etidronate and Osteogenesis Imperfecta studies

Etidronic Acid: A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.
etidronic acid : A 1,1-bis(phosphonic acid) that is (ethane-1,1-diyl)bis(phosphonic acid) having a hydroxy substituent at the 1-position. It inhibits the formation, growth, and dissolution of hydroxyapatite crystals by chemisorption to calcium phosphate surfaces.

Osteogenesis Imperfecta: COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.

Research Excerpts

Excerpt	Relevance	Reference
"A case of osteogenesis imperfecta (OI) that was successfully treated with oral etidronate and alfacalcidol is reported."	7.72	Effects of treatment with etidronate and alfacalcidol for osteogenesis imperfecta type I: a case report. ( Ichimura, S; Iwamoto, J; Matsu, K; Takeda, T; Uzawa, M, 2003)
"A case of osteogenesis imperfecta (OI) that was successfully treated with oral etidronate and alfacalcidol is reported."	3.72	Effects of treatment with etidronate and alfacalcidol for osteogenesis imperfecta type I: a case report. ( Ichimura, S; Iwamoto, J; Matsu, K; Takeda, T; Uzawa, M, 2003)
"Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates."	2.78	Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. ( Adami, S; Ahmed, SF; Antón, J; Arundel, P; Bishop, N; Burren, CP; Devogelaer, JP; Hangartner, T; Hosszú, E; Lane, JM; Lorenc, R; Mäkitie, O; Munns, CF; Paredes, A; Pavlov, H; Plotkin, H; Raggio, CL; Reyes, ML; Schoenau, E; Semler, O; Sillence, DO; Steiner, RD, 2013)
"Moderate to severe osteogenesis imperfecta is associated with multiple fractures in childhood."	2.75	A randomized, controlled dose-ranging study of risedronate in children with moderate and severe osteogenesis imperfecta. ( Ahmed, F; Bishop, N; Campbell, M; Chapman, S; Eastell, R; Hall, C; Harrison, R; Hill, C; Knowles, E; Rigby, A; Shaw, N; Sprigg, A, 2010)

Research

Studies (7)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Annualized Growth Velocity - Change From Baseline to Month 12, ITT Population

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (28.57)	29.6817
2010's	5 (71.43)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Ward, LM	1
Rauch, F	2
Bishop, N	2
Adami, S	1
Ahmed, SF	1
Antón, J	1
Arundel, P	1
Burren, CP	1
Devogelaer, JP	1
Hangartner, T	1
Hosszú, E	1
Lane, JM	1
Lorenc, R	1
Mäkitie, O	2
Munns, CF	2
Paredes, A	1
Pavlov, H	1
Plotkin, H	1
Raggio, CL	1
Reyes, ML	1
Schoenau, E	1
Semler, O	1
Sillence, DO	1
Steiner, RD	1
Arponen, H	1
Vuorimies, I	1
Haukka, J	1
Valta, H	1
Waltimo-Sirén, J	1
Land, C	1
Cheung, M	1
Glorieux, FH	1
Harrison, R	1
Ahmed, F	1
Shaw, N	1
Eastell, R	1
Campbell, M	1
Knowles, E	1
Hill, C	1
Hall, C	1
Chapman, S	1
Sprigg, A	1
Rigby, A	1
Bradbury, LA	1
Barlow, S	1
Geoghegan, F	1
Hannon, RA	1
Stuckey, SL	1
Wass, JA	1
Russell, RG	1
Brown, MA	1
Duncan, EL	1
Iwamoto, J	1
Matsu, K	1
Takeda, T	1
Ichimura, S	1
Uzawa, M	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children[NCT00106028]	Phase 3	143 participants (Actual)	Interventional	2004-11-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)] (NCT00106028)
Timeframe: Baseline and Month 12

Annualized Growth Velocity - Change From Baseline to Month 36, ITT Population

Intervention	Change in Annualized Growth Velocity (Least Squares Mean)
Placebo Daily	0.895
Risedronate Daily	1.002

Annualized Growth Velocity [= bone age change from baseline x (365.25/time in days between baseline and the bone age measurement)] (NCT00106028)
Timeframe: Baseline and Month 36

Bone Age (Years), Change From Baseline to Month 12, ITT Population

Intervention	Change in Annualized Growth Velocity (Least Squares Mean)
Placebo Daily	0.982
Risedronate Daily	1.011

Bone Age determined by visual assessment of hand / wrist radiographs. (NCT00106028)
Timeframe: Baseline and Month 12

