anastrozole and Bone Loss, Osteoclastic studies

Research Excerpts

Excerpt	Relevance	Reference
"Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures."	9.30	Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia. ( Blake, GM; Coleman, RE; Cuzick, J; Eastell, R; Patel, R; Sestak, I, 2019)
" Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer."	9.14	A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. ( Dixon, JM; Hannon, R; Macaskill, EJ; McCaig, FM; McHugh, M; Murray, J; Renshaw, L; Williams, L; Young, O, 2010)
"The aim of this study was to assess the effect of adjuvant anastrozole, alone or associated with risedronate, on BMD and bone fracture risk in women more than 70 years old with hormone receptor-positive early breast cancer (EBC)."	7.78	Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer. ( Basso, U; Berton, L; Brunello, A; Coin, A; Falci, C; Manzato, E; Monfardini, S; Perissinotto, E; Pintore, G; Sergi, G; Veronese, N, 2012)
"Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures."	5.30	Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia. ( Blake, GM; Coleman, RE; Cuzick, J; Eastell, R; Patel, R; Sestak, I, 2019)
" Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer."	5.14	A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. ( Dixon, JM; Hannon, R; Macaskill, EJ; McCaig, FM; McHugh, M; Murray, J; Renshaw, L; Williams, L; Young, O, 2010)
"The aim of this study was to assess the effect of adjuvant anastrozole, alone or associated with risedronate, on BMD and bone fracture risk in women more than 70 years old with hormone receptor-positive early breast cancer (EBC)."	3.78	Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer. ( Basso, U; Berton, L; Brunello, A; Coin, A; Falci, C; Manzato, E; Monfardini, S; Perissinotto, E; Pintore, G; Sergi, G; Veronese, N, 2012)
"The aim of this study was to determine whether the bone-resorption response to anastrozole differed according to initial patient age in postmenopausal women with breast cancer in a cross-sectional study."	3.77	Does anastrozole affect bone resorption similarly in early and late postmenopausal women? ( Cochrane, RA; Davie, MW; Powell, DE, 2011)
"Anastrozole treatment-related bone loss did not continue into the off-treatment follow-up period."	2.76	Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. ( Adams, J; Beckmann, MW; Clack, G; Coleman, RE; Cuzick, J; Eastell, R; Howell, A; Mackey, J, 2011)
"All three AIs induced increases in bone resorption markers, but no significant differences were observed in their effects on bone turnover markers."	2.73	Effects of third generation aromatase inhibitors on bone health and other safety parameters: results of an open, randomised, multi-centre study of letrozole, exemestane and anastrozole in healthy postmenopausal women. ( Clack, G; Eastell, R; Finkelman, RD; Fraser, WD; Hannon, RA; Lakner, G; McCloskey, EV; Miyamoto, A, 2007)
"Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men."	2.71	Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men. ( Finkelstein, JS; Leder, BZ, 2005)
"Anastrozole was associated with a significant increase in HDL-C (11."	2.71	Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial. ( Banerjee, S; Barker, P; Dowsett, M; Folkerd, L; Iqbal, J; Smith, IE, 2005)

Research

Studies (14)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Endothelial Progenitor Cells

