrogen peroxide	72 kDa type IV collagenase	Homo sapiens (human)
response to estrogen	72 kDa type IV collagenase	Homo sapiens (human)
negative regulation of vasoconstriction	72 kDa type IV collagenase	Homo sapiens (human)
ephrin receptor signaling pathway	72 kDa type IV collagenase	Homo sapiens (human)
macrophage chemotaxis	72 kDa type IV collagenase	Homo sapiens (human)
response to electrical stimulus	72 kDa type IV collagenase	Homo sapiens (human)
response to hyperoxia	72 kDa type IV collagenase	Homo sapiens (human)
face morphogenesis	72 kDa type IV collagenase	Homo sapiens (human)
bone trabecula formation	72 kDa type IV collagenase	Homo sapiens (human)
prostate gland epithelium morphogenesis	72 kDa type IV collagenase	Homo sapiens (human)
cellular response to amino acid stimulus	72 kDa type IV collagenase	Homo sapiens (human)
cellular response to interleukin-1	72 kDa type IV collagenase	Homo sapiens (human)
cellular response to estradiol stimulus	72 kDa type IV collagenase	Homo sapiens (human)
cellular response to UV-A	72 kDa type IV collagenase	Homo sapiens (human)
cellular response to fluid shear stress	72 kDa type IV collagenase	Homo sapiens (human)
positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	72 kDa type IV collagenase	Homo sapiens (human)
response to amyloid-beta	72 kDa type IV collagenase	Homo sapiens (human)
positive regulation of vascular associated smooth muscle cell proliferation	72 kDa type IV collagenase	Homo sapiens (human)
extracellular matrix organization	72 kDa type IV collagenase	Homo sapiens (human)
response to hypoxia	72 kDa type IV collagenase	Homo sapiens (human)
tissue remodeling	72 kDa type IV collagenase	Homo sapiens (human)
cholesterol biosynthetic process	Farnesyl pyrophosphate synthase	Homo sapiens (human)
geranyl diphosphate biosynthetic process	Farnesyl pyrophosphate synthase	Homo sapiens (human)
farnesyl diphosphate biosynthetic process	Farnesyl pyrophosphate synthase	Homo sapiens (human)
skeletal system development	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of protein phosphorylation	Matrix metalloproteinase-9	Homo sapiens (human)
proteolysis	Matrix metalloproteinase-9	Homo sapiens (human)
apoptotic process	Matrix metalloproteinase-9	Homo sapiens (human)
embryo implantation	Matrix metalloproteinase-9	Homo sapiens (human)
cell migration	Matrix metalloproteinase-9	Homo sapiens (human)
extracellular matrix disassembly	Matrix metalloproteinase-9	Homo sapiens (human)
macrophage differentiation	Matrix metalloproteinase-9	Homo sapiens (human)
collagen catabolic process	Matrix metalloproteinase-9	Homo sapiens (human)
cellular response to reactive oxygen species	Matrix metalloproteinase-9	Homo sapiens (human)
endodermal cell differentiation	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of apoptotic process	Matrix metalloproteinase-9	Homo sapiens (human)
negative regulation of apoptotic process	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of DNA binding	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of epidermal growth factor receptor signaling pathway	Matrix metalloproteinase-9	Homo sapiens (human)
ephrin receptor signaling pathway	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of keratinocyte migration	Matrix metalloproteinase-9	Homo sapiens (human)
cellular response to lipopolysaccharide	Matrix metalloproteinase-9	Homo sapiens (human)
cellular response to cadmium ion	Matrix metalloproteinase-9	Homo sapiens (human)
cellular response to UV-A	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of release of cytochrome c from mitochondria	Matrix metalloproteinase-9	Homo sapiens (human)
regulation of neuroinflammatory response	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of receptor binding	Matrix metalloproteinase-9	Homo sapiens (human)
response to amyloid-beta	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of vascular associated smooth muscle cell proliferation	Matrix metalloproteinase-9	Homo sapiens (human)
negative regulation of epithelial cell differentiation involved in kidney development	Matrix metalloproteinase-9	Homo sapiens (human)
negative regulation of intrinsic apoptotic signaling pathway	Matrix metalloproteinase-9	Homo sapiens (human)
negative regulation of cation channel activity	Matrix metalloproteinase-9	Homo sapiens (human)
negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	Matrix metalloproteinase-9	Homo sapiens (human)
extracellular matrix organization	Matrix metalloproteinase-9	Homo sapiens (human)
positive regulation of microglial cell activation	Neutrophil collagenase	Homo sapiens (human)
proteolysis	Neutrophil collagenase	Homo sapiens (human)
extracellular matrix disassembly	Neutrophil collagenase	Homo sapiens (human)
collagen catabolic process	Neutrophil collagenase	Homo sapiens (human)
positive regulation of tumor necrosis factor production	Neutrophil collagenase	Homo sapiens (human)
endodermal cell differentiation	Neutrophil collagenase	Homo sapiens (human)
cellular response to lipopolysaccharide	Neutrophil collagenase	Homo sapiens (human)
positive regulation of neuroinflammatory response	Neutrophil collagenase	Homo sapiens (human)
positive regulation of tumor necrosis factor-mediated signaling pathway	Neutrophil collagenase	Homo sapiens (human)
extracellular matrix organization	Neutrophil collagenase	Homo sapiens (human)
geranyl diphosphate biosynthetic process	Farnesyl diphosphate synthase	Escherichia coli K-12
farnesyl diphosphate biosynthetic process	Farnesyl diphosphate synthase	Escherichia coli K-12
isoprenoid biosynthetic process	Farnesyl diphosphate synthase	Escherichia coli K-12
angiogenesis	Matrix metalloproteinase-14	Homo sapiens (human)
ovarian follicle development	Matrix metalloproteinase-14	Homo sapiens (human)
response to hypoxia	Matrix metalloproteinase-14	Homo sapiens (human)
endothelial cell proliferation	Matrix metalloproteinase-14	Homo sapiens (human)
endochondral ossification	Matrix metalloproteinase-14	Homo sapiens (human)
proteolysis	Matrix metalloproteinase-14	Homo sapiens (human)
response to oxidative stress	Matrix metalloproteinase-14	Homo sapiens (human)
male gonad development	Matrix metalloproteinase-14	Homo sapiens (human)
response to mechanical stimulus	Matrix metalloproteinase-14	Homo sapiens (human)
positive regulation of myotube differentiation	Matrix metalloproteinase-14	Homo sapiens (human)
positive regulation of protein processing	Matrix metalloproteinase-14	Homo sapiens (human)
response to organic cyclic compound	Matrix metalloproteinase-14	Homo sapiens (human)
protein processing	Matrix metalloproteinase-14	Homo sapiens (human)
extracellular matrix disassembly	Matrix metalloproteinase-14	Homo sapiens (human)
protein catabolic process	Matrix metalloproteinase-14	Homo sapiens (human)
positive regulation of cell growth	Matrix metalloproteinase-14	Homo sapiens (human)
lung development	Matrix metalloproteinase-14	Homo sapiens (human)
positive regulation of cell migration	Matrix metalloproteinase-14	Homo sapiens (human)
collagen catabolic process	Matrix metalloproteinase-14	Homo sapiens (human)
zymogen activation	Matrix metalloproteinase-14	Homo sapiens (human)
endodermal cell differentiation	Matrix metalloproteinase-14	Homo sapiens (human)
chondrocyte proliferation	Matrix metalloproteinase-14	Homo sapiens (human)
astrocyte cell migration	Matrix metalloproteinase-14	Homo sapiens (human)
response to estrogen	Matrix metalloproteinase-14	Homo sapiens (human)
positive regulation of B cell differentiation	Matrix metalloproteinase-14	Homo sapiens (human)
negative regulation of Notch signaling pathway	Matrix metalloproteinase-14	Homo sapiens (human)
embryonic cranial skeleton morphogenesis	Matrix metalloproteinase-14	Homo sapiens (human)
branching morphogenesis of an epithelial tube	Matrix metalloproteinase-14	Homo sapiens (human)
tissue remodeling	Matrix metalloproteinase-14	Homo sapiens (human)
cell motility	Matrix metalloproteinase-14	Homo sapiens (human)
negative regulation of focal adhesion assembly	Matrix metalloproteinase-14	Homo sapiens (human)
head development	Matrix metalloproteinase-14	Homo sapiens (human)
craniofacial suture morphogenesis	Matrix metalloproteinase-14	Homo sapiens (human)
negative regulation of GDF15-GFRAL signaling pathway	Matrix metalloproteinase-14	Homo sapiens (human)
regulation of protein localization to plasma membrane	Matrix metalloproteinase-14	Homo sapiens (human)
positive regulation of macrophage migration	Matrix metalloproteinase-14	Homo sapiens (human)
response to odorant	Matrix metalloproteinase-14	Homo sapiens (human)
extracellular matrix organization	Matrix metalloproteinase-14	Homo sapiens (human)
skeletal system development	Matrix metalloproteinase-14	Homo sapiens (human)
response to hypoxia	Carbonic anhydrase 9	Homo sapiens (human)
morphogenesis of an epithelium	Carbonic anhydrase 9	Homo sapiens (human)
response to xenobiotic stimulus	Carbonic anhydrase 9	Homo sapiens (human)
response to testosterone	Carbonic anhydrase 9	Homo sapiens (human)
secretion	Carbonic anhydrase 9	Homo sapiens (human)
one-carbon metabolic process	Carbonic anhydrase 9	Homo sapiens (human)
xenobiotic metabolic process	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
negative regulation of gene expression	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bile acid and bile salt transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bilirubin transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
heme catabolic process	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic export from cell	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transepithelial transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
leukotriene transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
monoatomic anion transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transport across blood-brain barrier	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transport across blood-brain barrier	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
one-carbon metabolic process	Carbonic anhydrase 14	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
protein binding	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
signaling receptor binding	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
ATP binding	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type xenobiotic transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
glucuronoside transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type bile acid transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATP hydrolysis activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
icosanoid transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
guanine nucleotide transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
protein binding	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATP binding	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
prostaglandin transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
urate transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
purine nucleotide transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type bile acid transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
efflux transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATP hydrolysis activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
glutathione transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
zinc ion binding	Carbonic anhydrase 12	Homo sapiens (human)
carbonate dehydratase activity	Carbonic anhydrase 12	Homo sapiens (human)
protein binding	Bile salt export pump	Homo sapiens (human)
ATP binding	Bile salt export pump	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Bile salt export pump	Homo sapiens (human)
bile acid transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
canalicular bile acid transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
carbohydrate transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
ABC-type bile acid transporter activity	Bile salt export pump	Homo sapiens (human)
ATP hydrolysis activity	Bile salt export pump	Homo sapiens (human)
dimethylallyltranstransferase activity	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
farnesyltranstransferase activity	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
geranyltranstransferase activity	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
protein binding	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
identical protein binding	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
metal ion binding	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
prenyltransferase activity	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
arylesterase activity	Carbonic anhydrase 1	Homo sapiens (human)
carbonate dehydratase activity	Carbonic anhydrase 1	Homo sapiens (human)
protein binding	Carbonic anhydrase 1	Homo sapiens (human)
zinc ion binding	Carbonic anhydrase 1	Homo sapiens (human)
hydro-lyase activity	Carbonic anhydrase 1	Homo sapiens (human)
cyanamide hydratase activity	Carbonic anhydrase 1	Homo sapiens (human)
arylesterase activity	Carbonic anhydrase 2	Homo sapiens (human)
carbonate dehydratase activity	Carbonic anhydrase 2	Homo sapiens (human)
protein binding	Carbonic anhydrase 2	Homo sapiens (human)
zinc ion binding	Carbonic anhydrase 2	Homo sapiens (human)
cyanamide hydratase activity	Carbonic anhydrase 2	Homo sapiens (human)
fibronectin binding	72 kDa type IV collagenase	Homo sapiens (human)
endopeptidase activity	72 kDa type IV collagenase	Homo sapiens (human)
metalloendopeptidase activity	72 kDa type IV collagenase	Homo sapiens (human)
serine-type endopeptidase activity	72 kDa type IV collagenase	Homo sapiens (human)
protein binding	72 kDa type IV collagenase	Homo sapiens (human)
metallopeptidase activity	72 kDa type IV collagenase	Homo sapiens (human)
zinc ion binding	72 kDa type IV collagenase	Homo sapiens (human)
RNA binding	Farnesyl pyrophosphate synthase	Homo sapiens (human)
protein binding	Farnesyl pyrophosphate synthase	Homo sapiens (human)
metal ion binding	Farnesyl pyrophosphate synthase	Homo sapiens (human)
dimethylallyltranstransferase activity	Farnesyl pyrophosphate synthase	Homo sapiens (human)
geranyltranstransferase activity	Farnesyl pyrophosphate synthase	Homo sapiens (human)
endopeptidase activity	Matrix metalloproteinase-9	Homo sapiens (human)
metalloendopeptidase activity	Matrix metalloproteinase-9	Homo sapiens (human)
serine-type endopeptidase activity	Matrix metalloproteinase-9	Homo sapiens (human)
protein binding	Matrix metalloproteinase-9	Homo sapiens (human)
collagen binding	Matrix metalloproteinase-9	Homo sapiens (human)
peptidase activity	Matrix metalloproteinase-9	Homo sapiens (human)
metallopeptidase activity	Matrix metalloproteinase-9	Homo sapiens (human)
zinc ion binding	Matrix metalloproteinase-9	Homo sapiens (human)
identical protein binding	Matrix metalloproteinase-9	Homo sapiens (human)
endopeptidase activity	Neutrophil collagenase	Homo sapiens (human)
metalloendopeptidase activity	Neutrophil collagenase	Homo sapiens (human)
serine-type endopeptidase activity	Neutrophil collagenase	Homo sapiens (human)
peptidase activity	Neutrophil collagenase	Homo sapiens (human)
zinc ion binding	Neutrophil collagenase	Homo sapiens (human)
tumor necrosis factor binding	Neutrophil collagenase	Homo sapiens (human)
dimethylallyltranstransferase activity	Farnesyl diphosphate synthase	Escherichia coli K-12
geranyltranstransferase activity	Farnesyl diphosphate synthase	Escherichia coli K-12
prenyltransferase activity	Farnesyl diphosphate synthase	Escherichia coli K-12
protein binding	Farnesyl diphosphate synthase	Escherichia coli K-12
transferase activity	Farnesyl diphosphate synthase	Escherichia coli K-12
metal ion binding	Farnesyl diphosphate synthase	Escherichia coli K-12
endopeptidase activity	Matrix metalloproteinase-14	Homo sapiens (human)
metalloendopeptidase activity	Matrix metalloproteinase-14	Homo sapiens (human)
serine-type endopeptidase activity	Matrix metalloproteinase-14	Homo sapiens (human)
integrin binding	Matrix metalloproteinase-14	Homo sapiens (human)
protein binding	Matrix metalloproteinase-14	Homo sapiens (human)
zinc ion binding	Matrix metalloproteinase-14	Homo sapiens (human)
metalloaminopeptidase activity	Matrix metalloproteinase-14	Homo sapiens (human)
carbonate dehydratase activity	Carbonic anhydrase 9	Homo sapiens (human)
protein binding	Carbonic anhydrase 9	Homo sapiens (human)
zinc ion binding	Carbonic anhydrase 9	Homo sapiens (human)
molecular function activator activity	Carbonic anhydrase 9	Homo sapiens (human)
protein binding	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATP binding	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
organic anion transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bilirubin transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATP hydrolysis activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
zinc ion binding	Carbonic anhydrase 14	Homo sapiens (human)
carbonate dehydratase activity	Carbonic anhydrase 14	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
plasma membrane	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
external side of plasma membrane	Butyrophilin subfamily 3 member A1	Homo sapiens (human)
plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
basal plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
basolateral plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
nucleolus	Multidrug resistance-associated protein 4	Homo sapiens (human)
Golgi apparatus	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
basolateral plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
apical plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
platelet dense granule membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
external side of apical plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 12	Homo sapiens (human)
membrane	Carbonic anhydrase 12	Homo sapiens (human)
basolateral plasma membrane	Carbonic anhydrase 12	Homo sapiens (human)
apical plasma membrane	Carbonic anhydrase 12	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 12	Homo sapiens (human)
basolateral plasma membrane	Bile salt export pump	Homo sapiens (human)
Golgi membrane	Bile salt export pump	Homo sapiens (human)
endosome	Bile salt export pump	Homo sapiens (human)
plasma membrane	Bile salt export pump	Homo sapiens (human)
cell surface	Bile salt export pump	Homo sapiens (human)
apical plasma membrane	Bile salt export pump	Homo sapiens (human)
intercellular canaliculus	Bile salt export pump	Homo sapiens (human)
intracellular canaliculus	Bile salt export pump	Homo sapiens (human)
recycling endosome	Bile salt export pump	Homo sapiens (human)
recycling endosome membrane	Bile salt export pump	Homo sapiens (human)
extracellular exosome	Bile salt export pump	Homo sapiens (human)
membrane	Bile salt export pump	Homo sapiens (human)
nucleoplasm	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
cytoplasm	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
cytosol	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
Z disc	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
perinuclear region of cytoplasm	Geranylgeranyl pyrophosphate synthase	Homo sapiens (human)
cytosol	Carbonic anhydrase 1	Homo sapiens (human)
extracellular exosome	Carbonic anhydrase 1	Homo sapiens (human)
cytoplasm	Carbonic anhydrase 2	Homo sapiens (human)
cytosol	Carbonic anhydrase 2	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 2	Homo sapiens (human)
myelin sheath	Carbonic anhydrase 2	Homo sapiens (human)
apical part of cell	Carbonic anhydrase 2	Homo sapiens (human)
extracellular exosome	Carbonic anhydrase 2	Homo sapiens (human)
cytoplasm	Carbonic anhydrase 2	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 2	Homo sapiens (human)
apical part of cell	Carbonic anhydrase 2	Homo sapiens (human)
collagen-containing extracellular matrix	72 kDa type IV collagenase	Homo sapiens (human)
extracellular region	72 kDa type IV collagenase	Homo sapiens (human)
extracellular space	72 kDa type IV collagenase	Homo sapiens (human)
nucleus	72 kDa type IV collagenase	Homo sapiens (human)
mitochondrion	72 kDa type IV collagenase	Homo sapiens (human)
plasma membrane	72 kDa type IV collagenase	Homo sapiens (human)
sarcomere	72 kDa type IV collagenase	Homo sapiens (human)
collagen-containing extracellular matrix	72 kDa type IV collagenase	Homo sapiens (human)
extracellular space	72 kDa type IV collagenase	Homo sapiens (human)
nucleoplasm	Farnesyl pyrophosphate synthase	Homo sapiens (human)
cytosol	Farnesyl pyrophosphate synthase	Homo sapiens (human)
cytoplasm	Farnesyl pyrophosphate synthase	Homo sapiens (human)
extracellular region	Matrix metalloproteinase-9	Homo sapiens (human)
extracellular space	Matrix metalloproteinase-9	Homo sapiens (human)
collagen-containing extracellular matrix	Matrix metalloproteinase-9	Homo sapiens (human)
extracellular exosome	Matrix metalloproteinase-9	Homo sapiens (human)
tertiary granule lumen	Matrix metalloproteinase-9	Homo sapiens (human)
ficolin-1-rich granule lumen	Matrix metalloproteinase-9	Homo sapiens (human)
extracellular space	Matrix metalloproteinase-9	Homo sapiens (human)
extracellular region	Neutrophil collagenase	Homo sapiens (human)
extracellular space	Neutrophil collagenase	Homo sapiens (human)
specific granule lumen	Neutrophil collagenase	Homo sapiens (human)
collagen-containing extracellular matrix	Neutrophil collagenase	Homo sapiens (human)
tertiary granule lumen	Neutrophil collagenase	Homo sapiens (human)
extracellular space	Neutrophil collagenase	Homo sapiens (human)
cytoplasm	Farnesyl diphosphate synthase	Escherichia coli K-12
cytosol	Farnesyl diphosphate synthase	Escherichia coli K-12
cytoplasm	Matrix metalloproteinase-14	Homo sapiens (human)
plasma membrane	Matrix metalloproteinase-14	Homo sapiens (human)
extracellular space	Matrix metalloproteinase-14	Homo sapiens (human)
nucleus	Matrix metalloproteinase-14	Homo sapiens (human)
Golgi lumen	Matrix metalloproteinase-14	Homo sapiens (human)
cytosol	Matrix metalloproteinase-14	Homo sapiens (human)
plasma membrane	Matrix metalloproteinase-14	Homo sapiens (human)
focal adhesion	Matrix metalloproteinase-14	Homo sapiens (human)
extracellular matrix	Matrix metalloproteinase-14	Homo sapiens (human)
cytoplasmic vesicle	Matrix metalloproteinase-14	Homo sapiens (human)
melanosome	Matrix metalloproteinase-14	Homo sapiens (human)
macropinosome	Matrix metalloproteinase-14	Homo sapiens (human)
intermediate filament cytoskeleton	Matrix metalloproteinase-14	Homo sapiens (human)
extracellular space	Matrix metalloproteinase-14	Homo sapiens (human)
nucleolus	Carbonic anhydrase 9	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 9	Homo sapiens (human)
membrane	Carbonic anhydrase 9	Homo sapiens (human)
basolateral plasma membrane	Carbonic anhydrase 9	Homo sapiens (human)
microvillus membrane	Carbonic anhydrase 9	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 9	Homo sapiens (human)
plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
cell surface	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
apical plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
intercellular canaliculus	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
apical plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 14	Homo sapiens (human)
membrane	Carbonic anhydrase 14	Homo sapiens (human)
basolateral plasma membrane	Carbonic anhydrase 14	Homo sapiens (human)
apical plasma membrane	Carbonic anhydrase 14	Homo sapiens (human)
plasma membrane	Carbonic anhydrase 14	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (284)