Bone Age (Years), Change From Baseline to Month 24, ITT Population

Intervention	Years (Least Squares Mean)
Placebo Daily	0.956
Risedronate Daily	1.083

Bone Age determined by visual assessment of hand / wrist radiographs. (NCT00106028)
Timeframe: Baseline and Month 24

Bone Age (Years), Change From Baseline to Month 36, ITT Population

Intervention	Years (Least Squares Mean)
Placebo Daily	2.147
Risedronate Daily	2.155

Bone Age determined by visual assessment of hand / wrist radiographs. (NCT00106028)
Timeframe: Baseline and Month 36

Lumbar Spine Z-score - Percent Change From Baseline to Month 12, ITT Population

Intervention	Years (Least Squares Mean)
Placebo Daily	3.087
Risedronate Daily	3.096

"Lumbar Spine Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are best values and negative values are worst values." (NCT00106028)
Timeframe: Baseline and Month 12

Lumbar Spine Z-score - Percent Change From Baseline to Month 24, ITT Population

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	-6.028
Risedronate Daily	25.648

Lumbar Spine Z-score - Percent Change From Baseline to Month 36, ITT Population

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	15.608
Risedronate Daily	29.637

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 12, ITT Population

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 24, ITT Population

Percent Change From Baseline in Lumbar Spine BMC (Bone Mineral Content) at Month 36, ITT Population

Percent Change From Baseline in Lumbar Spine Bone Area at Month 12, ITT Population

Percent Change From Baseline in Lumbar Spine Bone Area at Month 24, ITT Population

Percent Change From Baseline in Lumbar Spine Bone Area at Month 36, ITT Population

Percent Change From Baseline in Total Body BMC at Month 12, ITT Population

Percent Change From Baseline in Total Body BMC at Month 24, ITT Population

Percent Change From Baseline in Total Body BMC at Month 36, ITT Population

Percent Change From Baseline in Total Body BMD at Month 12, ITT Population

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	19.325
Risedronate Daily	25.640

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	17.885
Risedronate Daily	28.218

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	42.367
Risedronate Daily	48.407

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	68.054
Risedronate Daily	68.333

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	8.803
Risedronate Daily	9.817

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	16.381
Risedronate Daily	17.266

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	24.952
Risedronate Daily	23.292

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	16.483
Risedronate Daily	21.977

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	36.465
Risedronate Daily	37.938

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	56.211
Risedronate Daily	56.526

Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA. (NCT00106028)
Timeframe: Baseline and Month 12

Percent Change From Baseline in Total Body BMD at Month 24, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	4.252
Risedronate Daily	5.806

Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA. (NCT00106028)
Timeframe: Baseline and Month 24

Percent Change From Baseline in Total Body BMD at Month 36, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	9.716
Risedronate Daily	10.214

Percent Change from baseline in Total Body Bone Mineral Density (BMD) measured by DXA. (NCT00106028)
Timeframe: Baseline and Month 36

Percent Change From Baseline in Total Body Bone Area Month 12, ITT Population

Percent Change From Baseline in Total Body Bone Area Month 24, ITT Population

Percent Change From Baseline in Total Body Bone Area Month 36, ITT Population

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 12, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	13.540
Risedronate Daily	13.076

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	11.405
Risedronate Daily	14.939

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	24.051
Risedronate Daily	25.116

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	37.109
Risedronate Daily	38.303

Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader. Duplicate scans obtained at screening and Month 12. (NCT00106028)
Timeframe: Baseline and Month 12

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 24, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	7.592
Risedronate Daily	16.159

Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader. (NCT00106028)
Timeframe: Baseline and Month 24

Percent Change From Baseline Lumbar Spine Bone Mineral Density (BMD) at Month 36, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	21.316
Risedronate Daily	25.754

Lumbar Spine Bone Mineral Density (BMD) measured by dual-energy x-ray absorptiometry (DXA)and read by central reader. (NCT00106028)
Timeframe: Baseline and Month 36

Serum BAP - Percent Change From Baseline to Month 12, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	33.216
Risedronate Daily	34.753

Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment. (NCT00106028)
Timeframe: Baseline and 12 Months

Serum BAP - Percent Change From Baseline to Month 24, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	6.783
Risedronate Daily	-4.895

Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment. (NCT00106028)
Timeframe: Baseline and 24 Months

Serum BAP - Percent Change From Baseline to Month 36, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	-11.196
Risedronate Daily	-11.128