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (7.14)	18.2507
2000's	7 (50.00)	29.6817
2010's	6 (42.86)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Sestak, I	1
Blake, GM	1
Patel, R	1
Coleman, RE	3
Cuzick, J	2
Eastell, R	4
McCaig, FM	1
Renshaw, L	1
Williams, L	1
Young, O	1
Murray, J	1
Macaskill, EJ	1
McHugh, M	1
Hannon, R	1
Dixon, JM	1
Adams, J	1
Clack, G	2
Howell, A	1
Mackey, J	1
Beckmann, MW	1
Powell, DE	1
Cochrane, RA	1
Davie, MW	1
Aihara, T	1
Suemasu, K	1
Takei, H	1
Hozumi, Y	1
Takehara, M	1
Saito, T	1
Ohsumi, S	1
Masuda, N	1
Ohashi, Y	1
Sergi, G	1
Pintore, G	1
Falci, C	1
Veronese, N	1
Berton, L	1
Perissinotto, E	1
Basso, U	1
Brunello, A	1
Monfardini, S	1
Manzato, E	1
Coin, A	1
Leder, BZ	2
LeBlanc, KM	1
Schoenfeld, DA	1
Finkelstein, JS	2
Banerjee, S	1
Smith, IE	1
Folkerd, L	1
Iqbal, J	1
Barker, P	1
Dowsett, M	1
Goss, PE	1
Hadji, P	1
Subar, M	1
Abreu, P	1
Thomsen, T	1
Banke-Bochita, J	1
McCloskey, EV	1
Hannon, RA	1
Lakner, G	1
Fraser, WD	1
Miyamoto, A	1
Finkelman, RD	1
Lea, CK	1
Flanagan, AM	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Gonadotropin-releasing Hormone Agonist Combined With Letrozole Compared With Megestrol Acetate or Medroxyprogesterone Acetate Alone as Fertility-sparing Treatment in Early Endometrial Cancer[NCT05247268]	Phase 2	104 participants (Anticipated)	Interventional	2022-03-11	Recruiting
Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men Title Changed With New Protocol (12/14/09): Hormonal Regulation of HDL-C in Men[NCT00729859]	Phase 2	31 participants (Actual)	Interventional	2008-12-31	Completed
Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men[NCT01686828]	Phase 1/Phase 2	53 participants (Actual)	Interventional	2013-06-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Number of CD33 + CD134+ cells as a percentage of all lymphocytes (NCT00729859)
Timeframe: Baseline, Day 28

Estradiol Concentration

Fasting Lipid Levels

Fasting Serum Insulin

Follicle Stimulating Hormone (FSH)

Homeostasis Model of Insulin Resistance (HOMA-IR)

Intervention	percentage of all lymphocytes (Mean)
	Baseline	Day 28
Group 1: Acyline + Placebo Gel + Placebo Pill	0.101	0.081

Intervention	pmol/L (Mean)
	Baseline	Day 28
Group 1: Acyline + Placebo Gel, Placebo Pill	95.4	31.9
Group 2: Acyline, Testosterone Gel	117.8	109.0
Group 3: Acyline, Testosterone Gel, Anastrozole Pill	96.3	36.5

Intervention	mmol/L (Mean)
	Total cholesterol Day 0	Total cholesterol Day 28	Total cholesterol Day 56	LDL choesterol Day 0	LDL cholesterol Day 28	LDL cholesterol Day 56	HDL cholesterol Day 0	HDL cholesterol Day 28	HDL cholesterol Day 56	Triglycerides Day 0	Triglycerides Day 28	Triglycerides Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill	4.97	5.44	4.95	2.95	3.29	2.87	1.19	1.37	1.19	1.79	1.73	1.89
Group 2: Acyline, Testosterone Gel, Placebo Pill	4.48	4.51	4.14	2.77	2.80	2.49	1.32	1.32	1.32	0.82	0.86	0.80
Group 3: Acyline, Testosterone Gel, Oral Anastrozole	4.56	4.56	4.27	2.67	2.75	2.51	1.40	1.32	1.30	1.08	1.08	1.02

Intervention	picomolar (Mean)
	Baseline	Day 28	Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill	54	69	54
Group 2: Acyline, Testosterone Gel, Placebo Pill	65	59	64
Group 3: Acyline, Testosterone Gel, Oral Anastrozole	50	42	50

Intervention	IU/L (Mean)
	Baseline	Day 28
Group 1: Acyline + Placebo Gel, Placebo Pill	4.2	0.42
Group 2: Acyline, Testosterone Gel	2.9	0.39
Group 3: Acyline, Testosterone Gel, Anastrazole Pill	2.5	0.87