Assay ID	Title	Year	Journal	Article
AID132683	Inhibition of bone resorption in the calvaria assay of mouse	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1584453	Induction of apoptosis in human RPMI8226 cells assessed as viable cells at 1 uM after 72 hrs by APC Annexin V/eFluor-780-viability double staining-based FACS analysis (Rvb = 87.3%)	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID1421112	Induction of mineralization in mouse MC3T3-E1 cells at >500 nM after 10 to 15 days by alizarin red dye based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1511947	Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 60 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	2019	ACS medicinal chemistry letters, Sep-12, Volume: 10, Issue:9	Synthesis and Bioactivity of the Alanyl Phosphonamidate Stereoisomers Derived from a Butyrophilin Ligand.
AID197532	Negative logarithm of inhibitory concentration against bone resorption	2003	Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14	A quantitative structure-activity relationship and pharmacophore modeling investigation of aryl-X and heterocyclic bisphosphonates as bone resorption agents.
AID390272	Induction of apoptosis in human K-562 cells expressing Bcr-Abl at 100 uM by flow cytometry	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID244679	Therapeutic index (TI) value as ratio of lethal dose (LD50) to the inhibitory concentration (IC50)	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID326141	Inhibition of human GGPPS	2007	Proceedings of the National Academy of Sciences of the United States of America, Jun-12, Volume: 104, Issue:24	Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AID1584455	Induction of apoptosis in human RPMI8226 cells assessed as late apoptotic cells at 1 uM after 72 hrs by APC Annexin V/eFluor-780-viability double staining-based FACS analysis (Rvb = 5.80%)	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID425653	Renal clearance in human	2009	Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15	Physicochemical determinants of human renal clearance.
AID1894084	Drug uptake in Beagle dog aorta at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1699997	Cytotoxicity against human BXPC-3 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	2020	Bioorganic & medicinal chemistry letters, 12-01, Volume: 30, Issue:23	Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility.
AID1054146	Cytotoxicity against human RPMI8226 cells after 72 hrs by MTT assay	2013	Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20	Thienopyrimidine bisphosphonate (ThPBP) inhibitors of the human farnesyl pyrophosphate synthase: optimization and characterization of the mode of inhibition.
AID1494455	Upregulation of CD69/CD25 levels in human CD8-positive T cells expressing alpha-beta TCR	2018	Journal of medicinal chemistry, 03-08, Volume: 61, Issue:5	Synthesis and Biological Evaluation of ( E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses.
AID248987	Inhibitory concentration against the growth of Toxoplasma gondii overexpressing FPPS enzyme in human foreskin fibroblast monolayer cells; (control = 0.60 uM, experiment 1)	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID1179734	Antiproliferative activity against mouse J774E cells after 72 hrs by MTT assay	2014	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 24, Issue:15	Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.
AID1421102	Inhibition of recombinant human C-terminal His6-tagged FPPS expressed in Escherichia coli BL21 at 1 uM using DMAPP and IPP as substrates pretreated for 15 mins followed by substrates addition and measured after 1 hr by colorimetric method relative to cont	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1617560	Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) assessed as using GPP and IPP as substrate preincubated for 30 mins followed by substrate addition in presence of 0.01 % Triton X-100	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID1617577	Induction of apoptosis in human PANC1 cells assessed as late apoptotic cells at 10 uM measured after 48 hrs by Annexin-V/FITC and propidium iodide staining based flow cytometry (Rvb = 1.86 %)	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID540213	Half life in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1700507	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on bone formation by measuring mineralizing surface per trabecular bone surface level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (27.90 +/ 8.22 %)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID270722	Antiproliferative activity against human MCF7 cell line by MTT assay	2006	Journal of medicinal chemistry, Sep-21, Volume: 49, Issue:19	Activity of nitrogen-containing and non-nitrogen-containing bisphosphonates on tumor cell lines.
AID235771	Therapeutic ratio comparing nephrotoxic potential versus bone antiresorptive potency (reciprocal of ED50 (TPTX assay) / the total urinary malate dehydrogenase excretion)	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1129545	Cytotoxicity against human HuH7 cells after 144 hrs by MTT assay	2014	European journal of medicinal chemistry, Apr-22, Volume: 77	Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells.
AID249161	Lethal dose required to inhibit the growth of human KB (nasopharyngeal carcinoma) cell line	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID390271	Induction of apoptosis in human HUT78 cells at 100 uM by flow cytometry	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1152905	Inhibition of human recombinant MMP-2 pretreated for 30 mins measured 2 to 4 hrs after Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate addition by fluorescence analysis	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID1421113	Induction of mineralization in C57BL mouse bone marrow cells at >50 nM supplemented with fresh medium containing compound every 3 days for 10 to 15 days by alizarin red dye based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1699999	Cytotoxicity against human PANC-1 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	2020	Bioorganic & medicinal chemistry letters, 12-01, Volume: 30, Issue:23	Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility.
AID197464	Effective dose for increased cancellous bone hydroxy proline in young intact rats after a treatment period of 10 days	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1700484	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as serum CTX-1 level in tibial diaphysis at 100 ug/kg, sc QD for 4 weeks (165.38 +/- 54.93 %)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID254970	Inhibition of recombinant Trypanosoma brucei soluble vacuolar pyrophosphatase expressed in Escherichia coli	2005	Journal of medicinal chemistry, Sep-22, Volume: 48, Issue:19	Bisphosphonate inhibition of the exopolyphosphatase activity of the Trypanosoma brucei soluble vacuolar pyrophosphatase.
AID246048	Effective concentration against human Gamma delta T cells	2005	Journal of medicinal chemistry, Apr-21, Volume: 48, Issue:8	Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption.
AID390274	Induction of apoptosis in human CEM-VBL300 cells expressing p-glycoprotein at 100 uM by flow cytometry	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID270723	Antiproliferative activity against human NCI-H460 cell line by MTT assay	2006	Journal of medicinal chemistry, Sep-21, Volume: 49, Issue:19	Activity of nitrogen-containing and non-nitrogen-containing bisphosphonates on tumor cell lines.
AID210170	Effective dose after subcutaneous administration to TPTX rats for 50% reduction of hypercalcemia	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1224403	Inhibition of FPPS in human SH-SY5Y cells assessed as blocking of tau metabolism by measuring ratio of tau phosphorylation to total tau level at 100 nM after 24 hrs by ELISA (Rvb = 0.012 no-unit)	2014	Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13	Multistage screening reveals chameleon ligands of the human farnesyl pyrophosphate synthase: implications to drug discovery for neurodegenerative diseases.
AID158550	In vitro growth inhibition against Plasmodium falciparum	2004	Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1	Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID1700505	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on bone formation by measuring number of osteoblasts per bone surface level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (4.55 +/ 2.53 /mm)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1179735	Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay	2014	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 24, Issue:15	Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.
AID390283	Induction of apoptosis in human K-562 cells expressing Bcr-Abl at <50 uM by flow cytometry	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1700510	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on bone formation by measuring osteocalcin level at 100 ug/kg, sc QD for 4 weeks (1.62 +/ 0.21 m3/um2/y)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID248977	Inhibitory concentration against the growth of Toxoplasma gondii overexpressing FPPS enzyme in human foreskin fibroblast monolayer cells; (control = 1.1 uM, experiment 2)	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID734802	Activation of human CD4+ Vgamma2/Vdelta2 T cell clone JN.23 assessed as TNF-alpha release after 16 hrs by sandwich ELISA in presence of antigen presenting cell line, CP.EBV	2013	ACS medicinal chemistry letters, Apr-11, Volume: 4, Issue:4	Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis.
AID1894095	Antiparasitic activity against Trypanosoma cruzi amastigotes infected in vero cells assessed as parasite growth inhibition incubated for 48 hrs by light microscopy	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1125514	Inhibition of human recombinant carbonic anhydrase 1 preincubated for 15 mins by stopped flow CO2 hydration method	2014	Bioorganic & medicinal chemistry letters, Apr-15, Volume: 24, Issue:8	Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.
AID1356185	Immunomodulatory activity in HUVEC assessed as inhibition of IFNgamma-induced MHC-1 expression at 10 uM pretreated for 1 hr followed by IFNgamma stimulation and measured after 48 hrs by immunostaining based flow cytometry relative to control	2018	Journal of natural products, 08-24, Volume: 81, Issue:8	Additional Insights into Hypericum perforatum Content: Isolation, Total Synthesis, and Absolute Configuration of Hyperbiphenyls A and B from Immunomodulatory Root Extracts.
AID689987	Inhibition of recombinant human FPPS expressed in Escherichia coli by scintillation counting	2011	Journal of medicinal chemistry, Sep-08, Volume: 54, Issue:17	Remarkable potential of the α-aminophosphonate/phosphinate structural motif in medicinal chemistry.
AID1617552	Competitive inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using DMAPP and GPP as substrate	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID275054	Antibacterial activity against Escherichia coli W3110	2006	Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25	Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.
AID1224396	Allosteric inhibition of human recombinant FPPS using GPP and [3H]IPP as substrate incubated with enzyme for 10 mins prior to substrate addition by liquid scintillation counting analysis	2014	Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13	Multistage screening reveals chameleon ligands of the human farnesyl pyrophosphate synthase: implications to drug discovery for neurodegenerative diseases.
AID1421103	Inhibition of recombinant human C-terminal His6-tagged FPPS expressed in Escherichia coli BL21 using DMAPP and IPP as substrates pretreated for 15 mins followed by substrates addition and measured after 1 hr by colorimetric method	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1421082	Antiproliferative activity against mouse J774A.1 cells assessed as change in cell proliferation at 100 uM after 72 hrs by crystal violet staining based assay relative to control	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1421083	Antiproliferative activity against mouse RAW264.7 cells assessed as change in cell proliferation at 100 uM after 72 hrs by crystal violet staining based assay relative to control	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1700483	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as cortical thickness level in tibial diaphysis at 100 ug/kg, sc QD for 4 weeks by microCT analysis (179.27 +/- 7.57 um)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID758729	Binding affinity to hydroxyapatite at 0.07 mmol up to 120 hrs by 31P NMR-spectroscopy relative to H3PO4	2013	European journal of medicinal chemistry, Jul, Volume: 65	Low toxicity and unprecedented anti-osteoclast activity of a simple sulfur-containing gem-bisphosphonate: a comparative study.
AID625292	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1421110	Induction of cell proliferation in C57BL mouse bone marrow cells at 100 nM after 72 hrs by crystal violet staining based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1129565	Antimigratory activity against human HuH7 cells at 100 uM after 24 hrs relative to control	2014	European journal of medicinal chemistry, Apr-22, Volume: 77	Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells.
AID1421092	Antiproliferative activity against human MG63 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1617556	Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged GGPPS expressed in Escherichia coli BL21 (DE3) using FPP and [14C] IPP as substrate preincubated for 15 mins with FPP followed by [14C] IPP addition and further incubated for 20 m	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID734803	Inhibition of His6-tagged human truncated FPPS (6-353) expressed in Escherichia coli BL21(DE3) cells using geranyl diphosphate and isopentenyl diphosphate as substrate preincubated with enzyme for 30 mins by spectrophotometric analysis	2013	ACS medicinal chemistry letters, Apr-11, Volume: 4, Issue:4	Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis.
AID1421107	Induction of mineralization in C57BL mouse bone marrow cells co-cultured with human PC3 cells at 50 to 100 nM supplemented with fresh medium containing compound every 3 days for 10 to 15 days by alizarin red dye based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID625284	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID390277	Antitumor activity against human BT-549 cells xenografted SCID mouse assessed as survival time prolongation at 5 ug, ip	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1894094	Antiparasitic activity against Trypanosoma brucei rhodesiense STIB900 bloodstream trypomastigotes assessed as parasite growth inhibition incubated for 3 days by Alamar Blue fluorometric assay	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1617588	Induction of apoptosis in human PANC1 cells at 20 uM measured after 48 hrs in presence of GGOH and FOH by Annexin-V FITC/propidium iodide staining-based flow cytometry	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID540209	Volume of distribution at steady state in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID625291	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1421099	Inhibition of recombinant human C-terminal His6-tagged GGPPS expressed in Escherichia coli BL21 at 100 uM using IPP and FPP as substrates pretreated for 15 mins followed by substrates addition and measured after 1 hr by colorimetric method relative to con	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1125515	Inhibition of human recombinant carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration method	2014	Bioorganic & medicinal chemistry letters, Apr-15, Volume: 24, Issue:8	Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.
AID326139	Inhibition of Saccharomyces cerevisiae GGPPS	2007	Proceedings of the National Academy of Sciences of the United States of America, Jun-12, Volume: 104, Issue:24	Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AID496826	Antimicrobial activity against Entamoeba histolytica	2010	Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6	Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1125518	Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method	2014	Bioorganic & medicinal chemistry letters, Apr-15, Volume: 24, Issue:8	Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.
AID1700480	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as trabecular pattern factor level in tibial metaphysis at 100 ug/kg, sc QD for 4 weeks by microCT analysis (17.17 +/- 3.41 um/day)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1205918	Inhibition of human FPPS pre-incubated for 30 mins using GPP and IPP by continuous spectrophotometric assay	2015	ACS medicinal chemistry letters, Mar-12, Volume: 6, Issue:3	Farnesyl diphosphate synthase inhibitors with unique ligand-binding geometries.
AID1700470	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as trabecular bone volume per tissue volume level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (11.67 +/- 2.37%)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1617559	Ratio of IC50 for Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using GPP and [14C] IPP as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID197466	Effective dose for increased radiographic bone density in young intact rats after a treatment period of 10 days	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1511948	Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 240 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	2019	ACS medicinal chemistry letters, Sep-12, Volume: 10, Issue:9	Synthesis and Bioactivity of the Alanyl Phosphonamidate Stereoisomers Derived from a Butyrophilin Ligand.
AID625285	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1700477	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as trabecular number level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (2.99 +/- 0.80 /mm)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1717389	Cytotoxicity against FPPS-positive human HCT116 cells assessed as reduction in cell viability measured after 48 hrs by MTT assay	2020	European journal of medicinal chemistry, Jan-15, Volume: 186	Structure-based virtual screening and biological evaluation of novel non-bisphosphonate farnesyl pyrophosphate synthase inhibitors.
AID326571	Inhibition of GST-tagged human recombinant GGDPS expressed in BL21 gold bacteria	2008	Bioorganic & medicinal chemistry, Jan-01, Volume: 16, Issue:1	Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.
AID197315	Effective dose for increased serum urea level rats after a treatment period of 1 hr in renal tolerability model	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1494449	Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cell-mediated lysis of human T24 cells preincubated for 4 hrs followed by compound washout measured after 18 hrs	2018	Journal of medicinal chemistry, 03-08, Volume: 61, Issue:5	Synthesis and Biological Evaluation of ( E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses.
AID1700001	Cytotoxicity against human SiHa cells assessed as cell growth inhibition	2020	Bioorganic & medicinal chemistry letters, 12-01, Volume: 30, Issue:23	Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility.
AID1474167	Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status	2016	Drug discovery today, Apr, Volume: 21, Issue:4	DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID67525	In vitro growth inhibition against Entamoeba histolytica	2004	Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1	Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID1700471	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on body weight at 100 ug/kg, sc QD for 4 weeks	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1152900	Inhibition of human recombinant carbonic anhydrase 2 pretreated for 15 mins by stopped flow CO2 hydrase assay	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID625280	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1894091	Drug uptake in Beagle dog liver at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1054150	Inhibition of human recombinant FPPS using GPP/[3H]IPP as substrate incubated for 10 mins prior to substrate addition measured after 8 mins by scintillation counting analysis	2013	Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20	Thienopyrimidine bisphosphonate (ThPBP) inhibitors of the human farnesyl pyrophosphate synthase: optimization and characterization of the mode of inhibition.
AID779761	Inhibition of MMP14 catalytic domain (unknown origin) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay	2013	Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21	Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors.
AID197476	Compound was tested for increased mucosal permeability of perfused ileal loop in rats after a treatment period of 2 hr in intestinal tolerability model	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID318595	Inhibition of bone resorption in rat assessed as phosphate	2008	Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7	Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
AID247940	Inhibitory concentration against Dictyostelium discoideum cell growth	2005	Journal of medicinal chemistry, Apr-21, Volume: 48, Issue:8	Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption.
AID1894082	Drug uptake in Beagle dog thyroid gland at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1125517	Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins by stopped flow CO2 hydration method	2014	Bioorganic & medicinal chemistry letters, Apr-15, Volume: 24, Issue:8	Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.
AID238531	Binding affinity towards Farnesyl diphosphate synthase from leishmania major	2005	Journal of medicinal chemistry, Apr-21, Volume: 48, Issue:8	Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption.
AID1894083	Drug uptake in Beagle dog knee cartilage at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID669082	Antiproliferative activity against human RPMI8266 after 72 hrs by MTT assay	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID318594	Inhibition of human recombinant FPPS expressed in Escherichia coli BL21 after 10 mins	2008	Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7	Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
AID1152901	Inhibition of human recombinant carbonic anhydrase 9 pretreated for 15 mins by stopped flow CO2 hydrase assay	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID1697964	Inhibition of recombinant Leishmania major FPPS expressed in Escherichia coli BL21(DE3) using GPP and [14C]IPP as substrate incubated for 15 mins by scintillation counting method	2020	Bioorganic & medicinal chemistry letters, 11-15, Volume: 30, Issue:22	A guanidinium-based inhibitor of a type I isopentenyl diphosphate isomerase.
AID197322	Effective dose for increased cancellous bone calcium in young intact rats after a treatment period of 10 days	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID390281	Antitumor activity against human BT-549 cells xenografted SCID mouse co-transfected with human gamma delta T lymphocytes assessed as survival time prolongation at 5 ug, ip coadministered with human recombinant IL2	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID391371	Inhibition of human recombinant geranylgeranyl diphosphate synthase	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.
AID540211	Fraction unbound in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1617575	Cytotoxicity against human MIAPaCa2 cells assessed as decrease in cell growth measured after 72 hrs by MTT assay	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID1894085	Drug uptake in Beagle dog heart at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1894092	Drug uptake in Beagle dog small intestine at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1129566	Antiinvasive activity against human HuH7 cells at 100 uM after 24 hrs by matrigel assay relative to control	2014	European journal of medicinal chemistry, Apr-22, Volume: 77	Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells.
AID1894093	Drug uptake in Beagle dog skin at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID625281	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1699998	Cytotoxicity against human CFPAC-1 cells assessed as cell growth inhibition measured after 72 hrs by MTT assay	2020	Bioorganic & medicinal chemistry letters, 12-01, Volume: 30, Issue:23	Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility.
AID255448	Ratio of ED50 against KB cell line to that of IC50 of TbVSP1	2005	Journal of medicinal chemistry, Sep-22, Volume: 48, Issue:19	Bisphosphonate inhibition of the exopolyphosphatase activity of the Trypanosoma brucei soluble vacuolar pyrophosphatase.
AID248989	Inhibitory concentration against the growth of Toxoplasma gondii overexpressing FPPS enzyme in human foreskin fibroblast monolayer cells; (control = 0.79 uM, experiment 3)	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID318593	Inhibition of human recombinant FPPS expressed in Escherichia coli BL21	2008	Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7	Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
AID1700506	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on bone formation by measuring osteoblast surface per trabecular bone surface level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (5.03 +/ 2.92 %)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID669081	Antiproliferative activity against human JJN-3 after 72 hrs by MTT assay	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID1152902	Inhibition of human recombinant carbonic anhydrase 12 pretreated for 15 mins by stopped flow CO2 hydrase assay	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID326140	Binding affinity to Saccharomyces cerevisiae GGPPS	2007	Proceedings of the National Academy of Sciences of the United States of America, Jun-12, Volume: 104, Issue:24	Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AID1717388	Cytotoxicity against FPPS-positive human Lovo cells assessed as reduction in cell viability measured after 48 hrs by MTT assay	2020	European journal of medicinal chemistry, Jan-15, Volume: 186	Structure-based virtual screening and biological evaluation of novel non-bisphosphonate farnesyl pyrophosphate synthase inhibitors.
AID390282	Inhibition of human FPP synthase expressed in Escherichia coli BL21 (DE3)	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1473741	Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1152899	Inhibition of human recombinant carbonic anhydrase 1 pretreated for 15 mins by stopped flow CO2 hydrase assay	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID1473739	Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1617550	Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using GPP and [14C] IPP as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by scintillation	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID779763	Inhibition of MMP8 catalytic domain (unknown origin) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay	2013	Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21	Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors.
AID1638632	Inhibition of human FPPS using IPP and GPP	2019	Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5	Discovery of Lipophilic Bisphosphonates That Target Bacterial Cell Wall and Quinone Biosynthesis.
AID625283	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID412958	Growth inhibition of Plasmodium falciparum	2008	Journal of medicinal chemistry, Dec-25, Volume: 51, Issue:24	Bisphosphonate inhibition of a Plasmodium farnesyl diphosphate synthase and a general method for predicting cell-based activity from enzyme data.
AID197320	Effective dose for increased cancellous bone area in young intact rats after a treatment period of 10 days	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1894098	Antiparasitic activity against Plasmodium falciparum 3D7 infected in human erythrocyte assessed as intraerythrocytic growth inhibition incubated for 24 hrs followed by [3H]hypoxanthine addition by microbeta scintillation counter analysis	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID412957	Inhibition of Plasmodium vivax FPPS expressed in Escherichia coli BL21 by spectrophotometric assay	2008	Journal of medicinal chemistry, Dec-25, Volume: 51, Issue:24	Bisphosphonate inhibition of a Plasmodium farnesyl diphosphate synthase and a general method for predicting cell-based activity from enzyme data.
AID625290	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID132685	Inhibition of mineralization in the calvaria assay of mouse	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID1421093	Antiproliferative activity against human PC3 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID248139	In vitro inhibitory concentration against bone resorption in 17 day old fetal mouse metatarsals	2005	Journal of medicinal chemistry, Apr-21, Volume: 48, Issue:8	Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption.
AID1421094	Antiproliferative activity against RANKL-differentiated mouse RAW264.7 cells assessed as reduction in cell viability at 100 uM after 72 hrs by CCK8 assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1540919	Inhibition of N-terminal His-tagged human FPPS (1 to 353 residues) expressed in Escherichia coli BL21 (DE3) pre-incubated for 10 mins before addition of GPP and [14C]-IPP by scintillation counting method	2019	Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21	Chirality-Driven Mode of Binding of α-Aminophosphonic Acid-Based Allosteric Inhibitors of the Human Farnesyl Pyrophosphate Synthase (hFPPS).
AID390275	Cytotoxicity against human CFU-GM cells at 100 uM after 48 hrs	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID248772	In vitro inhibitory concentration against the growth of Toxoplasma gondii in human foreskin fibroblast monolayer cells (HFF cells)	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
AID178213	Effective dose in inhibiting osteoclastic bone resorption	2003	Journal of medicinal chemistry, Jul-03, Volume: 46, Issue:14	A quantitative structure-activity relationship and pharmacophore modeling investigation of aryl-X and heterocyclic bisphosphonates as bone resorption agents.
AID1421104	Binding affinity to hydroxyapatite at 100 uM using sodium salt form of compound after 5 mins by ESI/MS analysis	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1197854	Reduction in hypercalcemia in sc dosed rat	2015	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 25, Issue:5	Probing the molecular and structural elements of ligands binding to the active site versus an allosteric pocket of the human farnesyl pyrophosphate synthase.
AID1152903	Inhibition of human recombinant carbonic anhydrase 14 pretreated for 15 mins by stopped flow CO2 hydrase assay	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID779762	Inhibition of MMP9 catalytic domain (unknown origin) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay	2013	Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21	Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors.
AID1511946	Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 15 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA	2019	ACS medicinal chemistry letters, Sep-12, Volume: 10, Issue:9	Synthesis and Bioactivity of the Alanyl Phosphonamidate Stereoisomers Derived from a Butyrophilin Ligand.
AID72651	Inhibitory activity against Leishmania major Farnesyl diphosphate synthase	2004	Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1	Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID390276	Antitumor activity against human BT-549 cells xenografted SCID mouse assessed as survival time prolongation at 2 ug, ip	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1421097	Inhibition of RANKL-induced osteoclastogenesis in mouse RAW264.7 cells after 72 hrs by TRAP staining based microscopic analysis	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID197477	Compound was tested for increased urinary excretion of MDH in rats after a treatment period of 14 days in renal tolerability model	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID256540	Dose to inhibit the growth of human KB carcinoma cell line	2005	Journal of medicinal chemistry, Sep-22, Volume: 48, Issue:19	Bisphosphonate inhibition of the exopolyphosphatase activity of the Trypanosoma brucei soluble vacuolar pyrophosphatase.
AID1584449	Antiproliferative activity against human RPMI8226 cells after 72 hrs by MTT assay	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID235247	Therapeutic index was expressed as ratio of LD50 for KB cell line to IC50 against Entamoeba histolytica	2004	Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1	Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID1421114	Induction of mineralization in C57BL mouse bone marrow cells co-cultured with human PC3 cells at >100 nM supplemented with fresh medium containing compound every 3 days for 10 to 15 days by alizarin red dye based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1054148	Inhibition of human recombinant FPPS using GPP/[3H]IPP as substrate up to 10 uM incubated for 10 mins prior to substrate addition measured after 8 mins by scintillation counting analysis	2013	Journal of medicinal chemistry, Oct-24, Volume: 56, Issue:20	Thienopyrimidine bisphosphonate (ThPBP) inhibitors of the human farnesyl pyrophosphate synthase: optimization and characterization of the mode of inhibition.
AID326147	Inhibition of Escherichia coli OPPS	2007	Proceedings of the National Academy of Sciences of the United States of America, Jun-12, Volume: 104, Issue:24	Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AID326146	Inhibition of Sulfolobus solfataricus HPPS	2007	Proceedings of the National Academy of Sciences of the United States of America, Jun-12, Volume: 104, Issue:24	Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AID734800	Inhibition of N-terminal His6-tagged Plasmodium vivax GGPPS expressed in Escherichia coli BL2-codon plus (DE3) RIL cells using geranyl diphosphate and isopentenyl diphosphate as substrate preincubated with enzyme for 30 mins by spectrophotometric analysis	2013	ACS medicinal chemistry letters, Apr-11, Volume: 4, Issue:4	Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis.
AID390270	Stimulation of human Vgamma9Vdelta2 T lymphocytes assessed as gamma delta expansion factor after 7 days	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1584456	Induction of apoptosis in human RPMI8226 cells assessed as necrotic cells at 1 uM after 72 hrs by APC Annexin V/eFluor-780-viability double staining-based FACS analysis (Rvb = 3.60%)	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID1617553	Competitive inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using GPP as substrate measured after 30 mins in presence of Mg2+	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID1700479	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as trabecular bone volume per tissue volume level in tibial metaphysis at 100 ug/kg, sc QD for 4 weeks by microCT analysis (17.49 +/- 2.91 %)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID275060	Inhibition of Escherichia coli FPPS	2006	Journal of medicinal chemistry, Dec-14, Volume: 49, Issue:25	Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.
AID689988	Inhibition of bone resorption in rat	2011	Journal of medicinal chemistry, Sep-08, Volume: 54, Issue:17	Remarkable potential of the α-aminophosphonate/phosphinate structural motif in medicinal chemistry.
AID425652	Total body clearance in human	2009	Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15	Physicochemical determinants of human renal clearance.
AID625279	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID326142	Binding affinity to human GGPPS	2007	Proceedings of the National Academy of Sciences of the United States of America, Jun-12, Volume: 104, Issue:24	Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AID1519530	Inhibition of FDPS (unknown origin)	2019	Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24	Novel benzimidazole phosphonates as potential inhibitors of protein prenylation.
AID1617557	Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using GPP and IPP as substrate preincubated for 30 mins followed by substrate addition by continuous spectrophotometric assay	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID1676481	Binding affinity to BTN3A1 in human PBMC-derived Vgamma9/Vdelta2 T cells assessed as increase in CD69/CD25 level incubated for overnight by flow cytometric analysis
AID1700000	Cytotoxicity against human HeLa cells assessed as cell growth inhibition	2020	Bioorganic & medicinal chemistry letters, 12-01, Volume: 30, Issue:23	Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility.
AID1894088	Drug uptake in Beagle dog sciatic nerve at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1700476	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as trabecular thickness level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (39.96 +/- 5.42 um)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1700481	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as degree of anisotropy (range 0-1) level in tibial metaphysis at 100 ug/kg, sc QD for 4 weeks by microCT analysis (0.53 +/- 0.07 No_unit)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1700482	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as structure model index level in tibial metaphysis at 100 ug/kg, sc QD for 4 weeks by microCT analysis (1.92 +/- 0.19 No_unit)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID390280	Antitumor activity against human BT-549 cells xenografted SCID mouse co-transfected with human gamma delta T lymphocytes assessed as survival time prolongation at 2 ug, ip coadministered with human recombinant IL2	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1129547	Cytotoxicity against human HuH7 cells at 250 uM after 144 hrs by MTT assay	2014	European journal of medicinal chemistry, Apr-22, Volume: 77	Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells.
AID1421111	Cytotoxicity against C57BL mouse bone marrow cells assessed as decrease in cell proliferation at 100 to 500 uM after 72 hrs by crystal violet staining based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1494447	Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by upregulation of CD69 and CD25 after 18 hrs	2018	Journal of medicinal chemistry, 03-08, Volume: 61, Issue:5	Synthesis and Biological Evaluation of ( E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses.
AID1894089	Drug uptake in Beagle dog pancreas at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID625289	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID779764	Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay	2013	Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21	Arylamino methylene bisphosphonate derivatives as bone seeking matrix metalloproteinase inhibitors.
AID1617551	Competitive inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using IPP as substrate	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID669075	Inhibition of human recombinant N-terminal-His6 tagged FPPS expressed in Escherichia coli BL21 using [3H]IPP and GPP as substrate at 1 uM incubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID1894090	Drug uptake in Beagle dog adrenal tissue at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1421091	Antiproliferative activity against mouse RAW264.7 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1421084	Antiproliferative activity against human MG63 cells assessed as change in cell proliferation at 100 uM after 72 hrs by crystal violet staining based assay relative to control	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1894097	Antiparasitic activity against Toxoplasma gondii tachyzoites infected in human foreskin fibroblast incubated for 48 hrs followed by [5,6-3H]uracil addition and measured after 4 hrs by scintillation counter analysis	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID184809	Bone resorption activity in rats.	2002	Journal of medicinal chemistry, Jul-04, Volume: 45, Issue:14	An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs.
AID1197852	Inhibition of human FPPS	2015	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 25, Issue:5	Probing the molecular and structural elements of ligands binding to the active site versus an allosteric pocket of the human farnesyl pyrophosphate synthase.
AID669077	Inhibition of human recombinant N-terminal-His6 tagged FPPS expressed in Escherichia coli BL21 using [3H]IPP and GPP as substrate measured after 10 mins by scintillation counting	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID540212	Mean residence time in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID625282	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID231757	Ratio of calvaria mineralization to calvaria bone resorption	2002	Journal of medicinal chemistry, Aug-15, Volume: 45, Issue:17	Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa).
AID669073	Inhibition of human recombinant N-terminal-His6 tagged FPPS expressed in Escherichia coli BL21 using [3H]IPP and GPP as substrate incubated for 10 mins prior to substrate addition measured after 20 mins by liquid scintillation counting	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID1494452	Binding affinity to butyrophilin 3A1 in human Vgamma9/Vdelta2 T-cells assessed as activation of Vgamma9/Vdelta2 T-cells by measuring levels of CD69 and CD25 at 10 uM after 18 hrs relative to control	2018	Journal of medicinal chemistry, 03-08, Volume: 61, Issue:5	Synthesis and Biological Evaluation of ( E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses.
AID1421090	Antiproliferative activity against mouse J774A.1 cells assessed as reduction in cell viability at 100 uM after 72 hrs by WST8 assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1617579	Induction of apoptosis in human PANC1 cells assessed as viable cells at 10 uM measured after 48 hrs by Annexin-V/FITC and propidium iodide staining based flow cytometry (Rvb = 95.5 %)	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID1638631	Inhibition of human GGPPS	2019	Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5	Discovery of Lipophilic Bisphosphonates That Target Bacterial Cell Wall and Quinone Biosynthesis.
AID734801	Binding affinity to human FPPS at 1 mM by X-ray crystallographic analysis	2013	ACS medicinal chemistry letters, Apr-11, Volume: 4, Issue:4	Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis.
AID669079	Inhibition of human recombinant N-terminal His6 tagged GGPPS expressed in Escherichia coli BL21 using FPP and [14C]IPP as substrate incubated for 10 mins prior to substrate addition by scintillation counting	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID270724	Antiproliferative activity against human SF-268 cell line by MTT assay	2006	Journal of medicinal chemistry, Sep-21, Volume: 49, Issue:19	Activity of nitrogen-containing and non-nitrogen-containing bisphosphonates on tumor cell lines.
AID1152906	Cytotoxicity against mouse J774 cells assessed as reduction in cell viability	2014	Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12	Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.
AID1443980	Inhibition of human BSEP expressed in fall armyworm sf9 cell plasma membrane vesicles assessed as reduction in vesicle-associated [3H]-taurocholate transport preincubated for 10 mins prior to ATP addition measured after 15 mins in presence of [3H]-tauroch	2010	Toxicological sciences : an official journal of the Society of Toxicology, Dec, Volume: 118, Issue:2	Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
AID1584477	Inhibition of GGPPS in human RPMI8226 cells assessed as reduction in Rap1A prenylation at 0.5 uM by Western blot analysis	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID390273	Induction of apoptosis in human CCRF-CEM cells at 100 uM by flow cytometry	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1617574	Cytotoxicity against human PANC1 cells assessed as decrease in cell growth measured after 72 hrs by MTT assay	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID625286	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1700478	Antiosteoporotic activity in C57BL6/J mouse model of OVX-induced bone loss assessed as trabecular separation level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (319.80 +/- 106.52 um)	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID625288	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1894086	Drug uptake in Beagle dog lung at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1421105	Induction of mineralization in mouse MC3T3-E1 cells at 30 to 50 nM after 10 to 15 days by alizarin red dye based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID496819	Antimicrobial activity against Plasmodium falciparum	2010	Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6	Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID326572	Inhibition of human GGDPS-mediated Rap1a geranylgeranylation in human K562 cells after 24 hrs by Western blot	2008	Bioorganic & medicinal chemistry, Jan-01, Volume: 16, Issue:1	Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.
AID1617561	Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged FPPS expressed in Escherichia coli BL21 (DE3) using GPP and IPP as substrate preincubated for 30 mins followed by substrate addition in absence of 0.01 % Triton X-100 by continuou	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID669083	Antiproliferative activity against human KMS-28PE after 72 hrs by MTT assay	2012	Journal of medicinal chemistry, Apr-12, Volume: 55, Issue:7	Design and synthesis of active site inhibitors of the human farnesyl pyrophosphate synthase: apoptosis and inhibition of ERK phosphorylation in multiple myeloma cells.
AID96034	Toxicity evaluated against human nasopharyngeal carcinoma KB cell line	2004	Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1	Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID1473740	Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID734799	Inhibition of Plasmodium falciparum growth after 72 hrs by LDH assay	2013	ACS medicinal chemistry letters, Apr-11, Volume: 4, Issue:4	Chemo-Immunotherapeutic Anti-Malarials Targeting Isoprenoid Biosynthesis.
AID235248	Therapeutic index was expressed as ratio of LD50 for KB cell line to IC50 against Plasmodium falciparum	2004	Journal of medicinal chemistry, Jan-01, Volume: 47, Issue:1	Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo.
AID1617576	Induction of apoptosis in human PANC1 cells assessed as necrotic cells at 10 uM measured after 48 hrs by Annexin-V/FITC and propidium iodide staining based flow cytometry (Rvb = 0.072 %)	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID1179733	Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay	2014	Bioorganic & medicinal chemistry letters, Aug-01, Volume: 24, Issue:15	Synthesis and antiproliferative activity of aromatic and aliphatic bis[aminomethylidene(bisphosphonic)] acids.
AID1421085	Antiproliferative activity against human PC3 cells assessed as change in cell proliferation at 100 uM after 72 hrs by crystal violet staining based assay relative to control	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1894087	Drug uptake in Beagle dog spleen at 0.15 mg/kg, iv administered as C14-lableled compound and assessed as radioactivity after 96 hrs by autoradiography	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1421106	Induction of mineralization in C57BL mouse bone marrow cells at 50 nM supplemented with fresh medium containing compound every 3 days for 10 to 15 days by alizarin red dye based assay	2018	European journal of medicinal chemistry, Oct-05, Volume: 158	Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis.
AID1617578	Induction of apoptosis in human PANC1 cells assessed as early apoptotic cells at 10 uM measured after 48 hrs by Annexin-V/FITC and propidium iodide staining based flow cytometry (Rvb = 2.61 %)	2019	Journal of medicinal chemistry, 12-12, Volume: 62, Issue:23	Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.
AID625287	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID390279	Antitumor activity against human BT-549 cells xenografted SCID mouse co-transfected with human gamma delta T lymphocytes assessed as survival time prolongation at 5 ug, ip	2008	Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21	Design, synthesis, and biological evaluation of novel aminobisphosphonates possessing an in vivo antitumor activity through a gammadelta-T lymphocytes-mediated activation mechanism.
AID1700002	Cytotoxicity against human Ca-Ski cells assessed as cell growth inhibition	2020	Bioorganic & medicinal chemistry letters, 12-01, Volume: 30, Issue:23	Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility.
AID1584501	Binding affinity to bone mineral hydroxyapatite at 50 uM by 1H NMR assay	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID1473738	Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID540210	Clearance in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1224404	Cytotoxicity against human SH-SY5Y cells assessed as LDH release after 48 hrs (Rvb = 0%)	2014	Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13	Multistage screening reveals chameleon ligands of the human farnesyl pyrophosphate synthase: implications to drug discovery for neurodegenerative diseases.
AID1717390	Cytotoxicity against FPPS-negative human MDA-MB-231 cells assessed as reduction in cell viability measured after 48 hrs by MTT assay	2020	European journal of medicinal chemistry, Jan-15, Volume: 186	Structure-based virtual screening and biological evaluation of novel non-bisphosphonate farnesyl pyrophosphate synthase inhibitors.
AID1894079	Anti-osteoclast activity rat assessed as inhibition of bone resorption relative to control	2021	Journal of medicinal chemistry, 02-11, Volume: 64, Issue:3	Bisphosphonates, Old Friends of Bones and New Trends in Clinics.
AID1125516	Inhibition of human recombinant carbonic anhydrase 9 preincubated for 15 mins by stopped flow CO2 hydration method	2014	Bioorganic & medicinal chemistry letters, Apr-15, Volume: 24, Issue:8	Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.
AID1474166	Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index	2016	Drug discovery today, Apr, Volume: 21, Issue:4	DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1700508	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on bone formation by measuring mineralizing mineral apposition rate level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (1.62 +/ 0.21 um/d (lcm))	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID1700509	Toxicity in C57BL6/J mouse model of OVX-induced bone loss assessed as effect on bone formation by measuring bone formation rate per trabecular bone surface level in femoral metaphysis at 100 ug/kg, sc QD for 4 weeks by histomorphometry (1.62 +/ 0.21 m3/um	2020	Journal of medicinal chemistry, 11-25, Volume: 63, Issue:22	Novel 2,7-Diazaspiro[4,4]nonane Derivatives to Inhibit Mouse and Human Osteoclast Activities and Prevent Bone Loss in Ovariectomized Mice without Affecting Bone Formation.
AID679983	TP_TRANSPORTER: inhibition of apoptosis in hMRP1-expressing HEK293 cells	2006	Cell biology international, Mar, Volume: 30, Issue:3	Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study.
AID1584454	Induction of apoptosis in human RPMI8226 cells assessed as early apoptotic cells at 1 uM after 72 hrs by APC Annexin V/eFluor-780-viability double staining-based FACS analysis (Rvb = 3.31%)	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1296008	Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening	2020	SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1	Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID504749	qHTS profiling for inhibitors of Plasmodium falciparum proliferation	2011	Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043	Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1745854	NCATS anti-infectives library activity on HEK293 viability as a counter-qHTS vs the C. elegans viability qHTS	2023	Disease models & mechanisms, 03-01, Volume: 16, Issue:3	In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.
AID1347411	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1745855	NCATS anti-infectives library activity on the primary C. elegans qHTS viability assay	2023	Disease models & mechanisms, 03-01, Volume: 16, Issue:3	In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.
AID1347089	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845	Primary qHTS for Inhibitors of ATXN expression
AID1347086	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347093	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1508630	Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay	2021	Cell reports, 04-27, Volume: 35, Issue:4	A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347090	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154	Primary screen GU AMC qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347091	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347082	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347097	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095	qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	2018	Oncotarget, Jan-12, Volume: 9, Issue:4	Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1801915	Radioactive Assay from Article 10.1021/acs.biochem.6b00486: \\Fluorescent Farnesyl Diphosphate Analogue: A Probe To Validate trans-Prenyltransferase Inhibitors.\\	2016	Biochemistry, Aug-09, Volume: 55, Issue:31	Fluorescent Farnesyl Diphosphate Analogue: A Probe To Validate trans-Prenyltransferase Inhibitors.
AID1799536	Enzymatic Assay from Article 10.1016/j.chembiol.2008.10.017: \\Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.\\	2008	Chemistry & biology, Dec-22, Volume: 15, Issue:12	Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.
AID1798541	GGPP Synthase Inhibition Assay from Article 10.1021/jm800325y: \\Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.\\	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation.
AID1801914	Fluorescent Assay from Article 10.1021/acs.biochem.6b00486: \\Fluorescent Farnesyl Diphosphate Analogue: A Probe To Validate trans-Prenyltransferase Inhibitors.\\	2016	Biochemistry, Aug-09, Volume: 55, Issue:31	Fluorescent Farnesyl Diphosphate Analogue: A Probe To Validate trans-Prenyltransferase Inhibitors.
AID1346818	Rat farnesyl diphosphate synthase (Lanosterol biosynthesis pathway)	2008	Toxicology in vitro : an international journal published in association with BIBRA, Jun, Volume: 22, Issue:4	Preclinical evidence for nitrogen-containing bisphosphonate inhibition of farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	24 (0.61)	18.2507
2000's	1055 (26.89)	29.6817
2010's	2207 (56.26)	24.3611
2020's	637 (16.24)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	620 (15.09%)	5.53%
Reviews	540 (13.15%)	6.00%
Case Studies	510 (12.41%)	4.05%
Observational	43 (1.05%)	0.25%
Other	2,395 (58.30%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (338)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
Zoledronate Early to Hip Fracture Patients - Safe and Effective? A Double-blinded Randomized Controlled Treatment Strategy Trial on Zoledronate in Hip Fracture Patients[NCT05025293]	Phase 4	300 participants (Anticipated)	Interventional	2021-12-15	Recruiting
Duration of Suppression of Bone Turnover Following Treatment With Zoledronic Acid in Men With Metastatic Castration Resistant Prostate Cancer[NCT01062503]		48 participants (Actual)	Observational	2010-01-31	Completed
A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa®) in the Treatment of Bone Metastases in Subjects With Advanced Breast Cancer[NCT00321464]	Phase 3	2,049 participants (Actual)	Interventional	2006-04-01	Completed
Randomized, Double-blind, Safety and Efficacy Trial With Intravenous Zoledronic Acid for the Treatment of Paget's Disease of Bone Using Risedronate as a Comparator, Including an Extended Observational Period[NCT00051636]	Phase 3	172 participants (Actual)	Interventional	2001-01-31	Completed
Thalidomide-Dexamethasone Incorporated Into Double Autologous Stem-Cell Transplantation for Patients Less Than 65 Years of Age With Newly Diagnosed Multiple Myeloma[NCT01341262]	Phase 2	378 participants (Actual)	Interventional	2002-03-31	Completed
Phase II Study of Sorafenib and Zoledronic Acid in Advanced HCC[NCT01259193]	Phase 2	50 participants (Anticipated)	Interventional	2010-10-31	Recruiting
A Prospective, Bi-centric,Randomized, Primary Double-blind, Placebo-controlled Phase III Study to Assess the Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome[NCT01348269]	Phase 3	63 participants (Actual)	Interventional	2011-05-31	Completed
Molecular Genetic Study of Suspected Cases of Osteogenesis Imperfecta Attending Assiut University Children Hospital[NCT03169192]		40 participants (Anticipated)	Observational	2017-06-01	Not yet recruiting
The Efficacy Study of Aclasta (Zoledronic Acid 5mg) on Prosthetic Fixation in Postmenopausal Women After Cementless Total Hip Arthroplasty (THA): a 24 Months, Single Center, Open- Label, Randomized, Parallel Controlled Study[NCT02333344]	Phase 4	0 participants (Actual)	Interventional	2015-07-30	Withdrawn(stopped due to Study halted prematurely, prior to enrollment of first participant, for strategic reasons)
Phase III Trial of Bisphosphonates as Adjuvant Therapy for Primary Breast Cancer[NCT00127205]	Phase 3	6,097 participants (Actual)	Interventional	2005-07-31	Completed
Phase II Study of Simvastatin, Zoledronic Acid, Bortezomib, Bendamustine and Methylprednisolone for Relapsed/Refractory Myeloma[NCT01332617]	Phase 2	0 participants (Actual)	Interventional	2011-04-30	Withdrawn(stopped due to Investigators no longer interested in activating study)
[NCT01344967]	Phase 2/Phase 3	21 participants (Actual)	Interventional	2009-02-28	Completed
Randomized Clinical Trial on the Prevention of Radiographic Progression With Zoledronic Acid in Patients With Early Rheumatoid Arthritis and Low Disease Activity[NCT02123264]	Phase 3	28 participants (Actual)	Interventional	2014-05-31	Terminated
An Open-labelled Pilot Study to Evaluate Dynamic Hip Screw System (DHS) Augmented With a Biphasic Apatite Sulphate Combined With Systemic or Local Bisphosphonate for Trochanteric Femur Fracture[NCT04498715]		20 participants (Anticipated)	Interventional	2021-06-01	Recruiting
Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid[NCT03735537]	Phase 4	380 participants (Anticipated)	Interventional	2016-11-01	Recruiting
TOPAZ: Trial of Parkinson's And Zoledronic Acid A Randomized Placebo-controlled Trial of Zoledronic Acid for the Prevention of Fractures in Patients With Parkinson's Disease[NCT03924414]	Phase 4	3,500 participants (Anticipated)	Interventional	2019-11-15	Recruiting
Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis[NCT03087851]	Phase 4	61 participants (Actual)	Interventional	2017-03-13	Completed
Assessment of the Antitumour Effect of Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse: Prospective Clinical Trial of the GEM/PETHEMA Group[NCT01087008]	Phase 4	103 participants (Anticipated)	Interventional	2010-04-30	Completed
A Phase 2b, Multicentre, Multinational, Double-blind, Dose-finding Study, Incorporating an Open Label Substudy, in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With Setrusumab (BPS804)[NCT03118570]	Phase 2	112 participants (Actual)	Interventional	2017-09-11	Completed
A Phase III Randomized Trial With NEOadjuvant Chemotherapy (TAC) With or Without ZOledronic Acid for Patients With HER2- Negative Large Resectable or Locally Advanced Breast Cancer(NEO-ZOTAC)[NCT01099436]	Phase 3	250 participants (Actual)	Interventional	2010-04-30	Completed
Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases From Lung, Breast, and Prostate Cancer[NCT00365105]	Phase 3	261 participants (Actual)	Interventional	2006-07-11	Completed
Phase III Randomized Study of the Effects on Bone Mineral Density of Tamoxifen, Letrozole, and Letrozole + Zoledronic Acid as Adjuvant Treatment of Patients With Early Breast Cancer; VERSION 2 AMENDED Phase 3 Study of Triptorelin and Tamoxifen, Letrozole,[NCT00412022]	Phase 3	1,294 participants (Actual)	Interventional	2004-03-31	Active, not recruiting
Prospective Breast Cancer Biobanking Project[NCT04488614]		1,200 participants (Anticipated)	Observational	2011-09-01	Enrolling by invitation
POPULATION PHARMACOMETRICS FOR ASSESSING RISK OF BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW (BRONJ)[NCT02069340]		0 participants (Actual)	Interventional	2016-06-30	Withdrawn
Multicenter Randomized Phase III Study Evaluating the Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies[NCT03408652]	Phase 3	1 participants (Actual)	Interventional	2019-03-15	Terminated(stopped due to lack of recruitment)
Randomized, Double-Blind, Safety and Efficacy Trial With Intravenous Zoledronic Acid for the Treatment of Paget's Disease of Bone Using Risedronate as a Comparator, Including an Extended Observation Period[NCT00103740]	Phase 3	185 participants (Actual)	Interventional	2002-04-30	Completed
Delayed Versus Immediate Use Of Zoledronic Acid For Postmenopausal Patients With ER/PR Positive Early Breast Cancer Who Are Using Adjuvant Letrozole[NCT05164952]	Phase 3	50 participants (Anticipated)	Interventional	2021-09-30	Recruiting
STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial[NCT00268476]	Phase 2/Phase 3	11,992 participants (Actual)	Interventional	2005-07-08	Active, not recruiting
COMPARE: Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Patients With Multiple Myeloma[NCT02739594]	Phase 3	89 participants (Actual)	Interventional	2006-02-28	Terminated(stopped due to Slow recruitment)
Phase 2 Study of the Efficacy of Zoledronic Acid in Low Back Pain Related to Vertebral Endplate Signal Changes, the So-called Modic Changes[NCT01330238]	Phase 2	40 participants (Actual)	Interventional	2008-12-31	Completed
The Efficacy of New Adjuvant Chemotherapy of Osteosarcoma Combined With Zoledronic Acid in Decrease the Lung Metastatic Rate of Osteosarcoma[NCT03932071]	Phase 4	150 participants (Anticipated)	Interventional	2017-01-01	Recruiting
Multicenter, Randomized, Phase II Study of Neoadjuvant Chemotherapy Associated or Not With Zoledronate and Atorvastatin in Triple Negative Breast Cancers - YAPPETIZER Study[NCT03358017]	Phase 2	54 participants (Actual)	Interventional	2018-03-05	Completed
Results of Phase III Study to Assess if Zoledronic Acid Have Antumor Activity in Multiple Myeloma[NCT01234129]		320 participants (Actual)	Observational	2002-06-30	Completed
Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancers[NCT01367288]	Phase 2	53 participants (Actual)	Interventional	2010-04-30	Completed
Department of Orthopedics, National Taiwan University Hospital[NCT03868033]	Phase 4	100 participants (Anticipated)	Interventional	2019-04-12	Recruiting
Pilot Study for Zoledronic Acid to Prevent High-Turnover Bone Loss After Bariatric Surgery[NCT03424239]	Phase 4	6 participants (Actual)	Interventional	2018-08-01	Completed
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis[NCT01218035]	Phase 4	49 participants (Actual)	Interventional	2007-05-31	Completed
A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid in the Treatment of Bone Disease in Subjects With Newly Diagnosed Multiple Myeloma[NCT01345019]	Phase 3	1,718 participants (Actual)	Interventional	2012-05-17	Completed
CREATE-1 Study: CRPS Treatment Evaluation 1 Study. A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of AXS-02 (Oral Zoledronate) Administered Orally to Subjects With Complex Regional Pain Syndrome Type I (CRPS-I)[NCT02504008]	Phase 3	190 participants (Anticipated)	Interventional	2015-07-31	Active, not recruiting
The Effect of Zoledronic Acid to Bone Fusion and Bone Metabolism of Patients With Lumbar Degenerative Disease After Lumbar Interbody Fusion[NCT01310465]	Phase 4	50 participants (Anticipated)	Interventional	2011-01-31	Recruiting
An Open-Label Phase II Study of Zometa as Adjuvant Treatment of Malignant Pleural Effusion Due to Non-Small Cell Lung Cancer[NCT01004510]	Phase 2	3 participants (Actual)	Interventional	2009-11-30	Terminated(stopped due to failure to accrue projected number of patients)
Feasibility and Dose Discovery Analysis of Zoledronic Acid With Concurrent Chemotherapy in the Treatment of Newly Diagnosed Metastatic Osteosarcoma[NCT00742924]	Phase 1	24 participants (Actual)	Interventional	2008-08-31	Completed
Phase II Study of Interleukin-2 in Combination With Zoledronic Acid in Patients With Untreated Metastatic Renal Cell Carcinoma[NCT00582790]	Phase 2	12 participants (Actual)	Interventional	2003-08-31	Terminated(stopped due to slow accrual)
A Randomised Controlled Trial of Bisphosphonate Therapy in Osteonecrosis of the Hip[NCT00781261]	Phase 2	120 participants (Anticipated)	Interventional	2009-08-31	Recruiting
A Randomised, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 785 in the Treatment of Postmenopausal Women With Low Bone Mineral Density[NCT00896532]	Phase 2	419 participants (Actual)	Interventional	2009-06-03	Completed
Bisphosphonates for Prevention of Post-Denosumab Bone Loss in Premenopausal Women With Idiopathic Osteoporosis[NCT03396315]	Phase 2	27 participants (Actual)	Interventional	2018-01-29	Active, not recruiting
[NCT02181101]	Phase 3	3,754 participants (Actual)	Interventional	2005-09-30	Completed
The Optimal Long Term Treatment Strategy of Anti-resorptive Medications---The Extension of Denosumab Sequential Therapy[NCT05091086]	Phase 4	60 participants (Anticipated)	Interventional	2021-11-20	Recruiting
The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass[NCT02499237]	Phase 4	57 participants (Actual)	Interventional	2015-07-31	Completed
Zoledronic Acid to Prevent Bone Loss After Acute Spinal Cord Injury[NCT01642901]	Phase 3	16 participants (Actual)	Interventional	2012-09-30	Completed
Combined Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Metastatic or Inoperable Leiomyosarcoma - DiTuSarc Study[NCT05080790]	Phase 2	10 participants (Anticipated)	Interventional	2021-11-15	Recruiting
Intravenous Bisphosphonate in Stress Fracture Treatment[NCT03576599]	Phase 4	5 participants (Actual)	Interventional	2017-06-29	Terminated(stopped due to difficult to include patients)
Phase I/II Study of Dasatinib in Combination With Zoledronic Acid for the Treatment of Breast Cancer With Bone Metastasis[NCT00566618]	Phase 1/Phase 2	31 participants (Actual)	Interventional	2007-11-01	Completed
The Optimised Use of Romozosumab Study[NCT06059222]	Phase 4	270 participants (Anticipated)	Interventional	2023-10-02	Recruiting
The Impact of Osteoporosis Medications on Muscle Health in Older Adults[NCT05666310]	Phase 4	20 participants (Anticipated)	Interventional	2023-02-14	Recruiting
Efficacy of Sequential Therapies After Osteoanabolic Treatment in Postmenopausal Women With Severe Osteoporosis: the Sequential Treatment After Romosozumab and Teriparatide (START) Study[NCT06164795]		150 participants (Anticipated)	Observational	2023-11-25	Recruiting
Augmentation of Pertrochanteric Fracture Proximal Femoral Nail Osteosynthesis Using Calcium Sulphate/Hydroxyapatite Combined With Systemic Bisphosphonate - A Pilot Study of the FARE (Fracture Anchorage and Bone REgeneration) Method[NCT06135298]	Phase 4	20 participants (Anticipated)	Interventional	2023-12-01	Recruiting
A Multicenter, Noninterventional, Prospective Study to Investigate the Efficacy and Safety After Administration of Daewoong Zoledronic Acid for the Purpose of Treatment or Prevention of Osteoporosis in Real-world Observational Study[NCT05614778]		3,000 participants (Anticipated)	Observational	2022-02-28	Recruiting
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention[NCT05204836]	Phase 1	56 participants (Anticipated)	Interventional	2023-05-16	Recruiting
Feasibility of Bisphosphonate Use on Sleeve Gastrectomy Associated Bone Loss: Healthy Body, Healthy Bones Trial[NCT04279392]	Phase 1/Phase 2	10 participants (Actual)	Interventional	2020-09-01	Completed
Denosumab to Prevent High-Turnover Bone Loss After Bariatric Surgery[NCT04087096]	Phase 4	36 participants (Actual)	Interventional	2020-08-24	Active, not recruiting
A Phase Ib/II Multicenter Dose-determination Study, With an Adaptive, Randomized, Placebo-controlled, Double-blind Phase II, Using Various Repeated IV Doses of BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients With Prio[NCT00741377]	Phase 1	28 participants (Actual)	Interventional	2009-01-31	Completed
Preserving Geriatric Muscle With an Osteoporosis Medication[NCT06118905]	Phase 4	248 participants (Anticipated)	Interventional	2024-01-01	Not yet recruiting
Single Dosing of Zoledronic Acid in Cancer Therapy Induced Bone Loss (CTIBL)[NCT00712985]	Phase 3	18 participants (Actual)	Interventional	2005-09-30	Completed
A Prospective, Open-label, Randomized Phase III Study to Evaluate the Efficacy of ZOMETA® (Zoledronic Acid) in Treatment of Bone Metastases in Patients With Stage IV Nasopharyngeal Cancer[NCT00697619]	Phase 2	60 participants (Actual)	Interventional	2005-09-30	Completed
Magnolia Study Prolonged Protection From Bone Disease in Multiple Myeloma. An Open Label Phase 3 Multicenter International Randomised Trial[NCT02286830]	Phase 4	158 participants (Anticipated)	Interventional	2015-01-31	Completed
Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma[NCT00987636]	Phase 3	907 participants (Actual)	Interventional	2009-10-01	Completed
A Single Center, Open-label, Parallel, Phase IV Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis[NCT05361408]	Phase 4	114 participants (Anticipated)	Interventional	2022-02-28	Recruiting
An International, Multicenter, Open-label, Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta[NCT00982124]	Phase 3	14 participants (Actual)	Interventional	2007-10-31	Completed
An Open-Label, Randomized, Multicenter Study to Evaluate the Use of Zoledronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women With Estrogen Receptor Positive and/or Progesterone Receptor Positive Breast Cancer Receivi[NCT00050011]	Phase 3	602 participants (Actual)	Interventional	2002-09-30	Completed
A Randomized Controlled Trial of Zoledronate in the Treatment of Osteopenia in Children and Adolescents With Crohn's Disease[NCT00798473]	Phase 3	13 participants (Actual)	Interventional	2004-09-30	Completed
Zoledronic Acid for Treatment of Osteopenia and Osteoporosis in Women With Primary Breast Cancer Undergoing Adjuvant Aromatase Inhibitor (Letrozole) Therapy[NCT00436917]		60 participants (Actual)	Interventional	2006-04-30	Completed
Towards Efficient Prediction and Prevention of Rheumatoid Arthritis[NCT04115397]	Phase 4	80 participants (Anticipated)	Interventional	2020-01-31	Not yet recruiting
Response of Bony Metastasis to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers With Actionable Driver Mutations[NCT03958565]		100 participants (Anticipated)	Observational	2020-04-28	Recruiting
Metronomic Cyclophosphamide and Methotrexate Combined With Zoledronic Acid and Sirolimus in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma. A Phase Ib Study From the French Sarcoma Group[NCT02517918]	Phase 1	23 participants (Actual)	Interventional	2015-02-28	Completed
Whole Exome Sequencing to Identify Genetic Predisposition to Atypical Femoral Fractures in Women Using Bisphosphonates for Osteoporosis[NCT02731040]		38 participants (Actual)	Observational	2016-04-30	Completed
A Multi-Center Phase II Study to Compare MER-101 (20mg) Tablets To Intravenous Zometa 4mg in Male Bisphosphonate-Naive Hormone Refractory Prostate Cancer Patients[NCT00636740]	Phase 2	30 participants (Actual)	Interventional	2008-02-29	Completed
Phase 1 Study of Zoledronic Acid in Sickle Cell Disease[NCT00639392]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2007-06-30	Withdrawn(stopped due to Ended early due to inability to identify eligible subjects)
Phase III Randomized, Controlled, Open, Multicentre Medical-economic Study Evaluating the Efficacy of Adding ZOlédronique Acid to STERéotaxique Radiotherapy in the Treatment of Vertebral Metastases[NCT03951493]	Phase 3	225 participants (Anticipated)	Interventional	2020-06-23	Recruiting
Phase II Trial of Zometa on Bone Mineral Density on Patients With Stage D Prostate Cancer Undergoing Androgen Ablation Therapy[NCT00582556]	Phase 2	44 participants (Actual)	Interventional	2003-04-30	Completed
Evaluation of Zoledronic Acid as a Single Agent and as an Adjuvant to Chemotherapy in the Management of High Grade Osteosarcoma[NCT00691236]	Phase 2/Phase 3	60 participants (Anticipated)	Interventional	2008-05-31	Recruiting
Bone Marker-directed Dosing of ZOMETA® (Zoledronic Acid) for the Prevention of Skeletal Complications in Patients With Advanced Multiple Myeloma.[NCT00622505]	Phase 4	121 participants (Actual)	Interventional	2007-11-07	Completed
Effect of Zoledronic Acid in Primary Knee Osteoarthritis: a Randomized Controlled Trial[NCT06051344]	Phase 4	92 participants (Anticipated)	Interventional	2023-01-01	Recruiting
A Two Year Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Fracture Efficacy and Safety of Intravenous Zoledronic Acid 5 mg Annually for the Treatment of Osteoporosis in Men[NCT00439647]	Phase 3	1,199 participants (Actual)	Interventional	2006-12-31	Completed
Effect of Zoledronic Acid on Chemotherapy Induced Bone Loss in Non-Hodgkin's Lymphoma Patients Receiving Chemotherapy[NCT00352846]	Phase 3	135 participants (Actual)	Interventional	2006-01-31	Completed
Bone-Targeted Therapy Combining Zoledronate With Atorvastatin in Renal Cell Carcinoma: A Phase II Study[NCT00490698]	Phase 2	11 participants (Actual)	Interventional	2006-10-31	Completed
A Prospective, Randomized, Double-blind, Stratified, Multi-center, 2-arm Trial of the Continued Efficacy and Safety of Zoledronic Acid (Every 4 Weeks vs. Every 12 Weeks) in in the 2nd Year of Treatment in Patients With Documented Bone Metastases From Brea[NCT00320710]	Phase 3	416 participants (Actual)	Interventional	2006-02-28	Completed
A Real-world Study Cohort of Postmenopausal Women With Osteoporosis Taking Zoledronic Acid or Oral Bisphosphonates[NCT00984893]		1,551 participants (Actual)	Observational	2008-11-30	Completed
A Multicenter,Open Label, Randomized Trial Evaluating the Duration of Infusion of Zoledronic Acid 4 mg IV in Multiple Myeloma Patients With Bone Metastases[NCT00104104]	Phase 4	179 participants (Actual)	Interventional	2004-10-31	Completed
A Phase III, Multicenter, Randomized, Controlled Study of Maximum Androgen Blockade With vs. Without Zoledronic Acid in Prostatic Cancer Patients With Metastatic Bone Disease[NCT00685646]	Phase 3	227 participants (Actual)	Interventional	2008-05-31	Completed
[NCT02595138]	Phase 3	430 participants (Anticipated)	Interventional	2015-10-31	Active, not recruiting
Efficacy and Safety Study of ZOMETA® in Treatment of High-level NTX Non Small Cell Lung Cancer With Bone Metastasis[NCT00762346]	Phase 4	156 participants (Actual)	Interventional	2008-09-30	Completed
Post US Approval Voluntary Registry Study to Determine Incidence of Hypocalcemia Post Reclast® Treatment in Patients With Paget's Disease After Institution of Educational Strategies to Improve Adherence to Calcium and Vitamin D Supplementation[NCT00668200]	Phase 4	81 participants (Actual)	Interventional	2008-05-31	Completed
A Phase IV, Multi-center, Open Label, Single Arm Clinical Trial to Evaluate the Relationship of Bone Remodeling Markers for Skeletal Complications in Metastatic Breast Cancer Patients[NCT00912938]	Phase 4	237 participants (Anticipated)	Interventional	2007-12-31	Active, not recruiting
A Multicenter, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly Compared to Placebo in Osteoporotic Children Treated With Glucocorticoids.[NCT00799266]	Phase 3	34 participants (Actual)	Interventional	2008-12-04	Completed
A Multicenter Prospective Real-world Study on Bisphosphonates Targeting Triple-negative Breast Cancer[NCT04045522]		120 participants (Anticipated)	Observational	2019-09-01	Recruiting
A Phase IV Study of the Safety and Feasibility of Rooms-based Infusion of Zoledronic Acid for Women With Post-menopausal Osteoporosis[NCT00745485]	Phase 4	186 participants (Actual)	Interventional	2008-08-31	Completed
Efficacy and Security of Annual and Biennial Zoledronic Acid for Osteoporosis Treatment in an HIV-infected Patients' Cohort[NCT00795483]	Phase 4	33 participants (Actual)	Interventional	2009-11-30	Completed
Phase I, Open-Label, Pharmacokinetic, Safety and Tolerability Study of Subcutaneously Administered Bisphosphonate With Recombinant Human Hyaluronidase (rHuPH20) vs Bisphosphonate[NCT00807963]	Phase 1	31 participants (Actual)	Interventional	2008-12-31	Completed
Treatment of the Hutchinson-Gilford Progeria Syndrome With a Combination of Pravastatin and Zoledronic Acid[NCT00731016]	Phase 2	15 participants (Actual)	Interventional	2008-10-31	Completed
A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells (IND # 28460) in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory, Relapsed, or Progressive Neuroblastoma[NCT05400603]	Phase 1	24 participants (Anticipated)	Interventional	2023-11-06	Recruiting
A Randomised Phase II Feasibility Study Investigating the Biological Effects of the Addition of Zoledronic Acid to Neoadjuvant Combination Chemotherapy on Invasive Breast Cancer[NCT00525759]	Phase 2	40 participants (Actual)	Interventional	2007-07-31	Completed
Long-Term Bone Quality in Women With Breast Cancer (A Companion Study to S0307)[NCT00873808]		0 participants (Actual)	Observational	2008-10-31	Withdrawn(stopped due to lack of accrual)
Intravenous Zoledronic Acid for the Treatment of Osteoporosis and Osteonecrosis in Children With Leukemia: A Pilot Study[NCT02632903]	Phase 2	0 participants (Actual)	Interventional	2016-10-31	Withdrawn(stopped due to While the clinical need for and the scientific merit remain valid, this regulated drug trial was not feasible logistically due to limited funds.)
Preventive Effects of Zoledronic Acid on Bone Metastasis in Patients With Stage IIIB and IV Lung Cancer[NCT02622607]	Phase 3	200 participants (Anticipated)	Interventional	2013-01-31	Recruiting
Phase II Study of Efficacy of Radiotherapy in Combination With Zoledronic Acid on Pain Relief in Bone Metastasis Patients With Gastrointestinal Tumors[NCT02784652]	Phase 2	60 participants (Actual)	Interventional	2014-06-30	Completed
A Phase II Prospective Pilot Study Evaluating Efficacy of Intravenous Zoledronic Acid Prophylaxis for Prevention of Aromatase Inhibitor Associated Musculoskeletal Symptoms: ZAP-AIMSS Trial[NCT01194440]	Phase 2	63 participants (Actual)	Interventional	2011-02-28	Completed
Zoledronic Acid in the Prevention of Cancer Therapy Induced Bone Loss[NCT00375505]	Phase 3	70 participants (Actual)	Interventional	2005-10-31	Completed
A Prospective, Randomized, Multi-center Comparative 2-arm Trial of Efficacy and Safety of Zoledronic Acid (Every 3-months vs. Every 4 Weeks) Beyond Approximately 1 Year of Treatment With Zoledronic Acid in Patients With Bone Lesions From Breast Cancer[NCT00375427]	Phase 3	430 participants (Actual)	Interventional	2006-02-28	Completed
Efficacy and Safety of Zoledronic Acid for the Treatment of Osteoporosis in Men[NCT00097825]	Phase 3	288 participants	Interventional	2004-04-30	Completed
Local Administration of Enriched Mononuclear Cells, Platelets and Zoledronic Acid for Preventing Collapse of the Femoral Head in the Early Stage of Osteonecrosis: a Prospective, Randomized, Parallel-controlled Clinical Trial[NCT02721940]		100 participants (Actual)	Interventional	2012-02-29	Active, not recruiting
A Randomised Phase II Feasibility Study of Docetaxel (Taxotere®) Plus Prednisolone vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Zoledronic Acid (Zometa®) vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Strontium-89 vs. Docetaxel (Taxotere®) Plus Pred[NCT00554918]	Phase 2	300 participants (Anticipated)	Interventional	2005-02-28	Completed
Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma: Assessment of Tolerability and In Vivo Expansion γδ T-Cells[NCT01404702]	Phase 1	4 participants (Actual)	Interventional	2011-08-31	Terminated(stopped due to Accrual slower than anticipated)
Prevention of Micro-architectural Bone Decay in Males With Non-metastatic Prostate Cancer Receiving Androgen Deprivation Therapy (ADT)[NCT01006395]	Phase 2/Phase 3	64 participants (Actual)	Interventional	2011-01-31	Completed
Influence of Zoledronic Acid on Bone Mineral Density and Bone Ultrasonometry in Premenopausal Women With Hormone Receptor Negative Breast Cancer and Adjuvant Chemotherapeutic Treatment[NCT00333229]	Phase 4	11 participants (Actual)	Interventional	2006-03-31	Terminated(stopped due to Due to rare patient population, planned number of patients could not be recruited in a reasonable timeframe. Recruitment was stopped prematurely.)
A Phase III Randomized Study to Evaluate the Efficacy of Zometa® for the Prevention of Osteoporosis and Associated Fractures in Patients Receiving Radiation Therapy and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer[NCT00329797]	Phase 3	109 participants (Actual)	Interventional	2006-03-31	Completed
Skeletal Histomorphometry in Patients on Teriparatide or Zoledronic Acid Therapy[NCT00927186]	Phase 4	69 participants (Actual)	Interventional	2009-07-31	Completed
Efficacy of Denosumab and Zoledronic Acid in the Treatment of Idiopathic Inflammatory Myopathies Related Reduced Bone Mineral Density: a Prospective Controlled Trial[NCT04034199]	Phase 3	40 participants (Anticipated)	Interventional	2019-08-15	Not yet recruiting
Efficacy and Safety of Zoledronic Acid in Acute Spinal Cord Injury: Prevention of Bone Loss[NCT00844480]	Phase 2	17 participants (Actual)	Interventional	2010-03-31	Terminated(stopped due to difficulty in enrollment)
Bone Retention of Bisphosphonate (Zometa) in Patients With Multiple Myeloma or Breast Cancer With Metastases to Bone[NCT00760370]	Phase 2	60 participants (Actual)	Interventional	2008-12-31	Completed
A 6 Months, Open-Label Phase IV Study to Confirm the Safety and Efficacy of Single Intravenous Dose of 5 mg Zoledronic Acid for the Patients of Paget's Disease of Bone (PDB) in China[NCT00774020]	Phase 4	9 participants (Actual)	Interventional	2008-10-30	Completed
A Phase II Randomized Study of the Effect of Zoledronic Acid Versus Observation on Bone Mineral Density of the Lumbar Spine in Women Who Elect to Undergo Surgery That Results in Removal of Both Ovaries[NCT00305695]	Phase 2	160 participants (Actual)	Interventional	2005-11-28	Completed
A 3-year, Multicenter, Double-blind, Randomized, Placebo-controlled Extension to CZOL446H2301E1 to Evaluate the Efficacy and Long Term Safety of 6 and 9 Years Zoledronic Acid Treatment of Postmenopausal Women With Osteoporosis[NCT00718861]	Phase 3	190 participants (Actual)	Interventional	2008-05-31	Completed
Antiangiogenic Treatment Strategy With Metronomic Chemotherapy Regimen Combined With a Cox-2 Inhibitor and a Bisphosphonate for Patients With Metastatic Breast Cancer[NCT01067989]	Phase 2	22 participants (Actual)	Interventional	2010-03-31	Terminated(stopped due to No satisfactory acrual)
Initial Fixation of Bisphosphonate-coated Dental Implants[NCT02044978]	Phase 2	16 participants (Anticipated)	Interventional	2014-01-31	Recruiting
Influence of Zoledronic Acid on Healing After Arthroscopic Repair of Chronic Rotator Cuff Lesions - A Prospective, Randomized, Placebo-controlled Phase II Trial[NCT05677152]	Phase 2	80 participants (Anticipated)	Interventional	2022-08-22	Recruiting
Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer[NCT00391690]	Phase 4	99 participants (Actual)	Interventional	2006-02-28	Completed
Adjuvant Zoledronic Acid in 'High Risk' Giant Cell Tumour of Bone (GCT) - A Randomized Phase II Study[NCT00889590]	Phase 2	15 participants (Actual)	Interventional	2008-12-31	Terminated(stopped due to low recruitment with registration denosumab)
The Use of Zoledronic Acid in Men on Androgen Deprivation Therapy for Prostate Cancer With Preexisting Osteoporosis[NCT00171639]	Phase 3	28 participants (Actual)	Interventional	2004-06-30	Completed
Efficacy and Tolerability of Intravenous Zometa® (Zoledronic Acid) 4 mg in Primary Breast Cancer Patients With Disseminated Tumor Cells in Bone Marrow. A Prospective, Randomized, Parallel Group, Open-label, Clinical Pilot Study.[NCT00172068]	Phase 2	96 participants (Actual)	Interventional	2002-01-31	Terminated
CHronic Nonbacterial Osteomyelitis International Registry (CHOIR)[NCT04725422]		2,000 participants (Anticipated)	Observational	2018-08-01	Recruiting
Zoledronic Acid to Prevent Bone Loss During Androgen Deprivation Therapy for Prostate Cancer[NCT00181584]	Phase 2	60 participants (Actual)	Interventional	2003-09-30	Completed
A Stratified, Randomized, Open-label, Multi-center Comparative 2-arm Trial of PK, PD, and Safety of Zoledronic Acid Infusions Administered Monthly vs. Every 3-month, in Multiple Myeloma Patients With Malignant Bone Lesions, and Breast Cancer Patients With[NCT00424983]	Phase 1	18 participants (Actual)	Interventional	2006-11-30	Completed
An Open Phase III Trial With Letrozole Alone or in Combination With Zoledronic Acid as Extended Adjuvant Treatment of Postmenopausal Patients With Primary Breast Cancer[NCT00332709]	Phase 3	83 participants (Actual)	Interventional	2006-01-31	Completed
A Multi-center, Randomized, Open-label, Controlled, One-year Trial to Measure the Effect of Zoledronic Acid and Alendronate on Bone Metabolism in Postmenopausal Women With Osteopenia and Osteoporosis[NCT00404820]	Phase 3	604 participants (Actual)	Interventional	2006-10-31	Completed
A One-year Partial Double-blinded, Randomized, Multi-center, Multi-national Study to Assess the Effects of Combination Therapy of Annual Zoledronic Acid (5 mg) and Daily Subcutaneous Teriparatide (2mcrg) on Postmenopausal Women With Severe Osteoporosis[NCT00439244]	Phase 3	412 participants (Actual)	Interventional	2006-12-31	Completed
A Multi-center, Randomized, Double-blind, Double-dummy Study in Postmenopausal Women With Low Bone Mineral Density to Compare the Effects of a Single Dose of i.v. Zoledronic Acid 5 mg, With Daily Oral Raloxifene 60 mg OD on Bone Turnover Markers[NCT00431444]	Phase 4	110 participants (Actual)	Interventional	2007-01-31	Completed
A 2-year Randomized, Multicenter, Double-blind, Placebo-controlled Study to Determine the Efficacy and Safety of Intravenous Zoledronic Acid 5 mg Administered Either Annually at Randomization and 12 Months, or Administered at Randomization Only in the Pre[NCT00132808]	Phase 3	581 participants (Actual)	Interventional	2004-07-31	Completed
Zoledronic Acid for the Prevention of Bone Loss Post-bone Marrow Transplantation for Thalassemia Major Patients: A Prospective Pilot Study[NCT01016093]	Phase 2/Phase 3	50 participants (Anticipated)	Interventional	2009-11-30	Active, not recruiting
A Randomized Phase II of Zoledronic Acid (Zometa) in the Prevention of Osteoporosis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation[NCT00321932]	Phase 2	61 participants (Actual)	Interventional	2005-07-31	Completed
A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa®) in the Treatment of Bone Metastases in Men With Hormone-Refractory Prostate Cancer[NCT00321620]	Phase 3	1,904 participants (Actual)	Interventional	2006-04-01	Completed
Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation[NCT00297830]	Phase 2/Phase 3	111 participants (Actual)	Interventional	2005-11-30	Completed
A Randomised Trial Investigating the Effect on Biochemical (PSA) Control and Survival of Different Durations of Adjuvant Androgen Deprivation in Association With Definitive Radiation Treatment for Localised Carcinoma of the Prostate.[NCT00193856]	Phase 3	1,071 participants (Actual)	Interventional	2003-10-31	Completed
A Randomized, Double-blind, Placebo-controlled, Phase IV Trial Evaluating the Palliative Benefit of Either Continuing Pamidronate or Switching to Second-line Zoledronic Acid in Breast Cancer Patients With High-risk Bone Metastases.[NCT01907880]	Phase 4	74 participants (Actual)	Interventional	2012-08-31	Completed
Phase 1 Dose Escalation of Early Infusion of Zoledronic Acid in Combination With Increasing Low-dose of Interleukin-2 in Order to Expand Vγ9Vδ2 T Cells After T-replete Haplo-identical Allogeneic Stem Cell Transplantation (SCT)[NCT03862833]	Phase 1	30 participants (Actual)	Interventional	2019-05-07	Completed
Effect of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastasis[NCT00237159]	Phase 4	284 participants (Actual)	Interventional	2002-10-31	Completed
Zoledronic Acid for Prevention of Bone Loss After BAriatric Surgery (ZABAS)[NCT04742010]	Phase 2	60 participants (Anticipated)	Interventional	2021-02-20	Recruiting
[NCT00087659]		0 participants	Interventional	2003-12-31	Completed
Randomized Multi-Center Study Comparing Prolonged Primary Systemic Endocrine Therapy With Letrozole Alone or in Combination With Zoledronic Acid in Early Breast Cancer (NEOadjuvant Study in CANada)[NCT00247650]	Phase 2	190 participants (Anticipated)	Interventional	2005-09-30	Completed
NMR Imaging and Stereological Analysis of Trabecular Bone in Female Subjects 60 and Older at Risk of Fracture Receiving Either Zoledronic Acid or Teriparatide[NCT01153425]	Phase 4	33 participants (Actual)	Interventional	2008-07-31	Completed
Evaluation of Romosozumab vs. Zoledronic Acid Effect in Patients With Spinal Cord Injury and Low Bone Mineral Density[NCT04597931]	Phase 4	30 participants (Anticipated)	Interventional	2020-11-01	Not yet recruiting
Investigation of Changes in Bone Scan Imaging Before and After Intravenous Bisphosphonate Therapy for Osseous Metastases From Breast Cancer[NCT00582920]	Phase 1	10 participants (Actual)	Interventional	2006-01-31	Completed
The Use of Zoledronic Acid to Prevent Cancer-treatment Bone Loss in Post-menopausal Women Receiving Adjuvant Letrozole for Breast Cancer[NCT00171314]	Phase 3	527 participants (Actual)	Interventional	2004-03-31	Completed
A Multicenter, Open-label, Randomized Trial to Evaluate the Anti-cancer Effects of Zoledronic Acid and Circulating Tumor Cell Measurements in Patients With HER2-negative Metastatic Breast Cancer Without Bone Metastasis[NCT01129336]	Phase 4	44 participants (Actual)	Interventional	2010-06-30	Completed
Innovative Approach to Geriatric Osteoporosis[NCT05058976]	Phase 4	200 participants (Anticipated)	Interventional	2021-09-15	Recruiting
A Randomized Phase II Study of the Efficacy and Safety of Hypofractionated Stereotactic Radiotherapy and 5FU or Capecitabine With and Without Zometa in Patients With Locally Advanced Pancreatic Adenocarcinoma[NCT03073785]	Phase 2	44 participants (Anticipated)	Interventional	2016-09-16	Recruiting
Stage I Multiple Myeloma Treatment[NCT00733538]	Phase 4	350 participants (Anticipated)	Interventional	2004-12-31	Active, not recruiting
Perioperative Treatment With Zoledronic Acid in Patients With Resectable Pancreas Cancer[NCT00892242]	Phase 1	24 participants (Actual)	Interventional	2009-12-31	Terminated(stopped due to Principal Investigator decided to close the study early.)
A 3-year, Double-blind Extension to CZOL446H2301 to Evaluate the Long-term Safety and Efficacy of Zoledronic Acid in the Treatment of Osteoporosis in Postmenopausal Women Taking Calcium and Vitamin D[NCT00145327]	Phase 3	2,456 participants (Actual)	Interventional	2005-05-31	Completed
A Phase II Study of Bone Marker Assessment of Multiple Myeloma Patients Treated With AminoBisphosphonates[NCT00577642]	Phase 2	29 participants (Actual)	Interventional	2007-10-31	Completed
A Single-Blinded, Randomized, Controlled, Phase 2 Pilot Study to Evaluate the Safety and Efficacy of Denosumab Compared to Zoledronic Acid for the Treatment of Osteoporosis in Children[NCT02632916]	Phase 2	10 participants (Actual)	Interventional	2016-08-31	Completed
The Effectiveness of Single or Repeat Zoledronate Infusion Versus Oral Alendronate in Consolidating the Bone Accrual Achieved With Denosumab: a Study Organised by the European Calcified Tissue Society[NCT05575167]		125 participants (Anticipated)	Observational	2023-11-28	Recruiting
A Pragmatic Randomised, Multicentre Trial Comparing 4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases From Either Castration-resistant Prostate Cancer or Breast Cancer - The REaCT-BTA Study[NCT02721433]	Phase 4	263 participants (Actual)	Interventional	2016-08-31	Completed
A One Year, Local, Open Label, Multicentre Trial Evaluating the Effects of Zoledronic Acid 5 mg Infusion on BMD and Biochemical Markers of Bone in PMO Pts Between the Ages of 50 and 65 Years[NCT00909961]	Phase 3	118 participants (Actual)	Interventional	2009-11-30	Completed
A 1-year, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy of Zoledronic Acid 5 mg (Aclasta®) on Bone Mineral Density in Patients With Multiple Sclerosis Followed by a 1-year Open-label Treatment Pha[NCT01166178]	Phase 3	29 participants (Actual)	Interventional	2010-10-31	Terminated
Effect of Periodontal Therapy and Bisphosphonates on Gingival Crevicular Fluid Levels of Nuclear Factor- κb Ligand (RANKL) and Osteoprotegerin in Postmenopausal Osteoporosis: Results of a 12-Month Study[NCT02808988]	Phase 4	47 participants (Actual)	Interventional	2013-10-31	Completed
Investigation on the Prevention of Periprosthetic Bone Loss After Total Hip Replacement by Annual Bisphosphonate Therapy: A Prospective Randomized Clinical Trial[NCT02838121]	Phase 3	62 participants (Actual)	Interventional	2009-12-31	Completed
Bisphosphonates in Multicentric Osteolysis, Nodulosis and Arthropathy (MONA) Spectrum Disorder - an Alternative Therapeutic Approach[NCT02823925]		3 participants (Actual)	Observational	2013-02-28	Completed
A 1-year, Multicenter, Open-label Extension to CZOL446H2337 to Evaluate Safety and Efficacy of Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids[NCT01197300]	Phase 3	25 participants (Actual)	Interventional	2010-10-25	Completed
A Prospective, Single-arm Multicenter Study to Evaluate Effect of Intravenous Zoledronic Acid on Bone Metabolism Given Over 4 Months in Patients With Prostate Cancer or Breast Cancer and Bone Metastasis[NCT00334139]	Phase 4	411 participants (Actual)	Interventional	2006-05-31	Completed
ZEST II for Osteoporotic Fracture Prevention[NCT02589600]	Phase 4	310 participants (Actual)	Interventional	2016-01-31	Completed
A Study to Evaluate the Efficacy and Tolerability of Zoledronic Acid in Patients With Metastatic Prostate Cancer Who Can be Treated With a Group of Medications Known as Bisphosphonates[NCT00172016]	Phase 4	43 participants (Actual)	Interventional	2004-01-31	Completed
Study to Assess Efficacy and Safety of Zoledronic Acid and the Value of Markers of Bone Resorption in the Prediction of Bone Metastases and Cancer Treatment-induced Bone Loss (CTIBL) in Patients With Prostate Cancer on Hormone Therapy[NCT00172055]	Phase 3	218 participants (Actual)	Interventional	2004-12-31	Completed
Effect of Zoledronic Acid on Prevention of Bone Loss in Acute Phase First-ever Stroke Patients[NCT04652128]		56 participants (Anticipated)	Interventional	2019-07-15	Recruiting
The Effects of Zoledronic Acid (Zometa) and Physical Activity on Bone Density in Women Receiving Chemotherapy for Breast Cancer[NCT00202059]	Phase 3	72 participants	Interventional	2003-06-30	Completed
Phase I/II Study of Adoptive Immunotherapy Comprising Pyrophosphomonoester Antigen-stimulated T Cells, IL-2, and Nitrogen-containing Bisphosphonates in Patients With Stage IV Renal Cell Carcinoma[NCT00588913]	Phase 1/Phase 2	20 participants (Anticipated)	Interventional	2006-01-31	Completed
Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases[NCT00219219]	Phase 4	0 participants	Interventional	2003-09-30	Completed
A Randomized, Double-blind, Multi-centre Study to Evaluate the Fficacy and Safety of Zometa as a Treatment in Patients With Bone Metastases of Any Solid Tumors or Multiple Myeloma[NCT00219258]	Phase 3	240 participants	Interventional	2005-07-31	Completed
A Randomised Trial Comparing Continuation or De-escalation of Bone Modifying Agents (BMA) in Patients Treated for Over 2 Years for Bone Metastases From Either Breast or Castration-resistant Prostate Cancer (REaCT-Hold BMA)[NCT04549207]	Phase 4	240 participants (Anticipated)	Interventional	2020-10-09	Recruiting
A Randomised, Multicentre, Pragmatic Trial Comparing a Single-Dose vs. Twice Yearly Zoledronate in Patients With Early Stage Breast Cancer (REaCT-ZOL)[NCT03664687]	Phase 4	211 participants (Actual)	Interventional	2018-10-31	Active, not recruiting
A Phase I-II, 24-Week, Multi-Center, Double-Blind, Randomized, Dose-Ranging Study To Evaluate The Safety And Efficacy Of A Humanized Monoclonal Antibody To PTHrP Versus Zoledronic Acid In Patients With Breast Cancer Metastatic To Bone[NCT00060138]	Phase 1/Phase 2	0 participants	Interventional	2002-11-30	Completed
Assessment of the Efficacy and Safety of Zoledronic Acid in the Treatment of Bone Metastases-related Pain in Patients With Prostate Cancer[NCT00375648]	Phase 3	61 participants (Actual)	Interventional	2005-06-30	Completed
A Randomized, Double-blind and Imitation, Parallel-control, Multicenter Phase II Study of AL2846 Versus Zoledronic Acid in Subjects With Advanced Non-small Cell Lung Cancer (NSCLC) With Bone Metastasis[NCT04325776]	Phase 2	60 participants (Anticipated)	Interventional	2020-09-24	Recruiting
Evaluation of Zoledronic Acid to Prevent Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer[NCT00489905]		24 participants (Anticipated)	Interventional	2005-04-30	Completed
Frequency of Zoledronic Acid to Prevent Further Bone Loss in Osteoporotic Patients Requiring Androgen Deprivation Therapy for Prostate Cancer[NCT00520052]		58 participants (Actual)	Interventional	2003-08-31	Completed
Randomized Phase 2 Study on the Relationship Between Circulating VEGF and Weekly or Every-four-week Zometa in Breast Cancer Patients With Bone Metastases[NCT00524849]	Phase 2/Phase 3	60 participants (Actual)	Interventional	2006-11-30	Completed
Zoledronic Acid With Intermittent Hormonal Therapy in Patients With Prostate Cancer[NCT00226954]	Phase 2	23 participants (Actual)	Interventional	2003-03-31	Terminated
Evaluating the Effect of Letrozole With or Without Concomitant Zoledronic Acid on Estrogen Responsive Targets in Postmenopausal Women[NCT00114270]		0 participants	Interventional	2004-05-31	Completed
Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV)[NCT01228318]	Phase 2	63 participants (Actual)	Interventional	2011-01-31	Completed
The Effect of Zoledronate on the Prevention of Pneumonia in Hip Fracture Patients (Zoo-P): An Open-label, Pragmatic, Randomised Controlled Trial[NCT05743179]	Phase 4	2,692 participants (Anticipated)	Interventional	2022-12-05	Recruiting
A Phase III Randomized Study of Zolendronate Bisphosphonate Therapy for the Prevention of Bone Loss in Men With Prostate Cancer Receiving Long-Term Androgen Deprivation[NCT00058188]	Phase 3	53 participants (Actual)	Interventional	2003-03-31	Terminated(stopped due to Closed by the research committee)
Phase 3 Study of the Effect of Zoledronic Acid in the Prevention of Osteoporosis in Early Breast Cancer Patients Receiving the Aromatase Inhibitor, Letrozole, in the Adjuvant Setting[NCT00376740]	Phase 3	90 participants (Actual)	Interventional	2005-09-30	Completed
A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Therapy.[NCT00556374]	Phase 3	3,420 participants (Actual)	Interventional	2006-12-18	Completed
Bisphosphonate Treatment of Osteogenesis Imperfecta[NCT00063479]	Phase 2	158 participants	Interventional	2003-06-30	Completed
A Study to Assess the Safety, Tolerability, and Efficacy of Switching Patients Currently on Oral Bisphosphonate to Zoledronic Acid[NCT00097812]	Phase 3	220 participants	Interventional	2004-05-31	Completed
Assessment of the Efficacy, Tolerability and Pharmaco-economic Impact of Zoledronic Acid Treatment in Prostate Cancer With Bone Metastasis[NCT00241111]	Phase 4	148 participants (Actual)	Interventional	2003-09-30	Completed
A Randomized, Double-blind Study of the Effect of Bondronat Compared With Zoledronic Acid on Pain in Patients With Malignant Bone Disease Experiencing Moderate to Severe Pain[NCT00099177]	Phase 3	96 participants (Actual)	Interventional	2005-08-31	Terminated
Impact of Neoadjuvant Chemotherapy With or Without Zometa on Occult Micrometastases and Bone Density in Women With Locally Advanced Breast Cancer[NCT00242203]	Phase 2	120 participants (Actual)	Interventional	2002-10-31	Completed
Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases[NCT00242554]	Phase 4	150 participants	Interventional	2002-10-31	Completed
Efficacy and Safety of Zoledronic Acid in the Prevention and Treatment of Corticosteroid Induced Osteoporosis[NCT00100620]	Phase 3	802 participants	Interventional	2004-06-30	Completed
Does Adjuvant Zoledronic Acid Reduce Recurrence in Patients With High Risk Localized Breast Cancer?[NCT00072020]	Phase 3	0 participants	Interventional	2003-08-31	Active, not recruiting
"Tartrate-Resistant Acid Phosphatase as a Bone Resorption Marker in Stage IV Breast Cancer Patients With Bone Metastasis During Zometa Treatment: A Pilot Study"[NCT00264082]		30 participants (Anticipated)	Observational	2004-09-30	Completed
An Exploratory Clinical Trial of Zoledronic Acid in Women With CIN 2/3 or 3[NCT00278434]	Phase 1	12 participants (Actual)	Interventional	2005-04-30	Terminated(stopped due to Accrual was insufficient to meet study endpoints)
[NCT00086268]	Phase 3	250 participants (Actual)	Interventional	2004-04-30	Completed
Study Comparing Full-dose Radiotherapy Versus Reduced Dose in the Management of Bone Metastasis in Patients With Breast Cancer Receiving Zoledronic Acid[NCT00172029]	Phase 4	116 participants (Actual)	Interventional	2003-04-30	Completed
Multicenter, Open-label, Randomized Phase III Trial for Administration of Zoledronate to Breast Cancer Metastatic Patients With Non-symptomatic Bone Lesions[NCT00130494]	Phase 3	97 participants (Actual)	Interventional	2002-08-29	Terminated(stopped due to Low recruitment)
Efficacy and Safety of Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta[NCT00131118]	Phase 2	127 participants	Interventional	2004-07-31	Completed
A Multicenter, Open-label Study to Determine the Effect of iv. Zoledronic Acid on Pain and Quality of Life in Patients With Bone Metastases With or Without Skeletal Related Events (SRE) Resulting From Breast Cancer and Prostate Cancer[NCT00434317]	Phase 4	80 participants (Actual)	Interventional	2005-08-31	Completed
A Randomized, Placebo-controlled, Double-blind Study of the Effect of Bondronat Compared With Zoledronic Acid on Pain in Patients With Malignant Bone Disease Experiencing Moderate to Severe Pain[NCT00099203]	Phase 3	163 participants (Actual)	Interventional	2005-07-31	Terminated
Bisphosphonate Therapy for HIV-Associated Osteopenia[NCT00102908]	Phase 2	30 participants (Anticipated)	Interventional	2005-05-31	Active, not recruiting
A Randomized, Double-blind, Placebo-controlled, Proof of Concept Study of Zoledronic Acid in Spontaneous Osteonecrosis of the Knee (SONK)[NCT00477217]	Phase 2	0 participants (Actual)	Interventional	2008-01-31	Withdrawn
To Assess the Efficacy of Over-the-counter Analgesics in the Prevention/Treatment of Transient Post-dose Symptoms Following Zoledronate Infusion in Post-menopausal Women[NCT00145275]	Phase 3	455 participants	Interventional	2004-12-31	Completed
Maintenance of Skeletal Integrity in Frail Elders[NCT00558012]		181 participants (Actual)	Interventional	2007-12-31	Completed
Bone Mineral Density Effects of Zoledronate in Postmenopausal Women With Breast Cancer[NCT00213980]	Phase 2	68 participants (Actual)	Interventional	2000-01-31	Completed
Extended Endocrine Therapy for Premenopausal Women With Breast Cancer[NCT00903162]	Phase 2	17 participants (Actual)	Interventional	2009-05-31	Completed
Multicenter, Open-labeled, Randomized Clinical Trial to Determine the Efficacy of Zoledronic Acid in Preventing Collapse of the Osteonecrotic Femoral Head[NCT00939900]	Phase 3	110 participants (Actual)	Interventional	2009-07-31	Completed
Cost-Effective Use of Bisphosphonates in Metastatic Bone Disease - A Comparison of Bone Marker Directed Zoledronic Acid Therapy to a Standard Schedule[NCT00458796]		1,500 participants (Anticipated)	Interventional	2006-03-31	Terminated(stopped due to Lower than expected recruitment)
Pilot Trial to Evaluate Change in Positron Emission Tomography Scanning (PET) as a Surrogate for Zoledronate (Zometa) Efficacy in Patients With Metastatic Prostate Cancer[NCT01205646]		11 participants (Actual)	Interventional	2010-09-30	Completed
An Evaluation of Estramustine, Docetaxel and Zoledronate in Patients With Hormone-Refractory Adenocarcinoma of the Prostate[NCT00151073]	Phase 2	28 participants (Actual)	Interventional	2002-04-30	Completed
Zoledronic Acid (Zometa) for the Management of Tumor-induced Hypercalcemia (TIH) and Malignant Bone Pain (MBP) in the Community: A Feasibility Study[NCT00126386]		11 participants (Actual)	Interventional	2004-01-31	Completed
A Phase IV Study of Zoledronic Acid Therapy in Patients With Bone Metastases From Breast Cancer or Hormone Resistant Prostate Cancer, or Bone Involvement From Multiple Myeloma, Assessing Long-term Efficacy and Safety[NCT00434447]	Phase 4	73 participants (Actual)	Interventional	2006-12-31	Completed
An Open-Label, Pilot Study of Samarium - Sm 153 Lexidronam (Quadramet) in Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain[NCT00482378]	Phase 1/Phase 2	39 participants (Anticipated)	Interventional	2005-03-21	Completed
A Randomized, Multicenter, Open Phase III Study Comparing the Postoperative Use of Zoledronic Acid Versus no Treatment in Patients With Histological Tumor Residuals After Preoperative Anthracycline and Taxane Containing Chemotherapy for Primary Breast Can[NCT00512993]	Phase 3	654 participants (Anticipated)	Interventional	2004-12-31	Completed
A Dual-Cohort, Prospective, Observational Study of Unresectable Stage IIIB/IV Non-Small Cell Lung Cancer Patients With and Without Bone Metastasis[NCT00099541]	Phase 4	300 participants	Interventional	2004-11-30	Completed
A Study of the Clinical Safety, Tolerability, and Efficacy of Zoledronic Acid Compared to an Oral Bisphosphonate[NCT00100555]	Phase 3	120 participants	Interventional	2004-06-30	Completed
A Randomized, Controlled, Open-Label Trial of Empiric Prophylactic vs. Delayed Use of Zoledronic Acid for Prevention of Bone Loss in Postmenopausal Women With Breast Cancer Initiating Therapy With Letrozole After Tamoxifen[NCT00107263]	Phase 3	558 participants (Actual)	Interventional	2005-01-31	Completed
The Effect Of The Bisphosphonate, Zoledronic Acid, On Bone Density In Liver Transplant Patients - A Prospective, Randomised, Controlled Clinical Trial[NCT00114556]	Phase 4	100 participants	Interventional	2000-02-29	Completed
An Open Label, Reclast®/Aclasta®, Re-treatment of Relapsed Patients With Paget's Disease of Bone Who Participated in the CZOL446K2304 and CZOL446K2305 Core Registration Studies[NCT00740129]	Phase 4	6 participants (Actual)	Interventional	2008-10-21	Completed
Phase III Trial of Intravenous Zoledronic Acid (Zometa) in the Prevention of Bone Loss in Localized Breast Cancer Patients With Chemotherapy-Induced Ovarian Failure[NCT00022087]	Phase 3	439 participants (Actual)	Interventional	2001-12-31	Completed
A Prospective, Multicenter, Open-label Clinical Evaluation of the Effect of IV Zoledronic Acid 4mg on PAIN, QUALITY OF LIFE and TIME IN INFUSION CHAIR in Breast Cancer, Multiple Myeloma, and Prostate Cancer Patients With Cancer-related Bone Lesions[NCT00029224]	Phase 4	500 participants	Interventional	2001-10-31	Completed
An Open-Label, Randomized, Multicentre Study to Evaluate the Efficacy of Two Zoledronic Acid Schedules on Bone Mineral Density in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy[NCT00391950]	Phase 3	300 participants (Anticipated)	Interventional	2006-10-31	Terminated
An Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Mineral Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis[NCT00035997]	Phase 4	261 participants (Actual)	Interventional	2002-04-30	Completed
OS2006 : Protocole de Traitement Des ostéosarcomes de l'Enfant, de l'Adolescent et de l'Adulte Comportant[NCT00470223]	Phase 3	318 participants (Actual)	Interventional	2007-03-31	Active, not recruiting
Bone Loss Prevention With Zoledronic Acid or Denosumab in Critically Ill Adults - A Randomised Controlled Trial[NCT04608630]	Phase 2	450 participants (Anticipated)	Interventional	2021-07-15	Recruiting
A Randomized, Placebo Controlled Trial Of Zoledronic Acid For The Prevention Of Bone Loss In Premenopausal Women With Early Stage Breast Cancer[NCT00049452]	Phase 3	120 participants (Anticipated)	Interventional	2001-12-31	Completed
A Randomized Phase III Trial Of Thalidomide (NSC # 66847) Plus Dexamethasone Versus Dexamethasone In Newly Diagnosed Multiple Myeloma[NCT00033332]	Phase 3	0 participants	Interventional	2002-04-30	Completed
The Effect of Zoledronic Acid Compared to Placebo on Bone Mineral Density in Patients Undergoing Androgen Deprivation Therapy[NCT00063609]	Phase 4	200 participants	Interventional	2003-04-30	Completed
A Phase II, Open-Label, Randomized Trial of Zoledronic Acid (Zometa™) and BMS-275291 (NSC#713763) in Patients With Hormone Refractory Prostate Cancer[NCT00039104]	Phase 2	50 participants (Actual)	Interventional	2002-04-30	Completed
Phase II, Randomized, Open-Label, Two-Arm, Multicenter Study of MEDI-522, a HuMA Directed Against the Human Alpha V Beta 3 Integrin, in Combination With Docetaxel, Prednisone, and Zoledronic Acid in the Treatment of Patients With Metastatic Androgen-Indep[NCT00072930]	Phase 2	150 participants	Interventional	2003-12-31	Completed
A Randomized Phase II Study of Bisphosphonate: Zoledronic Acid (Zometa) in the Management of Asymptomatic/Early Stage Multiple Myeloma: Hoosier Oncology Group MM02-35[NCT00216151]	Phase 2	3 participants (Actual)	Interventional	2005-06-30	Terminated(stopped due to Study terminated due to low patient enrollment.)
Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer[NCT00219271]	Phase 4	60 participants (Actual)	Interventional	2003-09-30	Completed
HORIZON-PFT: Pivotal Fracture Trial[NCT00049829]	Phase 3	7,700 participants	Interventional	2002-01-31	Completed
Comparison Between Pamidronate and Zoledronic Acid for the Treatment of Heart and Lung Transplant Related Osteopaenia and Osteoporosis[NCT00164008]	Phase 4	56 participants (Actual)	Interventional	2002-10-31	Completed
Evaluation of the Efficacy and Tolerability of Zoledronic Acid in Combination With Radiotherapy in Patients With Advanced Osteolytic Bone Lesions[NCT00171964]	Phase 4	75 participants (Actual)	Interventional	2002-05-31	Completed
Effect of Zoledronic Acid in Patients With Renal Cell Cancer and Bone Metastasis[NCT00172003]	Phase 4	50 participants (Actual)	Interventional	2004-09-30	Completed
[NCT00046254]	Phase 3	2,127 participants	Interventional	2002-02-28	Completed
Atrasentan and Zometa for Men With Androgen Independent Prostate Cancer Metastatic to Bone: A Randomized Pilot Study[NCT00181558]	Phase 2	44 participants	Interventional	2001-12-31	Completed
Denosumab vs Zoledronate in Patients With Osteoporotic Vertebral Compression Fracture After Percutaneous Vertebroplasty: A Randomized Controlled Trial[NCT05598606]	Phase 4	75 participants (Actual)	Interventional	2021-01-12	Completed
Open Label Proof of Concept Study of IV Zoledronic Acid (ZA) 5 mg After Forteo in Postmenopausal Women[NCT00361595]		35 participants (Actual)	Interventional	2006-08-31	Completed
Local Bisphosphonate Effect on Recurrence Rate in Extremity Giant Cell Tumor of Bone: A Prospective Randomized Controlled Trial[NCT03295981]	Phase 3	120 participants (Anticipated)	Interventional	2018-05-03	Recruiting
Generic Zoledronic Acid Versus Original Zoledronic Acid: A Multicenter, Randomized, Open, Paralled-controlled Clinical Postmenopausal Osteoporotic Women Efficacy and Safety Research.[NCT03158246]	Phase 4	466 participants (Anticipated)	Interventional	2017-06-01	Not yet recruiting
A Phase III, Parallel Group, Randomized, Open-label, Multi-centre Clinical Trial of Zoledronic Acid in Males Receiving Androgen Deprivation Therapy for Advanced Prostate Cancer.[NCT00242567]	Phase 3	522 participants (Actual)	Interventional	2005-12-31	Completed
A Phase III Randomized Trial of Thalidomide Plus Zoledronic Acid Versus Zoledronic Acid Alone in Patients With Early Stage Multiple Myeloma[NCT00432458]	Phase 3	68 participants (Actual)	Interventional	2003-07-31	Completed
An Open Label Dose Escalation Study of Intravenous Paricalcitol (ZEMPLAR™) [19-NOR-1 ALPHA, 25 - (OH)D] With Zoledronic Acid (Zometa™) in Patients With Multiple Myeloma[NCT00258258]	Phase 1	7 participants (Actual)	Interventional	2005-08-31	Terminated(stopped due to Withdrawn due to low accrual)
A Study to Evaluate the Safety and Efficacy of Zoledronic Acid in the Prevention or Delaying of Bone Metastasis in Patients With Stage IIIA and IIIB Non-small Cell Lung Cancer[NCT00172042]	Phase 3	437 participants (Actual)	Interventional	2005-03-31	Completed
Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I[NCT00171925]	Phase 3	143 participants (Actual)	Interventional	2000-08-31	Terminated(stopped due to Recruitment in study could not be reached after 8 yrs of recruiting)
A Phase IIb Randomised Clinical Trial of the Tolerability, Safety and Efficacy of Adjuvant Docetaxel-Zoledronic Acid After Prostatectomy for High-risk Early Prostate Cancer (AD-ZAP).[NCT00258765]	Phase 2	1 participants (Actual)	Interventional	2006-05-31	Terminated(stopped due to Poor recruitment & not feasible to continue)
An Open-Label, Randomized, MultiCenter Study to Evaluate the Use of Zolendronic Acid in the Prevention of Cancer Treatment-Related Bone Loss in Postmenopausal Women With Estrogen Positive and/or Progesterone Positive Breast Cancer Receiving Letrozole as A[NCT00171340]	Phase 3	1,065 participants (Actual)	Interventional	2003-05-31	Completed
Phase I Study of the Combination of Zoledronic Acid and Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer[NCT00415779]	Phase 1	36 participants (Anticipated)	Interventional	2006-07-31	Completed
Bone Response After Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients With Hormone Sensitive Metastatic Bone Disease: a Prospective, Phase II, Randomized, Multicenter Study[NCT03336983]	Phase 2	120 participants (Anticipated)	Interventional	2017-12-01	Recruiting
Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy.[NCT00237146]	Phase 4	38 participants (Actual)	Interventional	2003-11-30	Completed
An International, Multicenter, Non-Randomized, Open-Labeled Study to Evaluate the Efficacy of Lower Dose Dexamethasone/Thalidomide and Higher Frequency ZOMETA(TM) in the Treatment of Previously Untreated Patients With Multiple Myeloma[NCT00263484]	Phase 2	56 participants (Actual)	Interventional	2005-12-31	Completed
A Phase I Pilot Trial to Study the Safety and Efficacy of Concomitant Radiotherapy and Zoledronic Acid for the Palliation of Bone Metastases From Breast Cancer, Prostate Cancer and Lung Cancer[NCT00264420]	Phase 1	4 participants (Actual)	Interventional	2005-12-31	Completed
Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.[NCT00242528]	Phase 4	0 participants (Actual)	Interventional	2004-04-30	Withdrawn
The Pharmacokinetics and Pharmacodynamics Study of Intravenous Zoledronic Acid in Chinese Subjects With Low Bone Mass or Osteoporosis: a Randomized Placebo-controlled Trail[NCT04719650]	Phase 4	64 participants (Anticipated)	Interventional	2021-10-31	Not yet recruiting
Use of Bisphosphonates in the Treatment of Osteopathy After Liver Transplantation, a Prospective Randomised Study[NCT00302484]		96 participants	Interventional	2002-04-30	Active, not recruiting
A Prospective Multicentre Phase II Trial of Zoledronic Acid in Patients With Myelofibrosis With Myeloid Metaplasia (MMM)[NCT00287261]	Phase 2	17 participants (Actual)	Interventional	2006-02-28	Completed
A Phase II Pilot Study of Zoledronic Acid, Pravastatin, and Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathies[NCT00879034]	Phase 2	5 participants (Actual)	Interventional	2009-03-31	Completed
Randomised Open-label Multicenter Prosp. Clinical Study to Show the Efficacy of IV ZOMETA® 4mg for Prevention of Bone Metastases in Hormone-naïve High Risk Patients With Locally Advanced Prostate Cancer[NCT00294437]	Phase 3	376 participants (Actual)	Interventional	2003-12-31	Terminated(stopped due to underfunding)
Zoledronate Versus Ibandronate Comparative Evaluation: A Randomized Phase III, Open-Label, Multicenter, Parallel Group Clinical Trial to Evaluate and Compare the Efficacy, Safety Profile and Tolerability of Oral Ibandronate Versus Intravenous Zoledronate [NCT00326820]	Phase 3	1,404 participants (Actual)	Interventional	2006-01-31	Active, not recruiting
A Phase III Randomized, Multicenter Non-Inferiority Trial Evaluating the Efficacy of Oral Ibandronate Versus Intravenous Zoledronate in the Reduction of Skeletal-Related Events in Patients With Metastatic Breast Cancer[NCT00301886]	Phase 3	0 participants (Actual)	Interventional	2006-05-31	Withdrawn(stopped due to withdrawn support for study)
An Open,Multicentre,Prospective Study of Adjuvant Zoledronate Treatment in Osteoporosis Women With Breast Cancer[NCT01623908]		200 participants (Anticipated)	Interventional	2011-07-31	Terminated
The Effectiveness and Safety of Treating Operable Breast Cancer by the Adjuvant Therapy of Zoledronic Acid and Aromatase Inhibitors and/or Ovarian Function Inhibition[NCT01654367]	Phase 2/Phase 3	300 participants (Anticipated)	Interventional	2012-01-31	Recruiting
Randomised, Double Blind, Placebo Controlled Trial to Ascertain the Efficacy and Safety of Intravenous Zoledronic Acid in Adult Patients With Cystic Fibrosis.[NCT01702415]	Phase 4	0 participants (Actual)	Interventional	2013-10-31	Withdrawn(stopped due to Lack of funding)
[NCT01737216]	Phase 2	100 participants (Anticipated)	Interventional	2012-11-30	Active, not recruiting
A Randomized, Double-blind, Multi-center Phase 2 Trial of Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer[NCT01951586]	Phase 2	226 participants (Actual)	Interventional	2013-12-31	Completed
Phase 2 Study - The Use of a Single 5 mg Dose of Zoledronic Acid in Complex Regional Pain Syndrome Patient.[NCT01788176]	Phase 2	40 participants (Anticipated)	Interventional	2013-12-31	Not yet recruiting
Bone Demineralization Lesions in the Injured Marrow: Efficacy and Tolerability of Administration Early and Repeated the Zoledronic Acid. Comparative Study, Prospective, Double-blind Controlled[NCT01802658]	Phase 3	12 participants (Actual)	Interventional	2012-11-30	Terminated(stopped due to Recruiting Difficulty)
A Phase II, Randomised, Open-Label, Pilot Study to Evaluate the Safety and Effects on Bone Resorption of AZD0530 in Patients With Prostate Cancer or Breast Cancer With Metastatic Bone Disease.[NCT00558272]	Phase 2	139 participants (Actual)	Interventional	2008-02-29	Completed
Prevention of Bone Loss After Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength, and Use of Biomarkers to Guide Therapy[NCT02325414]	Phase 2	60 participants (Actual)	Interventional	2015-02-28	Completed
A Phase I Study of Bevacizumab With Bolus and Metronomic Cyclophosphamide and Zoledronic Acid in Children With Recurrent or Refractory Neuroblastoma[NCT00885326]	Phase 1	29 participants (Actual)	Interventional	2009-12-31	Completed
Multicenter, Open-label, Exploratory Phase I Pilot Study to Investigate Safety, Pharmacodynamics, and Pharmacokinetics of Immunological Effects and Activity of Combining Multiple Doses of IMAB362 With Immunomodulation (Zoledronic Acid, Interleukin-2) in P[NCT01671774]	Phase 1	32 participants (Actual)	Interventional	2012-10-16	Completed
A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa) in the Treatment of Bone Metastases in Subjects With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma.[NCT00330759]	Phase 3	1,779 participants (Actual)	Interventional	2006-06-01	Completed
A Prospective, Multicenter, Non-comparative, Open-label, Phase II Study to Evaluate the Effects of the Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Mineral Density, Bone Metabolism, Radiographically-detected Osteolytic Bone Lesions, Ske[NCT00972959]	Phase 2	17 participants (Actual)	Interventional	2009-07-31	Completed
Efficacy of a Single Infusion of Zoledronic Acid to Mitigate the Rebound Effect of Rapid Bone Loss Following Denosumab Treatment Discontinuation[NCT05405894]		20 participants (Anticipated)	Observational	2022-09-01	Recruiting
Zoledronic Acid as Adjuvant Therapy in Neovascular Age-related Macular Degeneration (The Z-AMD Study): A Randomized Controlled Pilot Study[NCT04304755]	Phase 2	40 participants (Actual)	Interventional	2021-10-25	Active, not recruiting
Effect of Zoledronic Acid on Femoral Bone Loss Following Total Hip Arthroplasty[NCT01267279]	Phase 4	51 participants (Actual)	Interventional	2005-01-31	Completed
A Pilot Phase 2 Study of Bisphosphonate Therapy (Zoledronic Acid) in Patients With Advanced Malignant Mesothelioma[NCT01204203]	Phase 2	8 participants (Actual)	Interventional	2009-06-30	Completed
A Randomized, Phase III Study of Standard Dosing Versus Longer Dosing Interval of Zoledronic Acid in Metastatic Cancer[NCT00869206]	Phase 3	1,822 participants (Actual)	Interventional	2009-03-31	Completed
A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early Versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men With Prostate Cancer Metastatic to Bone[NCT00079001]	Phase 3	645 participants (Actual)	Interventional	2004-01-31	Completed
A Randomized Placebo Controlled Trial Testing The Effect of Zoledronic Acid on Hip Osteoarthritis[NCT04303026]	Phase 3	70 participants (Anticipated)	Interventional	2020-03-02	Recruiting
Management of Osteoporosis in Patients With Primary Hyperparathyroidism[NCT04085419]	Phase 4	40 participants (Anticipated)	Interventional	2019-05-08	Enrolling by invitation
Pilot Study to Evaluate the Effect of Zoledronic Acid (Zometa) on Occult Malignant Bone Marrow Cells in Patients With High Risk Early Stage Breast Cancer[NCT00295867]	Phase 2	45 participants (Actual)	Interventional	2004-11-03	Completed
Phase II Study of Zometa (Zoledronic Acid) to Prevent Osteoporosis in Patients With Brain Tumors[NCT00301873]	Phase 2	60 participants (Actual)	Interventional	2006-05-31	Completed
Denosumab Versus Zoledronic Acid for Patients With Beta-Thalassemia Major-Induced Osteoporosis[NCT03040765]	Phase 3	17 participants (Actual)	Interventional	2018-05-14	Terminated(stopped due to failed to recruit eligible subjects)
A Randomized Controlled Study of Hepatic Arterial Infusion Chemotherapy of FOLFOX With or Without Zoledronic Acid for the Prevention of Bone Metastases in Advanced Hepatocellular Carcinoma Staged at BCLC C[NCT05866172]	Phase 3	264 participants (Anticipated)	Interventional	2023-05-10	Recruiting
Open Label Dose Escalation Phase I Study to Investigate the Safety and Pharmacokinetics of T121E01Fand T121E02F in Healthy Postmenopausal Women[NCT01721993]	Phase 1	71 participants (Actual)	Interventional	2013-01-31	Completed
Study of Efficacy of Zoledronic Acid in the Management of Osteoporosis in Children With Multiple Disabilities[NCT03301285]		60 participants (Actual)	Observational	2017-01-01	Completed
Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin Levels of Postmenopausal Women With Low Bone Mass: A Multicenter, Randomized, Head-to-head Clinical Trial[NCT01572545]		91 participants (Actual)	Interventional	2012-04-30	Completed
Anti-Osteoclast Therapy as Neoadjuvant in Treatment of Chondrosarcoma - Phase 1b Trial[NCT03173976]	Phase 1	20 participants (Anticipated)	Interventional	2017-07-18	Recruiting
Bone Metabolic Markers, TRAP, and Zometa's Effect on Bone Metastasis Due to Lung Cancer[NCT00265200]	Phase 2	28 participants (Actual)	Interventional	2005-02-28	Terminated(stopped due to funding discontinued by sponsor)
Evaluation of Efficacy of Zoledronic Acid in Patients With Haemoglobin Syndromes (Thalassemia and Sicle Cell Anaemia) and Risk of Skeletal Events[NCT00346242]	Phase 4	60 participants	Interventional	2004-03-31	Completed
FES-Rowing Versus Zoledronic Acid to Improve Bone Health in SCI: A Comparative Clinical Trial[NCT01426555]	Phase 2/Phase 3	70 participants (Actual)	Interventional	2011-02-28	Terminated(stopped due to Incomplete data set & analysis)
A Phase I Study of 1,25 Dihydroxy-Vitamin D3 (Calcitriol) in Patients With Prostate Cancer[NCT00004928]	Phase 1	0 participants	Interventional	1999-10-31	Completed
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Safety and Efficacy of Zoledronate (4 and 8 mg) Administered Intravenously as an Adjuvant to Anticancer Therapy to Patients With Any Cancer With Bone Metastases Other Than B[NCT00003884]	Phase 3	600 participants (Anticipated)	Interventional	1998-08-31	Completed
DCA114273: A Study Comparing Denosumab With Zoledronic Acid in Subjects of Asian Ancestry With Bone Metastases From Solid Tumors[NCT01920568]	Phase 3	487 participants (Actual)	Interventional	2013-08-31	Completed
Replication of the HORIZON Pivotal Fracture Trial in Healthcare Claims Data[NCT04736693]		18,028 participants (Actual)	Observational	2020-09-22	Completed
Tamoxifen Versus Anastrozole, Alone or in Combination With Zoledronic Acid, in Premenopausal, Hormone Receptor-positive Breast Cancer Patients (Stage I, II)[NCT00295646]	Phase 3	1,803 participants (Actual)	Interventional	1999-06-30	Completed
A Randomized Double-Blind Placebo Controlled Phase III Trial Evaluating Zoledronate Plus Standard Therapy Versus Placebo Plus Standard Therapy in Patients With Recurrent Carcinoma of the Prostate Who Are Asymptomatic With Castrate Levels of Testosterone a[NCT00005073]	Phase 3	544 participants (Actual)	Interventional	1999-09-30	Terminated
Efficacy and Tolerability of Intravenous Zoledronic Acid 4mg as an Adjunct to Standard Therapies Including Conversion From Pamidronate in Breast Cancer Patients With Metastatic Bone Lesions. A Prospective, Randomised, Open-label, Clinical Study[NCT00372710]	Phase 3	30 participants	Interventional	2002-08-31	Terminated
Randomized Phase II Study of Zoledronic Acid vs Observation on Bone Mineral Density and Incidence of Micrometastasis in Women Undergoing Pelvic Radiation for Cervical Cancer[NCT00966992]	Phase 2	3 participants (Actual)	Interventional	2009-08-31	Terminated(stopped due to Lack of enrollment)
Effects of Zoledronic Acid Versus Alendronate on Bone Loss After Kidney and Kidney/Pancreas Transplant[NCT00580047]		59 participants (Actual)	Interventional	2003-12-01	Completed
Examination of Bone Metabolism and Bone Mineral Density by Zoledronic Acid in Primary and Secondary Osteoporosis[NCT03183557]	Phase 2	100 participants (Anticipated)	Interventional	2017-10-12	Recruiting
A Exploratory Study of Vγ2Vδ2 T Lymphocyte-based Immunotherapy for MDR-TB[NCT05493267]	Phase 4	30 participants (Anticipated)	Interventional	2022-08-03	Recruiting
A Multicenter, Single-arm, Phase II Study to Evaluate the Activity of Pre-operative Zoledronate in Triple Negative Breast Cancer Patients, According to p53 Level[NCT02347163]	Phase 2	22 participants (Actual)	Interventional	2015-02-03	Terminated(stopped due to The study stopped prematurely due to the low accrual rate)
Attending Physician of Shenzhen People's Hospital[NCT05106517]	Phase 2/Phase 3	122 participants (Anticipated)	Interventional	2021-09-08	Recruiting
An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies[NCT00916747]	Phase 2	85 participants (Actual)	Interventional	2009-08-31	Active, not recruiting
Program of Continuous Passive Motion Exercises Against Heterotopic Ossification[NCT05906056]		20 participants (Anticipated)	Interventional	2023-05-12	Recruiting
Collaboration to Improve Bone Health[NCT05904353]		200 participants (Anticipated)	Interventional	2023-06-30	Recruiting
Denosumab and Teriparatide Study (DATA-HD and DATA-EX)[NCT02176382]	Phase 4	76 participants (Actual)	Interventional	2014-08-31	Completed
The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta[NCT01679080]	Phase 2	9 participants (Actual)	Interventional	2012-11-30	Terminated(stopped due to Eli Lilly has withdrawn support to the study of teriparatide and placebo pens. The study was not able to continue as a randomized study without the supply of placebo pens.)
TCR-αβ+ and CD19+ Depleted KIR/KIR Ligand-mismatched Haploidentical Hematopoietic Stem Cell Transplant and Zoledronate for Pediatric Relapsed/Refractory Hematologic Malignancies and High Risk Solid Tumors[NCT02508038]	Phase 1	22 participants (Anticipated)	Interventional	2016-02-12	Recruiting
A Pilot Study of the Impact of a Single Dose of Zoledronic Acid on Biomarkers in Breast Cancer[NCT01409811]		9 participants (Actual)	Interventional	2012-09-14	Terminated(stopped due to Study closed after it became too difficult to interest patients in participating.)
Phase III Randomized Trial of Thalidomide/Dexamethasone vs VAD as Induction Chemotherapy for Newly Diagnosed Myeloma Patients and Evaluation of the Effects of Zoledronate on Chemotherapy Induced Apoptosis and Antigen Presentation.[NCT00215943]	Phase 3	90 participants (Actual)	Interventional	2003-06-30	Terminated(stopped due to Poor accrual, changes in management of newly diagnosed myeloma patients, new drugs/more effective regimens.)
Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid[NCT01772719]		7 participants (Actual)	Interventional	2012-08-31	Terminated(stopped due to Principal Investigator left institution-study not continued)
A Prospective and Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year After Kidney Transplantation[NCT01675089]	Phase 4	34 participants (Actual)	Interventional	2012-07-31	Completed
A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer[NCT00081159]	Phase 2	80 participants (Actual)	Interventional	2004-07-31	Completed
Efficacy of 4 mg Zoledronic Acid Plus Colaren vs 4mg Zoledronic Acid + Conventional Treatment for Secondary Osteoporosis in HIV Positive and Negative Men[NCT03930992]	Phase 3	30 participants (Actual)	Interventional	2019-04-17	Completed
Zoledronic Acid Combined Radiotherapy for Bone Metastasis of Non-small Cell Lung Cancer: A Non-inferiority, Randomized, Open, Parallel and Controlled Prospective Clinical Study[NCT02480634]	Phase 4	280 participants (Anticipated)	Interventional	2019-06-30	Not yet recruiting
Zoledronic Acid or Methylprednisolone in the Management of Active Charcot's Neuroarthropathy of Foot in Patients With Diabetes Mellitus: A Randomized, Double-blind, Placebo Controlled Trial[NCT03289338]	Phase 2/Phase 3	36 participants (Actual)	Interventional	2016-06-01	Completed
Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis 2[NCT05655013]	Phase 4	200 participants (Anticipated)	Interventional	2023-05-10	Recruiting
A Randomized Double-blind Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates[NCT01732770]	Phase 4	643 participants (Actual)	Interventional	2012-11-07	Completed
The Optimal Sequential Therapy After Long Term Denosumab Treatment[NCT05091099]	Phase 4	44 participants (Anticipated)	Interventional	2021-11-20	Recruiting
Denosumab vs Zoledronate Efficacy in Osteopenic Patients With Lumbar Degenerative Disease After Lumbar Fusion Surgery[NCT05638399]	Phase 3	100 participants (Anticipated)	Interventional	2020-01-15	Recruiting
Solitary Plasmacytoma of Bone: Randomized Phase III Trial to Evaluate Treatment With Adjuvant Systemic Treatment and Zoledronic Acid Versus Zoledronic Acid After Definite Radiation Therapy[NCT02516423]	Phase 3	11 participants (Actual)	Interventional	2015-12-31	Active, not recruiting
The Efficacy of Zoledronic Acid in the Prevention of Bone Loss in Acute Spinal Cord Injury[NCT02042872]	Phase 4	21 participants (Actual)	Interventional	2006-05-31	Completed
Trial of Zoledronic Acid to Prevent Bone Loss in Hematopoietic Cell Transplant Recipients[NCT02451462]		0 participants (Actual)	Interventional	2015-09-30	Withdrawn(stopped due to Logistics)
Sustaining Skeletal Health in Frail Elderly[NCT02753283]	Phase 4	201 participants (Actual)	Interventional	2016-06-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Time to First and Subsequent On-Study Skeletal-Related Event