Serum Bone Alkaline Phosphatase (BAP - bone formation marker). Negative percent changes indicate response to treatment. (NCT00106028)
Timeframe: Baseline and 36 Months

Total Body Z-score- Percent Change From Baseline to Month 12, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	-19.884
Risedronate Daily	-24.570

"Total Body Z-score - number of standard deviations a patient's BMD differs from the average BMD of their age, sex, and ethnicity. Positive scores indicate BMD above the mean; Positive values are best values and negative values are worst values." (NCT00106028)
Timeframe: Baseline and Month 12

Total Body Z-score- Percent Change From Baseline to Month 24, ITT Population

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	-20.661
Risedronate Daily	16.933

Total Body Z-score- Percent Change From Baseline to Month 36, ITT Population

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	8.371
Risedronate Daily	7.879

Urine NTX/Cr - Percent Change From Baseline at Month 12, ITT Population

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	7.146
Risedronate Daily	-1.494

Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment. (NCT00106028)
Timeframe: Baseline and Endpoint / Month 12

Urine NTX/Cr - Percent Change From Baseline at Month 24, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	-14.556
Risedronate Daily	-41.185

Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment. (NCT00106028)
Timeframe: Baseline and Month 24

Urine NTX/Cr - Percent Change From Baseline at Month 36, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	-40.358
Risedronate Daily	-31.318

Urine type-I collagen N-telopeptide/creatinine (NTX/Cr; bone resorption marker). Negative percent changes indicate response to treatment. (NCT00106028)
Timeframe: Baseline and Month 36

Wong-Baker FACES Pain Rating Scale - Change From Baseline to Month 12, ITT Population

Intervention	Percent Change (Least Squares Mean)
Placebo Daily	-47.570
Risedronate Daily	-52.609

Wong-Baker FACES Pain Rating Scale (pain assessment scale using facial expressions, translated into a range from 0= no pain [smiling face] to 10= worst pain possible [distorted face with tears]; negative values indicate decrease in pain). Reference: Wong DL et al. (NCT00106028)
Timeframe: Baseline and Month 12

Categorization by Number of New Morphometric Vertebral Fracture at Month 12, ITT

Intervention	Units on a Scale (Least Squares Mean)
Placebo Daily	-0.056
Risedronate Daily	-0.409

Patients with 1 or more New Morphometric Vertebral Fracture as measured by SQ analysis of x-rays using the Genant scoring system (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). Incidence = SQ score is 0 at baseline and >0 at post-baseline. (NCT00106028)
Timeframe: Baseline and Month 12

Categorization by Number of New Morphometric Vertebral Fracture at Month 36, ITT

Intervention	Participants (Number)
	No New Fractured Vertebra	One Fractured Vertebra	Two Fractured Vertebra	Three or more Fractured Vertebra
Placebo Daily	40	3	2	3
Risedronate Daily	60	17	8	3

Incidence New Vertebral Fractures by SQ (Semi-Quantitative) Score, Patients Aged 4-9 Years, Month 12, ITT Population

Intervention	Participants (Number)
	No New Fractured Vertebra	One Fractured Vertebra	Two Fractured Vertebra	Three or more Fractured Vertebra
Placebo Daily	31	6	5	3
Risedronate Daily	62	10	7	3

Patients aged 4-9 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3. (NCT00106028)
Timeframe: Month 12

Incidence New Vertebral Fractures by SQ Score, Patients Aged 10-15 Years, Month 12, ITT Population

Intervention	Participants (Number)
	Number Patients with New Vertebral Fractures	Number of New Vertebral Fractures	Number Patients New Fractures & Mild SQ Score	Number Patients New Fractures & Mod/Sev SQ Score
Placebo Daily	7	19	7	3
Risedronate Daily	19	32	17	3

Patients aged 10-15 years with new morphometric vertebral fractures as measured by SQ analysis of x-rays using the Genant scoring system at Month 12 +/- 14 days. (Ref: Genant 1993). SQ Score mild - 0/no fracture to Grade 1, Moderate to Severe - change from 0/no fracture to Grade 2-3. (NCT00106028)
Timeframe: Month 12

New Morphometric Vertebral Fracture at Month 12, ITT Population

Intervention	Participants (Number)
	Number Patients with New Vertebral Fractures	Number of New Vertebral Fractures	Number Patients New Fractures & Mild SQ Score	Number Patients New Fractures & Mod/Sev SQ Score
Placebo Daily	1	1	1	0
Risedronate Daily	10	13	10	1