HOMA IR is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher HOMA IR numbers are associated with increased insulin resistance and decreased insulin sensitivity. (NCT00729859)
Timeframe: Baseline, Day 28, Day 56

Luteinizing Hormone Concentration (LH)

Quantitative Insulin Sensitivity Check Index (QUICKI)

Intervention	HOMA score (Mean)
	Baseline	Day 28	Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill	1.8	2.4	2.2
Group 2: Acyline, Testosterone Gel, Placebo Pill	2.0	1.9	1.9
Group 3: Acyline, Testosterone Gel, Oral Anastrozole	1.6	1.4	1.7

Intervention	IU/L (Mean)
	Baseline	Day 28
Group 1: Acyline + Placebo Gel, Placebo Pill	4.3	0.31
Group 2: Acyline, Testosterone Gel	4.7	0.69
Group 3: Acyline, Testosterone Gel, Anastrozole	4.4	1.55

QUICKI is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher QUICKI are associated with decreased insulin resistance and increased insulin sensitivity. (NCT00729859)
Timeframe: Baseline, Day 28, Day 56

Sex Hormone Binding Globulin (SHBG)

Testosterone Concentration

Changes in Adipose Tissue Gene Expression

Intervention	QUICKI index (Mean)
	Baseline	Day 28	Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill	0.36	0.34	0.35
Group 2: Acyline, Testosterone Gel, Placebo Pill	0.35	0.35	0.35
Group 3: Acyline, Testosterone Gel, Oral Anastrozole	0.36	0.38	0.36

Intervention	nmol/L (Mean)
	Baseline	Day 28
Group 1: Acyline + Placebo Gel, Placebo Pill	34.9	37.5
Group 2: Acyline, Testosterone Gel	23.0	22.1
Group 3: Acyline, Testosterone Gel, Anastrozole Pill	27.6	25.1

Intervention	nmol/L (Mean)
	Baseline testosterone concentration	Day 28 testosterone concentration
Group 1: Acyline + Placebo Gel, Placebo Pill	15.4	0.8
Group 2: Acyline, Testosterone Gel	16.3	17.8
Group 3: Acyline, Testosterone Gel, Anastrozole	16.5	19.0

We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s. (NCT01686828)
Timeframe: 4 weeks

Insulin Sensitivity Quantified by Matsuda Index

Intervention	gene copy number per ng RNA (Mean)
Acyline + Placebo Gel + Placebo Pills	7493
Acyline + Testosterone Gel (1.25g/d) + Placebo Pills	8224
Acyline + Testosterone Gel (5g/d) + Placebo Pills	7885
Acyline + Testosterone Gel (5g/d) + Letrozole	8320

Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*2+PG90*2+PG120)/8*(FPI+PI30*2+PI60*2+PI90*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load (NCT01686828)
Timeframe: 4 weeks

Changes in Body Composition

Intervention	units on a scale (Median)
Acyline & Placebo Gel & Placebo Pill	5.0
Acyline & Testosterone Gel 1.25g/d & Placebo Pill	9.4
Acyline & Testosterone Gel 5g/d & Placebo Pill	7.2
Acyline & Testosterone Gel & Letrozole	7.3

Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period (NCT01686828)
Timeframe: 4 weeks

Intervention	kg (Mean)
	Change in fat mass	Change in lean mass
Acyline & Placebo Gel & Placebo Pill	1.1	-1.2
Acyline & Testosterone Gel & Letrozole	0.5	-0.3
Acyline & Testosterone Gel 1.25g/d & Placebo Pill	0.7	-1.4
Acyline & Testosterone Gel 5g/d & Placebo Pill	-0.4	0.0