Time to first and subsequent on-study skeletal-related event (SRE) using a multiple event analysis. To be considered a subsequent SRE, the event must occur at least 21 days after the previous SRE. This outcome measure utilizes multiple event times, was analyzed based on a proportional mean model, and is therefore more appropriately summarized by the cumulative number of events. (NCT00321464)
Timeframe: Up to 34 months

Intervention	Events (Number)
Zoledronic Acid	608
Denosumab	474

Time to First On-Study Skeletal Related Event (SRE) (Non-inferiority)

Time to first on-study skeletal-related event (SRE) using a non-inferiority analysis. The median time to first skeletal-related event could not be estimated in one treatment arm, so the subject incidence is presented. (NCT00321464)
Timeframe: Up to 34 months

Intervention	Participants (Number)
Zoledronic Acid	372
Denosumab	315

Time to First On-Study Skeletal-Related Event (Superiority)

Time to first on-study skeletal-related event (SRE) using a superiority analysis. The median time to first skeletal-related event could not be estimated in one treatment arm, so the subject incidence is presented. (NCT00321464)
Timeframe: Up to 34 months

Intervention	Participants (Number)
Zoledronic Acid	372
Denosumab	315

Change in Pain Interference Score

Change in pain interference score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain. (NCT00051636)
Timeframe: Baseline and day 182

Intervention	Units on a scale (Mean)
Zoledronic Acid and Placebo to Risedronate	-0.2
Risedronate and Placebo to Zoledronic Acid	0.1

Change in Pain Severity Score

Change in pain severity score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain. (NCT00051636)
Timeframe: Baseline and day 182

Intervention	Units on a scale (Mean)
Zoledronic Acid and Placebo to Risedronate	-0.5
Risedronate and Placebo to Zoledronic Acid	-0.7

Number of Participants With a Disease Relapse During the Extended Observation Period

Extended observation period. A disease relapse was defined as the occurrence of a serum alkaline phosphatase level that was >= 80% of baseline serum alkaline phosphatase value. (NCT00051636)
Timeframe: 8 years was the maximum

Intervention	Participants (Number)
Zoledronic Acid and Placebo to Risedronate	0
Risedronate and Placebo to Zoledronic Acid	7

Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period

Extended observation period. A therapeutic response is defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess or normalization of serum alkaline phosphatase. (NCT00051636)
Timeframe: 8 years was the maximum

Intervention	Participants (Number)
Zoledronic Acid and Placebo to Risedronate	8
Risedronate and Placebo to Zoledronic Acid	29

Number of Participants With a Partial Disease Relapse During the Extended Observation Period

Extended observation period. A partial disease relapse was defined as an increase in serum alkaline phosphatase >= 50% from the serum alkaline phosphatase measurement at month 6 and at least 1.25 times the upper normal limit. (NCT00051636)
Timeframe: 8 years was the maximum

Intervention	Participants (Number)
Zoledronic Acid and Placebo to Risedronate	6
Risedronate and Placebo to Zoledronic Acid	26

Number of Patients Who Achieve Therapeutic Response at 6 Months.

Therapeutic response is defined as a reduction of at least 75% from baseline (Visit 1) in total serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase at the end of six months. (NCT00051636)
Timeframe: 6 months

Intervention	participants (Number)
Zoledronic Acid and Placebo to Risedronate	85
Risedronate and Placebo to Zoledronic Acid	60

Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline

Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. (NCT00051636)
Timeframe: Baseline and day 28

Intervention	Participants (Number)
Zoledronic Acid and Placebo to Risedronate	5
Risedronate and Placebo to Zoledronic Acid	0

Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28

The percent change in serum alkaline phosphatase from baseline to day 28 was measured. (NCT00051636)
Timeframe: Baseline and day 28

Intervention	percent change (Mean)
Zoledronic Acid and Placebo to Risedronate	-48.8
Risedronate and Placebo to Zoledronic Acid	-28.4

Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10

The percent change in serum C-telopeptide from baseline to day 10 was measured. (NCT00051636)
Timeframe: Baseline and day 10

Intervention	percent change (Mean)
Zoledronic Acid and Placebo to Risedronate	-85.4
Risedronate and Placebo to Zoledronic Acid	-36.7

Relative Change in Urine Alpha C-telopeptide (α-CTx) in ug/mmol at Day 10

The percent change in urine alpha C-telopeptide from baseline to day 10 was measured. (NCT00051636)
Timeframe: Baseline and day 10

Intervention	Percent change (Mean)
Zoledronic Acid and Placebo to Risedronate	-90.3
Risedronate and Placebo to Zoledronic Acid	-29.9

Time to First Therapeutic Response

A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase. (NCT00051636)
Timeframe: 182 days

Intervention	Days (Median)
Zoledronic Acid and Placebo to Risedronate	64
Risedronate and Placebo to Zoledronic Acid	78

Disease-free Survival

Time from date of registration to date of first observation of recurrence or death due to any cause. Patients last known to be alive who have not experienced recurrence of disease are censored at their last contact date. The outcome for the disease-free survival will be presented as 5 year survival rate. (NCT00127205)
Timeframe: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence

Intervention	percentage of analyzed participants (Number)
Arm I Zoledronate	88
Arm II Clodronate	88
Arm III Ibandronate	87

Overall Survival

Time from date of registration to date of death due to any cause. Patients last known to be alive are censored at their last contact date. The outcome for overall survival will be presented as 5 year overall survival rate. (NCT00127205)
Timeframe: follow up completed every 6 months for 5 years and then annually for 5 years or until death

Intervention	percentage of analyzable patients (Number)
Arm I Zoledronate	93
Arm II Clodronate	92
Arm III Ibandronate	93

Distributions of Sites of First Recurrence on the Three Arms.

All sites of invasive disease documented within 30 days of first documentation of invasive recurrence. (NCT00127205)
Timeframe: Disease assessments are completed every 6 months for 5 years then annually for 5 years or until death or recurrence

Intervention	Participants (Count of Participants)
	Local/Regional only	Contralateral only	Distant recurrence	Unknown location of recurrence	Bone as 1st site of distant recurrence	Bone only	Bone and nodes only	Bone and other distant sites (beside nodes)	Liver/lung/other visceral without bone recurrence	Brain/other CNS (+/- any other site)
Arm I Zoledronate	41	17	218	10	110	62	2	46	57	31
Arm II Clodronate	55	18	207	15	108	48	2	58	67	24
Arm III Ibandronate	36	17	146	10	82	44	2	36	40	22

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT00127205)
Timeframe: Toxicity assessment is repeated every 2 months for the first 6 months, then every 3 months until 3 years or end of treatment.