Morphometric Vertebral Fracture measured by semi-quantitative (SQ) analysis of x-rays using the Genant scoring system at endpoint. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and >0 at the specified end visit. (NCT00106028)
Timeframe: Baseline and Month 12

New Morphometric Vertebral Fracture at Month 36, ITT Population

Intervention	Participants (Number)
	At Least One New Fracture Vertebra	No New Fractured Vertebra
Placebo Daily	8	40
Risedronate Daily	28	60

Morphometric Vertebral Fracture measured by SQ analysis of x-rays using the Genant scoring system. (Ref: Genant 1993). SQ-Scores range from 0 (no fracture) to 3 (severe fracture). New fracture = SQ score is 0 at baseline and >0 at the specified end visit. (NCT00106028)
Timeframe: Baseline and Month 36

Number of Clinical Fractures, Month 12, ITT Population

Intervention	Participants (Number)
	At Least One New Fracture Vertebra	No New Fractured Vertebra
Placebo Daily	14	31
Risedronate Daily	20	62

Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture. (NCT00106028)
Timeframe: 12 Months

Probability of Fracture in 12 Months (Kaplan-Meier Cumulative Incidence), ITT Population

Intervention	Participants (Number)
	Number of Fractures	Number of Patients with Fractures	Number of Vertebral Fractures	Number Patients with Vertebral Fractures	Number of Non-Vertebral Fractures	Number Patients with Non-Vertebral Fractures	Number Long-Bone Non-Vertebral Fractures	Number Patients Long-Bone Non-Vertebral Fractures	Number Other Non-Vertebral Fractures	Number Patients with Other Non-Vertebral Fractures
Placebo Daily	38	24	0	0	38	24	27	17	11	10
Risedronate Daily	42	29	0	0	42	29	28	18	14	12

Long bones include radius, ulna, humerus, tibia, fibula, femur, upper limb and lower limb fracture. (NCT00106028)
Timeframe: Time to First Event (days) up to 12 Months

Intervention	Probability of Fractures (Number)
	Number Patients All Fractures	All Fractures/Kaplan-Meier Cumulative Incidence	Number Patients Vertebral Fractures	Vertebral Fractures/Kaplan-Meier Cumulative Incid.	Number Patients Non-Vertebral Fractures	Non-Vertebral Fractures/Kaplan-Meier Cum. Incid.	Number Patients Long Bone Non-Vertebral Fractures	Long Bone Non-Vertebral Fractures/Kaplan-Meier Cum	Number Patients Other Non-Vertebral Fractures	Other Non-Vertebral Fractures/Kaplan-Meier Cum.
Placebo Daily	24	0.5043	0	0	24	0.5043	17	0.3618	10	0.204
Risedronate Daily	29	0.314	0	0	29	0.314	18	0.1954	12	0.1311

Article	Year
Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet (London, England), 2013, Oct-26, Volume: 382, Issue:9902 Topics: Administration, Oral; Adolescent; Alkaline Phosphatase; Analysis of Variance; Bone Density; Bone Den	2013
Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009, Volume: 24, Issue:7 Topics: Administration, Oral; Adolescent; Biomarkers; Bone Density; Bone Density Conservation Agents; Child;	2009
A randomized, controlled dose-ranging study of risedronate in children with moderate and severe osteogenesis imperfecta. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2010, Volume: 25, Issue:1 Topics: Absorptiometry, Photon; Administration, Oral; Adolescent; Age Determination by Skeleton; Bone Densit	2010
Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2012, Volume: 23, Issue:1 Topics: Adolescent; Adult; Aged; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Remodeling	2012

Article	Year
Oral bisphosphonates for paediatric osteogenesis imperfecta? Lancet (London, England), 2013, Oct-26, Volume: 382, Issue:9902 Topics: Bone Density Conservation Agents; Etidronic Acid; Female; Humans; Male; Osteogenesis Imperfecta; Ris	2013
Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates. Journal of neurosurgery. Pediatrics, 2015, Volume: 15, Issue:3 Topics: Adolescent; Bone Density Conservation Agents; Child; Child, Preschool; Diphosphonates; Drug Administ	2015
Effects of treatment with etidronate and alfacalcidol for osteogenesis imperfecta type I: a case report. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2003, Volume: 8, Issue:2 Topics: Adult; Back Pain; Bone Density; Drug Therapy, Combination; Etidronic Acid; Humans; Hydroxycholecalci	2003

etidronate and Osteogenesis Imperfecta