Article	Year
Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia. Bone, 2019, Volume: 124 Topics: Anastrozole; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Breast Neoplasms; Female; Frac	2019
A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. Breast cancer research and treatment, 2010, Volume: 119, Issue:3 Topics: Adult; Aged; Aged, 80 and over; Anastrozole; Aromatase Inhibitors; Bone and Bones; Bone Resorption;	2010
Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Annals of oncology : official journal of the European Society for Medical Oncology, 2011, Volume: 22, Issue:4 Topics: Anastrozole; Antineoplastic Agents, Hormonal; Bone Density; Bone Resorption; Breast Neoplasms; Femal	2011
Effects of exemestane, anastrozole and tamoxifen on bone mineral density and bone turnover markers in postmenopausal early breast cancer patients: results of N-SAS BC 04, the TEAM Japan substudy. Oncology, 2010, Volume: 79, Issue:5-6 Topics: Aged; Aged, 80 and over; Anastrozole; Androstadienes; Antineoplastic Agents; Bone and Bones; Bone De	2010
Differential effects of androgens and estrogens on bone turnover in normal men. The Journal of clinical endocrinology and metabolism, 2003, Volume: 88, Issue:1 Topics: Administration, Cutaneous; Adult; Anastrozole; Androgens; Aromatase Inhibitors; Biomarkers; Bone Rem	2003
Differential effects of androgens and estrogens on bone turnover in normal men. The Journal of clinical endocrinology and metabolism, 2003, Volume: 88, Issue:1 Topics: Administration, Cutaneous; Adult; Anastrozole; Androgens; Aromatase Inhibitors; Biomarkers; Bone Rem	2003
Differential effects of androgens and estrogens on bone turnover in normal men. The Journal of clinical endocrinology and metabolism, 2003, Volume: 88, Issue:1 Topics: Administration, Cutaneous; Adult; Anastrozole; Androgens; Aromatase Inhibitors; Biomarkers; Bone Rem	2003
Differential effects of androgens and estrogens on bone turnover in normal men. The Journal of clinical endocrinology and metabolism, 2003, Volume: 88, Issue:1 Topics: Administration, Cutaneous; Adult; Anastrozole; Androgens; Aromatase Inhibitors; Biomarkers; Bone Rem	2003
Zoledronic acid prevents cancer treatment-induced bone loss. Oncology (Williston Park, N.Y.), 2005, Volume: 19, Issue:3 Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Resorption; Breast N	2005
Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2005, Volume: 16, Issue:12 Topics: Aged; Anastrozole; Aromatase Inhibitors; Biomarkers; Bone and Bones; Bone Resorption; Estradiol; Gly	2005
Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial. Annals of oncology : official journal of the European Society for Medical Oncology, 2005, Volume: 16, Issue:10 Topics: Aged; Anastrozole; Antineoplastic Agents, Hormonal; Biomarkers; Bone Resorption; Breast Neoplasms; D	2005
Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women. Breast cancer research : BCR, 2007, Volume: 9, Issue:4 Topics: Aged; Anastrozole; Androstadienes; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Biomarkers	2007
Effects of third generation aromatase inhibitors on bone health and other safety parameters: results of an open, randomised, multi-centre study of letrozole, exemestane and anastrozole in healthy postmenopausal women. European journal of cancer (Oxford, England : 1990), 2007, Volume: 43, Issue:17 Topics: Adrenal Glands; Alkaline Phosphatase; Anastrozole; Androstadienes; Aromatase Inhibitors; Biomarkers;	2007

Article	Year
Does anastrozole affect bone resorption similarly in early and late postmenopausal women? Calcified tissue international, 2011, Volume: 88, Issue:3 Topics: Age Factors; Aged; Anastrozole; Antineoplastic Agents, Hormonal; Bone Density; Bone Resorption; Brea	2011
Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer. Journal of bone and mineral metabolism, 2012, Volume: 30, Issue:4 Topics: Aged; Aged, 80 and over; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone De	2012
Physiological plasma levels of androgens reduce bone loss in the ovariectomized rat. The American journal of physiology, 1998, Volume: 274, Issue:2 Topics: Aging; Anastrozole; Androgen Antagonists; Androstenedione; Anilides; Animals; Body Weight; Bone Reso	1998

anastrozole and Bone Loss, Osteoclastic