Intervention	Participants (Number)
	ALT, SGPT (serum glutamic pyruvic transaminase)	AST, SGOT	Alkaline phosphatase	Allergic reaction/hypersensitivity	Anorexia	Arthritis (non-septic)	Auditory/Ear-Other (Specify)	Bilirubin (hyperbilirubinemia)	Blood/Bone Marrow-Other (Specify)	CNS cerebrovascular ischemia	Calcium, serum-low (hypocalcemia)	Cardiac General-Other (Specify)	Confusion	Constipation	Creatinine	Dehydration	Dental: periodontal disease	Dental: teeth	Diarrhea	Distention/bloating, abdominal	Dizziness	Dysphagia (difficulty swallowing)	Dyspnea (shortness of breath)	Edema: limb	Endocrine-Other (Specify)	Esophagitis	Extremity-upper (function)	Fatigue (asthenia, lethargy, malaise)	Febrile neutropenia	Fever in absence of neutropenia, ANC lt1.0x10e9/L	Flu-like syndrome	Fracture	Gastritis (including bile reflux gastritis)	Glucose, serum-high (hyperglycemia)	Heartburn/dyspepsia	Hemoglobin	Hemorrhage, GI - Rectum	Hemorrhage, GI - Stomach	Hot flashes/flushes	Hypertension	Hypotension	INR (of prothrombin time)	Incontinence, urinary	Inf (clin/microbio) w/Gr 3-4 neuts - Skin	Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue	Inf w/normal ANC or Gr 1-2 neutrophils - Bone	Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus	Inf w/normal ANC or Gr 1-2 neutrophils - Dental	Infection with unknown ANC - Appendix	Infection with unknown ANC - Liver	Infection with unknown ANC - Skin (cellulitis)	Insomnia	Irregular menses (change from baseline)	Irritability (children lt3 years of age)	Joint-function	Left ventricular systolic dysfunction	Leukocytes (total WBC)	Lymphopenia	Magnesium, serum-high (hypermagnesemia)	Magnesium, serum-low (hypomagnesemia)	Masculinization of female	Memory impairment	Metabolic/Laboratory-Other (Specify)	Mood alteration - anxiety	Mood alteration - depression	Mood alteration - euphoria	Mucositis/stomatitis (clinical exam) - Oral cavity	Muscle weakness, not d/t neuropathy - Extrem-lower	Muscle weakness, not d/t neuropathy - Extrem-upper	Muscle weakness, not d/t neuropathy - body/general	Nausea	Neuropathy: motor	Neuropathy: sensory	Neutrophils/granulocytes (ANC/AGC)	Obesity	Opportunistic inf associated w/gt=Gr 2 lymphopenia	Osteonecrosis (avascular necrosis)	Pain - Abdomen NOS	Pain - Back	Pain - Bone	Pain - Chest wall	Pain - Chest/thorax NOS	Pain - Extremity-limb	Pain - Head/headache	Pain - Joint	Pain - Muscle	Pain - Neck	Pain - Neuralgia/peripheral nerve	Pain - Oral cavity	Pain - Pain NOS	Pain - Stomach	Pain - Throat/pharynx/larynx	Pain - Vagina	Pain-Other (Specify)	Pancreatitis	Perforation, GI - Duodenum	Phosphate, serum-low (hypophosphatemia)	Platelets	Potassium, serum-high (hyperkalemia)	Potassium, serum-low (hypokalemia)	Proteinuria	Pruritus/itching	Rash/desquamation	Renal failure	Renal/Genitourinary-Other (Specify)	Retinal detachment	Rigors/chills	Secondary Malignancy-poss rel to cancer Tx	Sexual/Reproductive Function-Other (Specify)	Sodium, serum-low (hyponatremia)	Soft tissue necrosis - Head	Syncope (fainting)	Thrombosis/embolism (vascular access-related)	Thrombosis/thrombus/embolism	Tinnitus	Urticaria (hives, welts, wheals)	Vomiting	Weight gain	Weight loss
Arm I Zoledronic Acid	1	1	0	2	0	5	1	0	0	0	3	0	0	0	2	1	2	0	2	0	1	0	3	1	0	0	0	11	1	1	3	0	0	0	2	3	0	0	3	2	0	0	1	1	1	1	0	0	0	1	0	1	2	0	0	0	2	2	1	1	0	1	0	0	1	0	1	0	0	0	3	0	0	6	1	1	6	0	3	47	0	0	4	8	39	23	1	1	0	1	1	0	0	4	0	0	19	1	0	1	0	0	0	2	0	1	1	0	1	0	0	2	1	0	1	1	1	0	0
Arm II Clodronate	3	5	1	1	1	2	0	1	0	1	2	0	1	1	1	2	0	1	11	1	3	1	2	1	1	2	0	10	1	1	0	3	1	2	22	2	1	0	5	2	1	1	0	1	0	0	1	1	0	0	1	3	0	1	0	0	1	3	2	0	0	0	1	0	1	1	0	1	1	1	5	0	6	5	1	0	1	1	2	19	1	0	3	3	35	5	0	0	0	0	1	0	0	4	1	1	6	0	0	5	0	1	3	2	0	0	0	1	0	1	0	0	1	0	0	2	1	1	1
Arm III Ibandronate	1	3	0	1	0	2	0	1	1	0	1	1	0	1	4	0	0	0	5	0	0	1	3	4	0	5	1	7	0	0	0	1	1	0	22	1	0	1	4	1	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1	1	0	0	0	0	1	0	0	1	1	0	0	0	0	0	2	1	4	0	0	0	3	1	6	19	0	2	4	1	42	16	1	0	1	0	1	1	1	0	0	0	8	0	1	1	1	0	2	5	3	0	0	0	1	0	1	0	0	1	0	1	1	0	1

Change in Lumbar Spine BMD From Baseline to 6 Months After the Zoledronic Acid Infusion.

Change in lumbar spine BMD from baseline to 6 months after the zoledronic acid infusion. (NCT03087851)
Timeframe: baseline to 6 months after the zoledronic acid infusion

Intervention	percentage change (Mean)
6-month Group	-2.1
9-months Group	-4.3
Observation Group	-3.0

Changes in BMD From Baseline to One Year After the Zoledronic Acid Infusion.

Changes in lumbar spine BMD from baseline to one year after the zoledronic acid infusion. (NCT03087851)
Timeframe: from baseline to one year after the zoledronic acid infusion

Intervention	percentage change (Mean)
6-month Group	-4.8
9-months Group	-4.1
Observation Group	-4.7

Changes in BMD From Baseline to Two Years After the Zoledronic Acid Infusion.

Changes in lumbar spine BMD from baseline to two years after the zoledronic acid infusion. (NCT03087851)
Timeframe: from baseline to two years after the zoledronic acid infusion.

Intervention	percentage change (Mean)
6-month Group	-4.0
9-months Group	-4.1
Observation Group	-4.3

Changes in Cortical Porosity Measured by High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Scan at the Radius and Tibia From Baseline to One Year After the Zoledronic Acid Infusion.

Changes in cortical porosity measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) scan at the radius and tibia from baseline to one year after the zoledronic acid infusion. (NCT03087851)
Timeframe: from baseline to one year after the zoledronic acid infusion.

Intervention	percentage change (Mean)
6-month Group	-2.5
9-months Group	-1.6
Observation Group	-4.2

Changes in p-CTX From Baseline to 12 Months After the Zoledronic Acid Infusion.

Changes in p-CTX from baseline to 12 months after the zoledronic acid infusion. (NCT03087851)
Timeframe: from baseline to 12 months after the zoledronic acid infusion.

Intervention	ug/l (Mean)
6-month Group	0.58
9-months Group	0.40
Observation Group	0.49

Changes in p-CTX From Baseline to Six Months After the Zoledronic Acid Infusion.

Changes in p-CTX from baseline to six months after the zoledronic acid infusion. (NCT03087851)
Timeframe: from baseline to six months after the zoledronic acid infusion.

Intervention	ug/l (Mean)
6-month Group	0.60
9-months Group	0.47
Observation Group	0.47

Morphometric Vertebral Fractures Assessed by Vertebral Fracture Assessment (VFA) One and Two Years After the Zoledronic Acid Infusion.

Morphometric vertebral fractures assessed by vertebral fracture assessment (VFA) one and two years after the zoledronic acid infusion. (NCT03087851)
Timeframe: one and two years after the zoledronic acid infusion.

Intervention	participants (Number)
6-month Group	0
9-months Group	2
Observation Group	0

Number of Participants Who Fail to Maintain BMD

Failure is defined as ≥ 3 % BMD loss at the lumbar spine (NCT03087851)
Timeframe: 2 years after the first ZOL treatment

Intervention	participants (Number)
6-month Group	10
9-months Group	5
Observation Group	6

Change From Baseline in Radial Bone Strength (Failure Load) at Month 12

Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius. (NCT03118570)
Timeframe: Baseline, Month 12 (EOT)

Intervention	newton (N) (Least Squares Mean)
Setrusumab 20 mg/kg (Blinded)	61.25
Setrusumab 8 mg/kg (Blinded)	32.25
Setrusumab 2 mg/kg (Blinded)	8.86

Change From Baseline in Radial Bone Strength (Stiffness) at Month 12

Assessed by FEA of models generated from HRpQCT images of the distal radius. (NCT03118570)
Timeframe: Baseline, Month 12 (EOT)

Intervention	N/mm (Least Squares Mean)
Setrusumab 20 mg/kg (Blinded)	1638.70
Setrusumab 8 mg/kg (Blinded)	1422.00
Setrusumab 2 mg/kg (Blinded)	209.89

Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12

Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA). (NCT03118570)
Timeframe: Baseline, Month 12 (end of treatment [EOT])

Intervention	ratio (Number)
Setrusumab 20 mg/kg (Blinded)	1.004
Setrusumab 8 mg/kg (Blinded)	0.993
Setrusumab 2 mg/kg (Blinded)	0.992

Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12

(NCT03118570)
Timeframe: Baseline, Months 1, 3, 6, 9, 12 (EOT)

Intervention	µg/L (Least Squares Mean)
	Month 1	Month 3	Month 6	Month 9	Month 12
Setrusumab 2 mg/kg (Blinded)	0.060	0.640	-0.429	-2.254	4.428
Setrusumab 20 mg/kg (Blinded)	24.349	17.903	13.096	7.265	5.452
Setrusumab 8 mg/kg (Blinded)	14.288	6.735	6.665	0.238	4.172

Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12

(NCT03118570)
Timeframe: Baseline, Months 1, 3, 6, 9, 12 (EOT)

Intervention	µg/L (Least Squares Mean)
	Month 1	Month 3	Month 6	Month 9	Month 12
Setrusumab 2 mg/kg (Blinded)	-0.041	-0.043	-0.028	-0.031	-0.034
Setrusumab 20 mg/kg (Blinded)	-0.077	-0.044	-0.013	-0.020	-0.037
Setrusumab 8 mg/kg (Blinded)	-0.047	-0.029	-0.025	-0.039	-0.002

Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time

Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT), 18, and 24

Intervention	ratio (Number)
	Radial, Month 6	Radial, Month 12	Radial, Month 18	Radial, Month 24	Tibial, Month 6	Tibial, Month 12	Tibial, Month 18	Tibial, Month 24
Setrusumab 2 mg/kg (Blinded)	0.998	1.001	1.007	1.002	0.998	0.998	0.993	0.996
Setrusumab 20 mg/kg (Blinded)	1.004	1.005	1.011	1.011	1.012	1.017	1.024	1.020
Setrusumab 8 mg/kg (Blinded)	1.002	1.003	1.001	1.018	0.997	1.004	1.004	1.017

Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12

"The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is no problems and 5 is extreme problems. The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health)." (NCT03118570)
Timeframe: Baseline, Months 6 and 12 (EOT)

Intervention	score on a scale (Least Squares Mean)
	Month 6	Month 12
Setrusumab 2 mg/kg (Blinded)	-0.0383	0.0214
Setrusumab 20 mg/kg (Blinded)	0.0627	0.0424
Setrusumab 8 mg/kg (Blinded)	0.0362	0.0252

Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12

Lean and fat body mass was evaluated using whole body DXA (including the head). (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	grams (Least Squares Mean)
	Month 6: Lean	Month 12: Lean	Month 6: Fat	Month 12: Fat
Setrusumab 2 mg/kg (Blinded)	168.206	184.164	426.388	792.485
Setrusumab 20 mg/kg (Blinded)	519.152	867.668	42.567	421.266
Setrusumab 8 mg/kg (Blinded)	-410.664	-225.474	105.420	-85.495

Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12

BMD was evaluated by DXA. (NCT03118570)
Timeframe: Baseline, Month 12 (EOT)

Intervention	g/cm^2 (Least Squares Mean)
	Lumbar	Total Body	Femoral Neck
Setrusumab 2 mg/kg (Blinded)	2.50	1.06	1.90
Setrusumab 20 mg/kg (Blinded)	8.55	1.98	3.30
Setrusumab 8 mg/kg (Blinded)	6.79	2.03	2.65

Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6

BMD was evaluated by DXA. (NCT03118570)
Timeframe: Baseline, Month 6

Intervention	g/cm^2 (Least Squares Mean)
	Lumbar	Total Body	Femoral Neck
Setrusumab 2 mg/kg (Blinded)	1.58	1.21	1.61
Setrusumab 20 mg/kg (Blinded)	4.06	0.77	-0.42
Setrusumab 8 mg/kg (Blinded)	4.70	0.83	1.64

Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12

BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD. (NCT03118570)
Timeframe: Baseline, Month 12 (EOT)

Intervention	T-score (Least Squares Mean)
	Lumbar	Total Body	Femoral Neck
Setrusumab 2 mg/kg (Blinded)	0.174	0.108	0.104
Setrusumab 20 mg/kg (Blinded)	0.587	0.181	0.163
Setrusumab 8 mg/kg (Blinded)	0.486	0.199	0.159

Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6

BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD. (NCT03118570)
Timeframe: Baseline, Month 6

Intervention	T-score (Least Squares Mean)
	Lumbar	Total Body	Femoral Neck
Setrusumab 2 mg/kg (Blinded)	0.110	0.122	0.087
Setrusumab 20 mg/kg (Blinded)	0.273	0.072	-0.024
Setrusumab 8 mg/kg (Blinded)	0.338	0.071	0.102

Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12

The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	score on a scale (Least Squares Mean)
	Month 6	Month 12
Setrusumab 2 mg/kg (Blinded)	1.907	-1.630
Setrusumab 20 mg/kg (Blinded)	-5.980	-0.964
Setrusumab 8 mg/kg (Blinded)	-2.722	4.489

Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12

The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	score on a scale (Least Squares Mean)
	Month 6	Month 12
Setrusumab 2 mg/kg (Blinded)	-6.003	-7.178
Setrusumab 20 mg/kg (Blinded)	-3.990	-3.655
Setrusumab 8 mg/kg (Blinded)	-3.906	-4.968

Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12

The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	score on a scale (Least Squares Mean)
	Month 6	Month 12
Setrusumab 2 mg/kg (Blinded)	-0.649	-3.846
Setrusumab 20 mg/kg (Blinded)	-3.584	-1.668
Setrusumab 8 mg/kg (Blinded)	-1.848	-0.587

Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set

Intervention	ratio (Number)
	Radial: Month 6	Radial: Month 12	Radial: Month 18	Radial: Month 24	Tibial: Month 6	Tibial: Month 12	Tibial: Month 18	Tibial: Month 24
Setrusumab 2 mg/kg (Blinded)	0.998	0.992	0.979	0.979	0.990	0.973	0.983	1.017
Setrusumab 20 mg/kg (Blinded)	1.007	1.004	1.002	0.997	1.004	0.991	0.989	1.000
Setrusumab 8 mg/kg (Blinded)	1.000	0.993	0.992	0.998	1.016	1.018	1.042	1.062

Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12

The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	score on a scale (Least Squares Mean)
	Month 6	Month 12
Setrusumab 2 mg/kg (Blinded)	-1.133	-1.664
Setrusumab 20 mg/kg (Blinded)	0.966	2.807
Setrusumab 8 mg/kg (Blinded)	-0.492	-1.473

Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12

The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	score on a scale (Least Squares Mean)
	Month 6	Month 12
Setrusumab 2 mg/kg (Blinded)	1.342	2.171
Setrusumab 20 mg/kg (Blinded)	0.672	-1.178
Setrusumab 8 mg/kg (Blinded)	-0.463	-0.994

Change From Baseline in Total vBMD (Radial and Tibial) Over Time

Intervention	ratio (Number)
	Radial, Month 6	Radial, Month 12	Radial, Month 18	Radial, Month 24	Tibial, Month 6	Tibial, Month 12	Tibial, Month 18	Tibial, Month 24
Setrusumab 2 mg/kg (Blinded)	1.000	0.999	0.996	0.985	0.995	0.989	0.987	0.994
Setrusumab 20 mg/kg (Blinded)	1.011	1.017	1.013	0.998	1.017	1.024	1.020	1.001
Setrusumab 8 mg/kg (Blinded)	0.995	1.008	0.992	1.009	1.011	1.011	1.021	1.025

Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm

Assessed by FEA of models generated from HRpQCT images of the distal radius. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	N (Least Squares Mean)
	Radial: Month 6	Radial: Month 12	Tibial: Month 6	Tibial: Month 12
Setrusumab 20 mg/kg (Open-Label)	110.16	88.32	69.78	112.92

Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set

Assessed by FEA of models generated from HRpQCT images of the distal radius. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT), 18, 24

Intervention	N (Least Squares Mean)
	Radial: Month 6	Radial: Month 12	Radial: Month 18	Radial: Month 24	Tibial: Month 6	Tibial: Month 12	Tibial: Month 18	Tibial: Month 24
Setrusumab 2 mg/kg (Blinded)	-3.28	8.86	-10.53	-50.65	-65.33	-65.96	-49.50	-74.94
Setrusumab 20 mg/kg (Blinded)	31.22	61.25	50.39	-19.59	46.00	76.15	50.69	-24.75
Setrusumab 8 mg/kg (Blinded)	39.95	32.25	43.11	45.03	45.91	60.20	88.33	41.37

Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm

Assessed by FEA of models generated from HRpQCT images of the distal radius. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT)

Intervention	N/mm (Least Squares Mean)
	Radial: Month 6	Radial: Month 12	Tibial: Month 6	Tibial: Month 12
Setrusumab 20 mg/kg (Open-Label)	5056.51	4992.82	4225.92	5827.81

Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set

Assessed by FEA of models generated from HRpQCT images of the distal radius. (NCT03118570)
Timeframe: Baseline, Months 6, 12 (EOT), 18, 24

Intervention	N/mm (Least Squares Mean)
	Radial: Month 6	Radial: Month 12	Radial: Month 18	Radial: Month 24	Tibial: Month 6	Tibial: Month 12	Tibial: Month 18	Tibial: Month 24
Setrusumab 2 mg/kg (Blinded)	109.65	209.89	-215.92	-1258.55	-1356.71	-1428.87	-815.38	-1844.84
Setrusumab 20 mg/kg (Blinded)	795.67	1638.70	1295.98	-625.46	1344.84	2326.63	1047.16	-1250.69
Setrusumab 8 mg/kg (Blinded)	1048.61	1422.00	803.50	1172.45	1051.40	1543.85	1697.21	622.77

Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm

Intervention	ratio (Number)
	Radial: Month 6	Radial: Month 12	Tibial: Month 6	Tibial: Month 12
Setrusumab 20 mg/kg (Open-Label)	0.994	1.011	1.013	1.035

Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set

(NCT03118570)
Timeframe: Baseline, Month 6, Month 12 (EOT)

Intervention	Participants (Count of Participants)
	Month 6: Body Height	Month 6: Weight	Month 6: BMI	Month 12: Body Height	Month 12: Weight	Month 12: BMI
Setrusumab 2 mg/kg (Blinded)	0	0	0	0	0	0
Setrusumab 20 mg/kg (Blinded)	0	0	0	0	0	0
Setrusumab 8 mg/kg (Blinded)	0	0	0	0	0	0

Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14

Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor. (NCT03118570)
Timeframe: up to Month 14

,,,,

Intervention	percentage of participants (Number)
	Binding Antibodies	Neutralizing Antibodies	Both Binding and Neutralizing Antibodies
Placebo	15.0	0	0
Setrusumab 2 mg/kg (Blinded)	16.7	16.7	16.7
Setrusumab 20 mg/kg (Blinded)	16.1	16.1	16.1
Setrusumab 20 mg/kg (Open-Label)	9.5	0	0
Setrusumab 8 mg/kg (Blinded)	17.2	17.2	17.2

Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death

"An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a reasonable possibility of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication." (NCT03118570)
Timeframe: Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.)

,,,,

Intervention	percentage of participants (Number)
	All AEs	TEAEs	Treatment-Related TEAEs	Serious TEAEs	Treatment-Related Serious TEAEs	TEAEs Leading to Death	TEAEs Leading to Permanent Study Treatment Discontinuation
Placebo	90.0	80.0	25.0	10.0	0	0	5.0
Setrusumab 2 mg/kg (Blinded)	90.0	90.0	36.7	23.3	0	0	0
Setrusumab 20 mg/kg (Blinded)	100.0	100.0	71.0	12.9	6.5	0	6.5
Setrusumab 20 mg/kg (Open-Label)	100.0	95.2	42.9	23.8	9.5	0	9.5
Setrusumab 8 mg/kg (Blinded)	96.6	96.6	41.4	24.1	0	0	0

Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12

Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis. (NCT03118570)
Timeframe: Month 12 (EOT)

Intervention	percentage of participants (Number)
	Peripheral	Vertebral	Long-Bone	Any
Setrusumab 2 mg/kg (Blinded)	13.3	0	3.3	23.3
Setrusumab 20 mg/kg (Blinded)	6.5	0	3.2	16.1
Setrusumab 8 mg/kg (Blinded)	17.2	0	13.8	34.5

Change in Brief Pain Inventory (BPI) at One Year

"The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain. The BPI assesses severity (pain at its worst, least, average, and now), and interference (how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Patients rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function on a scale of 0 to 10, with 0=no pain/interference and 10=interferes completely/worst pain imaginable." (NCT00365105)
Timeframe: Baseline and 1 year

Intervention	units on a scale (Median)
Zoledronic Acid	1
Zoledronic Acid + Radiopharmaceuticals	0

Number of Patients Experiencing a Skeletal-related Event (SRE) Within One Year

Skeletal-related events are defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone. (NCT00365105)
Timeframe: From randomization to 1 year

Intervention	Participants (Count of Participants)
Zoledronic Acid	28
Zoledronic Acid + Radiopharmaceuticals	20

Overall Survival

Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (NCT00365105)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 101.7 months.

Intervention	months (Median)
Zoledronic Acid	32.1
Zoledronic Acid + Radiopharmaceuticals	26.9

Time to Development of a Malignant Skeletal-related Events (SRE)

Median time to development of a malignant skeletal related event (SRE), which is defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone is estimated using Kaplan-Meier method. The time of failure was measured from date of randomization to the date of a documented SRE. The analysis was planned to occur after 257 SRE have been observed, unless the criteria for early stopping are met. (NCT00365105)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 80.1 months.

Intervention	months (Median)
Zoledronic Acid	29.9
Zoledronic Acid + Radiopharmaceuticals	27.4

Change in EuroQol-5 Dimension 3-level (EQ-5D-3L) at One Year

The EQ-5D-3L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Change at one year is calculated as one-year score - baseline score with positive change indicating improved quality of life. (NCT00365105)
Timeframe: Baseline and 1 year

Intervention	units on a scale (Mean)
	Index Score	VAS Score
Zoledronic Acid	-0.04	-1.20
Zoledronic Acid + Radiopharmaceuticals	-0.06	-6.70

Change in Functional Assessment of Cancer Therapy - General (FACT-G) at One Year

The FACT-G is a validated 27-item measure in which a higher score represents higher quality of life (QOL). Physical, functional, social and emotional well-being subscale scores are added together to form the FACT-G total score. Responses range from 0=Not a lot to 4=Very much. Certain items must be reversed before being added, by subtracting the response from 4. Subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Total score ranges from 0-108; physical, social and functional subscales from 0-28; emotional subscale from 0-24. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing the subscale scores can be prorated. Change score at one year is calculated as one year score - baseline score with a positive change score indicating improvement in QOL. (NCT00365105)
Timeframe: Baseline and 1 year

Intervention	units on a scale (Median)
	FACT-G Total	Physical Well-Being	Social/Family Well-Being	Emotional Well-Being	Functional Well-Being
Zoledronic Acid	-1	-1	0	0	0
Zoledronic Acid + Radiopharmaceuticals	-2	-1	0	0	0

Change in Pain Interference at Day 182

Intervention	units on a scale (Mean)
Zoledronic Acid and Placebo to Risedronate	-0.5
Risedronate and Placebo to Zoledronic Acid	0.0

Change in Pain Severity at Day 182

Intervention	units on a scale (Mean)
Zoledronic Acid and Placebo to Risedronate	-0.5
Risedronate and Placebo to Zoledronic Acid	-0.1

Number of Participants With a Disease Relapse During the Extended Observation Period

Intervention	participants (Number)
Zoledronic Acid and Placebo to Risedronate	0
Risedronate and Placebo to Zoledronic Acid	15

Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period

Intervention	participants (Number)
Zoledronic Acid and Placebo to Risedronate	10
Risedronate and Placebo to Zoledronic Acid	42

Number of Participants With a Partial Disease Relapse During the Extended Observation Period

Extended observation period. A partial disease relapse was defined as an increase in serum alkaline phosphatase >= 50% from the serum alkaline phosphatase measurement at Month 6 and at least 1.25 times the upper normal limit. (NCT00103740)
Timeframe: 8 years was the maximum

Intervention	participants (Number)
Zoledronic Acid and Placebo to Risedronate	9
Risedronate and Placebo to Zoledronic Acid	37

Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28

Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. Central laboratory reference ranges for serum alkaline phosphatase: 31-110 U/L (female & male 20-58 years) and 35-115 U/L (female & male >58 years). (NCT00103740)
Timeframe: Day 28

Intervention	participants (Number)
Zoledronic Acid and Placebo to Risedronate	8
Risedronate and Placebo to Zoledronic Acid	1

Number of Patients Who Had Therapeutic Response at 6 Months

A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase (SAP) excess (difference between measured level and midpoint to the normal range) or normalization of SAP at the end of six months. (NCT00103740)
Timeframe: Baseline, 6 months

Intervention	participants (Number)
Zoledronic Acid and Placebo to Risedronate	84
Risedronate and Placebo to Zoledronic Acid	67

Relative Change in Serum Alkaline Phosphatase in U/L at Day 28

The percent change in serum alkaline phosphatase from baseline to Day 28 was measured. (NCT00103740)
Timeframe: Baseline and 28 days

Intervention	percent change (Mean)
Zoledronic Acid and Placebo to Risedronate	-49.1
Risedronate and Placebo to Zoledronic Acid	-24.3

Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10

The percent change in serum C-telopeptide from baseline to Day 10 was measured. (NCT00103740)
Timeframe: Baseline and day 10

Intervention	percent change (Mean)
Zoledronic Acid and Placebo to Risedronate	-74.2
Risedronate and Placebo to Zoledronic Acid	-40.1

Relative Change in Urine α-CTx in ug/mmol at Day 10

The percent change in urine α-CTx from baseline to Day 10 was measured. (NCT00103740)
Timeframe: Baseline and day 10

Intervention	percent change (Mean)
Zoledronic Acid and Placebo to Risedronate	-87.5
Risedronate and Placebo to Zoledronic Acid	-28.7

Time to First Therapeutic Response

Therapeutic response was defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase. (NCT00103740)
Timeframe: 182 days

Intervention	days (Median)
Zoledronic Acid and Placebo to Risedronate	64
Risedronate and Placebo to Zoledronic Acid	91

Number of Events of Osteonecrosis of Jaw for Each Participant

The number of events of osteonecrosis of jaw was averaged across all participants, including those participants who did not experience the event during the study. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	events of osteonecrosis of jaw (Mean)
Ibandronate	0.0
Zoledronate	0.0

Number of SREs for Each Participant

SREs were defined according to the Bondronat SmPC to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The number of SREs was averaged across all participants, including those participants who did not experience SREs during the study. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	SREs (Mean)
Ibandronate	0.3
Zoledronate	0.5

Number of Zoledronate Dose Reductions for Each Participant

The number of zoledronate dose reductions was averaged across all participants, including those participants who did not have any dose reductions during the study. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	dose reductions (Mean)
Zoledronate	0.8

Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30% from Baseline or an absolute value ≤30 mL/min at Week 92. The last available value on/before Week 92 was used in the calculation. The percentage of participants with deterioration in renal function at Week 92 was reported. (NCT02739594)
Timeframe: Baseline, Week 92

Intervention	percentage of participants (Number)
Ibandronate	14.6
Zoledronate	12.5

Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30 percent (%) from Baseline or an absolute value less than or equal to (≤) 30 milliliters per minute (mL/min) at Week 44. The last available value on/before Week 44 was used in the calculation. The percentage of participants with deterioration in renal function at Week 44 was reported. (NCT02739594)
Timeframe: Baseline, Week 44

Intervention	percentage of participants (Number)
Ibandronate	9.8
Zoledronate	12.5

Percentage of Participants With Osteonecrosis of Jaw

The percentage of participants with at least 1 event of osteonecrosis of jaw during the study was reported. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	percentage of participants (Number)
Ibandronate	0.0
Zoledronate	0.0

Percentage of Participants With Skeletal-Related Events (SREs)

SREs were defined according to the Bondronat Summary of Product Characteristics (SmPC) to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The percentage of participants with at least 1 SRE during the study was reported. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	percentage of participants (Number)
Ibandronate	22.0
Zoledronate	30.0

Percentage of Participants With Zoledronate Dose Reduction

The percentage of participants with at least 1 zoledronate dose reduction during the study was reported. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	percentage of participants (Number)
Zoledronate	30.0

Time to First SRE

SREs were defined according to the Bondronat SmPC to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. Time to first SRE was defined as the time from first dose of study drug to the time of SRE during the study. The median time to first SRE was estimated by Kaplan-Meier analysis and expressed in days. (NCT02739594)
Timeframe: From Baseline to end of study (up to Week 96)

Intervention	days (Median)
Ibandronate	393.0
Zoledronate	244.5

Percent Change From Baseline in Alpha (A) 1-Microglobulin

The percent change in A1-microglobulin was calculated as [Week 44 or 92 A1-microglobulin minus Baseline A1-microglobulin] divided by Baseline A1-microglobulin, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation. (NCT02739594)
Timeframe: Baseline and Weeks 44, 92

Intervention	percent change (Median)
	Week 44	Week 92
Ibandronate	0.0	0.0
Zoledronate	0.0	0.0

Percent Change From Baseline in CrCl

CrCl was calculated from blood samples using the Cockcroft-Gault formula, and was also measured by urinalysis. The percent change in CrCl was calculated as [Week 44 or 92 CrCl minus Baseline CrCl] divided by Baseline CrCl, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation. (NCT02739594)
Timeframe: Baseline and Weeks 44, 92

Intervention	percent change (Mean)
	Week 44, Calculated/Blood (n=41,40)	Week 44, Measured/Urinalysis (n=37,37)	Week 92, Calculated/Blood (n=41,40)	Week 92, Measured/Urinalysis (n=37,37)
Ibandronate	-0.5	6.9	-0.7	3.1
Zoledronate	-0.4	3.9	-4.3	2.0

Percent Change From Baseline in Gamma-Glutamyltransferase (GGT)

The percent change in GGT was calculated as [Week 44 or 92 GGT minus Baseline GGT] divided by Baseline GGT, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation. (NCT02739594)
Timeframe: Baseline and Weeks 44, 92

Intervention	percent change (Median)
	Week 44	Week 92
Ibandronate	-6.0	-2.5
Zoledronate	3.8	3.8

Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG)

The percent change in B-NAG was calculated as [Week 44 or 92 B-NAG minus Baseline B-NAG] divided by Baseline B-NAG, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation. (NCT02739594)
Timeframe: Baseline and Weeks 44, 92

Intervention	percent change (Median)
	Week 44	Week 92
Ibandronate	-15.7	-17.2
Zoledronate	10.6	9.3

Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline

Elevation in SCr was defined as an increase greater than (>) 0.5 milligrams per deciliter (mg/dL) for participants with Baseline SCr less than (<) 1.4 mg/dL, or an increase >1.0 mg/dL for participants with Baseline SCr greater than or equal to (≥) 1.4 mg/dL. For the Week 44 analysis, the last available value on/before Week 44 was used. For the Week 92 analysis, the last available value on/before Week 92 was used. The percentage of participants with elevation of SCr at Weeks 44 and 92 was reported. (NCT02739594)
Timeframe: Baseline and Weeks 44, 92

Intervention	percentage of participants (Number)
	Week 44	Week 92
Ibandronate	2.4	7.3
Zoledronate	2.5	2.5

Change From Baseline of Femoral Neck Bone Density Measured by DXA

Early changes in areal bone mineral density will be measured at the hip and spine by Dual-energy X-ray Absorptiometry (DXA). (NCT03424239)
Timeframe: Baseline and 6 months

Intervention	g/cm^2 (Mean)
Drug: Zoledronic Acid, Calcium+Vitamin D	-0.038

Change From Baseline of Spine Bone Density Measured by DXA

Early changes in areal bone mineral density will be measured at the hip and spine by Dual-energy X-ray Absorptiometry (DXA). (NCT03424239)
Timeframe: Baseline and 6 months

Intervention	g/cm^2 (Mean)
Drug: Zoledronic Acid, Calcium+Vitamin D	0.003

Change in Serum CTX

The primary aim of this study is to determine the postoperative changes in serum markers of bone turnover after a preoperative infusion of zoledronic acid. Serum C-terminal telopeptide of type 1 collagen (CTX) is marker of bone resorption. (NCT03424239)
Timeframe: Baseline and 6 months

Intervention	ng/ml (Mean)
Drug: Zoledronic Acid, Calcium+Vitamin D	0.228

Change in Total Hip Bone Mineral Density by DXA

Early changes in areal bone mineral density will be measured at the hip and spine by Dual-energy X-ray Absorptiometry (DXA). (NCT03424239)
Timeframe: Baseline and 6 months

Intervention	g/cm^2 (Mean)
Drug: Zoledronic Acid, Calcium+Vitamin D	-0.039

Change in Trabecular Spine Bone Mineral Density by QCT

Early changes in volumetric bone mineral density will be measured at the spine by Quantitative Computed Tomography (QCT). (NCT03424239)
Timeframe: Baseline and 6 months

Intervention	mg/cm^3 (Mean)
Drug: Zoledronic Acid, Calcium+Vitamin D	4.9

Number of Participants With Treatment-related Hypocalcemia Events as Assessed by CTCAE v4.0

Hypocalcemia, if detected, will be graded according to common terminology for adverse event criteria (CTCAE v.4). Adverse events considered related or possibly related are counted. (NCT03424239)
Timeframe: 6 months

Intervention	Participants (Count of Participants)
Drug: Zoledronic Acid, Calcium+Vitamin D	0

Overall Survival

Overall survival was defined as the time interval (in days) from the randomization date to the date of death. If a participant was still alive at the primary analysis data cut-off date or was lost to follow-up by the primary analysis data cut-off date, survival time was censored at their last contact date or the primary analysis data cut-off date, whichever was first. (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	days (Median)
Zoledronic Acid	NA
Denosumab	1507.0

Percentage of Participants Who Died

(NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	percentage of participants (Number)
Zoledronic Acid	15.0
Denosumab	14.1

Percentage of Participants With an On-study Skeletal Related Event

A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	percentage of participants (Number)
Zoledronic Acid	44.6
Denosumab	43.8

Time to First and Subsequent On-Study Skeletal Related Event - Number of Events Per Patient

"A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE.~A multiple event analysis was used, which accounts for both the absolute number of SREs and for the time between two consecutive events, and therefore, provides a more sensitive assessment of the risk of experiencing an SRE. The average number of events per patient is reported." (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	events/patient (Number)
Zoledronic Acid	0.66
Denosumab	0.66

Time to First and Subsequent On-Study Skeletal Related Event - Number of Events

"A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE.~A multiple event analysis was used, which accounts for both the absolute number of SREs and for the time between two consecutive events, and therefore, provides a more sensitive assessment of the risk of experiencing an SRE. The total number of events is reported." (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	skeletal-related events (Number)
Zoledronic Acid	565
Denosumab	565

Time to First On-study Skeletal Related Event - Superiority Analysis

A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first. (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	days (Median)
Zoledronic Acid	730.0
Denosumab	695.0

Time to First On-study Skeletal Related Event

A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first. (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Intervention	days (Median)
Zoledronic Acid	730.0
Denosumab	695.0

Kaplan-Meier Estimate of Percentage of Participants With an On-study Skeletal Related Event

A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. (NCT01345019)
Timeframe: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively. The Kaplan-Meier estimate at weeks 25, 49 and 109 is reported.

Intervention	percentage of participants (Number)
	At Week 25	At Week 49	At Week 109
Denosumab	35.9	43.7	50.5
Zoledronic Acid	36.5	43.2	50.6

Limiting Toxicity

"The occurrence of Limiting Toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:~Grade 3 nausea and vomiting controlled with adequate antiemetic prophylaxis.~Grade 3 transaminase (AST/ALT) that occurs during the evaluation period but resolves to ≤ Grade 2, before the planned dose of therapy after definitive surgery.~Grade 3 fever or infection.~Grade 3 or 4 hypocalcemia (see Section 5.1.1)~Grade 3 mucositis.~Grade 3 fatigue that returns to ≤ Grade 2, before the planned dose of therapy after definitive surgery.~Grade 3 joint range of motion, decreased or joint effusion that is related to the primary tumor." (NCT00742924)
Timeframe: Enrollment through the first 12 weeks of therapy.

Intervention	participants (Number)
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid	1
Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid	1
Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid	3
Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD	2

Number of Participants With Immunologic Responses

Blood was collected to analyze T-cell populations from all patients prior to treatment on day 1 of cycles 1 and 2, and days 4 and 8 of cycles 1 and 2. Changes in gamma delta T-cell population and CD3 T-cell populations were reported. (NCT00582790)
Timeframe: baseline to cycle 2 day 8

Intervention	participants (Number)
Low-dose IL2 and Zoledronic Acid	0

Number of Participants With Overall Survival and Progression-free Survival at 24 Weeks

All 12 patients were followed for survival until death. 8 participants who received more than one cycle of treatment and who were considered evaluable for response were followed until time to progression. Disease progression was determined by CT scans of the chest/abdomen/pelvis obtained every 2 cycles and based on RECIST version 1.0. Progression is defined using RECIST (V1.0) at least a 20% increase in the sum of the longest diameter (LD)of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions (NCT00582790)
Timeframe: Time frame is from study entry until time to disease progression and time to death, up to 50 months

Intervention	participants (Number)
IL2 and Zoledronic Acid	5

Number of Participants With Toxicities

Patients were observed for toxicities. The National Cancer Institute Common Terminology Criteria Version 2.0 was used to categorize and report adverse events. (NCT00582790)
Timeframe: Baseline to 30 days after last dose of study treatment

Intervention	participants (Number)
IL2 and Zoledronic Acid	11

Number of Subjects With Antitumor Response With Low-dose Interleukin-2 in Combination With Zoledronic Acid

Anti-tumor response was measured per RECIST criteria (V1.0) and assessed by chest/abdomen/pelvis CT: Complete Response (CR), disappearance of all target lessions; Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Response (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. (NCT00582790)
Timeframe: CT scans obtained at baseline, then every 2 cycles

Intervention	participants (Number)
IL2 and Zoledronic Acid	5

Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine

Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. (NCT00896532)
Timeframe: Baseline to 12 months

Intervention	percent change (Least Squares Mean)
Placebo	-0.1
Alendronate	4.1
Teriparatide	7.1
Romosozumab 70 mg QM	5.4
Romosozumab 140 mg Q3M	5.4
Romosozumab 140 mg QM	9.1
Romosozumab 210 mg Q3M	5.5
Romosozumab 210 mg QM	11.3
Romosozumab Monthly	8.6
Romosozumab Every 3 Months	5.5
Romosozumab 140 mg	7.3
Romosozumab 210 mg	8.4

Percent Change From Baseline at Month 12 in BMD of the Distal Radius

"Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.~Percent change from baseline in distal radius BMD was analyzed using an analysis of covariance (ANCOVA) model with the percent change from baseline to Month 12 in DXA BMD as dependent variable, baseline BMD value, machine type, interaction of baseline BMD and machine type, treatment (categorical) and geographic region as the independent class variables." (NCT00896532)
Timeframe: Baseline to 12 months

Intervention	percent change (Least Squares Mean)
Placebo	-0.9
Alendronate	-0.3
Teriparatide	-1.7
Romosozumab 70 mg QM	-1.8
Romosozumab 140 mg Q3M	-1.1
Romosozumab 140 mg QM	-1.0
Romosozumab 210 mg Q3M	-0.4
Romosozumab 210 mg QM	-1.2

Percent Change From Baseline at Month 12 in BMD of the Femoral Neck

"Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.~Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables." (NCT00896532)
Timeframe: Baseline to 12 months

Intervention	percent change (Least Squares Mean)
Placebo	-1.1
Alendronate	1.2
Teriparatide	1.1
Romosozumab 70 mg QM	0.6
Romosozumab 140 mg Q3M	1.8
Romosozumab 140 mg QM	4.2
Romosozumab 210 mg Q3M	1.4
Romosozumab 210 mg QM	3.7

Percent Change From Baseline at Month 12 in BMD of the Total Hip

Intervention	percent change (Least Squares Mean)
Placebo	-0.7
Alendronate	1.9
Teriparatide	1.3
Romosozumab 70 mg QM	1.3
Romosozumab 140 mg Q3M	1.3
Romosozumab 140 mg QM	3.4
Romosozumab 210 mg Q3M	1.9
Romosozumab 210 mg QM	4.1

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine

"Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.~Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables." (NCT00896532)
Timeframe: Baseline to 6 months

Intervention	percent change (Least Squares Mean)
Placebo	0.3
Alendronate	2.6
Teriparatide	4.8
Romosozumab 70 mg QM	4.1
Romosozumab 140 mg Q3M	4.2
Romosozumab 140 mg QM	7.1
Romosozumab 210 mg Q3M	4.4
Romosozumab 210 mg QM	8.2

Percent Change From Baseline at Month 6 in BMD of the Femoral Neck

Intervention	percent change (Least Squares Mean)
Placebo	-0.4
Alendronate	0.5
Teriparatide	0.5
Romosozumab 70 mg QM	0.2
Romosozumab 140 mg Q3M	0.4
Romosozumab 140 mg QM	2.1
Romosozumab 210 mg Q3M	0.9
Romosozumab 210 mg QM	1.9

Percent Change From Baseline at Month 6 in BMD of the Total Hip

Intervention	percent change (Least Squares Mean)
Placebo	-0.6
Alendronate	0.9
Teriparatide	0.5
Romosozumab 70 mg QM	0.5
Romosozumab 140 mg Q3M	0.9
Romosozumab 140 mg QM	2.2
Romosozumab 210 mg Q3M	1.1
Romosozumab 210 mg QM	2.9

Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)

Percent change from baseline in the bone turnover marker (BTM) BSAP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. (NCT00896532)
Timeframe: Baseline and months 1, 3, 6, 9, and 12

Intervention	percent change (Least Squares Mean)
	Month 3	Month 6	Month 9	Month 12
Alendronate	-30.5	-35.4	-32.5	-31.2
Teriparatide	21.8	29.8	41.8	45.7

Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)

,,,,,

Intervention	percent change (Least Squares Mean)
	Month 1	Month 3	Month 6	Month 9	Month 12
Placebo	-1.1	-7.6	-4.1	3.5	9.2
Romosozumab 140 mg Q3M	35.1	-18.0	-18.2	-12.5	-10.8
Romosozumab 140 mg QM	29.3	1.3	-6.6	-5.5	-5.0
Romosozumab 210 mg Q3M	47.5	-17.3	-20.0	-17.7	-12.4
Romosozumab 210 mg QM	60.9	27.4	13.1	10.4	9.2
Romosozumab 70 mg QM	11.7	-8.5	-8.7	-4.9	-2.6

Percent Change From Baseline in Osteocalcin

Percent change from baseline in the bone turnover marker (BTM) osteocalcin was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. (NCT00896532)
Timeframe: Baseline and months 1, 3, 6, 9, and 12

Intervention	percent change (Least Squares Mean)
	Month 3	Month 6	Month 9	Month 12
Alendronate	-28.7	-40.6	-50.9	-50.3
Teriparatide	104.7	106.7	99.9	91.6

Percent Change From Baseline in Osteocalcin

,,,,,

Intervention	percent change (Least Squares Mean)
	Month 1	Month 3	Month 6	Month 9	Month 12
Placebo	-1.6	4.1	-7.1	-6.0	-14.1
Romosozumab 140 mg Q3M	60.1	-5.6	-16.5	-29.0	-24.7
Romosozumab 140 mg QM	53.1	15.6	-7.4	-27.7	-31.1
Romosozumab 210 mg Q3M	77.9	-3.7	-23.2	-30.7	-26.2
Romosozumab 210 mg QM	78.6	41.6	10.0	-4.0	-12.5
Romosozumab 70 mg QM	28.1	-0.3	-11.8	-26.9	-27.3

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)

Percent change from baseline in the bone turnover marker (BTM) P1NP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. (NCT00896532)
Timeframe: Baseline and months 1, 3, 6, 9, and 12

Intervention	percent change (Least Squares Mean)
	Month 3	Month 6	Month 9	Month 12
Alendronate	-50.8	-57.0	-60.8	-60.8
Teriparatide	97.1	138.0	116.8	98.3

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)

,,,,,

Intervention	percent change (Least Squares Mean)
	Month 1	Month 3	Month 6	Month 9	Month 12
Romosozumab 140 mg Q3M	61.4	-15.5	-22.8	-23.8	-23.3
Romosozumab 140 mg QM	55.0	3.8	-18.6	-26.1	-31.2
Romosozumab 210 mg Q3M	75.8	-19.5	-25.5	-30.1	-29.7
Romosozumab 210 mg QM	92.2	25.6	6.9	-5.8	-17.2
Romosozumab 70 mg QM	24.2	-9.1	-20.0	-26.9	-23.0
Placebo	-0.7	-5.4	-5.9	-10.6	-8.7

Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)

Percent change from baseline in the bone turnover marker (BTM) CTX was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline. (NCT00896532)
Timeframe: Baseline and months 1, 3, 6, 9, and 12

Intervention	percent change (Least Squares Mean)
	Month 3	Month 6	Month 9	Month 12
Alendronate	-65.0	-64.2	-64.4	-66.7
Teriparatide	69.4	93.5	81.3	77.0

Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)

,,,,,

Intervention	percent change (Least Squares Mean)
	Month 1	Month 3	Month 6	Month 9	Month 12
Placebo	-3.9	-2.4	2.7	1.0	9.8
Romosozumab 140 mg Q3M	-19.2	-6.2	-8.4	1.3	12.2
Romosozumab 140 mg QM	-35.4	-26.5	-24.6	-27.7	-33.0
Romosozumab 210 mg Q3M	-33.0	-12.6	-10.5	-11.7	-6.6
Romosozumab 210 mg QM	-28.5	-3.7	-8.7	-17.2	-22.5
Romosozumab 70 mg QM	-22.1	-21.5	-18.1	-15.1	-20.3

Change in Areal Bone Mineral Density at Hip

"Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline.~This will compare aBMD at the hip." (NCT01642901)
Timeframe: one year

Intervention	percentage change (Mean)
	Total proximal femur	Intertrochanteric femur	Femoral neck
Normal Saline 0.9%	-21.3	-19.4	-17.0
Zoledronic Acid 5 mg IV Infusion	-8.2	-8.62	-3.93

Change in Areal Bone Mineral Density at Hip

"Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline.~This will compare aBMD at the hip." (NCT01642901)
Timeframe: 4 months

Intervention	percentage change (Mean)
	Total proximal femur	Intertrochanteric femur	Femoral neck
Normal Saline 0.9%	-12.0	-12.9	-9.37
Zoledronic Acid 5 mg IV Infusion	0.92	1.19	0.97

Change in Areal Bone Mineral Density at Knee

Intervention	percentage change (Mean)
	Distal femur	Proximal tibia
Normal Saline 0.9%	-10.0	-10.0
Zoledronic Acid 5 mg IV Infusion	-8.07	-4.54

Change in Areal Bone Mineral Density at Knee

"Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline.~This will compare aBMD at the distal femur and proximal tibia." (NCT01642901)
Timeframe: 4 months

Intervention	percentage change (Mean)
	Distal femur	Proximal tibia
Normal Saline 0.9%	-6.75	-8.56
Zoledronic Acid 5 mg IV Infusion	-0.78	-0.24

Change in Biomarkers of Bone Formation (P1NP)

Change in serum P1NP from baseline to 1- and 4-months post intervention. (NCT01642901)
Timeframe: 1 month, 4 months

Intervention	percentage change (Median)
	1 month	4 months
Normal Saline 0.9%	65.96	27.45
Zoledronic Acid 5 mg IV Infusion	5.66	32.43

Change in Biomarkers of Bone Resorption (sCTX)

Change in sCTX from baseline to 1- and 4-months post intervention and 12-months post-injury. (NCT01642901)
Timeframe: 1 month, 4 months, 12 months

Intervention	percentage change (Median)
	1 month	4 months	12 months
Normal Saline 0.9%	14.4	23.9	-5.11
Zoledronic Acid 5 mg IV Infusion	-64.1	-45.9	-43.6

Safety and Tolerability of Zoledronic Acid

Assessment of the safety and tolerability of zoledronic acid in the acute spinal cord injury population. This will be done by examination reportable adverse events including fevers, flu-like symptoms, GI upset as measures of safety and report of patient's willingness to have participate in physical therapy in the first week after receiving medication as a measure of tolerability (NCT01642901)
Timeframe: 72-hours and 1 month post intervention.

Intervention	Participants (Count of Participants)
	Fever > 100.9 within 72 hours of study drug infusion	Flu-like symptoms within 72 hours of study drug infusion	Acute kidney injury
Normal Saline 0.9%	1	1	1
Zoledronic Acid 5 mg IV Infusion	7	6	1

Objective Response in Bone From Time of Initiation of Therapy to > 6 Months

Objective response rate is defined as the clinical benefit rate (complete and partial response) + stable disease > 6 months in bone. (NCT00566618)
Timeframe: 6 months

Intervention	Participants (Count of Participants)
	Central Review	Site Review
Phase I/Phase II	8	7

Phase I - Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) for Dasatinib in Combination With Zoledronic Acid

To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) for dasatinib in combination with zoledronic acid. (NCT00566618)
Timeframe: day 1 (+/- 48 hours) prior to therapy during cycle 2 and all subsequent cycles

Intervention	mg (Number)
	Dasatinib	zoledronic acid
Phase I	100	4

Number of Participants With Urine and Serum NTx and Serum CTx Within Normal Range at 12 Months

17 women with early breast cancer receiving adjuvant Aromatase Inhibitor (AI) therapy were treated with a single 5 mg IV dose of zoledronic acid. Urine and serum NTx and serum CTx were measured at baseline and month 12. (NCT00712985)
Timeframe: One year

Intervention	participants (Number)
Zoledronic Acid 5 mg IV	13

Comparing the Level of Urinary N-telopeptide (uNTx) in the Two Arms .

(NCT00697619)
Timeframe: Baseline, the first, second and third month

Intervention	nM /mM (Median)
	Baseline	the first month	the second month	the third month
Control Group	94	88	52	45
Test Group	75	29	17	11

Incidence Rate of All Clinical Fractures

The number of participants who experienced a clinical fracture at month 36 was assessed. Initial x-ray (both AP and lateral views) of the lumbar and thoracic spine were performed at baseline to exclude participants with evidence of fracture. In addition, repeated bone scan and/or x-ray were performed at the Principal Investigator's discretion during the course of the study to confirm evidence of clinical fracture, or at month 36 if there was no evidence of clinical fracture (lumbar and thoracic spine - lateral view). X-ray films were sent to a central reader. (NCT00050011)
Timeframe: 3 years

Intervention	Participants (Number)
Zoledronic Acid Upfront	18
Zoledronic Acid Delayed Start	21

Percent Change From Baseline in Lumbar Spine (L1-L4) Bone Mineral Density (BMD)

Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader. Percent change = 100*((BMD at Month 12 - Baseline BMD)/Baseline BMD)). Missing data at month 12 were imputed by using the last observation carried forward (LOCF) method. Post-baseline non-missing data from month 6 were carried forward to month 12. Data prior to month 6 were not carried forward. (NCT00050011)
Timeframe: Baseline, 12 months

Intervention	Percentage of BMD (Mean)
Zoledronic Acid Upfront	1.955
Zoledronic Acid Delayed-start	-2.325

Rate of Change From Baseline in Lumbar Spine (L1-L4) BMD

The rate of change from baseline in BMD was assessed. (NCT00050011)
Timeframe: Baseline, 5 years

Intervention	g/sq cm/month (Mean)
Zoledronic Acid Upfront	0.01043
Zoledronic Acid Delayed Start	-0.00157

Rate of Change From Baseline in Total Hip BMD

The rate of change from baseline in BMD was assessed. (NCT00050011)
Timeframe: Baseline, 5 years

Intervention	g/sq. cm/month (Mean)
Zoledronic Acid Upfront	0.00226
Zoledronic Acid Delayed Start	-0.00625

Time to Disease Recurrence/Relapse

The median time to disease progression was assessed by Kaplan-Meier analysis. The Principal Investigator assessed each participant for disease recurrence at each visit. Further testing was performed at the discretion of the Principal Investigator and as clinically indicated. Disease progression was defined as chest wall and/or regional recurrence confirmed by positive cytology or biopsy, and/or distance recurrence of the 1) skin, subcutaneous tissue, and lymph nodes (other than local or regional), 2) bone marrow, 3) lung, 4) skeleton 5) liver and 6) central nervous system confirmed by positive cytology, biopsy, aspirate or radiology as appropriate. (NCT00050011)
Timeframe: over 5 years

Intervention	months (Median)
Zoledronic Acid Upfront	NA
Zoledronic Acid Delayed Start	NA

Percent Change From Baseline in Biochemical Markers of Bone Turnover, Serum N-Telopeptide (sNTX) and Bone-specific Alkaline Phosphatase (BSAP)

Blood samples from a subset of participants (231 participants in total) were collected to measure the sNTX and BSAP. Missing data at month 12 were imputed by using the LOCF method. Post-baseline non-missing data from months 6 and 9 were carried forward to month 12. Data prior to month 6 were not carried forward. Missing data beyond month 12 were not imputed by LOCF. (NCT00050011)
Timeframe: Baseline, 12 months, 2 years, 3 years, 5 years

Intervention	Percentage of biochemical markers (Mean)
	sNTX, 12 months (n=87,85)	sNTX, 2 years	sNTX, 3 years	sNTX, 5 years	BSAP, 12 months (n=88,90)	BSAP, 2 years (n=63,60)	BSAP, 3 years (n=59,52)	BSAP, 5 years (n=95,102)
Zoledronic Acid Delayed Start	21.7	NA	NA	NA	19.0	19.9	10.6	11.9
Zoledronic Acid Upfront	-20.1	NA	NA	NA	-7.8	-12.0	-12.4	-6.4

Percent Change From Baseline in Lumbar Spine (L1-L4) BMD

"Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader.~Percent change = 100*((BMD at Time Frame - Baseline BMD)/Baseline BMD)). Missing data beyond month 12 were not imputed by LOCF." (NCT00050011)
Timeframe: Baseline, 2 years, 3 years, 5 years

Intervention	Percentage of BMD (Mean)
	2 years (n=206,202)	3 years (n=189,190)	5 years (n=140,132)
Zoledronic Acid Delayed Start	-2.889	-2.990	-2.418
Zoledronic Acid Upfront	3.137	3.853	6.192

Percent Change From Baseline in Total Hip BMD

"Bone mineral density (BMD) measurements were assessed by dual energy x-ray absorptiometry (DXA). The DXA devices of participating sites were cross-calibrated and the DXA results were compiled and analyzed by a central reader.~Percent change = 100*((BMD at Time Frame - Baseline BMD)/Baseline BMD)). Missing data at month 12 were imputed by using the LOCF method. Post-baseline non-missing data from month 6 were carried forward to month 12. Data prior to month 6 were not carried forward." (NCT00050011)
Timeframe: Baseline, 12 months, 2 years, 3 years, 5 years

Intervention	Percentage of BMD (Mean)
	12 months (n=253,256)	2 years (n=208,200)	3 years (n=187,189)	5 years (n=141,132)
Zoledronic Acid Delayed Start	-1.883	-3.150	-3.463	-4.115
Zoledronic Acid Upfront	1.256	1.413	1.676	2.571

Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 1 Post Study Entry

Change: BMD values at year 1 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 1 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	5.66

Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 2 Post Study Entry

Change: BMD values at year 2 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 2 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	10.47

Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 3 Post Study Entry

Change: BMD values at year 3 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 3 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	8.44

Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 4 Post Study Entry

Change: BMD values at year 4 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 4 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	4.49

Average Intra-patient Change in Femoral Neck Bone Mineral Density (BMD) at Year 5 Post Study Entry

Change: BMD values at year 5 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 5 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	4.54

Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 2 Post Study Entry

Change: BMD values at year 2 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 2 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	4.94

Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 3 Post Study Entry

Change: BMD values at year 3 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 3 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	6.20

Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 4 Post Study Entry

Change: BMD values at year 4 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 4 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	6.99

Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD) at Year 5 Post Study Entry

Change: BMD values at year 5 post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 5 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	11.71

Average Intra-patient Change in Total Lumbar Spine (L1 to L4) Bone Mineral Density (BMD)

Change: BMD values at twelve months post study entry minus BMD values at baseline, expressed as a percentage of the baseline value. (NCT00436917)
Timeframe: Baseline and 1 year

Intervention	Percentage of the baseline value (Mean)
Zoledronic Acid	2.66

Maximum-Grade Toxicity Incidence at Least Possibly Related to Study Medications

Adverse events were assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1=Mild, Grade 2=Moderate. (NCT00436917)
Timeframe: 5 years

Intervention	Participants (Count of Participants)
	Grade 1 Arthralgia	Grade 2 Arthralgia	Grade 3 Arthralgia	Grade 1 Creatinine Increase	Grade 2 Creatinite increase	Grade 2 Desquamating Rash	Grade 2 Headache	Grade 2 Hot flashes	Grade 1 Nausea	Grade 3 Pain in extremity	Grade 1 Fever	Grade 1 Vomiting	Grade 1 Musculoskeletal disorder	Grade 2 Urogenital disorder
Zoledronic Acid	7	4	1	7	2	1	1	3	2	1	2	1	1	1

Number of Subjects Had a Significant Change in Immune Markers.

Immune markers were measured by isolating gamma-delta T cells one month after treatment with zoledronic acid. (NCT00582556)
Timeframe: 2 Years

Intervention	participants (Number)
Zometa Given 7 Days Prior to Beginning ADT	0
Zometa Given at Month 6	0
Zometa Given Monthly, Months 6-11	0

Number of Subjects With Decreases in Prostate Specific Antigen (PSA) After Zoledronic Acid Prior to Beginning Androgen Deprivation Therapy

"PSA response was measured by observing the serum PSA one week after beginning zoledronic acid and prior to beginning androgen deprivation therapy.~Arm 2 and Arm 3 were not able to be assessed for this endpoint as all subjects were on androgen deprivation prior to receiving zoledronic acid." (NCT00582556)
Timeframe: 2 Years

Intervention	participants (Number)
Zometa Given 7 Days Prior to Beginning ADT	0

The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover.

Serum bone-specific alkaline phosphatase was collected as the blood marker of bone turnover. (NCT00582556)
Timeframe: 2 years

Intervention	participants (Number)
Zometa Given 7 Days Prior to Beginning ADT	0
Zometa Given at Month 6	0
Zometa Given Monthly, Months 6-11	0

The Number of Subjects Who Had Either an Increase or Decrease on Bone Mineral Density of the Lumbar Spine and Femoral Neck in Men Undergoing Androgen Deprivation Therapy for Prostate Adenocarcinoma.

Effects on bone mineral density were measured at four locations at six month intervals for 24 months. (NCT00582556)
Timeframe: 2 years

Intervention	participants (Number)
Zometa Given 7 Days Prior to Beginning ADT	14
Zometa Given at Month 6	15
Zometa Given Monthly, Months 6-11	15

Percentage of Participants With ≥1 SRE at the End of 1 Year on Study

SRE was defined as pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or hypercalcemia of malignancy (HCM). SRE was assessed by centrally read radiographic bone surveys. (NCT00622505)
Timeframe: 1 year

Intervention	percentage of participants (Number)
Zoledronic Acid Every 12 Weeks	0
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.17

Time to Death

Time to death was defined as the time from the date of enrollment to the date of death. Participants who dropped out or completed the study were considered censored observations. Time to death was assessed by Kaplan-Meier method. (NCT00622505)
Timeframe: Up to 2 years

Intervention	years (Median)
Zoledronic Acid Every 12 Weeks	NA
Zoledronic Acid Every 4 Weeks or 12 Weeks	NA

Time to First SRE on Study

The time to first SRE is defined as the date of enrollment to the date of the first occurrence of any SRE on the study. SRE includes pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM. Participants who drop-out was treated as censored observations. Time to first SRE on the study was assessed by the Kaplan-Meier method. (NCT00622505)
Timeframe: Up to 2 years

Intervention	years (Median)
Zoledronic Acid Every 12 Weeks	NA
Zoledronic Acid Every 4 Weeks or 12 Weeks	NA

Change From Baseline in Urinary N-telopeptide of Type 1 Collagen (uNTx)

uNTx is a biomarker used to measure the rate of bone turnover found in urine. (NCT00622505)
Timeframe: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)

Intervention	nmol/mmol creatinine (Mean)
	Baseline	Change from Baseline to Week 12	Change from Baseline to Week 24	Change from Baseline to Week 36	Change from Baseline to Week 48	Change from Baseline to Week 60	Change from Baseline to Week 72	Change from Baseline to Week 84	Change from Baseline to Week 100
Zoledronic Acid Every 12 Weeks	19.8	0.2	-1.4	-2.0	-2.3	-2.5	-3.5	-3.0	-5.2
Zoledronic Acid Every 4 Weeks or 12 Weeks	24.1	4.3	-0.5	-0.9	1.7	-0.8	-6.7	-7.6	-7.4

Percentage of Participants Who Experienced HCM

HCM is defined as corrected serum calcium ≥ 12.0 milligrams per deciliter (mg/dL) (3.00 millimoles per liter [mmol/L]), or a lower level of hypercalcemia that was symptomatic and required active treatment other than rehydration. (NCT00622505)
Timeframe: Years 1 and 2

Intervention	percentage of participants (Number)
	Year 1	Year 2
Zoledronic Acid Every 12 Weeks	0.00	0.00
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.02	0.00

Percentage of Participants Who Experienced Pathologic Bone Fracture

Pathologic bone fractures are defined as bone fractures that occur spontaneously or as a result of trivial trauma. (NCT00622505)
Timeframe: Years 1 and 2

Intervention	percentage of participants (Number)
	Year 1	Year 2
Zoledronic Acid Every 12 Weeks	0.00	0.00
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.07	0.03

Percentage of Participants Who Experienced Radiation to Bone

Radiation therapy to bone events includes irradiation of bone to palliate painful lesions, to treat or prevent pathologic fractures, or to treat or prevent spinal cord compression. (NCT00622505)
Timeframe: Years 1 and 2

Intervention	percentage of participants (Number)
	Year 1	Year 2
Zoledronic Acid Every 12 Weeks	0.00	0.00
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.10	0.11

Percentage of Participants Who Experienced Spinal Cord Compression

Spinal cord compression is caused by the impingement of a tumor on the spinal cord and is associated with neurologic impairment and/or back pain. (NCT00622505)
Timeframe: Years 1 and 2

Intervention	percentage of participants (Number)
	Year 1	Year 2
Zoledronic Acid Every 12 Weeks	0.00	0.00
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.07	0.00

Percentage of Participants Who Experienced Surgery to Bone

Surgery to bone events includes surgical procedures that are performed to set or stabilize pathologic fractures or areas of spinal cord compression and surgical procedures that are performed to prevent an imminent pathologic fracture or spinal cord compression. (NCT00622505)
Timeframe: Years 1 and 2

Intervention	percentage of participants (Number)
	Year 1	Year 2
Zoledronic Acid Every 12 Weeks	0.00	0.00
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.02	0.00

Skeletal Related Event (SRE) Rate

The SRE rate for each participant was calculated as the number of SREs/total follow-up time. SRE included pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM. (NCT00622505)
Timeframe: Years 1 and 2

Intervention	number of SRE/total follow-up time (Mean)
	Year 1	Year 2
Zoledronic Acid Every 12 Weeks	0.00	0.00
Zoledronic Acid Every 4 Weeks or 12 Weeks	0.03	0.02

Number of Participants With First Clinical Fracture

Clinical fracture is painful fracture in any site which came to clinical attention, e.g., with increased pain, impaired mobility or functional limitations. Subjects who did not experience fracture were censored at end of study. End of study was defined as the earlier of last visit or date of death. (NCT00439647)
Timeframe: 24 months

Intervention	Participants (Number)
Zoledronic Acid	6
Placebo	11

Number of Participants With First Clinical Vertebral Fracture

Clinical vertebral fracture is a painful vertebral fracture which came to clinical attention, e.g., with increased back pain, impairment of mobility or functional limitations. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier. (NCT00439647)
Timeframe: 24 months

Intervention	Participants (Number)
Zoledronic Acid	1
Placebo	3

Number of Participants With First Non-vertebral Fracture

Non-vertebral fracture is any fracture which was not of the vertebrae. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier. (NCT00439647)
Timeframe: 24 months

Intervention	Participants (Number)
Zoledronic Acid	5
Placebo	8

Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months

Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height. (NCT00439647)
Timeframe: 12 months

Intervention	Percentage of participants (Number)
Zoledronic Acid	0.4
Placebo	1.9

Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months

Intervention	Percentage of participants (Number)
Zoledronic Acid	1.1
Placebo	3.0

Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months

Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height (NCT00439647)
Timeframe: 12 Months

Intervention	Percentage of participants (Number)
Zoledronic Acid	0.9
Placebo	2.8

Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months

Intervention	Percentage of Participants (Number)
Zoledronic Acid	1.6
Placebo	4.9

Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months

Worsening vertebral fracture (VF) was assessed based on morphometry. QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit, x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture) (NCT00439647)
Timeframe: Baseline, 12 months

Intervention	Percentage of Participants (Number)
Zoledronic Acid	1.3
Placebo	2.8

Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months

Worsening vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture) (NCT00439647)
Timeframe: Baseline, Month 24

Intervention	Percentage of Participants (Number)
Zoledronic Acid	2.0
Placebo	4.9

Mean Change in Height From Baseline

Height was measured using a stadiometer. Two measurements were taken in millimeters (mm), and repeated if the two measurements differed by greater than 4 mm. The average of the two (or four) height measurements was used for analysis (NCT00439647)
Timeframe: from Baseline to 12 months and 24 months

Intervention	mm (Mean)
	12 months	24 months
Placebo	-2.50	-4.61
Zoledronic Acid	-0.86	-2.33

Percentage Change From Baseline in Femoral Neck BMD (g/CM^2)

Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total femoral neck BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100*(endpoint - baseline) (NCT00439647)
Timeframe: Month 6, Month 12, Month 24

Intervention	Percent change in BMD (Least Squares Mean)
	Month 6 (n=60, n=63)	Month 12 (n=58, n=64)	Month 24 (n=56, n=63)
Placebo	0.58	0.59	0.09
Zoledronic Acid	2.21	2.06	3.39

Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD)

Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in BMD at lumbar spine at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100*(endpoint - baseline) (NCT00439647)
Timeframe: Month 6, Month 12, Month 24

Intervention	Percent change in BMD (Least Squares Mean)
	Month 6 (n=61, n=61)	Month 12 (n=60, n=62)	Month 24 (n=58, n=61)
Placebo	0.10	0.84	1.61
Zoledronic Acid	4.87	5.51	7.73

Percentage Change From Baseline in Total Hip BMD (g/CM^2)

Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total hip BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100*(endpoint - baseline) (NCT00439647)
Timeframe: Month 6, Month 12, Month 24

Intervention	Percent change in BMD (Least Squares Mean)
	Month 6 (n=60, n=63)	Month 12 (n=58, n=64)	Month 24 (n=56, n=63)
Placebo	-0.44	0.26	0.16
Zoledronic Acid	1.38	1.66	2.31

Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits

(NCT00439647)
Timeframe: Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24

Intervention	ng/mL (Mean)
	Baseline (n-64) (n=66)	Month 3 (n=63) (n=65)	Month 6 (n=62) (n=64)	Month 12 (n=63) (n=64)	Month 15 (n=55) (n=58)	Month 18 (n=55) (n=60)	Month 24 (n=55) (n=62)
Placebo	0.3933	0.3647	0.3540	0.4042	0.3576	0.3954	0.4060
Zoledronic Acid	0.3646	0.0990	0.1384	0.1669	0.0996	0.1320	0.1760

Percentage Change in Bone Mineral Density (BMD) T-Score From Baseline to 12 Months

The 12-month change from baseline in BMD at the total lumbar spine. BMD evaluation was performed at baseline and at 12 months after initiation of therapy at the lumbar spine. BMD was measured by dual-energy, x-ray absorptiometry scanners. T-Score is the number of standard deviations above or below the mean. A T-score >= -1 indicates a normal BMD, while T-scores between -1 and -2.5 indicate osteopenia and T-scores <= -2.5 indicate osteoporosis. (NCT00352846)
Timeframe: From baseline to 12 Months

Intervention	Percentage Change of BMD (Mean)
Vitamin D + Calcium Carbonate	0.08
Vitamin D + Calcium Carbonate + Zoledronic Acid	-0.09

Median Time to First Skeletal-related Event

Time to skeletal events, defined as a metastatic site requiring radiotherapy or any surgical intervention (eg, embolization, radiofrequency ablation, intrathecal catheter placement) or complications from skeletal metastatic lesions (eg, pathologic fracture, spinal cord compression). Time to skeletal events monitored every 8 weeks for at least 1 year. (NCT00490698)
Timeframe: Up to 1 year

Intervention	months (Median)
Zoledronate + Atorvastatin	9

Change From Baseline in Mean Analgesic Score

The analgesic score indicates the types of pain medication used. The scores range as follows: 0 = none medication; 1 = minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.); 2 = Tranquilizers, antidepressants, muscle relaxants, and steroids; 3 = Mild narcotics (oxycodone, meperidine, codeine, etc.); and 4 = Strong narcotics (morphine, hydromorphone, etc.). A positive change from baseline indicates worsening. (NCT00320710)
Timeframe: baseline, 52 weeks

Intervention	score (Mean)
Zoledronic Acid Every (q) 4 Weeks	0.5
Zoledronic Acid q 12 Weeks	0.5

Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score

Participants completed a BPI short form which is a 9 item self-administered questionnaire used to evaluate the severity of a participant's pain and the impact of this pain on the participant's daily functioning. The participant rates his or her worst, least, average, and current pain intensity, lists current treatments and perceived effectiveness, and rates the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale. The BPI composite score, which was calculated as the average of items 3, 4, 5 and 6 (worst pain, least pain, average pain and pain right now), ranged from 0 (best possible outcome, no pain) to 10 (worst possible outcome, pain as bad as you can imagine). A positive change from baseline indicates worsening. (NCT00320710)
Timeframe: baseline, 52 weeks

Intervention	scores on a scale (Mean)
Zoledronic Acid Every (q) 4 Weeks	0.24
Zoledronic Acid q 12 Weeks	0.31

Change From Baseline in Serum Bone Specific Alkaline Phosphatase

Serum samples were collected to obtain bone specific alkaline phosphatase values. (NCT00320710)
Timeframe: baseline, 48 weeks

Intervention	mcg/L (Mean)
Zoledronic Acid Every (q) 4 Weeks	0.797
Zoledronic Acid q 12 Weeks	4.514

Change From Baseline in Urinary N-telopeptide / Creatinine Ratio

Urine samples were collected to obtain n-telopeptide and creatinine values. (NCT00320710)
Timeframe: baseline, 48 weeks

Intervention	ratio (Mean)
Zoledronic Acid Every (q) 4 Weeks	10.612
Zoledronic Acid q 12 Weeks	14.697

Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE)

An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone. (NCT00320710)
Timeframe: 52 weeks

Intervention	Percentage of participants (Number)
Zoledronic Acid Every (q) 4 Weeks	22
Zoledronic Acid q 12 Weeks	23.2

Skeletal Morbidity Rate

"An SMR for a patient was defined as the number of occurrences of any (or a particular) SRE allowing for only 1 event in any 3-week interval, divided by the time at risk in years. The number of occurrences and the time at risk were counts of SRE and the time from the randomization date. Counting began from randomization in the way that every counted event was followed by a 20-day period during which no SRE was counted, nor was the time counted as at risk. For example, if a patient had 1 SRE during the study, the time at risk was calculated as the total number of days in the study minus the 20-day follow-up period for that SRE. If a patient had no SRE events, the entire study period was counted as time at risk. This SMR calculation method had the advantage of avoiding multiple counts of possibly interdependent SREs (e.g. having 1 fracture increases the probability of having a subsequent SRE)." (NCT00320710)
Timeframe: 52 weeks

Intervention	Number of events per year (Mean)
Zoledronic Acid Every (q) 4 Weeks	0.46
Zoledronic Acid q 12 Weeks	0.50

Time to First SRE

An SRE was defined as a pathologic bone fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone, or surgery to bone. The time to first individual SRE was defined as the date of randomization to the date of first occurrence of any SRE. (NCT00320710)
Timeframe: 52 weeks

Intervention	Days (Median)
Zoledronic Acid Every (q) 4 Weeks	NA
Zoledronic Acid q 12 Weeks	NA

Time to First Individual Type of SRE

Types of SREs analyzed were pathologic fractures (vertebral and non-vertebral), spinal cord compression, radiation to bone and surgery to bone. The time to first indvidual SRE was defined as the date of randomization to the date of the first occurrence of any individual SRE. (NCT00320710)
Timeframe: 52 weeks

Intervention	Weeks (Median)
	Vertebral pathologic fractures	Non-vertebral pathologic fractures	Spinal cord compression	Radiation to bone	Surgery to bone
Zoledronic Acid Every (q) 4 Weeks	NA	NA	NA	NA	NA
Zoledronic Acid q 12 Weeks	NA	NA	NA	NA	NA

The Number of Participants With a Significant Increase in Serum Creatinine at 12 Months

The primary renal safety endpoint was the number of participants with a clinically relevant increase in serum creatinine at 12 months. Serum creatinine was determined prior to each zoledronic acid infusion for all Participants and was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value. (NCT00104104)
Timeframe: Baseline and 12 Months

Intervention	Participants (Number)
15 - Minute Infusion	17
30 - Minute Infusion	13

The Number of Participants With a Significant Increase in Serum Creatinine at 24 Months

Serum Creatinine was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value. (NCT00104104)
Timeframe: Baseline and 24 Months

Intervention	Participants (Number)
15 - Minute Infusion	24
30 - Minute Infusion	23

The Number of Participants With Disease Progression

(NCT00104104)
Timeframe: 24 Months

Intervention	Participants (Number)
15 - Minute Infusion	28
30 - Minute Infusion	20

Time to First Significant Increase in Serum Creatinine

Median time to event in participants who had a clinically relevant increase in serum creatinine. (NCT00104104)
Timeframe: Up to 24 months

Intervention	weeks (Median)
15 - Minute Infusion	21.6
30 - Minute Infusion	24.4

Zoledronic Acid Concentrations

Samples for drug concentration analysis were drawn at 10 and 15 minutes into the infusion for participants in the 15-minute infusion group and at 25 and 30 minutes into the infusion for patients in the 30-minute infusion group. The mean and median zoledronic acid concentrations were greater in the 15-minute group than in the 30-minute group at both sampling timepoints. (NCT00104104)
Timeframe: 24 months

Intervention	ng/mL (Mean)
	First Collection (10 minutes, 25 minutes)	Second Collection (15 minutes, 30 minutes)
15 - Minute Infusion	231.1	248.8
30 - Minute Infusion	186.3	172.0

Change From Baseline in Serum Calcium (mmol/L) - Safety Population

Change from baseline = endpoint - baseline, at each time point, only participants with a value at baseline and that time point are included in the change from baseline column. In case of multiple assessments, for baseline visit the last measurement prior to the first dose was used in the analysis, and for Visits 2 and 3, the lowest serum calcium in the visit window was used. (NCT00668200)
Timeframe: Baseline, Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30)

Intervention	mmol/L (Mean)
	Visit 2 n=76	Visit 3 n=2
Zoledronic Acid	-0.024	0.04

Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population)

The end of study is not a separate time point. It is the last post-baseline, for majority the end of study was visit 2. There were 2 patients who had the end of study at Visit 3. If calcium at visit 2 was abnormal it was measured again at visit 3. (NCT00668200)
Timeframe: End of study: Visit 2 (days 9 - 11 post-infusion) or visit 3 (day 30)

Intervention	percentage of patients (Number)
	Tingling around your mouth n=76	Tingling in fingers n=66	Cramps in hands n=62	Cramps in leg or feet n=50	Involuntary movements of hands n=73	Involuntary movements of feet n=70	Involuntary movements of facial muscles n=71	Generalized (epileptic) seizures n=76
Zoledronic Acid	1.3	3	3.2	0	2.7	1.4	0	0

Percentage of Patients With Serum Calcium <2.07 mmol/L at 9-11 Days After Receiving Zoledronic Acid.

To be included in the analysis, patients were required to have a baseline serum calcium of at least 2.07 mmol/L and at least one serum calcium measurement 9-11 days post-infusion of zoledronic acid. In case of multiple assessments, for baseline visit the last measurement prior to the first dose was used in the analysis, and for Visits 2 and 3, the lowest serum calcium in the visit window was used. hypocalcemia was defined as treatment-emergent serum calcium <2.07 mmol/L at 9-11 days after the study drug infusion. (NCT00668200)
Timeframe: at Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30)

Intervention	percentage of patients (Number)
	Visit 2	Visit 3
Zoledronic Acid	1.3	0.0

Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12

Left posteroanterior (PA) hand/wrist X-ray were taken at Visit 1 and at the Month 12 visit to assess bone age and the between-treatment differences for change in 2nd metacarpal cortical width at Month 12 relative to baseline. If a fracture of the left upper extremity precluded radiographic imaging, then the right hand was evaluated for this purpose. In this case, the right hand was be imaged at both Visit 1 and at Month 12. The information was used in the assessment of bone density. (NCT00799266)
Timeframe: Month 12

Intervention	millimeter (mm) (Least Squares Mean)
Zoledronic Acid	-0.01
Placebo	0.03

Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12

Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition. (NCT00799266)
Timeframe: Month 12

Intervention	Z-score (Least Squares Mean)
Zoledronic Acid	0.582
Placebo	0.168

Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6

Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 6. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition. (NCT00799266)
Timeframe: Month 6

Intervention	Z-score (Least Squares Mean)
Zoledronic Acid	0.447
Placebo	0.157

Mean Change From Baseline in Vertebral Morphometry at Month 12

Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader. (NCT00799266)
Timeframe: Month 12

Intervention	Ratio (Least Squares Mean)
Zoledronic Acid	-0.018
Placebo	-0.0003

Number of Participants With New Vertebral Fractures at Month 12

New vertebral fractures were defined as fractures of Genant Grade 1 or higher that occurred at lumbar or thoracic spine from first dose infusion to the end of the study. (NCT00799266)
Timeframe: Month 12

Intervention	Participants (Count of Participants)
Zoledronic Acid	0
Placebo	2

Urinary Concentration of Zoledronic Acid at Month 12

Urine was collected overnight or for at least 4 waking hours from all patients able to provide specimens, to measure urinary concentration of zoledronic acid at Month 12. Only descriptive analysis done. (NCT00799266)
Timeframe: Month 12

Intervention	ng/mL (Mean)
Zoledronic Acid	1643.3

Mean Change From Baseline in BSAP at Months 6 and 12

Bone specific alkaline phosphatase (BSAP) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. (NCT00799266)
Timeframe: Month 6, Month 12

Intervention	nanogram per milliliter (ng/mL) (Least Squares Mean)
	BSAP Change at Month 6	BSAP Change at Month 12
Placebo	3.810	6.450
Zoledronic Acid	-7.413	-13.984

Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12

Lumbar Spine BMC was determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals. (NCT00799266)
Timeframe: Month 6, Month 12

Intervention	g (Least Squares Mean)
	Lumbar Spine (LS) BMC Change at Month 6	Lumbar Spine (LS) BMC Change at Month 12
Placebo	2.131	4.295
Zoledronic Acid	4.110	6.450

Mean Change From Baseline in Serum NTX at Months 6 and 12

Serum Cross linked N-telopeptide (NTX) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. (NCT00799266)
Timeframe: Month 6, Month 12

Intervention	nmol BCE/L (Least Squares Mean)
	NTX Change at Month 6	NTX Change at Month 12
Placebo	7.192	7.440
Zoledronic Acid	-13.746	-20.134

Mean Change From Baseline in Serum P1NP at Months 6 and 12

Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. (NCT00799266)
Timeframe: Month 6, Month 12

Intervention	nanogram per milliliter (ng/mL) (Least Squares Mean)
	P1NP Change at Month 6	P1NP Change at Month 12
Placebo	77.497	150.166
Zoledronic Acid	-134.285	-230.966

Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12

Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. (NCT00799266)
Timeframe: Month 6, Month 12

Intervention	U/L (Least Squares Mean)
	TRAP 5b Change at Month 6	TRAP 5b Change at Month 12
Placebo	0.313	0.109
Zoledronic Acid	-1.561	-1.728

Mean Change From Baseline in Total Body BMC at Month 6 and 12

Total body BMC was all determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals. (NCT00799266)
Timeframe: Month 6, Month 12

Intervention	g (Least Squares Mean)
	Total BMC Change at Month 6	Total BMC Change at Month 12
Placebo	95.214	140.064
Zoledronic Acid	129.272	220.805

Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12

Pain was evaluated at each visit (in office and telephone visit) at randomization, Months 3, 6, 9 and 12 using the Faces Pain Scale-Revised (FPS-R). Children were selecting the face that best fits their pain. The pain score ranged from 0 (No Pain) to 10 (Very Much Pain). The reduction in pain from baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline. If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'. (NCT00799266)
Timeframe: Month 3, Month 6, Month 9 and Month 12

Intervention	Percentage of Patients (Number)
	Month 3	Month 6	Month 9	Month 12
Placebo	53.8	50.0	46.2	57.1
Zoledronic Acid	37.5	37.5	33.3	31.3

Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids

Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that zoledronic acid is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis done. (NCT00799266)
Timeframe: Baseline through Month 12

Intervention	Percentage of Participants (Number)
	AEs by Primary System Organ Class (SOC)	SAEs by Primary System Organ Class (SOC)
Placebo	75.0	6.3
Zoledronic Acid	83.3	27.8

Number of Participants Who Discontinue or Change Aromatase Inhibitor (AI) Therapy

(NCT01194440)
Timeframe: 12 months

Intervention	Participants (Count of Participants)
Arm I	5

Number of Participants With Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)

(NCT01194440)
Timeframe: 12 months

Intervention	Participants (Count of Participants)
Arm I	22

AIMSS as Determined by Health Assessment Questionnaire Disability Index (HAQ-DI) Score

The HAQ-DI score ranges from 0-3 with a higher score reflective of greater disability or increased incidence of AIMSS. (NCT01194440)
Timeframe: Baseline, 1 month, 3 months, 6 months, 12 months

Intervention	score on a scale (Median)
	Baseline	1 month	3 months	6 months	12 months
Arm I	0.2	0.2	0.1	0.2	0.4

AIMSS as Determined by Visual Analog Scale (VAS) Score

VAS is a visual measurement tool to assess AIMSS. It is a visual scale that ranges from 0 centimeters (cm) to 10cm. The VAS score ranges from zero (0cm) to 10 (10cm), with a higher score reflecting a greater frequency of AIMSS. (NCT01194440)
Timeframe: Baseline, 1 month, 3 months, 6 months, 12 months

Intervention	score on a scale (Median)
	Baseline	1 month	3 months	6 months	12 months
Arm I - IV Zoledronic Acid Prophylaxis	0.8	1	1.4	1.2	1.9

Change in Aminoterminal Propeptide on Type I Procollagen (P1NP) From Baseline to Month 24

Change in Aminoterminal propeptide on type I procollagen (P1NP) from baseline to month 24. P1NP is a marker for bone formation. It is a specific indicator of type 1 collagen deposition. P1NP is increased in states of high bone turnover (NCT00375505)
Timeframe: baseline, month 24

Intervention	ng/ml (Mean)
Placebo	16.729
Zometa	-21.476

Change in Anti-Mueller Hormone (AMH) From Baseline to Month 24

Change in anti-Mueller hormone (AMH) from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	ng/ml (Mean)
Placebo	-0.584
Zometa	-0.878

Change in Bone Mineral Density (BMD) at Lumbar Spine (L2-L4) From Baseline to Month 24 or Last Visit Measure by T-score

Bone mineral density (BMD) at lumbar spine (L2-L4) by T-score. Your T-score is the number of units that your bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates that it is likely osteoporosis. (NCT00375505)
Timeframe: baseline, month 24

Intervention	T-score (Mean)
Placebo	-0.622
Zometa	0.309

Change in Bone Mineral Density (BMD) at Lumbar Spine (L2-L4) From Baseline to Month 24 or Last Visit Measure by Z-score

Bone mineral density (BMD) at lumbar spine (L2-L4) measured by Z-score. If Z-score is -2 or lower, it may suggest that something other than aging is causing abnormal bone loss. (NCT00375505)
Timeframe: baseline, month 24

Intervention	Z-score (Mean)
Placebo	-0.658
Zometa	0.309

Change in Bone Mineral Density (BMD) Measured by Dual (Energy) X-ray Absorptiometry (DXA) at Lumbar Spine (L2-L4) From Baseline to Month 24

Bone mineral density (BMD) by DXA at lumbar spine (L2-L4); DXA assessments of the BMD at dual hips. (BMD). Two X-ray beams with different energy levels are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. (NCT00375505)
Timeframe: baseline, month 24

Intervention	Z-score (Mean)
Placebo	-0.075
Zometa	0.037

Change in Estradiol (E2) From Baseline to Month 24

Change in Estradiol from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	ng/L (Mean)
Placebo	-119.026
Zometa	-10.421

Change in Follicle- Stimulating Hormone (FSH) From Baseline to Month 24

Change in Follicle- Stimulating Hormone (FSH) from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	mIU/ml (Mean)
Placebo	-0.593
Zometa	0.860

Change in Parathyroid Hormone (PTH) From Baseline to Month 24

Change in Parathyroid Hormone (PTH) from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	pg/ml (Mean)
Placebo	7.288
Zometa	4.729

Change in Serum CTX-carboxy-terminal Collagen Crosslinks From Baseline to Month 24

CTX is a telopeptide that can be used as a biomarker in the serum to measure the rate of bone turnover. The test used to detect the CTX marker is specific to bone resorption. (NCT00375505)
Timeframe: baseline, month 24

Intervention	ng/mL (Mean)
Placebo	0.137
Zometa	-0.118

Change in Sex Hormone Binding Globulin (SHGB) From Baseline to Month 24

Change in Sex Hormone binding globulin (SHGB) from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	nmol/l (Mean)
Placebo	5.609
Zometa	12.806

Change in Testosterone From Baseline to Month 24

Change in Testosterone from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	ng/ml (Mean)
Placebo	0.039
Zometa	0.015

Change in Vitamine D From Baseline to Month 24

Change in Vitamine D from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	ng/ml (Mean)
Placebo	11.163
Zometa	9.638

Percent Change in Bone Mineral Density for L2-L4 From Baseline to Month 24 or Last Visit

Bone mineral density (BMD) at lumbar spine (L2-L4) measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done in the lumbar vertebrae (L2-L4) (NCT00375505)
Timeframe: baseline, month 24

Intervention	percentage change (Mean)
Placebo	-6.429
Zometa	3.139

Change in Bone Mineral Density Os Calcis (Right and Left Side) From Baseline to Month 24 as Measured by Broadband Ultrasound Attenuation (BUA)

Bone mineral density (BMD) for Os calcis (right and left side) is measured by BUA; BUA is a Quantitative ultrasonography scanning and measures bone mass and strength and assesses bone microarchitecture by detecting the transmission of high-frequency sound waves through bone. (NCT00375505)
Timeframe: baseline, month 24

Intervention	dB/MHz (Mean)
	Os calcis (right)	Os calcis (left)
Placebo	-0.306	-2.417
Zometa	1.824	1.848

Change in Bone Mineral Density Os Calcis (Right and Left Side) From Baseline to Month 24 as Measured by Speed of Sound (SOS)

Bone mineral density (BMD) for Os calcis (right and left side) is measured by SOS; SOS is a Quantitative ultrasonography scanning and measures bone mass and strength and assesses bone microarchitecture by detecting the transmission of high-frequency sound waves through bone. (NCT00375505)
Timeframe: baseline, month 24

Intervention	m/s (Mean)
	Os calcis (right)	Os calcis (left)
Placebo	-13.139	-13.028
Zometa	-10.853	-13.485

Change in Bone Mineral Density Phalanges II, III, IV, and V From Baseline to Month 24 or Last Visit as Measured by Amplitude-dependent Speed of Sound (ADSOS)

Bone mineral density (BMD) for Phalanges II, III, IV, and V is measured by ADSOS; ADSOS is a Quantitative ultrasonography scanning and measures bone mass and strength and assesses bone microarchitecture by detecting the transmission of high-frequency sound waves through bone. (NCT00375505)
Timeframe: baseline, month 24

Intervention	m/s (Mean)
	Phalanges II (n=35, 33)	Phalanges III (n=35, 33)	Phalanges IV (n=35, 33)	Phalanges V (n=35, 33)
Placebo	-48.514	-62.971	-49.086	-35.000
Zometa	-21.485	-19.879	0.455	0.303

Change in Inhibin A and Inhibin B From Baseline to Month 24

Change in Inhibin A and Inhibin B from baseline to month 24 (NCT00375505)
Timeframe: baseline, month 24

Intervention	pg/ml (Mean)
	Inhibin A (n=34,34)	Inhibin B (n=34,34)
Placebo	-19.079	-28.200
Zometa	-10.209	-39.126

Percentage Change in Bone Mineral Density for Femoral Neck (Right and Left Side) From Baseline to Month 24

Bone mineral density (BMD) for femoral neck (right and left side) is measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done on femoral neck (right and left side) (NCT00375505)
Timeframe: baseline, month 24

Intervention	Percentage Change (Mean)
	femoral neck (right)	femoral neck (left)
Placebo	-0.023	-0.023
Zometa	0.011	0.008

Percentage Change in Bone Mineral Density for Total Femoral Neck (Right and Left Side) From Baseline to Month 24

Bone mineral density (BMD) for total femoral neck (right and left side) is measured by using Lunar or Hologic dual-energy X-ray absorptiometry (DXA) Instruments. Measurements were done on femoral neck (right and left side) (NCT00375505)
Timeframe: baseline, month 24

Intervention	percentage change (Mean)
	femoral neck (right)	femoral neck (left)
Placebo	-0.039	-0.036
Zometa	0.013	0.014

Annual Overall Skeletal Morbidity Rate (SMR)

"The SMR was computed by summing all Skeletal Related Event(s) (SREs)which occurred during the observation period and dividing it by the ratio days of observation period / 365.25, for each participant. SRE was defined as: pathologic bone fracture, spinal cord compression, surgery to bone both curative and prophylactic, radiation therapy to bone, or hypercalcemia of malignancy.~SMR (years) = 365.25 x SMR(days) where SMR (days) = total number of SREs / total SRE risk period (days). Risk period for SMR was computed as the days from randomization date to the date of last visit." (NCT00375427)
Timeframe: 12 months

Intervention	Number of Skeletal Events per Year (Mean)
Zoledronic Acid Every 3 Months	0.26
Zoledronic Acid Every 4 Weeks	0.22

Median Time to First Skeletal Related Event(s) (SRE)

Median Time to first skeletal related event (SRE) is defined as the time from randomization to the date of first occurrence of any SRE which includes at least one of the following: radiation therapy to bone, pathologic bone fracture, spinal cord compression, surgery to bone, and hypercalcemia of malignancy (HCM). Due to the few numbers of SRE, Kaplan-Meier estimate never reaches a failure probability >=25%; so median time, 25th and 75th percentiles are not determined.For this reason only the estimated percentage of patient SRE free are reported at each time point. (NCT00375427)
Timeframe: 12 month

Intervention	Day (Number)
Zoledronic Acid Every 3 Months	NA
Zoledronic Acid Every 4 Weeks	NA

Annual Incidence of Any Skeletal Related Events (SREs)

"Skeletal Related Events (SREs) are defined as a:~pathologic bone fracture such as non-vertebral and vertebral~spinal cord compression identified by X-rays evidence~surgery to bone both curative and prophylactic~radiation therapy to bone including palliative, therapeutic or prophylactic~hypercalcemia of malignancy, defined as a corrected serum calcium > 12 mg/dl (3.00 mmol/l) or a lower level of hypercalcemia which is symptomatic and which requires active treatment other than rehydration. Annual incidence for each SRE was computed in the same way as annual overall SMR." (NCT00375427)
Timeframe: 12 months

Intervention	Number of SRE per Year (Mean)
	Vertebral pathological fracture rate	Non-vertebral pathological fracture rate	Spinal cord compression rate	Radiation to bone rate	Surgery to bone rate	Hypercalcemia of malignancy rate
Zoledronic Acid Every 3 Months	0.02	0.08	0.01	0.17	0.02	0.01
Zoledronic Acid Every 4 Weeks	0.02	0.03	0.00	0.14	0.00	0.02

Assessment of the Eastern Cooperative Oncology Group (ECOG) Performance Score

ECOG Performance Score has 4 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. Outcome is given as median score for participants at Baseline and 3, 6 , 9 and 12 months of treatment (NCT00375427)
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

Intervention	score on a scale (Median)
	Baseline	Month 3	Month 6	Month 9	Month 12
Zoledronic Acid Every 3 Months	0	0	0	0	0
Zoledronic Acid Every 4 Weeks	0	0	0	0	0

Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire

Bone pain was assessed by means of a pain score obtained using the Brief Pain Inventory (BPI) questionnaire. The BPI can produce three pain scores: worst pain, a composite pain score, and a pain interference score. The composite pain score, which is the average of questions 3, 4, 5 and 6 of the questionnaire was used in this study. Pain was rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The outcome is given as the median score for participants at baseline, and 3, 6, 9 and 12 months of treatment (NCT00375427)
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

Intervention	score on a scale (Mean)
	Baseline (N= 186, 185)	Month 3 (N= 156, 163)	Month 6 (N= 143, 160)	Month 9 (N= 131, 130)	Month 12 (N= 135, 124)
Zoledronic Acid Every 3 Months	2.0	2.3	2.3	2.3	2.4
Zoledronic Acid Every 4 Weeks	2.1	2.2	1.9	2.1	2.1

Evaluation of Pain According to Verbal Rating Scale (VRS) Based on Median Score Value

Pain intensity at rest and on movement is rated by the patient by means of a validated 6-point Verbal Rating Scale (VRS) and refers to the pain which occurred during the last week before the assessment. Median score value is the median of all the observed scores (none=0, very mild=1, mild=2, moderate=3, severe=5 and very severe=6) at each time point. (NCT00375427)
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

Intervention	score on a scale (Median)
	At Rest: Baseline	At Rest: Month 3	At Rest: Month 6	At Rest: Month 9	At Rest: Month 12	At Movement : Baseline	At Movement : Month 3	At Movement : Month 6	At Movement : Month 9	At Movement : Month 12
Zoledronic Acid Every 3 Months	1	2	2	1	2	2	2	2	2	2.5
Zoledronic Acid Every 4 Weeks	1	2	1	1	1	2	2	2	2	2

Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)

"Skeletal Related Events (SREs) are defined as a:~pathologic bone fracture such as non-vertebral and vertebral compression fractures~spinal cord compression identified by positive diagnosis documented by X-ray evidence~surgery to bone both curative and prophylactic~radiation therapy to bone including palliative, therapeutic or prophylactic~hypercalcemia of malignancy, defined as a corrected serum calcium > 12 mg/dl (3.00 mmol/l) or a lower level of hypercalcemia which is symptomatic and which requires active treatment other than rehydration." (NCT00375427)
Timeframe: 12 month

Intervention	Percentage of Participants (Number)
	Patient with any SRE	Vertebral pathological fracture	Non vertebral pathological fracture	Spinal cord compression	Radiation to bone	Surgery to bone	Hypercalcemia of malignancy
Zoledronic Acid Every 3 Months	14.83	1.44	3.35	0.96	10.53	0.96	0.48
Zoledronic Acid Every 4 Weeks	15.28	1.85	2.31	0.46	11.11	0.46	1.85

Percentage of Participants Skeletal Related Event (SRE) Free

"Percentage of participants SRE free is defined as the Kaplan-Meier estimate of participants free of any Skeletal Related Events(SRE) at each time point.~Skeletal Related Events (SREs) are:~pathologic bone fracture; non-vertebral and vertebral~spinal cord compression identified by X-rays~surgery to bone both curative and prophylactic~radiation therapy to bone (palliative, therapeutic or prophylactic)~hypercalcemia of malignancy, defined as a corrected serum calcium > 12 mg/dl (3.00 mmol/l) or a lower level which is symptomatic and requires treatment other than rehydration." (NCT00375427)
Timeframe: 12 months

Intervention	Percentage of participants (Number)
	At Month 1	At Month 2	At Month 3	At Month 4	At Month 5	At Month 6	At Month 7	At Month 8	At Month 9	At Month 10	At Month 11	At Month 12
Zoledronic Acid Every 3 Months	99	98	96	94	94	93	88	86	85	84	83	78
Zoledronic Acid Every 4 Weeks	98	98	97	95	93	92	90	88	85	83	83	82

Use Of Analgesic Medications According to the Analgesic Score Scale

"The analgesic score used for this study is modified from the Radiation Therapy Oncology Group (RTOG) analgesic score scale. The scale represents type of medication administered from 0 to 4 where:~0 = None~= Minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.)~= Tranquilisers, antidepressants, muscle relaxants, and steroids~= Mild narcotics (oxycodone, meperidine, codeine, etc.)~= Strong narcotics (morphine, hydromorphone, etc.) The outcome is given a the median score for the participants at Baseline and 3, 6, 9 and 12 months of treatment" (NCT00375427)
Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

Intervention	score on a scale (Median)
	Baseline	Month 3	Month 6	Month 9	Month 12
Zoledronic Acid Every 3 Months	0	0	0	0	0
Zoledronic Acid Every 4 Weeks	0	0	0	0	0

Freedom From Any Bone Fracture (FABF) Rate at Three Years

The time of failure was measured from the date of randomization to the date of documented bone fractures, defined as any fracture of the bone. The three-year FABF rate will be estimated by the Kaplan-Meier method. (NCT00329797)
Timeframe: From randomization to 3 years

Intervention	percentage of participants (Number)
Zoledronic Acid	98.0
Control	97.4

Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years

The FACT-G is a validated, 27-item measure. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for the physical, social and functional subscales, and 0-24 for the emotional subscale. Certain items, identified on the FACT-G scoring guides, must be reversed before it is added by subtracting the response from 4. All subscale totals are added together to form the FACT-G total score. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicates better QOL. (NCT00329797)
Timeframe: Baseline, 3 years from start of treatment

Intervention	units on a scale (Mean)
	Physical Subscale	Social Subscale	Emotional Subscale	Functional Subscale	Total
Control	0.06	-1.13	1.15	-2.76	-2.77
Zoledronic Acid	-1.03	-0.69	1.83	-1.10	-1.00

Percent Change in Bone Mineral Density at 3 Years

Bone mineral density (BMD) was measured by DXA scan (Dual X-ray absorptiometry) for five locations: lumbar, right total hip, left total hip, right femoral neck, and left femoral neck. The percent change at 3 years was calculated for each location by the following formula: Percent Change BMD = (BMD_3 years - BMD_Baseline)/ BMD_Baseline * 100. (NCT00329797)
Timeframe: Baseline, 3 years from start of treatment

Intervention	percentage of baseline value (Mean)
	Lumbar	Hip - Right	Hip - Left	Femoral - Right	Femoral - Left
Control	-5	-5	-8	-6	-8
Zoledronic Acid	6	-2	1	1	3

Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

The length of tetracycline double labels is a measure of the extent of bone formation in the cancellous compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. (NCT00927186)
Timeframe: 24 months

Intervention	millimeter (mm) (Median)
Teriparatide	0.23
Zoledronic Acid	0.29

Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Intervention	millimeter (mm) (Median)
Teriparatide	0.35
Zoledronic Acid	0.24

Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint

CTX is a measure of bone resorption. (NCT00927186)
Timeframe: Baseline, 12 months

Intervention	nanogram/milliliter (ng/mL) (Median)
Teriparatide	0.42
Zoledronic Acid	-0.23

Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint

OC is a measure of osteoblast function. (NCT00927186)
Timeframe: Baseline, 12 months

Intervention	microgram/liter (µg/L) (Median)
Teriparatide	32.98
Zoledronic Acid	-12.32

Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint

PINP is a measure of bone formation. (NCT00927186)
Timeframe: Baseline, 12 months

Intervention	microgram/liter (µg/L) (Median)
Teriparatide	93.50
Zoledronic Acid	-33.00

Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

MS/BS in CC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation. (NCT00927186)
Timeframe: 24 months

Intervention	percentage of surface (Median)
Teriparatide	3.00
Zoledronic Acid	0.07

Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Intervention	percentage of surface (Median)
Teriparatide	5.60
Zoledronic Acid	0.16

Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams. (NCT00927186)
Timeframe: 24 months

Intervention	micrometer (µm) (Median)
Teriparatide	5.71
Zoledronic Acid	3.98

Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Osteoid thickness (OTh.) in the cancellous compartment is a measure of the average thickness of osteoid seams. (NCT00927186)
Timeframe: 6 months

Intervention	micrometer (µm) (Median)
Teriparatide	4.92
Zoledronic Acid	3.77

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Eroded surface/bone surface (ES/BS) in the cancellous compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption. (NCT00927186)
Timeframe: 24 months

Intervention	percentage of surface (Median)
Teriparatide	4.44
Zoledronic Acid	2.39

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Intervention	percentage of surface (Median)
Teriparatide	4.59
Zoledronic Acid	2.71

Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid. (NCT00927186)
Timeframe: 24 months

Intervention	percentage of surface (Median)
Teriparatide	11.19
Zoledronic Acid	1.26

Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Osteoid surface (OS) in the cancellous compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid. (NCT00927186)
Timeframe: 6 months

Intervention	percentage of surface (Median)
Teriparatide	11.34
Zoledronic Acid	2.51

Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid). (NCT00927186)
Timeframe: 24 months

Intervention	percentage of volume (Median)
Teriparatide	1.33
Zoledronic Acid	0.18

Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Osteoid volume (OV) in the cancellous compartment is the percent of a given volume of bone tissue that consists of unmineralized bone (osteoid). (NCT00927186)
Timeframe: 6 months

Intervention	percentage of volume (Median)
Teriparatide	1.32
Zoledronic Acid	0.24

Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets. (NCT00927186)
Timeframe: 24 months

Intervention	micrometer (µm) (Median)
Teriparatide	31.37
Zoledronic Acid	29.26

Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Wall thickness (WTh.) in the cancellous compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets. (NCT00927186)
Timeframe: 6 months

Intervention	µm (Median)
Teriparatide	31.29
Zoledronic Acid	28.63

Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Ac.f in CC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	new cycles/year (Median)
	DL and NL (n=9, 6)	DL, Imputed SL (ISL) and NL (n=10, 9)
Teriparatide	0.19	0.18
Zoledronic Acid	0.00	0.00

Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Ac.f in CC represents the frequency of activation of new remodeling cycles on BS (bone formation rate [BFR]/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 micrometer (µm)/day or counted as missing. (NCT00927186)
Timeframe: 6 months

Intervention	new cycles/year (Median)
	DL and NL (n=28, 28)	DL, Imputed SL (ISL) and NL (n=28, 30)
Teriparatide	0.37	0.37
Zoledronic Acid	0.01	0.01

Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Ac.f in EC represents the frequency of activation of new remodeling cycles on the bone surface (BFR/BS divided by wall thickness) and is expressed in units of new cycles per unit of time. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	new cycles/year (Median)
	DL and NL at 6 Months (n=23, 20)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	DL and NL at 24 Months (n=8, 7)	DL, ISL and NL at 24 Months (n=9, 8)
Teriparatide	0.83	0.83	0.25	0.24
Zoledronic Acid	0.00	0.01	0.00	0.00

Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

a. FP in CC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	year (Median)
	DL and NL (n=9, 2)	DL, Imputed SL (ISL) and NL (n=10, 5)
Teriparatide	0.19	0.19
Zoledronic Acid	0.19	0.25

Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Intervention	year (Median)
	DL and NL (n=28, 16)	DL, ISL and NL (n=28, 18)
Teriparatide	0.15	0.15
Zoledronic Acid	0.16	0.16

Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

a. FP in EC is the mean time required to rebuild a new bone structural unit, calculated as wall thickness divided by MAR. Participants were given T for two 3 day-periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	year (Median)
	DL and NL at 6 Months (n=23, 6)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	DL and NL at 24 Months (n=8, 2)	DL, ISL and NL at 24 Months (n=9, 3)
Teriparatide	0.20	0.20	0.23	0.24
Zoledronic Acid	0.20	0.28	0.22	0.25

Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Aj.AR in CC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	micrometer (µm)/day (Median)
	DL and NL (n=9, 6)	DL, Imputed SL (ISL) and NL (n=10, 9)
Teriparatide	0.13	0.12
Zoledronic Acid	0.00	0.02

Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Intervention	µm/day (Median)
	DL and NL (n=28, 28)	DL, ISL and NL (n=28, 30)
Teriparatide	0.34	0.34
Zoledronic Acid	0.02	0.02

Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Aj.AR in EC is MAR averaged over the entire osteoid surface and in a steady state is an estimate of the mean rate of matrix apposition. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	micrometer (µm)/day (Median)
	DL and NL at 6 Months (n=23, 20)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	DL and NL at 24 Months (n=8, 7)	DL, ISL and NL at 24 Months (n=9, 8)
Teriparatide	0.41	0.41	0.35	0.32
Zoledronic Acid	0.00	0.03	0.00	0.00

Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

The length of tetracycline double labels is a measure of the extent of bone formation in the endocortical compartment within individual remodeling units and is measured in millimeters (mm). Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	millimeter (mm) (Median)
	6 months (n=23, 6)	24 months (n=8, 2)
Teriparatide	0.34	0.27
Zoledronic Acid	0.30	0.30

Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	mm³/mm²/year (Median)
	DL and NL (n=9, 6)	DL, Imputed SL (ISL) and NL (n=10, 9)
Teriparatide	0.0057	0.0057
Zoledronic Acid	0.0000	0.0001

Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

BFR in CC is the volume of mineralized bone formed per unit surface bone per unit time (cubic millimeter/square millimeter/year [mm³/mm²/year]); calculated as mineral apposition rate (MAR) times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 months

Intervention	mm³/mm²/year (Median)
	DL and NL (n=28, 28)	DL, ISL and NL (n=28, 30)
Teriparatide	0.0116	0.0116
Zoledronic Acid	0.0002	0.0002

Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

BFR in EC is the volume of mineralized bone formed per unit surface bone per unit time (mm³/mm²/year); calculated as MAR times MS/BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	mm³/mm²/year (Median)
	DL and NL at 6 Months (n=23, 20)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	DL and NL at 24 Months (n=8, 7)	DL, ISL and NL at 24 Months (n=9, 8)
Teriparatide	0.0307	0.0307	0.0093	0.0090
Zoledronic Acid	0.0000	0.0003	0.0000	0.0000

Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint

CTX is a measure of bone resorption. (NCT00927186)
Timeframe: Baseline, 1, 3, 6 months

Intervention	nanogram/milliliter (ng/mL) (Median)
	Change at 1 month (n= 32, 31)	Change at 3 months (n= 32, 29)	Change at 6 months (n= 25, 28)
Teriparatide	0.06	0.26	0.31
Zoledronic Acid	-0.37	-0.35	-0.32

Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint

OC is a measure of osteoblast function. (NCT00927186)
Timeframe: Baseline, 1, 3, 6 months

Intervention	µg/L (Median)
	Change at 1 month (n= 32, 32)	Change at 3 months (n=32, 30)	Change at 6 months (n= 25, 29)
Teriparatide	22.35	29.93	30.85
Zoledronic Acid	-3.39	-12.30	-14.06

Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint

PINP is a measure of bone formation. (NCT00927186)
Timeframe: Baseline, 1, 3, 6 months

Intervention	microgram/Liter (µg/L) (Median)
	Change at 1 month (n= 32, 31)	Change at 3 months (n= 32, 29)	Change at 6 months (n= 25, 28)
Teriparatide	65.50	66.00	84.00
Zoledronic Acid	-15.00	-39.00	-37.50

Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	micrometer (µm)/day (Median)
	DL and NL (n=9, 6)	DL, Imputed SL (ISL) and NL (n=10, 9)
Teriparatide	0.44	0.43
Zoledronic Acid	0.00	0.30

Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

MAR in CC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive T labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 months

Intervention	micrometer (µm)/day (Median)
	DL and NL (n=28, 28)	DL, ISL and NL (n=28, 30)
Teriparatide	0.56	0.56
Zoledronic Acid	0.35	0.33

Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

MAR in EC is a measure of the linear rate of production of mineralized bone matrix by osteoblasts and is measured by the mean distance between two consecutive labels divided by the time interval. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	micrometer (µm/day) (Median)
	DL and NL at 6 Months (n=23, 20)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 29)	DL and NL at 24 Months (n=8, 7)	DL, ISL and NL at 24 Months (n=9, 8)
Teriparatide	0.50	0.50	0.43	0.42
Zoledronic Acid	0.00	0.30	0.00	0.00

Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	day (Median)
	DL and NL (n=9, 2)	DL, Imputed SL (ISL) and NL (n=10, 5)
Teriparatide	38.84	45.33
Zoledronic Acid	45.67	128.37

Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Mlt in CC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as Osteoid Thickness (O.Th) divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 months

Intervention	day (Median)
	DL and NL (n=28, 16)	DL, ISL and NL (n=28, 18)
Teriparatide	13.63	13.63
Zoledronic Acid	75.72	75.72

Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Mlt in EC is the period between deposition and subsequent mineralization of osteoid. Mlt is calculated as O.Th divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	day (Median)
	DL and NL at 6 Months (n=23, 6)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	DL and NL at 24 Months (n=8, 2)	DL, ISL and NL at 24 Months (n=9, 3)
Teriparatide	12.63	12.63	15.67	17.04
Zoledronic Acid	26.97	26.70	42.86	29.03

Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

MS/BS in EC is a measure of the proportion of BS on which new mineralized bone is deposited at the time of tetracycline (T) labeling and is calculated as sum of total extent of double label (DL) plus half the extent of single label (SL) divided by BS. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in the biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under a microscope. DL indicates active bone formation, SL or no label (NL) suggests suppression of bone formation. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	percentage of surface (Median)
	6 months (n=23, 29)	24 months (n=9, 8)
Teriparatide	18.64	5.82
Zoledronic Acid	0.30	0.00

Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the cancellous compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. (NCT00927186)
Timeframe: 24 months

Intervention	samples (Number)
	No Label	Single Label Only	Double Label Only	Single and Double Label
Teriparatide	0	1	0	9
Zoledronic Acid	4	3	0	2

Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Intervention	samples (Number)
	No Label	Single Label Only	Double Label Only	Single and Double Label
Teriparatide	0	0	0	28
Zoledronic Acid	12	2	3	13

Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Number of samples with single or double tetracycline labels, both single and double labels, or no labels in the endocortical compartment were compared between teriparatide and zoledronic acid treated participants. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	samples (Number)
	No Label at 6 months (n=23, 29)	Single Label Only at 6 months (n=23, 29)	Double Label Only at 6 months (n=23, 29)	Single and Double Label at 6 months (n=23, 29)	No Label at 24 months (n=9, 8)	Single Label Only at 24 months (n=9, 8)	Double Label Only at 24 months (n=9, 8)	Single and Double Label at 24 months (n=9, 8)
Teriparatide	0	0	0	23	0	1	0	8
Zoledronic Acid	14	9	0	6	5	1	0	2

Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Omt in CC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	day (Median)
	DL and NL (n=9, 2)	DL, Imputed SL (ISL) and NL (n=10, 5)
Teriparatide	13.42	13.52
Zoledronic Acid	17.38	13.92

Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Intervention	day (Median)
	DL and NL (n=28, 16)	DL, ISL and NL (n=28, 18)
Teriparatide	9.99	9.99
Zoledronic Acid	9.05	9.05

Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Omt in EC is the period between the onset of deposition and onset of mineralization of a given amount of osteoid. Omt is calculated as O.Th divided by MAR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 Months

Intervention	day (Median)
	DL and NL at 6 Months (n=23, 6)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	DL and NL at 24 Months (n=8, 2)	DL, ISL and NL at 24 Months (n=9, 3)
Teriparatide	10.57	10.57	12.30	13.03
Zoledronic Acid	11.27	11.34	14.94	12.12

Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Osteoid thickness (OTh.) in the endocortical compartment is a measure of the average thickness of osteoid seams. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	micrometer (µm) (Median)
	6 months (n=23, 29)	24 months (n=9, 8)
Teriparatide	4.94	5.23
Zoledronic Acid	3.70	3.53

Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months

The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the cancellous compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. (NCT00927186)
Timeframe: 24 months

Intervention	percentage of tetracycline labels (Median)
	sLS/BS	dLS/BS
Teriparatide	2.25	1.69
Zoledronic Acid	0.15	0.00

Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months

Intervention	percentage of tetracycline labels (Median)
	sLS/BS	dLS/BS
Teriparatide	3.19	4.13
Zoledronic Acid	0.02	0.07

Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

The percent of single or double tetracycline labels per bone surface (sLS/BS, dLS/BS) in the endocortical compartment. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	percentage of tetracycline labels (Median)
	sLS/BS at 6 months (n=23, 29)	dLS/BS at 6 months (n=23, 29)	sLS/BS at 24 months (n=9, 8)	dLS/BS at 24 months (n=9, 8)
Teriparatide	5.56	13.46	3.75	2.77
Zoledronic Acid	0.25	0.00	0.00	0.00

Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Eroded surface/bone surface (ES/BS) in the endocortical compartment is the fraction of the entire trabecular surface occupied by resorption bays, including both those with and without osteoclasts. It is an indicator of bone resorption. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	percentage of surface (Median)
	6 months (n=23, 29)	24 months (n=9, 8)
Teriparatide	4.06	3.43
Zoledronic Acid	1.87	1.88

Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Osteoid surface (OS) in the endocortical compartment is the fraction (%) of the entire trabecular bone surface that is covered by osteoid. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	percentage of surface (Median)
	6 months (n=23, 29)	24 months (n=9, 8)
Teriparatide	16.33	7.48
Zoledronic Acid	1.87	1.55

Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months

Tt.FP in CC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 24 months

Intervention	year (Median)
	DL and NL (n=9, 2)	DL, Imputed SL (ISL) and NL (n=10, 5)
Teriparatide	0.60	0.68
Zoledronic Acid	0.51	2.62

Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months

Intervention	year (Median)
	DL and NL (n=28, 16)	DL, ISL and NL (n=28, 18)
Teriparatide	0.24	0.24
Zoledronic Acid	1.46	1.46

Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months

Tt.FP in EC is a measure of bone formation and is calculated as wall thickness divided by Aj.AR. Participants were given T for two 3-day periods, 14 days apart. T fluoresces under certain light and temporarily binds to new bone. New bone in biopsy is seen as the amount of bone between 2 fluorescently T labeled lines under microscope. DL indicates active bone formation, SL or NL suggests suppression of bone formation. SL cases were imputed to a value of 0.3 µm/day or counted as missing. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	year (Median)
	DL and NL at 6 Months (n=23, 6)	DL, Imputed SL (ISL) and NL at 6 Months (n=23, 15)	DL and NL at 24 Months (n=8, 2)	DL, ISL and NL at 24 Months (n=9, 3)
Teriparatide	0.24	0.24	0.27	0.31
Zoledronic Acid	0.43	0.54	0.62	0.86

Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months

Wall thickness (WTh.) in the endocortical compartment is measured as the mean distance from the cement line to the marrow space of completed trabecular bone packets. (NCT00927186)
Timeframe: 6 and 24 months

Intervention	micrometer (µm) (Median)
	6 months (n=23, 29)	24 months (n=9, 8)
Teriparatide	36.30	34.00
Zoledronic Acid	32.39	32.45

Bone Mass Density (BMD) at Total Hip

bone mineral density measured by DXA at the total hip (NCT00844480)
Timeframe: 6 months

Intervention	%change in BMD from baseline (Mean)
Zoledronic Acid	-3.7
Placebo	-12.3

BMD at Other Skeletal Sites

BMD at spine, femoral neck, distal femur, proximal tibia, heel (NCT00844480)
Timeframe: 6 months

Intervention	percentage of baseline BMD (Mean)
	spine BMD	right femoral neck BMD	distal femur	proximal tibia
Placebo	-2.5	-8.6	-9.1	-13.8
Zoledronic Acid	2.4	-2.2	-8.2	-3.3

Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 18 Months

To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 18 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA). (NCT00305695)
Timeframe: 18 months

Intervention	g/cm2 (Mean)
Arm I (Zoledroic Acid)	-0.001
Arm II (Clinical Observation)	-0.094

Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 9 Months

To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 9 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA). (NCT00305695)
Timeframe: 9 Months

Intervention	g/cm2 (Mean)
Arm I (Zoledroic Acid)	-0.025
Arm II (Clinical Observation)	-0.086

Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip

To compare the effect of zoledronic acid on the change in BMD of the left hip following treatment, evaluated by measuring the change from baseline to 18 months (NCT00305695)
Timeframe: 18 months

Intervention	g/cm2 (Mean)
Arm I (Zoledroic Acid)	-0.003
Arm II (Clinical Observation)	-0.058

Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip

To compare the effect of zoledronic acid on the change in BMD of the right hip following treatment, evaluated by measuring the change from baseline to 18 months (NCT00305695)
Timeframe: 18 months

Intervention	g/cm2 (Mean)
Arm I (Zoledroic Acid)	0.101
Arm II (Clinical Observation)	-0.052

Mean of Time to First Clinical Fracture

The mean of time to the first clinical fracture is estimated from the area under the Kaplan-Meier curve. (NCT00718861)
Timeframe: over 3 years of study duration

Intervention	Days (Mean)
Z9 (Zoledronic Acid 9)	1212.05
Z6P3 (Zoledronic Acid 6 Placebo 3)	1204.65

Percentage Change in Total Hip Bone Mineral Density BMD at Year 6 (Baseline) and Year 9

Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 6 = 100*(Year 9 - Year 6)/Year 6. (NCT00718861)
Timeframe: Year 6 (baseline) and Year 9

Intervention	Percentage Change of BMD (Least Squares Mean)
Z9 (Zoledronic Acid 9)	-0.54
Z6P3 (Zoledronic Acid 6 Placebo 3)	-1.31

Biomarkers (Bone Markers) Serum Bone-specific Alkaline Phosphatase (BSAP). at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9

Bone marker analysis: All patients had blood samples collected for analysis of serum bone-specific alkaline phosphatase (BSAP).Bone-specific alkaline phosphatase (BSAP) is a useful marker of active bone formation. (NCT00718861)
Timeframe: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9

Intervention	ng/ml (Median)
	Year 6 (n=59, 62)	Year 7 (n=58, 65)	Year 8 (n=54, 57)	Year 9 (n=52, 56)
Z6P3 (Zoledronic Acid 6 Placebo 3)	8.95	10.00	9.57	9.94
Z9 (Zoledronic Acid 9)	8.16	8.4	7.84	8.46

Biomarkers (Bone Markers) Serum C-terminal Telopeptide of Type I Collagen (CTx) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9

Bone marker analysis: All patients had blood samples collected for analysis of serum c-terminal telopeptide of type I collagen (CTx). Serum CTX assays measure a fragment of the C-terminal telopeptide of type 1 collagen released during resorption of mature bone (NCT00718861)
Timeframe: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9

Intervention	ng/ml (Median)
	Year 6 (n=59, 58)	Year 7 (n=56, 51)	Year 8 (n=51, 52)	Year 9 (n=51,54)
Z6P3 (Zoledronic Acid 6 Placebo 3)	0.18	0.22	0.2	0.22
Z9 (Zoledronic Acid 9)	0.19	0.2	0.22	0.22

Biomarkers (Bone Markers)Serum N-terminal Propeptide of Type I Collagen (P1NP) at Year 6 (Extension 2 Baseline), Year 7, Year 8, Year 9

Bone marker analysis: All patients had blood samples collected for analysis of serum n-terminal propeptide of type I collagen (P1NP) The P1NP concentration is directly proportional to the amount of new collagen laid down during bone formation. (NCT00718861)
Timeframe: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9

Intervention	ng/ml (Median)
	Year 6 (n=88, 86)	Year 7 (n=58, 65)	Year 8 (n=54, 57)	Year 9 (n=52,56)
Z6P3 (Zoledronic Acid 6 Placebo 3)	24.98	27.79	25.19	27.41
Z9 (Zoledronic Acid 9)	25.89	25.69	26.07	26.74

Change in Height at Years 7, 8 and 9 Relative to Year 6

Height was measured using a stadiometer in millimeters (mm). A stadiometer is a piece of medical equipment used for measuring height. It is usually constructed out of a ruler and a sliding horizontal headpiece which is adjusted to rest on the top of the head. (NCT00718861)
Timeframe: Year 6 (extension 2 baseline), Year 7, Year 8, Year 9

Intervention	millimeters (mm) (Least Squares Mean)
	Year 7 (n=58, 51)	Year 8 (n=55, 49)	Year 9 (n=52, 48)
Z6P3 (Zoledronic Acid 6 Placebo 3)	-4.84	-9.90	-11.65
Z9 (Zoledronic Acid 9)	-5.29	-10.16	-13.31

Number of Participants With New/Worsening Morphometric Vertebral Fractures at Year 9 Compared to Year 6

Morphometric vertebral fracture (VF) was assessed based on morphometry. QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit, x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A fracture was defined as an SQ reading that was greater than the baseline SQ reading. (NCT00718861)
Timeframe: Year 6 (extension 2 baseline), Year 9 (3 years of study duration)

Intervention	participants (Number)
	New Morphometric vertebral fracture	New/worsening Morphometric vertebra
Z6P3 (Zoledronic Acid 6 Placebo 3)	5	5
Z9 (Zoledronic Acid 9)	3	3

Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0

Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 0 = 100*(Year 9 - Year 0)/Year 0. (NCT00718861)
Timeframe: Year 0 (core baseline), Year 7, Year 8, Year 9

Intervention	percentage change of BMD (Least Squares Mean)
	Year 7 (n=83,75)	Year 8 (n=72,71)	Year 9 (n=67,68)
Z6P3 (Zoledronic Acid 6 Placebo 3)	3.86	4.43	3.88
Z9 (Zoledronic Acid 9)	5.11	6.12	4.16

Percentage Change of Femoral Neck Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 6

Intervention	percentage change of BMD (Least Squares Mean)
	Year 7 (n=83,76)	Year 8 (n=73,72)	Year 9 (n=67,69)
Z6P3 (Zoledronic Acid 6 Placebo 3)	-1.24	-0.88	-1.17
Z9 (Zoledronic Acid 9)	-0.78	0.00	-1.11

Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7 and 8 Compared to Year 6

Intervention	percentage change of BMD (Least Squares Mean)
	Year 7 (n=83,76)	Year 8 (n=73,72)
Z6P3 (Zoledronic Acid 6 Placebo 3)	-0.83	-1.06
Z9 (Zoledronic Acid 9)	-0.28	-0.14

Percentage Change of Total Hip Bone Mineral Density (BMD) at Year 7, 8 and 9 Compared to Year 0

Bone Mineral Density (BMD) measured by dual energy x-ray absorptiometry (DXA). DXA consists of two X-ray beams with different energy levels that are aimed at the patient's bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone. Percentage change from Year 0 = 100*(Year 9 - Year 0)/Year 0. (NCT00718861)
Timeframe: Year 0 (core baseline), Year 7, Year 8, Year 9

Intervention	percentage change of BMD (Least Squares Mean)
	Year 7 (n=83,75)	Year 8 (n=72,71)	Year 9 (n=67,68)
Z6P3 (Zoledronic Acid 6 Placebo 3)	3.73	3.65	3.68
Z9 (Zoledronic Acid 9)	4.81	5.35	4.64

Change in Bone Mineral Density (BMD) From Baseline to Month 36

Change in bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in lumbar spine (L1-L4). Change calculated by (Month 36 BMD-Baseline BMD)/Baseline BMD*100. (NCT00332709)
Timeframe: at 36 months as compared to baseline

Intervention	Percent (Mean)
Letrozole	-0.11
Letrozole + Zoledronic Acid	0.03

Change in Bone Mineral Density From Baseline to 12 Months

Intervention	g/cm^2 (Mean)
Letrozole	-0.04
Letrozole + Zoledronic Acid	0.02

Change in T-Score From Baseline to Month 12

BMD measured by DXA (dual energy x-ray absorptiometry) at lumbar spine, L1-L4. The T-Score is a comparison of a patient's BMD to that of a healthy 30 year of the same sex and ethnicity. The criteria of the World Health Organization are Normal is a T-Score of 1.0 or higher. Osteopenia is defined as between - 1.0 and -2.5. Osteoporosis is defined as -2.5 or lower, meaning a bone density that is two and half standard deviations below the mean of a 30 year old man/woman. (NCT00332709)
Timeframe: Baseline, Month 12

Intervention	T-Score (Mean)
Letrozole	-0.31
Letrozole + Zoledronic Acid	0.25

Change in T-score From Baseline to Month 36

Intervention	T-Score (Mean)
Letrozole	-0.90
Letrozole + Zoledronic Acid	0.46

Change in Z Score From Baseline to Month 36

Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA). The Z-Score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex and ethnicity. A Z-score of less than minus -1.5 raises concern of factors other than aging as contributing to osteoporosis. (NCT00332709)
Timeframe: Baseline, month 36

Intervention	Z-Score (Mean)
Letrozole	-0.31
Letrozole + Zoledronic Acid	0.25

Change in Z-Score From Baseline to Month 12

(DXA). The Z-Score is the number of standard deviations a patient's BMD differs from the average BMD of their age, sex and ethnicity. A Z-score of less than minus -1.5 raises concern of factors other than aging as contributing to osteoporosis (NCT00332709)
Timeframe: Baseline, Month 12

Intervention	Z-Score (Mean)
Letrozole	-0.26
Letrozole + Zoledronic Acid	0.37

Percent Change in Bone Mineral Density (BMD) From Baseline to Month 36

"Bone Mineral Density is measured by dual energy x-ray absorptiometry (DXA) scan.~ANCOVA model was used in the analysis where: Variable = Baseline, Center, Treatment BMD = (Month 36 BMD-Baseline BMD)/Baseline BMD*100." (NCT00332709)
Timeframe: Baseline, Month 36

Intervention	Percent Change in BMD (Mean)
Letrozole	-11.34
Letrozole + Zoledronic Acid	3.31

Number of Participants With Any Kind of Fractures, by Visit.

Number of participants with fractures of any type since the last visit (NCT00332709)
Timeframe: Baseline, Month 6, 12, 18, 24 , 30 and 36

Intervention	Participants (Number)
	Baseline	Month 6	Month 12	Month 18	Month 24	Month 30	Month 36
Letrozole	0	0	0	0	0	0	0
Letrozole + Zoledronic Acid	0	0	0	0	0	0	0

Change in Body Height From Baseline to Month 12

Body height was measured at Baseline and at the end of the study (Month 12) and the change in height calculated. (NCT00404820)
Timeframe: Baseline to end of study (Month 12)

Intervention	cm (Mean)
Zoledronic Acid 5 mg	-0.1
Alendronate 70 mg	0.0

Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12

The Qualeffo-41 QoL questionnaire was completed by the patient at Baseline and at Month 12. The questionnaire includes 41 questions covering 7 domains (pain, physical function and activities of daily living, physical function and jobs around the house, physical function and mobility, leisure and social activities, general health perception, mental function). Scores on each question range from 1 to 3, 4, or 5. The total score summed over all questions ranges from 41-205 points; the lower the score the higher the quality of life. A negative change score indicates improvement. (NCT00404820)
Timeframe: Baseline to end of study (Month 12)

Intervention	Units on a scale (Mean)
Zoledronic Acid 5 mg	-1.2
Alendronate 70 mg	-0.6

Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Intent-to-Treat Population

The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study. (NCT00404820)
Timeframe: Screening to end of study (Month 12)

Intervention	ng/ml (Mean)
Zoledronic Acid 5 mg	0.282
Alendronate 70 mg	0.270

Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Per Protocol Population

Intervention	ng/ml (Mean)
Zoledronic Acid 5 mg	0.293
Alendronate 70 mg	0.294

Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12

The level of bone activity as measured by P1NP over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study. (NCT00404820)
Timeframe: Screening to end of study (Month 12)

Intervention	ng/ml (Mean)
Zoledronic Acid 5 mg	28.2
Alendronate 70 mg	25.5

Number of Patients With a Clinical Fracture From Baseline to Month 12

A diagnosis of clinical fracture was based on physical examination findings, ie, swelling, tenderness, limited movement, pain. (NCT00404820)
Timeframe: Baseline to end of study (Month 12)

Intervention	Participants (Number)
Zoledronic Acid 5 mg	10
Alendronate 70 mg	4

Therapy Preference at End of Study (Month 12)

Patients were administered a questionnaire at the end of the study in which they were asked which type of therapy, weekly oral or yearly iv, they preferred. (NCT00404820)
Timeframe: Month 12

Intervention	Participants (Number)
	No data available	Yearly iv	Weekly oral
Alendronate 70 mg	16	82	93
Zoledronic Acid 5 mg	30	330	48

Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 52

BMD measurements of the lumbar spine (L1-L4) by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the Final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation. (NCT00439244)
Timeframe: Baseline through Week 52

Intervention	Percent change (Least Squares Mean)
Zoledronic Acid Plus Teriparatide	7.51
Zoledronic Acid	4.37
Placebo Zoledronic Acid Plus Teriparatide	7.05

Bone Resorption and Formation Biochemical Markers : Beta C-terminal Telopeptides of Type I Collagen (β-CTx)

Specialized tests for markers of bone formation such as β-CTx were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum β-CTx was determined by the central laboratory. (NCT00439244)
Timeframe: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52

Intervention	ng/mL (Mean)
	At Baseline (n= 126, 129, 121)	At Week 4 (n= 109, 110, 104)	At Week 8 (n= 106, 107, 98)	At Week 26 (n= 116, 119, 114)	At Week 39 (n= 110, 115, 110)	At Week 52 (n= 110, 113, 112)
Placebo Zoledronic Acid Plus Teriparatide	0.46	0.45	0.60	0.90	0.89	0.83
Zoledronic Acid	0.44	0.05	0.07	0.12	0.15	0.17
Zoledronic Acid Plus Teriparatide	0.45	0.05	0.09	0.43	0.57	0.64

Bone Resorption and Formation Biochemical Markers : N-terminal Propeptide of Type I Collagen (P1NP)

Specialized tests for markers of bone formation such as n-terminal propeptide of type I collagen (P1NP) were performed at Baseline, and Weeks 4, 8, 26, 39, and 52. The amount of serum P1NP was determined by the central laboratory. (NCT00439244)
Timeframe: At Baseline, Week 4, Week 8, Week 26, Week 39 and Week 52

Intervention	ng/mL (Mean)
	At Baseline (n= 126, 129, 121)	At Week 4 (n= 109, 110, 104)	At Week 8 (n= 106, 107, 98)	At Week 26 (n= 116, 119, 114)	At Week 39 (n= 110, 115, 110)	At Week 52 (n= 110, 113, 112)
Placebo Zoledronic Acid Plus Teriparatide	55.69	93.63	99.27	156.97	153.92	137.53
Zoledronic Acid	53.64	39.57	21.68	18.32	20.69	23.49
Zoledronic Acid Plus Teriparatide	52.72	61.74	39.91	65.26	97.00	112.87

Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Week 13 and Week 26

Intervention	Percent Change (Least Squares Mean)
	At Week 13 (n= 127, 131, 131)	At Week 26 (n= 128, 130, 132)
Placebo Zoledronic Acid Plus Teriparatide	2.88	4.45
Zoledronic Acid	2.97	3.87
Zoledronic Acid Plus Teriparatide	4.65	6.31

Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at Week 13, Week 26 and Week 52

BMD measurements of the total hip by Dual X-ray absorptiometry (DXA) were performed on all patients at screening, and Weeks 13, 26, and 52 (or early termination). Every attempt was made to obtain the BMD measurements at the scheduled visit. If this was not possible, a BMD measurement ± 7 days from the scheduled visit was obtained. For the final DXA at Week 52, the window was 10 - 15 days prior to the final study visit. BMD scans were acquired locally and all results sent to a central reader for evaluation. (NCT00439244)
Timeframe: Baseline through Week 13, Week 26 and Week 52

Intervention	Percent Change (Least Squares Mean)
	At Week 13 (n= 127, 133, 133)	At Week 26 (n= 128, 130, 133)	At Week 52 (n= 123, 129, 129)
Placebo Zoledronic Acid Plus Teriparatide	0.75	0.89	1.10
Zoledronic Acid	1.53	1.73	2.16
Zoledronic Acid Plus Teriparatide	2.54	2.31	2.33

Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months

(NCT00431444)
Timeframe: Baseline and 2 months

Intervention	U/L (Mean)
	Baseline (n= 50, 48)	At Month 2 (n= 51, 51)	Change from baseline to Month 2 (n= 47, 46)
Raloxifene	27.094	26.424	-1.085
Zoledronic Acid	30.104	20.855	-8.947

Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months

(NCT00431444)
Timeframe: Baseline and 4 months

Intervention	U/L (Mean)
	Baseline (n= 50, 48)	At Month 4 (n= 49, 47)	Change from baseline to Month 4 (n= 45, 42)
Raloxifene	27.094	25.111	-2.000
Zoledronic Acid	30.104	18.218	-11.442

Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months

(NCT00431444)
Timeframe: Baseline and 6 months

Intervention	U/L (Mean)
	Baseline (n= 50, 48)	At Month 6 (n= 51, 47)	Change from baseline to Month 6 (n= 47, 42)
Raloxifene	27.094	24.981	-2.250
Zoledronic Acid	30.104	19.237	-10.572

Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.)

The primary efficacy variable was the change from baseline in urine NTx (corrected by creatinine). The primary analysis time point was at 6 months of treatment. The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine. (NCT00431444)
Timeframe: Baseline and 6 months

Intervention	nM BCE/mM Cr (Mean)
	Baseline (n = 52, 53)	6 months (n = 49, 47)	Change from baseline to Month 6 (n= 48, 47)
Raloxifene	44.460	34.183	-8.362
Zoledronic Acid	49.054	23.676	-24.646

Change From Baseline in Urine NTx at 2 Months

The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine. (NCT00431444)
Timeframe: Baseline and 2 months

Intervention	nM BCE/mM Cr (Mean)
	Baseline (n= 52, 53)	At Month 2 (n= 54, 50)	Change from baseline to Month 2 (n= 52, 50)
Raloxifene	44.460	40.756	-4.000
Zoledronic Acid	49.054	17.774	-31.065

Change From Baseline in Urine NTx at 4 Months

The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine. (NCT00431444)
Timeframe: Baseline and 4 months

Intervention	nM BCE/mM Cr (Mean)
	Baseline (n= 52 , 53)	At Month 4 (n= 48, 46)	Change from baseline to Month 4 (n= 47, 46)
Raloxifene	44.460	38.143	-3.920
Zoledronic Acid	49.054	20.802	-27.832

Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire

"The study coordinator (nurse) was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: not at all, a little, somewhat, quite, or completely." (NCT00431444)
Timeframe: Immediately after infusion procedure

Intervention	Participants (Number)
	Not at all / A little / Somewhat	Quite	Completely	Missing
Raloxifene	0	3	35	15
Zoledronic Acid	0	4	29	21

Overall Patient Satisfaction Assessed by Satisfaction Questionnaire

"Patients were asked to complete the satisfaction questionnaire at baseline. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: not at all, a little, somewhat, quite, or completely." (NCT00431444)
Timeframe: Immediately after infusion procedure

Intervention	Participants (Number)
	Not at all	A little	Somewhat	Quite	Completely	Missing
Raloxifene	1	1	1	7	42	1
Zoledronic Acid	1	0	1	9	43	0

Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire

"The investigator was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: not at all, a little, somewhat, quite, or completely." (NCT00431444)
Timeframe: Immediately after infusion procedure

Intervention	Participants (Number)
	Not at all / A little	Somewhat	Quite	Completely	Missing
Raloxifene	0	1	3	11	38
Zoledronic Acid	0	3	2	16	33

Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens

"At the end-of-study visit, Month 6, patients were asked to complete a questionnaire to assess preference for the different treatment modalities (annual i.v. infusion vs. daily oral capsule). The possible answers to question were: once a year i.v. infusion, once daily pill, or both are equal." (NCT00431444)
Timeframe: At 6 month visit

Intervention	Participants (Number)
	Once a year intravenous infusion	Once daily pill	Both are equal	Missing
Raloxifene	46	4	3	0
Zoledronic Acid	47	3	3	1

Biochemical Marker of Bone Formation: Bone Serum Alkaline Phosphatase (BSAP), by Stratum

Biomarker: BSAP levels at Months 6, 12, 18 and 24 by stratum. (NCT00132808)
Timeframe: Months 6, 12, 18 and 24

Intervention	ng/mL (Mean)
	Stratum I - Month 6	Stratum I - Month 12	Stratum I - Month 18	Stratum I - Month 24	Stratum II - Month 6	Stratum II - Month 12	Stratum II - Month 18	Stratum II - Month 24
Placebo	13.982	14.127	14.149	14.353	13.394	13.650	13.222	13.902
Zoledronic Acid 1x5 mg	8.841	10.539	11.233	11.764	7.925	9.139	10.023	10.916
Zoledronic Acid 2x5 mg	8.718	9.945	8.365	9.799	8.219	9.678	8.357	9.730

Biochemical Marker of Bone Formation: Serum N-terminal Propeptide of Type 1 Collagen (P1NP), by Stratum

Biomarker: Serum P1NP levels at Months 6, 12, 18 and 24 by stratum. (NCT00132808)
Timeframe: Months 6, 12, 18 and 24

Intervention	ng/mL (Mean)
	Stratum I - Month 6	Stratum I - Month 12	Stratum I - Month 18	Stratum I - Month 24	Stratum II - Month 6	Stratum II - Month 12	Stratum II - Month 18	Stratum II - Month 24
Placebo	59.449	55.166	55.775	56.315	50.271	49.581	46.943	51.621
Zoledronic Acid 1x5 mg	20.752	30.500	35.561	38.743	19.423	26.363	29.569	34.418
Zoledronic Acid 2x5 mg	20.851	28.231	20.102	28.288	19.369	28.333	19.031	26.211

Biochemical Marker of Bone Resorption: Serum Beta C-telopeptides (b-CTx), by Stratum

Biomarker: Serum b-CTx levels at Months 6, 12, 18 and 24 by stratum. (NCT00132808)
Timeframe: Months 6, 12, 18 and 24

Intervention	ng/mL (Mean)
	Stratum I - Month 6	Stratum I - Month 12	Stratum I - Month 18	Stratum I - Month 24	Stratum II - Month 6	Stratum II - Month 12	Stratum II - Month 18	Stratum II - Month 24
Placebo	0.6439	0.6634	0.6444	0.6640	0.5802	0.5634	0.5742	0.6012
Zoledronic Acid 1x5 mg	0.2286	0.3111	0.3605	0.3777	0.1888	0.2484	0.2854	0.3254
Zoledronic Acid 2x5 mg	0.2217	0.2861	0.2187	0.2864	0.1918	0.2696	0.1986	0.2554

Percentage Change in Femoral Neck BMD at Month 24 Relative to Baseline, by Stratum.

The percentage change in femoral neck BMD at Month 24 relative to baseline was derived as 100 x (femoral neck BMD at 24 Month - femoral neck BMD at baseline) / (femoral neck BMD at baseline). (NCT00132808)
Timeframe: Baseline, Month 24

Intervention	Percentage change in BMD (Least Squares Mean)
	Stratum I (Women < 5 Years From Menopause)	Stratum II (Women >= 5 Years From Menopause)
Placebo	-1.55	-1.18
Zoledronic Acid 1x5 mg	2.01	1.46
Zoledronic Acid 2x5 mg	2.04	2.35

Percentage Change in Lumbar Spine Bone Mineral Density (BMD) at Month 24 Relative to Baseline, by Stratum

The percentage change in lumbar spine BMD at Month 24 relative to baseline was derived as 100 x (lumbar spine BMD at 24 Month - lumbar spine BMD at baseline) / (lumbar spine BMD at baseline). (NCT00132808)
Timeframe: Baseline, Month 24

Intervention	Percentage change in BMD (Least Squares Mean)
	Stratum I (Women < 5 Years From Menopause)	Stratum II (Women >= 5 Years From Menopause)
Placebo	-2.24	-0.65
Zoledronic Acid 1x5 mg	4.03	4.76
Zoledronic Acid 2x5 mg	4.62	5.60

Percentage Change in Total Hip BMD at Month 24 Relative to Baseline, by Stratum.

The percentage change in total hip BMD at Month 24 relative to baseline was derived as 100 x (total hip BMD at 24 Month - total hip BMD at baseline) / (total hip BMD at baseline). (NCT00132808)
Timeframe: Baseline, Month 24

Intervention	Percentage change in BMD (Least Squares Mean)
	Stratum I (Women < 5 Years From Menopause)	Stratum II (Women >= 5 Years From Menopause)
Placebo	-2.10	-1.04
Zoledronic Acid 1x5 mg	2.55	2.11
Zoledronic Acid 2x5 mg	2.66	3.04

Mean Change in Bone Mineral Density

"Change in bone mineral density of the femoral neck measured from baseline to 12 months after transplant utilizing Dual-energy X-ray absorptiometry (DEXA) scan. Comparison of difference between the standard of care group (receiving calcium and vitamin D)and the Zometa group. The measurement consists of baseline bone mineral density measurements with followup measurements at 12 months.~This will be analyzed as a continuous variable. Percent change in bone mineral density (BMD) will be calculated as (BMD change) x 100/BMD baseline." (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	percent (Mean)
Arm I (Standard of Care)	-0.0714
Arm II (Treatment With Zometa)	-0.0036

Mean Change in Follicle-Stimulating Hormone

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Follicle-stimulating hormone is a hormone produced by the anterior pituitary gland. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	IU/L (Mean)
Arm I (Standard of Care)	14.0
Arm II (Treatment With Zometa)	6.6

Mean Change in Luteinizing Hormone

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Luteinizing hormone is a hormone produced by the anterior pituitary gland. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	IU/L (Mean)
Arm I (Standard of Care)	18.8
Arm II (Treatment With Zometa)	12.8

Mean Change in Serum Bone Specific Alkaline Phosphate

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. The decrease in serum bone-specific alkaline phosphatase predicts bone mineral density response to hormone replacement therapy in early postmenopausal women. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	U/L (Mean)
Arm I (Standard of Care)	-3.0
Arm II (Treatment With Zometa)	-4.3

Mean Change in Serum Osteocalcin

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. As osteocalcin is produced by osteoblasts, it is often used as a marker for the bone formation process. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	ng/ml (Mean)
Arm I (Standard of Care)	-3.6
Arm II (Treatment With Zometa)	-11.3

Mean Change in Thyroid Function Test 4

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Individuals who have hyperthyroidism will have an elevated thyroxine (FT4). Low serum thyroxine can also indicate a pituitary problem. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	ng/dL (Mean)
Arm I (Standard of Care)	-0.6
Arm II (Treatment With Zometa)	-0.2

Mean Change in Total Testosterone

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Testosterone affects the brain, bone and muscle mass, fat distribution, the vascular system, energy levels, genital tissues, and sexual functioning. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	ng/dL (Mean)
Arm I (Standard of Care)	-65.4
Arm II (Treatment With Zometa)	-23.6

Mean Change in Ultrasensitive Estradiol

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. In women estradiol is responsible for growth of the breast and reproductive epithelia, maturation of long bones and development of the secondary sexual characteristics. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	pg/ml (Mean)
Arm I (Standard of Care)	-3.6
Arm II (Treatment With Zometa)	-6.3

Mean Change in Urinary N-terminal Telopeptide

Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. In bone physiology, the N-terminal telopeptide is a biomarker used to measure the rate of bone turnover. (NCT00321932)
Timeframe: From Time of Transplant to 12 Months Post-Transplant

Intervention	nM Bone Collagen Equivalents/mM creatini (Mean)
Arm I (Standard of Care)	-22.5
Arm II (Treatment With Zometa)	-103.0

Time to the First On-Study SRE (Non-inferiority)

Time to the first on-study skeletal-related event (SRE) analyzed for non-inferiority. Kaplan-Meier estimates of the median and its dispersion are reported. (NCT00321620)
Timeframe: Up to 40.5 months

Intervention	Days (Median)
Zoledronic Acid	521.0
Denosumab	629.0

Time to the First On-Study SRE (Superiority)

Time to the first on-study skeletal-related event (SRE), analyzed for superiority of denosumab. Kaplan-Meier estimates of the median and its dispersion are reported. (NCT00321620)
Timeframe: Up to 40.5 months

Intervention	Days (Median)
Zoledronic Acid	521.0
Denosumab	629.0

Time to the First-And-Subsequent On-Study SRE

"Time to the first-and-subsequent on-study skeletal-related event (SRE), analyzed for superiority of denosumab using multiple event analysis, the event must occur at least 21 days after the previous SRE.~This outcome measure utilizes multiple event times, was analyzed based on a proportional mean model, and is therefore more appropriately summarized by the cumulative mean number of events." (NCT00321620)
Timeframe: Up to 40.5 months

Intervention	Events (Number)
Zoledronic Acid	584
Denosumab	494

Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months

BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. (NCT00297830)
Timeframe: Baseline, 12 months

Intervention	percent change (Mean)
Active Zoledronic Acid and Placebo Alendronate	0.28
Placebo Zoledronic Acid and Active Alendronate	-0.57
Reference Group	-3.3

Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months

Intervention	percent change (Mean)
Active Zoledronic Acid and Placebo Alendronate	1.98
Placebo Zoledronic Acid and Active Alendronate	-0.45
Reference Group	-2.6

Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months

Intervention	percent change (Mean)
Active Zoledronic Acid and Placebo Alendronate	0.39
Placebo Zoledronic Acid and Active Alendronate	-0.21
Reference Group	-2.2

Percentage of Change in Bone Volume Fraction (BVF)

Average fractional content of bone expressed in percent (NCT01153425)
Timeframe: Change between baseline and 12 months

Intervention	Percentage of Change (Mean)
Teriparatide (Forteo)	1.0
Zoledronic Acid (Reclast)	0.6

Percentage of Change in Trabecular Surface-to-curve Ratio

Ratio of the volume densities of surface (S) and curve (C)-type voxels, S/C (NCT01153425)
Timeframe: Change between baseline and 12 months

Intervention	Percentage of Change (Mean)
Teriparatide (Forteo)	9.1
Zoledronic Acid (Reclast)	7.1

Percent Change in Lumbar Spine (L2-L4) BMD After 12 Months of Letrozole Therapy

Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = [(BMD at Visit - BMD at Baseline) / BMD at Baseline] * 100. (NCT00171314)
Timeframe: From Baseline - 12 months

Intervention	Percent Change (Mean)
Upfront Zoledronic Acid	2.680
Delayed Zoledronic Acid	-3.314

Percentage of Participants With Radiological (Vertebra) Fractures Which Were Not Present at Baseline But Were Present at Year 3

Radiological Fracture at 36 months which was not present at baseline = (new fracture/number participant analyzed)*100. Evaluation of radiological fractures were based on central lab X-ray data. A subject with multiple fractures at the same time or multiple fractures with the same grade is counted only once for that treatment. (NCT00171314)
Timeframe: Year 3

Intervention	Percentage of Participants (Number)
Upfront Zoledronic Acid	2.8
Delayed Zoledronic Acid	3.3

Percent Change in Lumbar Spine (L1-L4) BMD at Year 1, Year 2, Year 3, Year 4 and Year 5

Intervention	Percent Change (Mean)
	Year 1 (n=123, 156)	Year 2 (n=122, 142)	Year 3 (n=199, 133)	Year 4 (n=104, 122)	Year 5 (n=86, 102)
Delayed Zoledronic Acid	-3.532	-3.934	-4.292	-4.713	-4.692
Upfront Zoledronic Acid	2.330	3.994	4.523	5.051	5.476

Percent Change in Lumbar Spine (L2-L4) BMD at 2 Years, 3 Years, 4 Years and 5 Years

Intervention	Percent Change (Mean)
	Year 2 (n=122,142)	Year 3 (n=119,133)	Year 4 (n=104, 122)	Year 5 (n=86, 102)
Delayed Zoledronic Acid	-3.924	-4.297	-4.746	-4.572
Upfront Zoledronic Acid	4.136	4.777	5.462	6.013

Percent Change in Total Hip BMD at Year 1, Year 2, Year 3, Year 4 and Year 5

Intervention	Percent Change (Mean)
	Year 1 (n=173, 187)	Year 2 (n=169, 168)	Year 3 (n=163, 162)	Year 4 (n=145, 152)	Year 5 (n=119, 121)
Delayed Zoledronic Acid	-1.644	-2.628	-3.011	-3.074	-4.012
Upfront Zoledronic Acid	1.637	2.119	1.991	2.439	2.788

Time to Progression (TTP)

Time to progression is defined as the time from the date of enrollment to the date of first documented disease progression or death due to metastatic breast cancer. (NCT01129336)
Timeframe: up to 18 months

Intervention	Days (Median)
Patients Without Bone Metastases	190
Patients With Bone Metastases	297

Change From Baseline in Urine NTX by Month

NTX= N-telopeptide of type 1 collagen (nmol bce/mmol [nanomoles of bone collagen equivalents per millimole of creatinine]). Baseline was defined as the last predose measurement for patients who received any study drug and as the later of the screening visit or visit 2 value for patients who did not receive study drug. (NCT01129336)
Timeframe: Baseline, Month 2, Month 4

Intervention	nmol bce/mmol (Mean)
	Change from baseline at Month 2	Change from baseline at Month 4
Patients With Bone Metastases	-27.619	-23.476
Patients Without Bone Metastases	-5.25	-4.750

Number of Participants With Progression Free Survival (PFS)

Complete Response (CR): disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have exhibited a reduction in short axis to < 10 mm. Partial Response (PR): at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): at least 20% increase in sum of diameters of target lesions taking as reference the smallest sum on study accompanied by an absolute increase of at least 5 mm or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters. PFS is time from enrollment to date of first documented disease progression or death due to any cause. A participant is considered to be censored when data on time to event is missing due to a subject being lost to follow-up or non-occurrence of the outcome event before the completion of the trial. (NCT01129336)
Timeframe: up to 18 months

Intervention	Participants (Number)
	Event	Censor
Patients With Bone Metastases	19	10
Patients Without Bone Metastases	9	6

Percentage of Patients With Circulating Tumor Cell Levels of at Least 5 Per 7.5 mL of Peripheral Blood by Month

Circulating tumor cells (CTCs) have been associated with poor patient prognosis and outcomes in patients receiving treatment for MBC. CTCs have been evaluated as a potential biomarker for predicting treatment effects and overall survival. Baseline was defined as the last predose measurement for patients who received any study drug and as the later of the screening visit or Visit 2 value for patients who did not receive the study drug. Percentage was calculated as the number of patients with CTC ≥5/7.5 mL against the number of patients with nonmissing CTC values (represented as 'n' in the categories). (NCT01129336)
Timeframe: Baseline, Month 1, 2, 4, 6, 9 and 18

Intervention	Percentage of Participants (Number)
	Baseline (n=15,28)	Month 1 (n=8,0)	Month 2 (n=12,24)	Month 4 (n=8,20)	Month 6 (n=7,19)	Month 9 (n=2,14)	Month 18 (n=2,1)
Patients With Bone Metastases	57.1	NA	25.0	15.0	15.8	35.7	100.0
Patients Without Bone Metastases	26.7	12.5	8.3	0	0	0	0

Bone Resorption and Formation Biochemical Markers at Year 4.5: P1NP

The amount of serum n-terminal propeptide of type I collagen (P1NP) as determined by the central laboratory. (NCT00145327)
Timeframe: Year 4.5

Intervention	ng/mL (Mean)
Zoledronic Acid 6	18.842
Zoledronic Acid 3 Placebo 3	29.677
Placebo 3 Zoledronic Acid 3	17.256

Bone Resorption and Formation Biochemical Markers at Year 6: P1NP

The amount of serum P1NP as determined by the central laboratory (NCT00145327)
Timeframe: Year 6

Intervention	ng/mL (Mean)
Zoledronic Acid 6	27.356
Zoledronic Acid 3 Placebo 3	30.344
Placebo 3 Zoledronic Acid 3	25.926

Change in Serum Creatinine From Baseline to 9-11 Days Post Year 3 Infusion

Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after study drug infusion in Z6 patients compared to Z3P3 patients and in P3Z3 patients. (NCT00145327)
Timeframe: Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 3 infusion

Intervention	μmol/L (Mean)
Zoledronic Acid 6	1.96
Zoledronic Acid 3 Placebo 3	1.28
Placebo 3 Zoledronic Acid 3	0.21

Change in Serum Creatinine From Baseline to 9-11 Days Post Year 4 Infusion

Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 4 study drug infusion. (NCT00145327)
Timeframe: Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 4 infusion

Intervention	μmol/L (Mean)
Zoledronic Acid 6	3.35
Zoledronic Acid 3 Placebo 3	2.23
Placebo 3 Zoledronic Acid 3	2.47

Change in Serum Creatinine From Baseline to 9-11 Days Post Year 5 Infusion

Serum creatinine measurements performed by a central laboratory was used to evaluate acute changes in renal function 9-11 days after Year 5 study drug infusion. (NCT00145327)
Timeframe: Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to 9-11 days after the Year 5 infusion

Intervention	μmol/L (Mean)
Zoledronic Acid 6	3.46
Zoledronic Acid 3 Placebo 3	0.71
Placebo 3 Zoledronic Acid 3	1.04

Percentage Change in BMD of Distal Radius at Year 4.5 Relative to Year 3

The percentage change in BMD as measured by DXA at Year 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3). (NCT00145327)
Timeframe: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)

Intervention	Percentage change in BMD (Mean)
Zoledronic Acid 6	0.378
Zoledronic Acid 3 Placebo 3	-0.924
Placebo 3 Zoledronic Acid 3	0.386

Percentage Change in BMD of Distal Radius at Year 6 Relative to Year 3

The percentage change in BMD as measured by DXA at Year 6 relative to Year 3. It was derived as 100 * (BMD at Year 6 - BMD at Year 3)/(BMD at Year 3). (NCT00145327)
Timeframe: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72)

Intervention	Percentage change in BMD (Mean)
Zoledronic Acid 6	0.178
Zoledronic Acid 3 Placebo 3	-0.567
Placebo 3 Zoledronic Acid 3	0.299

Percentage Change in BMD of Lumbar Spine at Year 4.5 Relative to Year 3

Intervention	Percentage Change in BMD (Mean)
Zoledronic Acid 6	2.618
Zoledronic Acid 3 Placebo 3	1.196
Placebo 3 Zoledronic Acid 3	6.551

Percentage Change in BMD of Lumbar Spine at Year 6 Relative to Year 3

Intervention	Percentage change in BMD (Mean)
Zoledronic Acid 6	3.473
Zoledronic Acid 3 Placebo 3	1.606
Placebo 3 Zoledronic Acid 3	8.875

Percentage Change in Bone Mineral Density (BMD) of Femoral Neck at Year 6 Relative to Year 3

The primary efficacy variable was the percentage change in BMD of the femoral neck as measured by dual x-ray absorptiometry (DXA) at Year 6 relative to Year 3. It was derived as 100 *(femoral neck BMD at Year 6 - femoral neck BMD at Year 3) / (femoral neck BMD at Year 3). (NCT00145327)
Timeframe: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6 (Month 72; end of extension study)

Intervention	Percentage Change in BMD (Mean)
Zoledronic Acid 6	0.557
Zoledronic Acid 3 Placebo 3	-0.493
Placebo 3 Zoledronic Acid 3	3.337

Number of Participants With Incidence of Clinical Fracture

Clinical fracture excludes finger, toe, and facial bone fractures. Clinical vertebral fracture includes thoracic spine fracture and lumbar spine fracture. Non-vertebral fracture excludes clinical vertebral, finger, toe, and facial bone fractures. (NCT00145327)
Timeframe: Extension Baseline (Year 3; Month 36) to Year 6

Intervention	Participants (Number)
	Clinical fracture	Clinical vertebral fractures	Non-vertebral fractures	Hip fracture
Placebo 3 Zoledronic Acid 3	91	7	85	10
Zoledronic Acid 3 Placebo 3	51	4	47	8
Zoledronic Acid 6	51	7	45	7

Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 4.5 Relative to Year 3

The percentage change in BMD as measured by DXA at 4.5 relative to Year 3. It was derived as 100 * (BMD at Year 4.5 - BMD at Year 3)/(BMD at Year 3). (NCT00145327)
Timeframe: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 4.5 (Month 54)

Intervention	Percentage change in BMD (Mean)
	Femoral Neck	Total Hip	Trochanter
Placebo 3 Zoledronic Acid 3	2.697	3.228	4.611
Zoledronic Acid 3 Placebo 3	0.210	-0.070	0.041
Zoledronic Acid 6	0.738	0.479	0.813

Percentage Change in BMD of Femoral Neck, Total Hip and Trochanter at Year 6 Relative to Year 3

Intervention	Percentage change in BMD (Mean)
	Femoral Neck	Total Hip	Trochanter
Placebo 3 Zoledronic Acid 3	3.337	3.815	6.072
Zoledronic Acid 3 Placebo 3	-0.493	-1.151	-0.903
Zoledronic Acid 6	0.577	0.083	0.628

Percentage of Patients With New and New/Worsening Morphometric Vertebral Fractures

Lateral vertebral x-rays were performed at the final core study visit and at Year 6 and read by a central expert reader at a central imaging laboratory to assess for new or new/worsening morphometric vertebral fracture. The percentage of patients with new morphometric vertebral fractures (observed for the first time) and patients with either new or worsening morphometric vertebral fractures was calculated. (NCT00145327)
Timeframe: Year 3 (Extension Baseline; Month 36 prior to the first treatment of the extension study) and Year 6

Intervention	Percentage of patients (Number)
	New morphometric vertebral fracture	New/Worsening morphometric vertebral fracture
Placebo 3 Zoledronic Acid 3	2.9	3.1
Zoledronic Acid 3 Placebo 3	6.2	7.0
Zoledronic Acid 6	3.0	3.4

Qualitative Bone Biopsy Parameters

Unpaired transiliac crest bone biopsy was performed for histomorphometry, which was obtained after double tetracycline labeling. No data were collected for Patients who received Placebo for the first 3 years of the study (Placebo 3 Zoledronic Acid 3). (NCT00145327)
Timeframe: End of Study Visit at Year 6

Intervention	Participants (Number)
	Osteomalacia	Woven bone	Cortical trabeculation	Marrow fibrosis	Normal mineralization and normal osteoid	Contained double labeling
Zoledronic Acid 3 Placebo 3	0	0	0	0	2	2
Zoledronic Acid 6	0	0	0	0	3	3

The Number of Participants With Clinically Significant Laboratory Parameters

Evaluate the laboratory key profile such as Calcium, Creatinine and Urea. The number of patients with clinically significant calcium, creatinine and urea were reported. (NCT00145327)
Timeframe: Extension Baseline (Year 3; Month 36 prior to the first treatment of the extension study) to Year 6

Intervention	Participants (Number)
	Creatinine <18 μmol/L	Creatinine >221 μmol/L	Calcium <1.87 mmol/L	Calcium >2.89 mmol/L	Urea < 0.7 mmol/L	Urea >14.3 mmol/L
Placebo 3 Zoledronic Acid 3	1	2	1	4	0	17
Zoledronic Acid 3 Placebo 3	0	0	0	0	0	10
Zoledronic Acid 6	1	3	0	4	0	9

Number of Participants With New Morphometric Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.

Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader. A new morphometric vertebral fractures during the 12 month Extension Period was defined as a morphometric vertebral fracture present at Month 24 X-ray which was not present at the Extension Baseline (Baseline 2). (NCT01197300)
Timeframe: Month 24 (Visit 15/Final Extension Visit)

Intervention	Participants (Count of Participants)
Core Treatment Zoledronic Acid	1
Core Treatment: Placebo	1

Number of Participants With New Vertebral Fractures During the 12 Month Extension Period by Core Treatment Group.

New vertebral fractures are defined as fractures of Genant grade 1 or higher that occur at lumbar or thoracic spine from first extension dose infusion to the end of the study in a previously normal vertebra. (NCT01197300)
Timeframe: Month 24 (Visit 15/Final Extension Visit)

Intervention	Participants (Count of Participants)
Core Treatment Zoledronic Acid	1
Core Treatment: Placebo	1

Long-term Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids.

Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that zoledronic acid given long-term, over an additional 12 months from the Core study (CZOL446H2337), is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters. (NCT01197300)
Timeframe: Baseline 1 (Visit 1 of the Core Study) through Month 24 (Visit 15/Final Extension Visit)

Intervention	Participants (Count of Participants)
	On-treatment Adverse Events (AEs)	On-treatment Serious Adverse Events (SAEs)	On-treatment Deaths
Core Treatment Zoledronic Acid	7	3	0
Core Treatment: Placebo	12	0	0

Mean Change From Baseline (Core and Extension) in 2nd Metacarpal Cortical Width at Month 24 by Core Treatment Group.

Left postero-anterior (PA) hand/wrist X-ray were taken at the final visit of Core study and at Visit 15/EOS (Month 24) to assess bone age. The change in 2nd metacarpal cortical width at Month 24 relative to the respective Baseline was calculated. If a fracture of the left upper extremity precluded radiographic imaging, (or precluded this X-ray in the Core study) then the right hand was evaluated for this purpose. In this case, an image of the right hand was carried out at both Visit 8 and at Visit 15/EOS (Month 24). The information was used in the assessment of bone density. (NCT01197300)
Timeframe: Baseline 1 (Visit 1 of the Core Study) and Baseline 2 (Visit 9 of the Extension Study) through Month 24 (Visit 15/Final Extension Visit)

Intervention	millimeter (mm) (Least Squares Mean)
	2nd metacarpal cortical width change from BL1	2nd metacarpal cortical width change from BL2
Core Treatment Zoledronic Acid	-0.04	-0.09
Core Treatment: Placebo	-0.03	0.02

Mean Change From Baseline 1 (Visit 1 of the Core Study) in BSAP at Month 18 and 24 by Core Treatment Group.

Bone specific alkaline phosphatase (BSAP) was collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	nanogram per milliliter (ng/mL) (Least Squares Mean)
	BSAP Change at Month 18	BSAP Change at Month 24
Core Treatment Zoledronic Acid	-13.716	-9.675
Core Treatment: Placebo	3.975	-6.013

Mean Change From Baseline 1 (Visit 1 of the Core Study) in Lumbar Spine Bone Mineral Content (BMC) at Month 18 and 24 by Core Treatment Group.

Lumbar Spine Bone Mineral Content (BMC) was determined by the central imaging vendor at the final visit of Core study (Visit 8) or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension Study visit/EOS) of Extension study. The methods to be used to measure BMC were described in the respective DXA Manuals. Positive changes from Core baseline indicated an improvement in condition. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	gram (Least Squares Mean)
	Lumbar Spine BMC Change at Month 18	Lumbar Spine BMC Change at Month 24
Core Treatment Zoledronic Acid	12.293	15.845
Core Treatment: Placebo	9.933	14.666

Mean Change From Baseline 1 (Visit 1 of the Core Study) in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 18 and 24 by Core Treatment Group.

Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor at the final visit of Core study (Visit 8) or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension Study visit/EOS) of Extension study. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from Core baseline indicated an improvement in condition. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	Z-score (Least Squares Mean)
	Lumbar Spine BMD Z-score Change at Month 18	Lumbar Spine BMD Z-score Change at Month 24
Core Treatment Zoledronic Acid	-40.648	-46.161
Core Treatment: Placebo	-44.348	-67.913

Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum NTX at Month 18 and 24 by Core Treatment Group.

Serum Cross linked N-telopeptide (NTX) was collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	nmol BCE/L (Least Squares Mean)
	Serum NTX Change at Month 18	Serum NTX Change at Month 24
Core Treatment Zoledronic Acid	-17.577	-17.450
Core Treatment: Placebo	-12.916	-14.891

Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum P1NP at Month 18 and 24 by Core Treatment Group.

Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	nanogram per milliliter (ng/mL) (Least Squares Mean)
	Serum P1NP Change at Month 18	Serum P1NP Change at Month 24
Core Treatment Zoledronic Acid	-169.837	-228.068
Core Treatment: Placebo	-22.157	-95.631

Mean Change From Baseline 1 (Visit 1 of the Core Study) in Serum TRAP-5b at Month 18 and 24 by Core Treatment Group.

Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) were collected at the final visit Core study at Visit 8, or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension study Visit/EOS) of Extension study according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy. Decrease or negative changes from Core baseline indicated a pharmacological response to therapy. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	U/L (Least Squares Mean)
	Serum TRAP-5b Change at Month 18	Serum TRAP-5b Change at Month 24
Core Treatment Zoledronic Acid	-2.661	-2.670
Core Treatment: Placebo	-1.179	-2.260

Mean Change From Baseline 1 (Visit 1 of the Core Study) in Total Body BMC at Month 18 and 24 by Core Treatment Group.

Total body BMC were determined by the central imaging vendor at the final visit of Core study (Visit 8) or at 1st infusion visit (Visit 9), and thereafter at Visit 12 (Month 18) and Visit 15 (Month 24) (final Extension Study visit/EOS) of Extension study. The methods to be used to measure BMC were described in the respective DXA Manuals. Positive changes from Core baseline indicated an improvement in condition. (NCT01197300)
Timeframe: Month 18 (Visit 12 of the Extension Study), Month 24 (Visit 15/Final Extension Visit)

Intervention	gram (Least Squares Mean)
	Total body BMC Change at Month 18	Total body BMC Change at Month 24
Core Treatment Zoledronic Acid	387.721	496.997
Core Treatment: Placebo	266.592	431.323

Percentage of Patients With Reduction in Pain From Baseline 1 (Visit 1 of the Core Study) at Month 15, 18, 21 and 24 by Core Treatment Group.

Pain was evaluated at each visit (at office and telephone visit) at the final visit of the Core study and first visit of the Extension study (Visit 9), Visits 11 (Month 15), 12 (Month 18), 14 (Month 21) and 15 (Month 24) using the Faces Pain Scale-Revised (FPS-R). Children were selecting the face that best fits their pain. The pain score ranged from 0 (No Pain) to 10 (Very Much Pain). The reduction in pain from Core baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline. If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'. (NCT01197300)
Timeframe: Month 15, Month 18, Month 21, Month 24

Intervention	Percentage of Patients (Number)
	Reduction in Pain at Month 15	Reduction in Pain at Month 18	Reduction in Pain at Month 21	Reduction in Pain at Month 24
Core Treatment Zoledronic Acid	55.6	30.0	30.0	30.0
Core Treatment: Placebo	46.2	50.0	50.0	38.5

Non-traumatic Incidental Fractures (Vertebral and Nonvertebral [Identified by X-ray, CT, MRI, VFA Imaging] Per Person-year)

Number of fractures divided by number of person-years. Effectiveness of fracture reduction will be demonstrated by total non-traumatic incidental fractures (vertebral and nonvertebral [identified by x-ray, CT, MRI, VFA imaging) except those viewed as severe trauma (fall from a height higher than a stool or chair or severe trauma other than a fall), cancer-related or fractures of the toes, finger or facial bones. (NCT02589600)
Timeframe: 3 years

Intervention	Fractures per person-year (Number)
Active Medication Group	1.06093
Placebo Group	1.01563

Baseline-Adjusted Means of Osteocalcin

Osteocalcin was evaluated to examine the inhibitory effect of single dose zoledronic acid on HAART associated changes in markers of bone turnover. Osteocalcin is released from bone during resorption and higher levels in the circulatory system indicate increased bone turnover. HIV-infected individuals are expected to have increased bone resorption. The baseline-adjusted osteocalcin mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at the Week 144 clinic visit. Baseline-adjusted means of osteocalcin at week 144 are presented. (NCT01228318)
Timeframe: Baseline, Week 144

Intervention	ng/ml (Least Squares Mean)
Zoledronic Acid	9.176
Placebo	13.597

Percentage of Participants With Virological Suppression by Week 144

The percentage of participants achieving viral load suppression by study week 144. Virologic suppression was defined as HIV RNA polymerase chain reaction (PCR) (viral loads) less than 50 copies per mL. (NCT01228318)
Timeframe: Week 144

Intervention	percentage of participants (Number)
Zoledronic Acid	91
Placebo	100

Baseline-Adjusted Means for C-terminal Telopeptide of Collagen (CTx) Levels

Serum C-terminal telopeptide of collagen (CTx) levels through week 144 were examined by evaluating the baseline-adjusted means. The baseline-adjusted CTx mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at each scheduled clinical visit. The expected outcome is that HIV-infected individuals will display increased indices of bone resorption (CTx) as a result of diminished bone mineral density (BMD). Lower CTx values indicate that better maintenance of bone mineral density. (NCT01228318)
Timeframe: Baseline, Week 12 through Week 144

Intervention	ng/ml (Least Squares Mean)
	Week 12	Week 24	Week 48	Week 72	Week 96	Week 120	Week 144
Placebo	0.297	0.331	0.264	0.242	0.321	0.201	0.200
Zoledronic Acid	0.092	0.122	0.122	0.138	0.126	0.137	0.148

Baseline-Adjusted Means of Dual-energy X-ray Absorptiometry (DXA)

Development of osteoporosis was assessed by examining bone mineral density (BMD) by DXA scan. Baseline-adjusted means of DXA scan Z-scores are presented for the lumbar spine (L1-L4), left hip, and femur neck. The baseline-adjusted BMD mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at the Week 144 clinic visit. Bone density Z-scores tell how close to the average that a person is (adjusted for age, race, and gender). A Z-score of 0 means the value matches that of the average person. Z-score values below 0 indicate lower than average bone density while values above 0 indicate higher bone density than the average person. (NCT01228318)
Timeframe: Baseline, Week 144

Intervention	Z score (Least Squares Mean)
	Lumbar Spine	Hip	Femoral Neck
Placebo	-0.836	-1.092	-0.817
Zoledronic Acid	-0.177	-0.860	-0.665

CD4 T Cell Count

Immunologic response measured by CD4 T cell count by treatment arm and weeks on study. (NCT01228318)
Timeframe: Baseline, Week 144

Intervention	cells/uL (Mean)
	Baseline	Week 144
Placebo	155	439
Zoledronic Acid	102	347

Bone Metastases-free Survival (BMFS)

BMFS was defined as the time interval from randomization to first occurrence of bone metastasis or death from any cause, whichever comes first. Participants last known to be alive, who did not experience bone metastasis, were censored at their last assessment (i.e., bone scan) date or at the last contact date, whichever comes first. (NCT00556374)
Timeframe: From randomization until end of main study, maximum time on main study was 152 months

Intervention	Days (Median)
Placebo	NA
Denosumab	NA

Disease-free Survival (DFS)

DFS was defined as the time interval from the randomization date to the date of first evidence of local or distant metastases, contra-lateral breast cancer, secondary carcinoma, or death from any cause (whichever occurred first). Participants last known to be alive, who did not experience recurrence of disease, were censored at their last contact date or at the data cut-off date whichever came first. (NCT00556374)
Timeframe: From randomization until the DFS data cut-off date of 15 September 2015; maximum time on main study at the cut-off was 102 months

Intervention	Days (Median)
Placebo	NA
Denosumab	NA

Number of Participants With New or Worsening Vertebral Fractures

"Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height.~A new vertebral fracture was defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays. Worsening of pre-existing fractures was defined as an increase in fracture severity of at least 1 grade on the semiquantitative scale." (NCT00556374)
Timeframe: 36 months

Intervention	Participants (Count of Participants)
Placebo	55
Denosumab	31

Number of Participants With New Vertebral Fractures

Intervention	Participants (Count of Participants)
Placebo	49
Denosumab	27

Overall Survival (OS)

OS was defined as the time from randomization to death from any cause. (NCT00556374)
Timeframe: Randomization until end of main study, maximum duration of main study was 152 months

Intervention	Days (Median)
Placebo	NA
Denosumab	NA

Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites

Bone mineral density was assessed by dual x-ray absorptiometry. (NCT00556374)
Timeframe: Baseline and Month 36

Intervention	Percent Change in BMD (Least Squares Mean)
Placebo	-3.10
Denosumab	3.41

Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites

Bone mineral density was assessed by dual x-ray absorptiometry. (NCT00556374)
Timeframe: Baseline and Month 36

Intervention	Percent Change in BMD (Least Squares Mean)
Placebo	-3.32
Denosumab	4.60

Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites

Bone mineral density was assessed by dual x-ray absorptiometry. (NCT00556374)
Timeframe: Baseline and Month 36

Intervention	Percent Change in BMD (Least Squares Mean)
Placebo	-2.75
Denosumab	7.27

Time to First Clinical Fracture

The time to first on-study clinical fracture was defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier. (NCT00556374)
Timeframe: From randomization until the primary analysis cut-off date of 26 March 2014; maximum time on main study at the cut-off was 87 months

Intervention	Days (Median)
Placebo	NA
Denosumab	NA

Bone Mineral Density (BMD) of the Total Hip and Spine

BMD is the bone mineral density of the lumbar spine and total hip measured using dual-energy xray absorptiometry (DXA) scan (NCT00558012)
Timeframe: Baseline, 12 months, 24 month

Intervention	Percent change (Mean)
	Spine BMD at 24 months	Spine BMD at 12 months	Total Hip BMD at 24 months	Total Hip BMD at 12 months
Active Medication Group	4.5	3.0	2.6	2.8
Placebo	0.7	1.1	-1.5	-0.5

Clinical Toxicity of ZA

Tolerability and side effects of ZA, measured by the number of participants experiencing adverse events. (NCT00213980)
Timeframe: Up to 1 year

Intervention	Participants (Count of Participants)
Zoledronic Acid (ZA)	36
Observation	23

Overall Survival

Number of participants who survived from the start of treatment through off treatment, up to 10 years. (NCT00213980)
Timeframe: Up to 10 years

Intervention	Participants (Count of Participants)
Zoledronic Acid (ZA)	24
Observation	22

Change in Bone Mineral Density (BMD) From Baseline to 1 Year

To determine whether zoledronate 4 mg IV every 12 weeks x 4 doses is associated with increases in bone mineral density at the lumbar spine and femoral head, calculated from baseline and 1 year data. Participants who missed one or more DXA were not evaluated. (NCT00213980)
Timeframe: Up to 1 year

Intervention	grams per cubic centimeter (Mean)
	Lumbar Spine L1-L4 (L1-L4)	Femoral neck (FN)	Total femur (TF)	Trochanter (T)	Calcaneal (OC)
Observation	0.007	0.005	0.004	0.005	0.001
Zoledronic Acid (ZA)	0.048	0.014	0.019	0.023	0.010

Tolerability at One Year of Ovarian Function Suppression (OFS) Using Leuprolide and Letrozole.

The tolerability at one year of ovarian function suppression (OFS) using leuprolide and letrozole in this patient population. Specifically, the number of patients who discontinued treatment prior to one year due to toxicity. (NCT00903162)
Timeframe: 1 year

Intervention	participants (Number)
Letrozole-Leuprolide	4

Number of Participants With Femoral Head Collapse Within 24 Months

(NCT00939900)
Timeframe: Measurements were done at 6, 12, 24 months

Intervention	participants (Number)
Aclasta	29
Control	22

Change in Bone Scans

Change in bone scans using per cent change in SUVmax. (NCT01205646)
Timeframe: Four weeks after initiating zoledronate therapy

Intervention	percentage of change of SUVmax (Median)
Zometa & PET Scans	-10.08

PET Response Rate in Metastatic Prostate Cancer Patients Treated With Zoledronate Therapy.

"PET response rate was pre-defined in Section 5.0 of the protocol based on the magnitude of change in the mean standardized uptake value (SUVmean), which is measured at each PET scan. Specifically, a decline in SUVmean of at least 15% pre/post Zometa was taken as evidence of a PET response. Per the protocol, Scan 2 was used as the pre-Zometa measure of SUVmean, and Scan 3 (1-2 weeks later) was used as the post-Zometa measure of SUVmean." (NCT01205646)
Timeframe: Within 3 weeks

Intervention	Proportion of participants with response (Number)
Zometa & PET Scans	.091

The Change in PSA After Zoledronate Therapy

The change in PSA after zoledronate therapy using per cent change. (NCT01205646)
Timeframe: Four weeks after initiating Zoledronate therapy

Intervention	percentage of change in PSA (Median)
Zometa & PET Scans	38.99

Changes in Bone Turnover Markers

Changes in bone turnover markers using per cent change of BSAP and NTx (NCT01205646)
Timeframe: Four weeks after initiating zoledronte therapy

Intervention	percentage of change in bio-marker (Median)
	BSAP	NTx
Zometa & PET Scans	-1.66	-68.18

Number of Participants With At Least One or More Treatment-Emergent Adverse Events (TEAEs)

Adverse event was the appearance or worsening of any undesirable sign, symptom, or medical condition that occurred after starting the study drug even if the event was not considered to be related to study drug. TEAEs were defined as AEs that were absent prior to, but occurred after the i.v. infusion of study drug. TEAEs also included those that were present prior to the i.v. study drug infusion (i.e., as part of the extended observation period) but occurred at an increased severity after the i.v. infusion of study drug. (NCT00740129)
Timeframe: 6 months

Intervention	Participants (Count of Participants)
Zoledronic Acid 5 mg	1

Percentage of Participants With Serum Alkaline Phosphatase Within the Normal Range at Month 6 Last Observation Carried Forward (LOCF)

Normalization of serum alkaline phosphatase (SAP) occurred if the SAP measurement fell within the normal ranges. The lower and upper limits of normal ranges were 31 and 110 Units/Liter (U/L) for participants with age ≤ 58 years old and 35 and 115 U/L for participants with age > 58 years old, respectively. Last observation carried forward (LOCF) was defined as the last post-baseline SAP value prior to month 6 for a participant who did not have an SAP value at month 6. (NCT00740129)
Timeframe: Month 6

Intervention	Percentage of Participants (Number)
Zoledronic Acid 5 mg	83.3

Percentage Change From Baseline in Serum Alkaline Phosphatase (SAP) Levels

The percentage change in SAP at Months 3 and 6 relative to baseline were measured. (NCT00740129)
Timeframe: Baseline, Months 3 and 6

Intervention	percentage change (Mean)
	Percentage Change From Baseline in SAP Level at Month 3	Percentage Change From Baseline in SAP Level at Month 6
Zoledronic Acid 5 mg	-53.12	-49.51

Percentage of Participants With SAP Within the Normal Range

Normalization of SAP occurred if the SAP measurement fell within the normal ranges. The lower and upper limits of normal ranges were 31 and 110 Units/Liter (U/L) for participants with age ≤ 58 years old and 35 and 115 U/L for participants with age > 58 years old, respectively. (NCT00740129)
Timeframe: Months 3 and 6

Intervention	percentage of participants (Number)
	Month 3	Month 6
Zoledronic Acid 5 mg	100.0	83.3

Change in Bone Density (Grams/cm^2) at the Total Hip at 6 and 12 Months

Change in bone density (grams/cm^2) at the total hip at 6 and 12 months. 12 month reported based on usual interval for bone density follow-up in clinical practice. (NCT00361595)
Timeframe: 6 months and 12 months

Intervention	grams/cm^2 (Mean)
Open Label	2.4

Change in Lumbar Spine BMD (Bone Mineral Density) in g/cm^2 From Baseline to Month 12 Relative to Baseline as Measured by DXA (Dual-energy X-ray Absorptiometry)

(NCT00361595)
Timeframe: Baseline and 12 months

Intervention	grams/cm^2 (Mean)
Open Label	2.2

Change in Serum C-telopeptide Type 1 Collagen (CTX) (at Day 10 and Months 2, 6, 9 and 12)

Change in serum c-telopeptide type 1 collagen (CTX) (at day 10 and months 2, 6, 9 and 12. 12 month values reported based on 12 month duraton of zolendronic acid effect. (NCT00361595)
Timeframe: 12 months

Intervention	ng/ml (Mean)
Open Label	-49.1

Change in Serum N-propeptide Type 1 Collagen (P1NP) (at Day 10 and Months 2, 6, 9 and 12)

Change in serum n-propeptide type 1 collagen (P1NP) (at day 10 and months 2, 6, 9 and 12. 12 month values reported based on 12 month duraton of zolendronic acid effect. (NCT00361595)
Timeframe: 12 months

Intervention	mcg/ml (Mean)
Open Label	-66.2

Skeletal-related Event(SRE)-Free Survival

Time from randomization until the first detected SRE. Patients who were still SRE-free at 3 years were censored. (NCT00242567)
Timeframe: 36 months

Intervention	Days (Median)
Early Group	NA
Delayed Group	NA

Time to Occurrence of Skeletal Related Event or Death

Time from randomization to the first detected skeletal related event or death. This endpoint is the same as the primary endpoint with the modification that deaths are considered events. (NCT00242567)
Timeframe: 18 Months

Intervention	Days (Median)
Early Group	NA
Delayed Group	NA

Time to Occurrence of Skeletal Related Event or Death

Intervention	Days (Median)
Early Group	NA
Delayed Group	NA

Overall Survival at 18 Months and 3 Years

Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause. (NCT00242567)
Timeframe: month 18, year 3

Intervention	participants (Number)
	Patients with event (s) - 18 months	Patients without event - 18 months	Patients with event (s) - 36 months	Patients without event - 36 months
Delayed Group	21	242	44	219
Early Group	31	228	49	210

Skeletal-related Event-free Survival in Men With Bone Metastases From Prostate Cancer

Skeletal-related event free survival is the time from randomization until the first detected Skeletal Related Event (SRE). Patients who were still SRE-free at 18 months were censored. (NCT00242567)
Timeframe: 18 months

Intervention	participants (Number)
	Patients with event (s)	Patients without event (censored)
Delayed Group	49	214
Early Group	58	201

12-month Progression-free Survival (PFS)

PFS at 12 months is a dichotomized outcome indicating whether or not a participant was progression free (and alive) at 12 months from the date of randomization. (NCT00432458)
Timeframe: 12 months

Intervention	participants (Number)
Arm I: Thal/ZLD	30
Arm II: ZLD	18

Duration of Response (Complete Response, Partial Response, and Very Good Partial Response)

Duration of response (DOR) is defined as the time from first documentation of response (CR, VGPR or PR) to disease progression. The median DOR with 95% CI was estimated using the Kaplan Meier method (NCT00432458)
Timeframe: time from start of response to progression (up to 5 years)

Intervention	years (Median)
Arm I: Thal/ZLD	3.3

Number of Participants With a Confirmed Response (Complete Response [CR], Very Good Partial Response [VGPR] or Partial Response [PR]) on Two Consecutive Evaluations at Least 2 Weeks Apart in the First 12 Months of Treatment

"Response is defined as follows:~CR: Complete disappearance of M-protein from serum & urine on immunofixation, <5% plasma cells in bone marrow (BM)~VGPR: >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM~PR: >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels" (NCT00432458)
Timeframe: 12 months

Intervention	participants (Number)
Arm I: Thal/ZLD	13
Arm II: ZLD	0

Number of Participants With Severe (Grade 3, 4 or 5) Adverse Events

"Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 2.~Description of Grades:~Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death" (NCT00432458)
Timeframe: During treatment (up to 5 years)

Intervention	participants (Number)
Arm I: Thal/ZLD	17
Arm II: ZLD	13

Time to Disease Progression (TTP)

Time to disease progression (TTP) was defined as the time from randomization to the earliest documentation of disease progression. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method, a two-sided (stratified) log-rank test was calculated. (NCT00432458)
Timeframe: randomization to progression (up to 5 years)

Intervention	years (Median)
Arm I: Thal/ZLD	2.4
Arm II: ZLD	1.2

Time to Treatment Failure

Time to treatment failure (TTF) was defined as the time from randomization to the date at which the patient was removed from (protocol) treatment due to disease progression, unacceptable toxicity, participant refusal or death. The median TTF with 95% CI was estimated using the Kaplan Meier method (NCT00432458)
Timeframe: time from randomization to treatment failure (up to 5 years)

Intervention	months (Median)
Arm I: Thal/ZLD	16.5
Arm II: ZLD	11.1

Progression-Free Survival

Progression-free survival is defined as the time from randomization to the date of the first documented progression or recurrence of disease or death from any cause. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months. (NCT00172042)
Timeframe: Up to 24 months

Intervention	Months (Median)
Zoledronic Acid	9.0
Control	11.3

Kaplan-Meier Estimate of the Time to Occurrence of Bone Metastases

Time to occurrence of bone metastases was defined as the time from randomization to the date of the first documented bone metastases which could be asymptomatic or symptomatic at the time of detection. Bone scans were scheduled at screening and at 6-monthly intervals after study entry, or when symptoms suggested the presence of bone metastases. Positive bone scans required confirmation by x-ray, magnetic resonance imaging (MRI), or computed tomography (CT). (NCT00172042)
Timeframe: Months 6, 12, 18, and 24

Intervention	Percentage of participants (Number)
	6 months	12 months	18 months	24 months
Control	1.9	9.0	12.6	13.7
Zoledronic Acid	2.7	4.2	11.1	12.4

Kaplan-Meier Estimates for Overall Survival

(NCT00172042)
Timeframe: Months 6, 12, 18, and 24

Intervention	Percentage of participants (Number)
	6 months	12 months	18 months	24 months
Control	93.6	81.8	71.0	63.6
Zoledronic Acid	92.8	81.8	72.4	59.5

Kaplan-Meier Estimates for Progression-free Survival

Intervention	Percentage of participants (Number)
	6 months	12 months	18 months	24 months
Control	67.9	48.8	40.6	36.0
Zoledronic Acid	63.0	44.4	30.7	25.7

Kaplan-Meier Estimates of the Time to the First Skeletal Related Event (SRE)

Time to the first skeletal related event defined as the time from randomization to the date of occurrence of the first SRE. Skeletal Related Events were defined as radiation therapy or surgery to bone, spinal cord compression event or a pathologic bone fracture event (NCT00172042)
Timeframe: Months 6,12, 18, and 24

Intervention	Percentage of participants (Number)
	6 month	12 month	18 month	24 month
Control	0.0	1.8	1.8	1.8
Zoledronic Acid	1.0	2.7	2.7	2.7

Percentage of Participants With Bone Metastases at 6, 12, 18, and 24 Months

Percentage of participants developing at least 1 bone metastasis, whether or not symptomatic. Bone scans were scheduled at screening and at 6-monthly intervals after study entry, or when symptoms suggested the presence of bone metastases. Positive bone scans required confirmation by x-ray, magnetic resonance imaging (MRI), or computed tomography (CT). (NCT00172042)
Timeframe: Months 6, 12, 18 and 24

Intervention	Percentage of participants (Number)
	6 months	12 months	18 months	24 months
Control	4.3	7.1	8.1	9.0
Zoledronic Acid	2.2	4.0	6.2	6.6

Percentage of Participants With Progression-Free Survival Events

Percentage of Participants with the Progression-free survival events: disease progression and death. Time to disease progression (TTP) was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines with evaluations every 3 months. (NCT00172042)
Timeframe: Up to 24 months

Intervention	Percentage of participants (Number)
	Disease Progression	Death
Control	55.5	5.7
Zoledronic Acid	60.2	8.4

Percentage of Participants With Skeletal Related Events (SREs) at 12 and 24 Months From Study Entry

Skeletal Related Events were defined as radiation therapy or surgery to bone, spinal cord compression event or a pathologic bone fracture event. (NCT00172042)
Timeframe: Months 12 and 24

Intervention	Percentage of participants (Number)
	12 months	24 months
Control	1.4	1.4
Zoledronic Acid	2.2	2.2

Days of Progression Free Survival

"Progression-free survival was defined as time from date of randomization to death from any cause or one of the following events:~progression to stage II or III according to Salmon & Durie classification~skeletal related events (pathologic fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or hypercalcemia)~unequivocal progression of osteolytic lesions (at least a 20% increase in the largest diameter of one existing osteolytic lesion which is measured in at least one dimension as 20 mm with conventional techniques), determined radiologically." (NCT00171925)
Timeframe: 48 months

Intervention	Days (Mean)
Zoledronic Acid (ZOL446)	1078.1
Control	992.80

Number of Patients With Progression by Individual Criteria

Number of patients with progression by individual criteria consisting of Progression of disease overall, Skeletal-related events (including pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or Hypercalcemia), Progression to stage II or III according to Salmon & Durie classification, and unequivocal progression of osteolytic lesion. Patients are counted separately for every type of progression, but only once for Overall Progression. (NCT00171925)
Timeframe: 48 months

Intervention	Participants (Number)
	Progression of disease overall	Skeletal-related events	Progression to stage II or III	Unequivocal progression of osteolytic lesion
Control	26	4	24	10
Zoledronic Acid (ZOL446)	19	0	17	3

The Number of Participants With the Development of Skeletal Complications

"Pathologic fracture: bone fractures that occur spontaneously or from trivial trauma. New vertebral compression fracture defined as a decrease in vertebral height of 25% from baseline~Spinal cord compression: the impingement of tumor on the spinal cord confirmed by radiography~Bone Radiotherapy: Bone irradiation to palliate painful lesions, treat or prevent pathologic fractures or spinal cord compression~Surgery on bone: surgical procedures performed to set, stabilize or prevent pathologic fractures or areas of spinal cord compression~Hypercalcemia: Corrected serum calcium ≥ 12.0 mg/dl" (NCT00171925)
Timeframe: 48 months

Intervention	Participants (Number)
	Skeletal events overall	Pathological fracture	Initiation of radiotherapy or surgery on bone	Spinal cord compression	Hypercalcemia
Control	4	1	1	2	0
Zoledronic Acid (ZOL446)	0	0	0	0	0

Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 12 Months of Therapy.

Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by energy x-ray absorptiometry (DXA). (NCT00171340)
Timeframe: Baseline, 12 months

Intervention	Percentage change in BMD (Mean)
Zoledronic Acid 4 mg Upfront	2.208
Zoledronic Acid 4 mg Delayed	-3.617

Percentage of Participants With Clinical Fractures at 3 Years of Therapy Which Were Not Present at Baseline

At 3 years of therapy the percentage of participants with fractures as detected by X-ray and/ or bone scan. (NCT00171340)
Timeframe: Baseline,3 years

Intervention	Percentage of Participants (Number)
Zoledronic Acid 4 mg Upfront	0.6
Zoledronic Acid 4 mg Delayed	1.5

Percentage Change in Bone Mineral Density (BMD) of the Lumbar Spine (L2-L4) at 2, 3, 4 and 5 Years of Therapy.

Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA) (NCT00171340)
Timeframe: Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.

Intervention	Percentage change in BMD (Mean)
	At 2 years (n=339,343)	At 3 years (n=313,311)	At 4 years (n=290,294)	At 5 years (n=264,264)
Zolendronic Acid 4 mg Delayed	-4.601	-4.871	-5.154	-5.414
Zolendronic Acid 4 mg Upfront	3.463	3.730	3.782	4.308

Percentage Change in Bone Mineral Density (BMD) of the Total Hip at 12 Months, 2 Years, 3 Years, 4 Years and 5 Years After Therapy.

Bone Mineral Density (g/cm^2) of the Lumbar Spine (L2-L4) as measured by dual energy x-ray absorptiometry (DXA) (NCT00171340)
Timeframe: Baseline, 12 months. Baseline, 2 years. Baseline, 3 years. Baseline, 4 years. Baseline, 5 years.

Intervention	Percentage change in BMD (Mean)
	At 12 months (n=419,434)	At 2 years (n=394,393)	At 3 years (n=376,365)	At 4 years (n=336,349)	At 5 years (n=306,314)
Zolendronic Acid 4 mg Delayed	-2.239	-2.990	-3.302	-3.922	-4.162
Zolendronic Acid 4 mg Upfront	1.222	1.649	1.754	1.716	1.615

Percentage Change in Bone Mineral Density (BMD)of the Lumbar Spine (L1-L4) Over 5 Years of Therapy.

Bone Mineral Density (g/cm^2) of the Lumbar Spine (L1-L4)as measured by dual energy x-ray absorptiometry (DXA) (NCT00171340)
Timeframe: Baseline, 5 years.

Intervention	Percentage change in BMD (Mean)
	At 12 months (n=360,369)	At 2 years (n=339,343)	At 3 years (n=313,311)	At 4 years (n=290,294)	At 5 years (n=264,264)
Zolendronic Acid 4 mg Delayed	-3603	-4.521	-4.869	-5.148	-5.427
Zolendronic Acid 4 mg Upfront	2.128	3.300	3.521	3.529	3.898

The Primary Objective of This Study is to Evaluate the Feasibility of Administering Intravenous Zoledronic Acid, Oral Pravastatin and Oral Lonafarnib, to Patients With Progeria for a Minimum of 4 Weeks

Feasibility was assessed by determining the number of participants with adverse events occurring over the course of the 4 week study. (NCT00879034)
Timeframe: 4 weeks

Intervention	Participants (Count of Participants)
Zoledronic Acid, Pravastatin, and Lonafarnib	0

To Describe Any Acute and Chronic Toxicities Associated With Treating Progeria Patients With the Combination of Zoledronic Acid, Pravastatin and Lonafarnib

Number of participants with acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib (NCT00879034)
Timeframe: 4 weeks

Intervention	Participants (Count of Participants)
Zoledronic Acid, Pravastatin, and Lonafarnib	0

To Investigate Which Clinical and Laboratory Studies Are Needed to Monitor or Alter Therapy to Prevent Unacceptable Toxicity

The number of participants with abnormal CBC w/diff panel, LFTs, renal functions and lipid panels. (NCT00879034)
Timeframe: 4 weeks

Intervention	Participants (Count of Participants)
Zoledronic Acid, Pravastatin, and Lonafarnib	0

To Obtain Baseline Clinical and Laboratory Data so That Longer-term Measures of Efficacy Will be Achievable if Treatment Continues Beyond the 4-week Feasibility Study Period.

The number of participants from whom baseline clinical and Laboratory data was obtained. (NCT00879034)
Timeframe: 4 weeks

Intervention	Participants (Count of Participants)
Zoledronic Acid, Pravastatin, and Lonafarnib	5

Clinical Benefit Rate

Clinical benefit rate was defined as the percentage of participants with an objective response (CR or PR) or stable disease (SD) or better for at least 16 weeks achieved over the study duration. If a participant underwent surgical resection while on study, the participant was not evaluated for response after the surgery. Participants who did not meet the criteria for clinical benefit by the analysis cutoff date were considered as non-responders. (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	percentage of participants (Number)
Placebo	53.9
Denosumab	47.9

Objective Response Rate

"Objective response rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) based on modified RECIST 1.1 achieved over the study duration.~CR: Disappearance of all target and non target lesions, normalization of tumor marker levels and no new lesions.~PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, disappearance of target lesions with persistence of one or more non-target lesions and/or maintenance of tumor marker levels above normal limits and no new lesions.~Participants who underwent surgical resection while on study were not evaluated for response after the surgery. Participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non-responders." (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	percentage of participants (Number)
Placebo	43.4
Denosumab	36.8

Overall Survival (OS)

Overall survival was calculated as the time from the date of randomization to the date of death from any cause. Participants last known to be alive were censored at the last contact date. (NCT01951586)
Timeframe: From randomization until the end of study; median time on study was 9.64 months.

Intervention	months (Median)
Placebo	10.9
Denosumab	10.7

Progression-free Survival (PFS)

Progression-free survival was defined as the time from randomization to the first observed disease progression per modified RECIST 1.1 criteria or death from any cause. Participants last known to be alive who did not experience disease progression were censored at their last imaging assessment date, last contact date if they were in the survival follow up phase, end of the study date, or the primary analysis cut-off date, whichever was first. If a participant underwent surgical resection while on study, the participant was censored at the last evaluable imaging assessment prior to the surgery. (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	months (Median)
Placebo	5.7
Denosumab	5.2

Correlation of Tumor Tissue RANK Expression With Objective Response Rate

"To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANK protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.~The correlation between RANK expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANK expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported." (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	odds ratio (Number)
	Cytoplasm all intensity	Membrane all intensity	Total all intensity	Cytoplasm H-score	Membrane H-score	Total H-score
Denosumab	0.88	0.82	0.88	0.87	0.82	0.87
Placebo	1.00	1.18	1.16	1.00	1.14	1.14

Correlation of Tumor Tissue RANK Expression With Overall Survival

"To assess whether the treatment effect on overall survival was correlated with receptor activator of nuclear factor (NF)-κB (RANK) protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.~The correlation between RANK expression level and OS was evaluated using a Cox proportional hazard models that included RANK expression level stratified by the randomization stratification factors in the corresponding treatment group." (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	hazard ratio (Number)
	Cytoplasm all intensity	Membrane all intensity	Total all intensity	Cytoplasm H-score	Membrane H-score	Total H-score
Denosumab	1.00	0.92	1.00	1.00	0.93	1.00
Placebo	0.84	0.72	0.80	0.83	0.72	0.80

Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival

"To assess whether the treatment effect on overall survival was correlated with RANK ligand (RANKL) protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.~The correlation between RANKL expression level and OS was evaluated using a Cox proportional hazard models that included RANKL expression level stratified by the randomization stratification factors in the corresponding treatment group." (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	hazard ratio (Number)
	Cytoplasm all intensity	Cytoplasm H-score
Denosumab	0.93	0.93
Placebo	0.77	0.79

Correlation of Tumor Tissue RANKL Expression With Objective Response Rate

"To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANKL protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.~The correlation between RANKL expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANKL expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported." (NCT01951586)
Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Intervention	odds ratio (Number)
	Cytoplasm all intensity	Cytoplasm H-score
Denosumab	1.10	1.09
Placebo	1.27	1.25

Number of Participants With Treatment-emergent Adverse Events

"An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment.~A serious adverse event is defined as an AE that meets at least 1 of the following criteria~fatal~life threatening~requires in-patient hospitalization or prolongation of existing hospitalization~results in persistent or significant disability/incapacity~congenital anomaly/birth defect~other medically important serious event Treatment-related AEs include only TEAEs for which the investigator indicated there was a reasonable possibility they may have been caused by study drug.~Fatal adverse events include only deaths reported on the Adverse Event Case Report Form." (NCT01951586)
Timeframe: From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively.

Intervention	participants (Number)
	All adverse events (AEs)	Serious adverse events	AEs leading to discontinuation of study drug	Fatal adverse events	Treatment-related adverse events (TRAEs)	Treatment-related serious adverse events	TRAEs leading to discontinuation of study drug	Treatment-related fatal adverse events
Denosumab	144	129	20	113	51	6	7	0
Placebo	76	68	6	53	24	0	0	0

Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing

Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL. (NCT01951586)
Timeframe: Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24.

Intervention	ng/mL (Mean)
	Dose 2 - Day 8	Dose 3 - Week 3	Dose 4 - Week 6	Dose 5 - Week 9	Dose 6 - Week 12	Dose 7 - Week 15	Dose 8 - Week 18	Dose 9 - Week 21	Dose 10 - Week 24
Denosumab	8590	12200	19700	19600	22800	24300	22700	22100	23300

Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing

Intervention	ng/mL (Mean)
	Dose 2 - Day 8	Dose 3 - Week 4	Dose 4 - Week 8	Dose 5 - Week 12	Dose 6 - Week 16	Dose 7 - Week 20	Dose 8 - Week 24
Denosumab	8990	10900	15700	14500	13000	15400	15900

N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	ng.h/ml (Median)
AZD0530 175 mg	1069

N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	Ratio (Median)
AZD0530 175 mg	0.1420

N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	ng/ml (Median)
AZD0530 175 mg	62.80

N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	ng/ml (Median)
AZD0530 175 mg	34.30

N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	h (Median)
AZD0530 175 mg	2.0

Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4

Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. (NCT00558272)
Timeframe: Baseline to Week 4

Intervention	Percentage change in betaCTX (Geometric Mean)
AZD0530 175 mg	-71.1
Zoledronic Acid 4 mg	-68.4

Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4

Intervention	Percentage change in bALP (Geometric Mean)
AZD0530 175 mg	-13.2
Zoledronic Acid 4 mg	-3.1

Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4

Intervention	Percentage change in ICTP (Geometric Mean)
AZD0530 175 mg	-40.2
Zoledronic Acid 4 mg	7.4

Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4

Intervention	Percentage change in PINP (Geometric Mean)
AZD0530 175 mg	-26.1
Zoledronic Acid 4 mg	-29.5

Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4

Intervention	Percentage change in TRAP5b (Geometric Mean)
AZD0530 175 mg	-36.9
Zoledronic Acid 4 mg	-43.4

Percentage Change From Baseline in Urine Alpha-alpha C-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (aaCTx/Cr) at Week 4

Intervention	Percentage change in aaCTx/Cr (Geometric Mean)
AZD0530 175 mg	-68.2
Zoledronic Acid 4 mg	-82.8

Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4

Intervention	Percentage change in NTx/Cr (Geometric Mean)
AZD0530 175 mg	-57.2
Zoledronic Acid 4 mg	-70.1

Saracatinib: Area Under the Curve at Steady State (AUCss)

Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses. (NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	ng•hr/ml (Median)
AZD0530 175 mg	7261

Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	ng/ml (Median)
AZD0530 175 mg	396.0

Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	ng/ml (Median)
AZD0530 175 mg	229.0

Saracatinib: Plasma Clearance at Steady State (CLss/F)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	L/h (Median)
AZD0530 175 mg	24.10

Saracatinib: Time to Cssmax (Tmax)

(NCT00558272)
Timeframe: Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29

Intervention	h (Median)
AZD0530 175 mg	4.0

Percent Change in Bone Mass Density (BMD) in the Hip

Percent change of bone mass density (BMD) in the total hip (as measured by DXA) (NCT02325414)
Timeframe: 0-12 months

Intervention	percent change in bone mass density (Median)
Zoledronic Acid	-2.21
Placebo	-12.82

Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur

Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT. (NCT02325414)
Timeframe: 0-12 months

Intervention	percent change (Median)
Zoledronic Acid (Zol)	-9.6
Placebo (Pla)	-22.90

Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur

Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT (NCT02325414)
Timeframe: 0-12 months

Intervention	percent change (Median)
Zoledronic Acid (Zol)	-4.73
Placebo (Pla)	-8.88

Percent Change of Bone Mass Density (BMD) in the Femoral Neck

Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA) (NCT02325414)
Timeframe: 0-12 months

Intervention	percent change in bone mass density (Median)
Zoledronic Acid (Zol)	-1.72
Placebo (Pla)	-11.34

Time to First On-Study Skeletal-Related Event (Superiority)

Time to first on-study skeletal-related event (SRE) using a test for superiority. Median was estimated using the Kaplan-Meier method. (NCT00330759)
Timeframe: up to 33 months

Intervention	Days (Median)
Zoledronic Acid	496.0
Denosumab	625.0

Time to the First On-Study Skeletal-Related Event (Non-Inferiority)

Time to the first on-study skeletal-related event (SRE) using a non-inferiority analysis. Median was estimated using the Kaplan-Meier method. (NCT00330759)
Timeframe: up to 33 months

Intervention	Days (Median)
Zoledronic Acid	496.0
Denosumab	625.0

Time to the First-and-Subsequent On-Study Skeletal-Related Event

"Time to the first-and-subsequent on-study skeletal-related event (SRE) using multiple event analysis. To be considered a subsequent SRE, the event must occur at least 21 days after the previous SRE.~This outcome measure utilizes multiple event times, was analyzed based on a proportional mean model, and is therefore more appropriately summarized by the cumulative mean number of events." (NCT00330759)
Timeframe: up to 33 months

Intervention	Events (Number)
Zoledronic Acid	436
Denosumab	392

Bone Pain

"Bone pain was measured with the use of the Visual Analogue Scale on day 21 of cycle 4 (day 84).~Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.~The VAS for Bone Pain was constructed as follows:~None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome." (NCT00972959)
Timeframe: On the day 84

Intervention	units on a scale (Median)
Bortezomib/Dexamethasone/Zoledronic Acid	1.5

Bone Pain

"Bone pain was measured with the use of the Visual Analogue Scale on day 21 of cycle 8 (day 168).~Bone pain was measured with the use of the Visual Analogue Scale. The visual analogue scale or visual analog scale (VAS) is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured.~The VAS for Bone Pain was constructed as follows:~None Mild Moderate Severe Worst possible 1,2 3,4 5,6 7,8 9,10 Lower values are considered to be of a better outcome, higher values are considered to be of a worst outcome." (NCT00972959)
Timeframe: On the day 168

Intervention	units on a scale (Median)
Bortezomib/Dexamethasone/Zoledronic Acid	0.3

Bone Remodelling

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA) bone formation marker [bone-specific alkaline phosphatase (bALP)]. (NCT00972959)
Timeframe: day 84

Intervention	U/L (Median)
Bortezomib/Dexamethasone/Zoledronic Acid	22.5

Bone Remodelling

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA): bone formation marker [bone-specific alkaline phosphatase (bALP) ]. (NCT00972959)
Timeframe: day 168

Intervention	U/L (Median)
Bortezomib/Dexamethasone/Zoledronic Acid	24.8

New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)

New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery) after 18 months post VD (NCT00972959)
Timeframe: 18 months

Intervention	participants (Number)
Bortezomib/Dexamethasone/Zoledronic Acid	0

New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)

New Skeletal-related events (SRE: pathologic fractures, need for bone radiation therapy or surgery) following 8 cycles (day 168) of therapy (NCT00972959)
Timeframe: day 168

Intervention	participants (Number)
Bortezomib/Dexamethasone/Zoledronic Acid	0

Skeletal Survey for New Osteolytic Lesions/Fractures

Skeletal survey was measured using conventional radiography [imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)] every 6 months for up to 18 months (NCT00972959)
Timeframe: 18 months

Intervention	participants (Number)
Bortezomib/Dexamethasone/Zoledronic Acid	0

Skeletal Survey for New Osteolytic Lesions/Fractures

Skeletal survey was measured using conventional radiography [imaging of the whole skeleton (skull, cervical spine, thoracic spine, lumbar spine, pelvis, humeri, femoral bones)] on day 21 of cycle 8 (day 168) (NCT00972959)
Timeframe: day 168

Intervention	participants (Number)
Bortezomib/Dexamethasone/Zoledronic Acid	0

Bone Mineral Density (BMD)

BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by Dual Energy X-Absorptiometry scan (DEXA-scan) using a Hologic QDR-1000 scanner on day 21 of cycle 8 (day 168) (NCT00972959)
Timeframe: day 168

Intervention	T-score (Median)
	Lumbar spine (L1-L4)	Femoral neck (FN)
Bortezomib/Dexamethasone/Zoledronic Acid	1.63	-1.44

Bone Mineral Density (BMD)

BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner on day 21 of cycle 4 (day 84) (NCT00972959)
Timeframe: day 84

Intervention	T-scores (Median)
	Lumbar spine (L1-L4)	Femoral neck (FN)
Bortezomib/Dexamethasone/Zoledronic Acid	0.14	-2.68

Bone Remodelling

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 4 (day 84) using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation markers [osteocalcin (OC)]. (NCT00972959)
Timeframe: day 84

Intervention	ng/ml (Median)
	CTX	OC
Bortezomib/Dexamethasone/Zoledronic Acid	0.25	7.4

Bone Remodelling

Bone remodelling was studied by the measurement of the following serum indices on day 21 of cycle 8 (day 168) using an enzyme-linked immunosorbent assay (ELISA): i) bone resorption marker C-terminal cross-linking telopeptide of collagen type I (CTX) and ii) bone formation marker [osteocalcin (OC)]. (NCT00972959)
Timeframe: day 168

Intervention	ng/ml (Median)
	CTX	OC
Bortezomib/Dexamethasone/Zoledronic Acid	0.17	10.2

Bone Mineral Density (BMD)

Change in bone mineral density (BMD) (per dual energy x-ray absorptiometry (DXA) imaging) from 1 week post-operative data in the Standard and Custom Gruen Zones around the femoral stem. (NCT01267279)
Timeframe: 2 years post-operative

Intervention	Percent change (Mean)
	Gruen Zone 1: 2 years	Gruen Zone 7: 2 years
Placebo	-3.97	-27.3
Zoledronic Acid	14.30	-9.58

Overall Survival (OS)

Overall Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced death or lost to follow-up. (NCT01204203)
Timeframe: Baseline up to 28 months

Intervention	months (Median)
Zometa	7

Progression Free Survival (PFS)

Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experienced evidence of disease progression, as determined by radiological or clinical progression. (NCT01204203)
Timeframe: Baseline up to 28 months

Intervention	Months (Median)
Zometa	2

Tumor Response Rate Following Zoledronic Acid (Zometa)

The modified Response Evaluation Criteria in Solid Tumors Criteria (RECIST 2004) will be used for target lesions and assessed by CT scans. Complete Response (CR) is the disappearance of target lesions; Partial Response (PR) is greater than or equal to 30% reduction in the total tumor measurement; Stable Disease (SD) is the absence of response or progression; and Progressive Disease (PD) is a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions. (NCT01204203)
Timeframe: Baseline up to 28 months or until progressive disease or death

Intervention	percentage of responders (Number)
Zometa	12.5

Average ECOG Performance Status

To compare functional status (ECOG performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. ECOG performance status is a measurement of a patients disability ranging from 0, fully active and able to carry out all pre disease performance without restriction, to 5, dead. The average performance status is reported below by arm. (NCT00869206)
Timeframe: from baseline up to 2 years

Intervention	score on a scale (Mean)
Arm I (Zoledronic Acid Every 4 Weeks)	0.82
Arm II (Zoledronic Acid Every 12 Weeks)	0.84

Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire

To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted for the mean interference score. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. The score of the BPI questionnaire ranges from 0 being no pain to 10 being the most pain. The average score is reported for each arm below. (NCT00869206)
Timeframe: from baseline up to 2 years

Intervention	score on a scale (Mean)
Arm I (Zoledronic Acid Every 4 Weeks)	2.06
Arm II (Zoledronic Acid Every 12 Weeks)	2.09

Incidence of Osteonecrosis of the Jaw

To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of participants with osteonecrosis is reported here. (NCT00869206)
Timeframe: from baseline up to 2 years

Intervention	percentage of participants (Number)
Arm I (Zoledronic Acid Every 4 Weeks)	2.0
Arm II (Zoledronic Acid Every 12 Weeks)	1.0

Incidence of Renal Dysfunction

To compare the incidence of renal dysfunction of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of patients with renal dysfunction, defined as grade 3 or grade 4 increased creatinine (Common Terminology Criteria for Adverse Events version 3.0), will be reported here. (NCT00869206)
Timeframe: from baseline up to 2 years

Intervention	percentage of participants (Number)
Arm I (Zoledronic Acid Every 4 Weeks)	1.2
Arm II (Zoledronic Acid Every 12 Weeks)	.5

Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization

To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion of patients who would have experienced at least one skeletal related event within 24 months after randomization. (NCT00869206)
Timeframe: 2 years

Intervention	percentage of participants (Number)
Arm I (Zoledronic Acid Every 4 Weeks)	67.6
Arm II (Zoledronic Acid Every 12 Weeks)	67.9

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Breast Cancer

To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with breast cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization. (NCT00869206)
Timeframe: from baseline up to 24 months

Intervention	Participants (Count of Participants)
Breast Cancer 4 Weeks	113
Breast Cancer 12 Weeks	119

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Multiple Myeloma

To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization. (NCT00869206)
Timeframe: from baseline up to 24 months

Intervention	Participants (Count of Participants)
Multiple Myeloma 4 Weeks	35
Multiple Myeloma 12 Weeks	30

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Prostate Cancer

To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with prostate cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization. (NCT00869206)
Timeframe: from baseline up to 24 months

Intervention	Participants (Count of Participants)
Prostate Cancer 4 Weeks	107
Prostate Cancer 12 Weeks	101

Skeletal Morbidity Rate

To compare the skeletal morbidity rate, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing. (NCT00869206)
Timeframe: from baseline up to 2 years

Intervention	SRE's per year (Mean)
Arm I (Zoledronic Acid Every 4 Weeks)	.4
Arm II (Zoledronic Acid Every 12 Weeks)	.4

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer)

To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here. (NCT00869206)
Timeframe: from baseline up to 2 years

Intervention	Participants (Count of Participants)
	Low CTX (<0.415ng/ml)	High CTX (>0.415ng/ml)
Breast Cancer 12 Weeks	75	54
Breast Cancer 4 Weeks	83	54

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Multiple Myeloma)

Intervention	Participants (Count of Participants)
	Low CTX (<0.415ng/ml)	High CTX (>.0.415ng/ml)
Multiple Myeloma 12 Weeks	19	17
Multiple Myeloma 4 Weeks	15	23

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer)

Intervention	Participants (Count of Participants)
	Low CTX (<0.415ng/ml)	High CTX (>.0.415ng/ml)
Prostate Cancer 12 Weeks	49	54
Prostate Cancer 4 Weeks	34	70

Overall Survival

Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method. (NCT00079001)
Timeframe: Up to 10 years

Intervention	months (Median)
Zoledronic Acid + Androgen Deprivation Therapy	37.9
Placebo + Androgen Deprivation Therapy	36.0

Progression-free Survival

"Progression Free Survival (PFS) was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method.~Progression is defined as one or more of the following: new bone metastases, biochemical progression of PSA, treatment with radiation therapy while on treatment." (NCT00079001)
Timeframe: Up to 10 years

Intervention	months (Median)
Zoledronic Acid + Androgen Deprivation Therapy	10.6
Placebo + Androgen Deprivation Therapy	9.2

Time to First Skeletal Related Event

Time to first skeletal related event (SRE) was defined as the time from randomization to first skeletal event. Skeletal events are defined as radiation to bone, clinical fracture, surgery to bone and spinal cord compression and death due to prostate cancer. The median with 95% CI was estimated using the Kaplan Meier method. (NCT00079001)
Timeframe: Up to 10 years

Intervention	months (Median)
Zoledronic Acid + Androgen Deprivation Therapy	31.9
Placebo + Androgen Deprivation Therapy	28.8

Number of Patients With Incidences of Distant Recurrence

Distant breast cancer recurrence is when the cancer has spread to another organ within the body. (NCT00295867)
Timeframe: up to 5 years post initiation of treatment

Intervention	participants (Number)
Zoledronic Acid	6

Response of Bone Marrow Micrometastases

Median change in disseminated tumor cells (DTCs)/mL from baseline after 24 months (NCT00295867)
Timeframe: up to 2 years

Intervention	DTCs/mL (Median)
Zoledronic Acid	-4.5

Skeletal-related Complications

Number of patients who experience skeletal-related complications during the administration of Zoledronate. (NCT00301873)
Timeframe: 1 year

Intervention	participants (Number)
IV Zometa	0

Mean Change in Bone Mass Density (BMD)

Mean change in the combined t-score was measured by Dexa-scan. The patients bone density was determined by Dexa-scan at baseline, after 6 months Zometa and after 12 months of Zometa. The t-score, which is a comparison of a person's bone density with that of a healthy 30-year old of the same sex, was generated by Dexa-scan for the spine and femur. A lower t-score implies a lower BMD. The combined t-score is the minimum of the t-score for the spine and that for the femur. BMD change from baseline at 6 and 12 months in the combined t-score was defined as the follow-up combined t-score minus the baseline combined t-score. (NCT00301873)
Timeframe: 6 & 12 months

Intervention	T score units (Mean)
	Change in combined BMD at 6 months (n=27)	Change in combined BMD at 12 months (n=19)
IV Zometa	.01	-.06

Percent of Patients With Change in Combined Bone Mass Density T-score <= -0.5.

Percent of patients who failed treatment as defined by a decrease of 0.5 or more from baseline in the combined T-score as measured by Dexa-scan. The patient's bone densitometry was determined by Dexa-scan at baseline, after 6 months of Zometa and after 1 year of Zometa. The t-score, which is a comparison of a person's bone density with that of a healthy 30-year-old of the same sex, was generated by Dexa-scan for the spine and femur. The combined T-score is the minimum of the T-score for the spine and femur. A lower t-score implies a lower BMD. (NCT00301873)
Timeframe: 6 and 12 months

Intervention	percentage of patients (Number)
	At 6 months (n=27)	At 12 months (n=19)
IV Zometa	3.7	10.5

Average Percent Change From Baseline in TRAP Levels at 2 Weeks

Change was calculated as 100% (value at baseline minus value at 2 weeks)/value at baseline (NCT00265200)
Timeframe: TRAP levels at Baseline and 2 weeks after first Zometa infusion

Intervention	Percent change (Mean)
	NTx	TRAP-5b	bALP
Zoledronic Acid	37.3	44.9	12.9

Percent Change (Chg) From Baseline (BL) to Week (Wk)13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr)

uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment (trt). uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Primary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Asian ancestry with bone metastases from solid tumors. BL value is the most recent, non-missing value prior to or on the 1st study trt dose date. Chg from BL is the value at Wk13 minus BL value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value. (NCT01920568)
Timeframe: Baseline (BL) and Week (Wk) 13

Intervention	Percent change (Least Squares Mean)
Denosumab 120 mg	-81.9
Zoledronic Acid 4 mg	-75.2

Percent Change From Baseline in the Serum Bone-specific Alkaline Phosphatase (s-BALP) at Week 13.

Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Indicated visit minus Baseline value. Percent change from Baseline is the change from Baseline divided by Baseline value multiplied by 100. (NCT01920568)
Timeframe: Baseline and Week 13

Intervention	Percent change (Median)
Denosumab 120 mg	-36.8
Zoledronic Acid 4 mg	-30.3

Percentage Change From Baseline to Week 13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) in Chinese Participants.

uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment. uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Secondary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in par. of Chinese ancestry with bone metastases from solid tumors. Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Week 13 minus Baseline value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value. (NCT01920568)
Timeframe: Baseline and Week 13

Intervention	Percent change (Least Squares Mean)
Denosumab 120 mg	-82.2
Zoledronic Acid 4 mg	-75.6

Percentage Change From Baseline to Week 13 in Urinary Amino-terminal Cross-linking Telopeptide of Type I Collagen of Type I Collagen Corrected for Urine Creatinine (uNTx/uCr) in Participants With Advanced Breast Cancer.

uNTx/uCr is the bone turnover marker correlated with the presence and extent of metastases, and the prognosis and response to bone targeted treatment. uNTx/uCr was expressed in nanomoles bone collagen equivalent per millimole (nM BCE/mM). Secondary objective: to compare the effect of denosumab with that of zoledronic acid on % chg from BL in uNTx/uCr at Wk 13 in breast cancer par. with bone metastases from solid tumors. Baseline value is the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline is the value at Week 13 minus Baseline value. Percent chg from BL is the chg from BL / BL value * 100. For missing Wk 13 observations, the last post-BL value was carried forward to obtain the Wk 13 value. (NCT01920568)
Timeframe: Baseline and Week 13

Intervention	Percent change (Least Squares Mean)
Denosumab 120 mg	-80.9
Zoledronic Acid 4 mg	-72.4

Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (Non-fatal Serious Adverse Events and Fatal Serious Adverse Events)

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or other events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcome listed above, liver injury and impaired liver function and grade 4 laboratory abnormalities. Number of participants with any AEs, non-fatal SAEs, fatal SAEs have been presented. (NCT01920568)
Timeframe: From start of IP through the Study Phase (49 weeks post-dose) (assessed up to 73 weeks)

Intervention	Participants (Number)
	Any AEs	Any SAEs	Any Fatal SAEs	Any Non-Fatal SAEs
Denosumab 120 mg	291	46	25	25
Zoledronic Acid 4 mg	145	14	7	7

Number of Participants With Confirmed Anti-denosumab Antibody Formation at Day 1, Week 25 and Week 53.

Anti-denosumab antibody formation was assessed at Day 1, Week 25 and Week 53. Binding antibody assay was used to assess number of participants with anti-denosumab antibody. (NCT01920568)
Timeframe: Day 1, Week 25 and Week 53

Intervention	Participants (Number)
	Day 1, n = 326, 158	Week 25, n = 256, 115	Week 53, n = 180, 76
Denosumab 120 mg	0	0	0
Zoledronic Acid 4 mg	0	0	0

Number of Participants With Worst-case (WC) On-therapy Increase in the Indicated Clinical Chemistry Parameters From Baseline Grade to the Indicated Grade.

Clinical chemistry parameters were measured at the Screening and Weeks 2, 5, 9, 13, 25, 37, and 53 visits. Clinical chemistry parameters measured on-study included albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, calcium (Ca), creatinine, magnesium, and phosphorous (P) inorganic. All reported values are of participants with worst-case on-therapy increase to the specified grade: Any increase, that is, worst-case increase to grade 1, 2, 3, or 4 (any grade); worst-case increase to grade 3 (WC G3); and worst-case increase to grade 4 (WC G4). The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) was used for grading. Participants with missing Baseline grade were assumed to have a Baseline grade of 0. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. (NCT01920568)
Timeframe: Baseline and up to last study-related visit (up to 53 weeks)

Intervention	Participants (Number)
	Albumin (hyperalbuminemia), any grade, n=324, 156	Albumin (hyperalbuminemia), WC G3, n=324, 156	Albumin (hyperalbuminemia), WC G4, n=324, 156	Albumin (hypoalbuminemia), any grade, n=324, 156	Albumin (hypoalbuminemia), WC G3, n=324, 156	Albumin (hypoalbuminemia), WC G4, n=324, 156	ALP, any grade, n=324, 156	ALP, WC G3, n=324, 156	ALP, WC G4, n=324, 156	ALT, any grade, n=324, 156	ALT, WC G3, n=324, 156	ALT, WC G4, n=324, 156	AST, any grade, n=323, 155	AST, WC G3, n=323, 155	AST, WC G4, n=323, 155	Total Bilirubin, any grade, n=324, 155	Total Bilirubin, WC G3, n=324, 155	Total Bilirubin, WC G4, n=324, 155	Calcium (hypercalcemia), any grade, n=324, 156	Calcium (hypercalcemia), WC G3, n=324, 156	Calcium (hypercalcemia), WC G4, n=324, 156	Calcium (hypocalcemia), any grade, n=324,156	Calcium (hypocalcemia), WC G3, n=324, 156	Calcium (hypocalcemia), WC G4, n=324, 156	Creatinine, any grade, n=324, 156	Creatinine, WC G3, n=324, 156	Creatinine, WC G4, n=324, 156	Magnesium (hypermagnesemia), any grade, n=324, 156	Magnesium (hypermagnesemia), WC G3, n=324, 156	Magnesium (hypermagnesemia), WC G4, n=324, 156	Magnesium (hypomagnesemia), any grade, n=324, 156	Magnesium (hypomagnesemia), WC G3, n=324, 156	Magnesium (hypomagnesemia), WC G4, n=324, 156	P,inorganic(hyperphosphatemia),any grade,n=323,156	P, inorganic (hyperphosphatemia),WC G3, n=323, 156	P, inorganic (hyperphosphatemia),WC G4, n=323, 156	P,inorganic(hypophosphatemia),any grade,n=323, 156	P, inorganic (hypophosphatemia),WC G3, n=323, 156	P, inorganic (hypophosphatemia), WC G4, n=323, 156
Denosumab 120 mg	0	0	0	45	1	0	67	7	0	137	7	0	117	7	0	34	2	2	4	0	0	78	5	1	16	1	0	4	2	0	8	0	0	0	0	0	124	35	1
Zoledronic Acid 4 mg	0	0	0	26	0	0	31	2	0	59	4	0	61	4	0	16	0	1	3	0	1	28	0	0	13	0	0	0	0	0	2	0	0	0	0	0	35	9	0

Number of Participants With Worst-case On-therapy Increase in the Indicated Hematology Parameters From Baseline Grade to the Indicated Grade.

Hematology parameters included hemoglobin, lymphocytes, platelet count, total neutrophils, white blood cell (WBC) count. All reported values are of participants with worst-case on-therapy increase to the specified grade: Any increase, that is, worst-case increase to grade 1, 2, 3, or 4 (any grade); worst-case increase to grade 3 (WC G3); and worst-case increase to grade 4 (WC G4). Participants with missing Baseline grade were assumed to have a Baseline grade of 0. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. (NCT01920568)
Timeframe: Baseline and up to last study-related visit (up to 53 weeks)

Intervention	Participants (Number)
	Hemoglobin, any grade, n=316, 147	Hemoglobin, WC G3, n=316, 147	Hemoglobin, WC G4, n=316, 147	Lymphocyte count decreased, any grade, n=315, 147	Lymphocyte count decreased, WC G3, n=315, 147	Lymphocyte count decreased, WC G4, n=315, 147	Lymphocyte count increased, any grade, n=315, 147	Lymphocyte count increased, WC G3, n=315, 147	Lymphocyte count increased, WC G4, n=315, 147	Platelet count, any grade, n=314, 144	Platelet count, WC G3, n=314, 144	Platelet count, WC G4, n=314, 144	Total neutrophils, any grade, n=315, 147	Total neutrophils, WC G3, n=315, 147	Total neutrophils, WC G4, n=315, 147	WBC count, any grade, n=315, 147	WBC count, WC G3, n=315, 147	WBC count, WC G4, n=315, 147
Denosumab 120 mg	139	24	0	77	21	1	2	0	0	77	2	2	124	40	12	138	25	2
Zoledronic Acid 4 mg	69	11	0	47	14	1	2	0	0	48	5	1	58	19	8	78	19	1

Serum Concentration of Denosumab on Day 1, at Week 2, Week 5, Week 9, Week 13, Week 17, Week 19, Week 21, Week 25 and Week 49

Blood samples were drawn on study Day 1, pre-dose; 4 hours, 24 hours, and at Week 2 (168 hours); then pre-dose at Week 5, Week 9, Week 13, Week 17, Week 19 (no dose), Week 21, Week 25, and Week 49. (NCT01920568)
Timeframe: Samples were collected at pre-dose (Day 1); 4 hours, 24 hours, 168 hours post-dose; pre-dose at Week 5, Week 9, Week 13, Week 17; Week 19 (at 336 hours); pre-dose at Week 21, Week 25, Week 49

Intervention	micrograms per milliliter (µg/mL) (Geometric Mean)
	Day 1, Pre-dose, n=26	Day 1, 4 hours post-dose, n=26	Day 1, 24 hours post-dose, n=26	Week 2, 168 hours post-dose, n=26	Week 5, Pre-dose, n=25	Week 9, Pre-dose, n=25	Week 13, Pre-dose, n=25	Week 17, Pre-dose, n=24	Week 19, 336 hours, n=22	Week 21, Predose, n=21	Week 25, Predose, n=22	Week 49, Predose, n=19
Denosumab 120 mg	0	777.1	5521.6	11701.1	8658.1	12086.4	14867.5	16543.3	20802.4	14508.0	16619.0	20029.2

Compliance With Zoledronic Acid, Alendronate and/or Calcium/Vitamin D Supplementation

Compare compliance where a study coordinator interviewed patients as to how often they missed the once a week oral alendronate, missed taking calcium and vitamin D supplementation, or missed the once a year IV Reclast. (NCT00580047)
Timeframe: 24 months

Intervention	percentage of compliance (Number)
Intravenous Bisphosphonate Post Transplantation	100
Oral Bisphosphonate Post Transplantation	80
Placebo Group Post Transplantation	80

Percentage Change in Posterior Anterior (PA) Spine Bone Density From Baseline to 24 Months Post Transplant

Posterior Anterior (PA) spine bone density was measured by dual energy x-ray absorptiometry (DXA) at baseline and 24 months post transplant. The percentage change in the PA spine bone density was then compared from baseline to 24 months post transplant. (NCT00580047)
Timeframe: 24 months

Intervention	percentage of change of bone density (Number)
Intravenous Bisphosphonate Post Transplantation	8.1
Oral Bisphosphonate Post Transplantation	6.6
Placebo Group Post Transplantation	6.5

Percent Change From Baseline in Spine Bone Mineral Density by Dual X-ray Absorptiometry (DXA)

(NCT02176382)
Timeframe: Baseline and 42 months

Intervention	percent change in BMD (Mean)
Standard Dose Teriparatide	7.69
High Dose Teriparatide	12.70

Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline

After the trial's premature closure, no data were collected for the primary endpoints; however, data on 14 of 30 secondary endpoints were obtained and are summarized below. Serum level (pg/mL) per biomarker was log-transformed. Change from baseline over time was evaluated using a generalized linear mixed model where follow-up time was represented by terms for the sequence of post-baseline samples or for (log)day on study. To recognize regression to the mean across repeated samples, a term for biomarker level at baseline, with or without interaction by time, was included when it improved the model's fit to the observed data. With 14 biomarkers sampled twice after baseline, there were 28 evaluations of change in biomarker level with exposure to study drug. Therefore, to control the False Discovery Rate (FDR), only evaluations that maintained the study's FDR at no more than 5 percent were accepted as true. (NCT01409811)
Timeframe: "48-72 hrs and Surgery (10-23 days)"

Intervention	(log)pg/mL (Mean)
	MIG @ 48-72 hrs	MIG @ Surgery (Day 10-23)	IP-10 @ 48-72 hrs	IP-10 @ Surgery (Day 10-23)	IL-12 @ 48-72 hrs	IL-12 @ Surgery (Day 10-23)	Eotaxin @ 48-72 hrs	Eotaxin @ Surgery (Day 10-23)	IL-2R @ 48-72 hrs	IL-2R @ Surgery (Day 10-23)	IFN-gamma @ 48-72 hrs	IFN-gamma @ Surgery (Day 10-23)	MIP1B @ 48-72 hrs	MIP1B @ Surgery (Day 10-23)	EGF @ 48-72 hrs	EGF @ Surgery (Day 10-23)	MCP-1 @ 48-72 hrs	MCP-1 @ Surgery (Day 10-23)	IFN-alpha per (log)Day until Surgery (Day 10-23)	MIP1A per (log)Day until Surgery (Day 10-23)
Treatment (Zoledronic Acid)	2.31	0.62	1.47	0.16	0.23	-0.01	-0.23	0.02	0.17	0.10	0.04	-0.01	0.37	0.28	-0.18	0.25	0.15	-0.02	-0.026	0.12

Number of Participants With Progression Free Survival (PFS), by Treatment Arm

"Number of participants with PFS for thalidomide/Dexamethasone vs. VAD with respect to progression free survival in newly diagnosed MM. Progressive Disease (PD): (for patients not in CR) Requires one or more of the following; > 25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation.~> 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg and confirmed on a repeat investigation.~>25% increase in plasma cells in a bone marrow aspirate, which also must be an absolute increase of at least 10%. Definite increase in the size of existing lytic lesions or plasmacytomas. Development of new bone lesions or plasmacytomas (except compression fractures). Development of hypercalcemia (corrected calcium > 11.5 mg/dL not attributable to other causes)." (NCT00215943)
Timeframe: 4 Months

Intervention	participants (Number)
Active Comparator: VAD Treatment	2
Active Comparator: Thalidomide and Dexamethasone Treatment	1

Overall Survival (OS), by Treatment Arm

"Median OS for thalidomide/Dexamethasone participants vs. VAD participants. Months from On Study to Expired/Last Date Known Alive.~Investigators had planned to accrue 176 participants to calculate median overall survival." (NCT00215943)
Timeframe: Up to 10 Years

Intervention	months (Median)
Active Comparator: VAD Treatment	57
Active Comparator: Thalidomide and Dexamethasone Treatment	56.5

Number of Participants With Adverse Events, by Group

Number of participants with toxicities of Thalidomide/Dexamethasone vs. VAD as induction regimens in newly diagnosed multiple myeloma (MM). (NCT00215943)
Timeframe: 4 Years, 7 Months

Intervention	participants (Number)
	Serious Adverse Events (SAEs)	Adverse Events (AEs)
Active Comparator: Thalidomide and Dexamethasone Treatment	1	37
Active Comparator: VAD Treatment	0	36

Response Rates of VAD vs. Thalidomide/Dexamethasone

Blade (15) criteria for remission in multiple myeloma was used to assess response. Complete Response (CR)includes: Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of 6 weeks by immunofixation studies. Partial Response (PR) includes: At least a 50% reduction in the level of serum monoclonal protein for at least two determinations 6 weeks apart. Minimal Response (MR)includes: At least a 25% to 49% reduction in the level of serum monoclonal protein for at least 2 determinations 2 weeks apart. (NCT00215943)
Timeframe: End of Cycle 4 - 4 Months per Participant

Intervention	participants (Number)
	Complete Response	Partial Response	Minimal Response
Active Comparator: Thalidomide and Dexamethasone Treatment	1	16	2
Active Comparator: VAD Treatment	1	9	6

Major Bone Scan Response

Bone scan performed at baseline and at Week 13 provided if baseline scan was positive for metastases. A major bone scan response was considered with a substantial resolution of participant bone metastases on the bone scans, i.e. complete resolution of the osseous metastases on the bone scan. (NCT00081159)
Timeframe: Week 13

Intervention	participants (Number)
HAT, Doxorubicin, Zoledronate + Strontium Chloride	0
HAT, Doxorubicin + Zoledronate	0

Overall Survival (OS)

Overall Survival defined as the length of time from the start of treatment till time that participants are still alive. (NCT00081159)
Timeframe: Up to 90 months

Intervention	Months (Median)
HAT, Doxorubicin, Zoledronate + Strontium Chloride	47.4
HAT, Doxorubicin + Zoledronate	53.5

Progression Free Survival (PFS)

Study's primary endpoint of PFS duration/time to progression was defined as the time from the date of randomization to the date of first evidence of disease progression or patient death. Prostate-specific antigen (PSA) progression is usually the first evidence of progression. PSA progression is defined as a 25% increase over the baseline or the nadir provided that the increase is a minimum of 1 ng/ml. (NCT00081159)
Timeframe: Up to 90 months with evaulation in 4 week intervals for up to 6 months of treatment, then follow up until disease progression

Intervention	Months (Median)
HAT, Doxorubicin, Zoledronate + Strontium Chloride	12.9
HAT, Doxorubicin + Zoledronate	18.5

Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis

(NCT01732770)
Timeframe: Baseline and Month 12

Intervention	percent change (Least Squares Mean)
Zoledronic Acid 5 mg Q12M	1.1
Denosumab 60 mg Q6M	3.2

Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis

Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility. (NCT01732770)
Timeframe: Baseline and Month 12

Intervention	percent change (Least Squares Mean)
Zoledronic Acid 5 mg Q12M	1.1
Denosumab 60 mg Q6M	3.2

Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis

BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility. (NCT01732770)
Timeframe: Baseline and Month 12

Intervention	percent change (Least Squares Mean)
Zoledronic Acid 5 mg Q12M	0.6
Denosumab 60 mg Q6M	1.9

Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis

(NCT01732770)
Timeframe: Baseline and Month 12

Intervention	percent change (Least Squares Mean)
Zoledronic Acid 5 mg Q12M	0.6
Denosumab 60 mg Q6M	1.9

Bone Mineral Density (BMD) at the Distal Femur and Proximal Tibia at Baseline and Month 12.

An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the distal femur and proximal tibia by using a customized research software program supplied by the manufacturer. This measurement will be the primary determinant (dependent measure) of difference among the treatment and control groups, and they will be followed over time at the previously specified time points. (NCT02042872)
Timeframe: Baseline and 12 months

Intervention	g/cm2 (Mean)
	Baseline Distal Femur	12 Month Distal Femur	Baseline Proximal Tibia	12 Month Proximal Tibia
No Treatment	1.134	1.038	1.341	1.237
Zoledronic Acid	1.102	0.898	1.274	1.022

Bone Mineral Density (BMD) at the Total Hip at Baseline and Month 12

An imaging method known as dual energy x-ray absorptiometry (DXA) was used to obtain BMD of the total hip. (NCT02042872)
Timeframe: Baseline and 12 months

Intervention	g/cm2 (Mean)
	Baseline Total Hip	12 Month Total Hip
No Treatment	1.020	0.814
Zoledronic Acid	1.125	1.042

Article	Year
Long-term consequences of osteoporosis therapy with bisphosphonates. Archives of endocrinology and metabolism, Nov-10, Volume: 68	2023
Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts. BMC oral health, 05-27, Volume: 23, Issue: 1	2023
Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation. International journal of molecular sciences, May-25, Volume: 23, Issue: 11	2022
Intractable Fractures of the Bilateral Proximal Ulnae After 8 Years of Zoledronate Treatment for Breast Cancer Bone Metastasis. The Journal of hand surgery, Volume: 47, Issue: 4	2022
Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw. Journal of bone and mineral metabolism, Volume: 39, Issue: 3	2021
Atypical femoral fracture in patients with bone metastasis receiving denosumab therapy: a retrospective study and systematic review. BMC cancer, Oct-22, Volume: 19, Issue: 1	2019
Incidence of osteonecrosis of the jaw by the use of osteoclast inhibitors in patients with bone metastases: a retrospective cohort study. Cirugia y cirujanos, Volume: 87, Issue: 4	2019
Zoledronate and Raloxifene combination therapy enhances material and mechanical properties of diseased mouse bone. Bone, Volume: 127	2019
Uncommon presentation of medication-related osteonecrosis of the mandible in a patient with metastatic prostate cancer. BMJ case reports, Feb-26, Volume: 12, Issue: 2	2019
Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Volume: 33, Issue: 4	2019
THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis. European journal of endocrinology, Volume: 179, Issue: 1	2018
Randomized trial comparing efficacies of zoledronate and alendronate for improving bone mineral density and inhibiting bone remodelling in women with post-menopausal osteoporosis. Journal of clinical pharmacy and therapeutics, Volume: 41, Issue: 5	2016
PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells. Clinical oral investigations, Volume: 20, Issue: 3	2016
Mevalonates restore zoledronic acid-induced osteoclastogenesis inhibition. Journal of dental research, Volume: 94, Issue: 4	2015
Continuous effect with long-term safety in zoledronic acid therapy for polyostotic fibrous dysplasia with severe bone destruction. Rheumatology international, Volume: 35, Issue: 4	2015
Zoledronate for metastatic bone disease and pain: a meta-analysis of randomized clinical trials. Pain medicine (Malden, Mass.), Volume: 14, Issue: 2	2013
Bisphosphonate-related osteonecrosis of the jaws--a case report. Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995), Volume: 33, Issue: 5	2012
Mandibular bisphosphonate-related osteonecrosis after dental implant rehabilitation: a case report. Implant dentistry, Volume: 21, Issue: 6	2012
Low-dose zoledronic acid reduces spinal cord metastasis in pulmonary adenocarcinoma with neuroendocrine differentiation. Anti-cancer drugs, Volume: 23, Issue: 9	2012
The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells. Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery, Volume: 40, Issue: 8	2012
Bisphosphonates cause osteonecrosis of the jaw-like disease in mice. The American journal of pathology, Volume: 177, Issue: 1	2010
Biphosphonate-associated osteonecrosis can be controlled by nonsurgical management. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics, Volume: 104, Issue: 4	2007
Zoledronic acid is effective in preventing and delaying skeletal events in patients with bone metastases secondary to genitourinary cancers. BJU international, Volume: 96, Issue: 7	2005
Recommendations for zoledronic acid treatment of patients with bone metastases. The oncologist, Volume: 10, Issue: 1	2005
Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer, Jun-15, Volume: 100, Issue: 12	2004
Safety and convenience of a 15-minute infusion of zoledronic acid. The oncologist, Volume: 9, Issue: 3	2004
Loss of vertebral bone and mechanical strength in estrogen-deficient rats is prevented by long-term administration of zoledronic acid. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, Volume: 15, Issue: 9	2004
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Evaluation of estimated glomerular function (eGFR) versus creatinine clearance (CrCl) to predict acute kidney injury when using zoledronate for the treatment of osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, Volume: 33, Issue: 3	2022
Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study. Calcified tissue international, Volume: 110, Issue: 1	2022
Efficacy of Zoledronic Acid in Maintaining Areal and Volumetric Bone Density After Combined Denosumab and Teriparatide Administration: DATA-HD Study Extension. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Volume: 36, Issue: 5	2021
The association between change in bone marrow lesion size and change in tibiofemoral cartilage volume and knee symptoms. Rheumatology (Oxford, England), 06-18, Volume: 60, Issue: 6	2021
Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions: A Randomized Clinical Trial. JAMA, 04-21, Volume: 323, Issue: 15	2020
The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain. BMC musculoskeletal disorders, Jun-23, Volume: 18, Issue: 1	2017
Safety, pharmacokinetics, and changes in bone metabolism associated with zoledronic acid treatment in Japanese patients with primary osteoporosis. Journal of bone and mineral metabolism, Volume: 35, Issue: 6	2017
Pharmacokinetic and therapeutic efficacy of intrapulmonary administration of zoledronate for the prevention of bone destruction in rheumatoid arthritis. Journal of drug targeting, Volume: 24, Issue: 6	2016
Pharmacokinetic and imaging evaluation of (99m)Tc-HBIDP as a potential bone imaging agent. Pakistan journal of pharmaceutical sciences, Volume: 28, Issue: 3	2015
Assessing treatment response of osteolytic lesions by manual volumetry, automatic segmentation, and RECIST in experimental bone metastases. Academic radiology, Volume: 21, Issue: 9	2014
The effect of zoledronic acid on the volume of the fusion-mass in lumbar spinal fusion. Clinics in orthopedic surgery, Volume: 5, Issue: 4	2013
Dosing related effects of zoledronic acid on bone markers and creatinine clearance in patients with multiple myeloma and metastatic breast cancer. Acta oncologica (Stockholm, Sweden), Volume: 53, Issue: 4	2014
Pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses. American journal of veterinary research, Volume: 74, Issue: 4	2013
Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength. Acta orthopaedica, Volume: 84, Issue: 1	2013
Pharmacokinetic evaluation of zoledronic acid. Expert opinion on drug metabolism & toxicology, Volume: 7, Issue: 7	2011
Physicochemical determinants of human renal clearance. Journal of medicinal chemistry, Aug-13, Volume: 52, Issue: 15	2009
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug metabolism and disposition: the biological fate of chemicals, Volume: 36, Issue: 7	2008
Renal safety of zoledronic acid with thalidomide in patients with myeloma: a pharmacokinetic and safety sub-study. BMC clinical pharmacology, Mar-31, Volume: 8	2008
The pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with varying degrees of renal function. Journal of clinical pharmacology, Volume: 43, Issue: 2	2003
Pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with bone metastases. Journal of clinical pharmacology, Volume: 42, Issue: 11	2002
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Functionalization of Octacalcium Phosphate Bone Graft with Cisplatin and Zoledronic Acid: Physicochemical and Bioactive Properties. International journal of molecular sciences, Jul-19, Volume: 24, Issue: 14	2023
Chitosan modified with lanthanum ions as implantable hydrogel for local delivery of bisphosphonates. International journal of biological macromolecules, Mar-01, Volume: 230	2023
Quantification of Low Amounts of Zoledronic Acid by HPLC-ESI-MS Analysis: Method Development and Validation. International journal of molecular sciences, May-25, Volume: 23, Issue: 11	2022
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular pharmacology, Volume: 96, Issue: 5	2019
Designing of Stable Co-crystals of Zoledronic Acid Using Suitable Coformers. Chemical & pharmaceutical bulletin, Volume: 67, Issue: 8	2019
Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro. Clinical oral investigations, Volume: 22, Issue: 7	2018
Effects of local delivery of BMP2, zoledronate and their combination on bone microarchitecture, biomechanics and bone turnover in osteoporotic rabbits. Scientific reports, 06-22, Volume: 6	2016
Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA. Molecular pharmaceutics, Apr-04, Volume: 13, Issue: 4	2016
Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer. Scientific reports, Nov-18, Volume: 5	2015
Oral delivery of zoledronic acid by non-covalent conjugation with lysine-deoxycholic acid: In vitro characterization and in vivo anti-osteoporotic efficacy in ovariectomized rats. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Jan-20, Volume: 82	2016
Pharmacokinetic and therapeutic efficacy of intrapulmonary administration of zoledronate for the prevention of bone destruction in rheumatoid arthritis. Journal of drug targeting, Volume: 24, Issue: 6	2016
Self-assembly nanoparticles for the delivery of bisphosphonates into tumors. International journal of pharmaceutics, Jan-17, Volume: 403, Issue: 1-2	2011
[Antitumor properties of the bisphosphonate zoledronate and potential therapeutic implications in the clinic]. Bulletin du cancer, Volume: 97, Issue: 8	2010
Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model. A pilot study. European cells & materials, Jul-31, Volume: 16	2008
Bisphosphonates inhibit the growth of mesothelioma cells in vitro and in vivo. Clinical cancer research : an official journal of the American Association for Cancer Research, May-01, Volume: 12, Issue: 9	2006
Bisphosphonates to prevent skeletal complications in men with metastatic prostate cancer. The Journal of urology, Volume: 170, Issue: 6 Pt 2	2003
Zoledronate once-yearly increases bone mineral density--implications for osteoporosis. Expert opinion on pharmacotherapy, Volume: 3, Issue: 7	2002
Intravenous zoledronic acid in postmenopausal women with low bone mineral density. The New England journal of medicine, Feb-28, Volume: 346, Issue: 9	2002
Oral bisphosphonates: A review of clinical use in patients with bone metastases. Cancer, Jan-01, Volume: 88, Issue: 1	2000
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Article	Year
Immunological effects and activity of multiple doses of zolbetuximab in combination with zoledronic acid and interleukin-2 in a phase 1 study in patients with advanced gastric and gastroesophageal junction cancer. Journal of cancer research and clinical oncology, Volume: 149, Issue: 9	2023
Percutaneous kyphoplasty combined with zoledronic acid for the treatment of primary osteoporotic vertebral compression fracture: a prospective, multicenter study. Archives of orthopaedic and trauma surgery, Volume: 143, Issue: 7	2023
Efficacy Evaluation of Zoledronic Acid Combined with Chemotherapy in the Treatment of Lung Cancer Spinal Metastases on Computed Tomography Images on Intelligent Algorithms. Computational and mathematical methods in medicine, Volume: 2022	2022
Percutaneous Vertebroplasty Combined with Zoledronic Acid in Treatment and Prevention of Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis of Comparative Studies. World neurosurgery, Volume: 157	2022
Clinical Efficacy and Safety of Zoledronic Acid Combined with PVP/PKP in the Treatment of Osteoporotic Vertebral Compression Fracture: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. BioMed research international, Volume: 2021	2021
Effectiveness and safety of percutaneous kyphoplasty combined with zoledronic acid in treatment of osteoporotic vertebral compression fractures: a meta-analysis. Archives of orthopaedic and trauma surgery, Volume: 142, Issue: 10	2022
Comparison of Efficacy of Teriparatide (Parathyroid Hormone 1-34) Alone and in Combination with Zoledronic Acid for Osteoporosis in Postmenopausal Women. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, Volume: 31, Issue: 2	2021
Expression changes of IL-17 in zoledronic acid combined with PVP technology in the treatment of postmenopausal osteoporotic vertebral compression fracture and its predictive value of relapse. Journal of musculoskeletal & neuronal interactions, 12-01, Volume: 20, Issue: 4	2020
[Treatment of severely osteoporotic vertebral compression fractures with the vertebral body stent system and percutanous kyphoplasty combined with zoledronic acid]. Zhongguo gu shang = China journal of orthopaedics and traumatology, Sep-25, Volume: 33, Issue: 9	2020
[Clinical application of zoledronic acid combined with vitamin K2 in percutaneous vertebroplasty for multi-segment osteoporotic vertebral compression fractures]. Zhongguo gu shang = China journal of orthopaedics and traumatology, Sep-25, Volume: 33, Issue: 9	2020
Functional electrical stimulation (FES)-assisted rowing combined with zoledronic acid, but not alone, preserves distal femur strength and stiffness in people with chronic spinal cord injury. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, Volume: 32, Issue: 3	2021
Radiation therapy combined with bone-modifying agents ameliorates local control of osteolytic bone metastases in breast cancer. Journal of radiation research, May-22, Volume: 61, Issue: 3	2020
Successful percutaneous treatment of bone tumors using microwave ablation in combination with Zoledronic acid infused PMMA cementoplasty. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, Volume: 76	2020
Therapeutic effect of percutaneous kyphoplasty combined with anti-osteoporosis drug on postmenopausal women with osteoporotic vertebral compression fracture and analysis of postoperative bone cement leakage risk factors: a retrospective cohort study. Journal of orthopaedic surgery and research, Dec-18, Volume: 14, Issue: 1	2019
Zoledronic acid combined with percutaneous kyphoplasty in the treatment of osteoporotic compression fracture in a single T12 or L1 vertebral body in postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, Volume: 30, Issue: 7	2019
Strong CD8+ lymphocyte infiltration in combination with expression of HLA class I is associated with better tumor control in breast cancer patients treated with neoadjuvant chemotherapy. Breast cancer research and treatment, Volume: 175, Issue: 3	2019
Effectiveness Analysis of Percutaneous Kyphoplasty Combined with Zoledronic Acid in Treatment of Primary Osteoporotic Vertebral Compression Fractures. Pain physician, Volume: 22, Issue: 1	2019
Evaluation of effects of radiation therapy combined with either pamidronate or zoledronate on canine osteosarcoma cells. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire, Volume: 83, Issue: 1	2019
Clinical effect of intravenous infusion of zoledronic acid combined with oral medication of cinobufagin in the treatment of metastatic bone tumors. Pakistan journal of pharmaceutical sciences, Volume: 31, Issue: 4(Special)	2018
Radiotherapy combined with zoledronate can reduce skeletal-related events in renal cell carcinoma patients with bone metastasis. International journal of clinical oncology, Volume: 23, Issue: 6	2018
PD-1 blockade in combination with zoledronic acid to enhance the antitumor efficacy in the breast cancer mouse model. BMC cancer, Jun-19, Volume: 18, Issue: 1	2018
Percutaneous kyphoplasty combined with zoledronic acid infusion in the treatment of osteoporotic thoracolumbar fractures in the elderly. Clinical interventions in aging, Volume: 13	2018
Valproic Acid Combined with Zoledronate Enhance γδ T Cell-Mediated Cytotoxicity against Osteosarcoma Cells Frontiers in immunology, Volume: 9	2018
Clinical Efficacy Analysis of Percutaneous Kyphoplasty Combined with Zoledronic Acid in the Treatment and Prevention of Osteoporotic Vertebral Compression Fractures. Journal of investigative surgery : the official journal of the Academy of Surgical Research, Volume: 31, Issue: 5	2018
Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer. Cancer letters, 02-01, Volume: 386	2017
Treatment of osteoporotic intertrochanteric fractures by zoledronic acid injection combined with proximal femoral nail anti-rotation. Chinese journal of traumatology = Zhonghua chuang shang za zhi, Oct-01, Volume: 19, Issue: 5	2016
Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a randomised, multicentre, open-label, phase 3 trial. The Lancet. Oncology, Volume: 17, Issue: 8	2016
TBCRC-010: Phase I/II Study of Dasatinib in Combination with Zoledronic Acid for the Treatment of Breast Cancer Bone Metastasis. Clinical cancer research : an official journal of the American Association for Cancer Research, Dec-01, Volume: 22, Issue: 23	2016
Periodontal disease preceding osteonecrosis of the jaw (ONJ) in cancer patients receiving antiresorptives alone or combined with targeted therapies: report of 5 cases and literature review. Oral surgery, oral medicine, oral pathology and oral radiology, Volume: 120, Issue: 6	2015
A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. British journal of haematology, Volume: 167, Issue: 3	2014
Phase II study of zoledronic acid combined with docetaxel for non-small-cell lung cancer: West Japan Oncology Group. Cancer science, Volume: 105, Issue: 8	2014
An effective therapy to painful bone metastases: cryoablation combined with zoledronic acid. Pathology oncology research : POR, Volume: 20, Issue: 4	2014
Zoledronic acid in combination with alfacalcidol has additive effects on trabecular microarchitecture and mechanical properties in osteopenic ovariectomized rats. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, Volume: 19, Issue: 4	2014
In vitro antitumor effect of sodium butyrate and zoledronic acid combined with traditional chemotherapeutic drugs: a paradigm of synergistic molecular targeting in the treatment of Ewing sarcoma. Oncology reports, Volume: 31, Issue: 2	2014
Percutaneous vertebroplasty combined with zoledronic acid for the treatment of painful osteolytic spinal metastases in patients with breast cancer. Journal of vascular and interventional radiology : JVIR, Volume: 24, Issue: 12	2013
Mechanisms of the antitumor activity of human Vγ9Vδ2 T cells in combination with zoledronic acid in a preclinical model of neuroblastoma. Molecular therapy : the journal of the American Society of Gene Therapy, Volume: 21, Issue: 5	2013
Cisplatin in combination with zoledronic acid: a synergistic effect in triple-negative breast cancer cell lines. International journal of oncology, Volume: 42, Issue: 4	2013
Zoledronic acid in combination with serine/threonine phosphatase inhibitors induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer cell lines by decreasing the activities of PP1 and PP2A. BJU international, Volume: 110, Issue: 11 Pt C	2012
Zoledronic acid inhibits aromatase activity and phosphorylation: potential mechanism for additive zoledronic acid and letrozole drug interaction. The Journal of steroid biochemistry and molecular biology, Volume: 132, Issue: 3-5	2012
A novel bisphosphonate inhibitor of squalene synthase combined with a statin or a nitrogenous bisphosphonate in vitro. Journal of lipid research, Volume: 52, Issue: 11	2011
Zoledronic acid combined with chemotherapy bring survival benefits to patients with bone metastases from nasopharyngeal carcinoma. Journal of cancer research and clinical oncology, Volume: 137, Issue: 10	2011
Phase I/II study of adoptive transfer of γδ T cells in combination with zoledronic acid and IL-2 to patients with advanced renal cell carcinoma. Cancer immunology, immunotherapy : CII, Volume: 60, Issue: 8	2011
The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Experimental hematology, Volume: 39, Issue: 1	2011
[Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University, Volume: 30, Issue: 6	2010
Death receptor 5 agonist TRA8 in combination with the bisphosphonate zoledronic acid attenuated the growth of breast cancer metastasis. Cancer biology & therapy, Volume: 8, Issue: 12	2009
[Clinical analysis of therapeutic effect of zoledronic acid combined with radiotherapy for metastatic bone cancer]. Zhonghua zhong liu za zhi [Chinese journal of oncology], Volume: 30, Issue: 7	2008
RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid. The Prostate, Jun-01, Volume: 68, Issue: 8	2008
Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. Lung cancer (Amsterdam, Netherlands), Volume: 47, Issue: 1	2005
Antiproliferative efficacy of the third-generation bisphosphonate, zoledronic acid, combined with other anticancer drugs in leukemic cell lines. International journal of hematology, Volume: 79, Issue: 1	2004
Effects of oral UFT combined with or without zoledronic acid on bone metastasis in the 4T1/luc mouse breast cancer. International journal of cancer, Oct-10, Volume: 106, Issue: 6	2003
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

zoledronic acid

Description

Cross-References

Synonyms (93)

Research Excerpts

Overview

Effects

Actions

Treatment

Roles (1)

Drug Classes (2)

Pathways (1)

Protein Targets (25)

Potency Measurements

Inhibition Measurements

Activation Measurements

Other Measurements

Biological Processes (158)

Molecular Functions (49)

Ceullar Components (42)

Bioassays (284)

Research

Studies (3,923)

Study Types

Clinical Trials (338)

Trial Overview

Trial Outcomes

Time to First and Subsequent On-Study Skeletal-Related Event

Time to First On-Study Skeletal Related Event (SRE) (Non-inferiority)

Time to First On-Study Skeletal-Related Event (Superiority)

Change in Pain Interference Score

Change in Pain Severity Score

Number of Participants With a Disease Relapse During the Extended Observation Period

Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period

Number of Participants With a Partial Disease Relapse During the Extended Observation Period

Number of Patients Who Achieve Therapeutic Response at 6 Months.

Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline

Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28

Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10

Relative Change in Urine Alpha C-telopeptide (α-CTx) in ug/mmol at Day 10

Time to First Therapeutic Response

Disease-free Survival

Overall Survival

Distributions of Sites of First Recurrence on the Three Arms.

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Change in Lumbar Spine BMD From Baseline to 6 Months After the Zoledronic Acid Infusion.

Changes in BMD From Baseline to One Year After the Zoledronic Acid Infusion.

Changes in BMD From Baseline to Two Years After the Zoledronic Acid Infusion.

Changes in Cortical Porosity Measured by High-resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Scan at the Radius and Tibia From Baseline to One Year After the Zoledronic Acid Infusion.

Changes in p-CTX From Baseline to 12 Months After the Zoledronic Acid Infusion.

Changes in p-CTX From Baseline to Six Months After the Zoledronic Acid Infusion.

Morphometric Vertebral Fractures Assessed by Vertebral Fracture Assessment (VFA) One and Two Years After the Zoledronic Acid Infusion.

Number of Participants Who Fail to Maintain BMD

Change From Baseline in Radial Bone Strength (Failure Load) at Month 12

Change From Baseline in Radial Bone Strength (Stiffness) at Month 12

Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12

Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12

Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12

Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time

Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12

Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12

Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12

Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6

Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12

Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6

Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12

Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12

Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12

Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set

Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12

Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12

Change From Baseline in Total vBMD (Radial and Tibial) Over Time

Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm

Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set

Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm

Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set

Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm

Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set

Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14

Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death