Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health.

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Bone Loss after Initiation of Androgen Deprivation Therapy in Patients with Prostate Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0183 ◽

2005 ◽

Vol 90 (12) ◽

pp. 6410-6417 ◽

Cited By ~ 252

Author(s):

Susan L. Greenspan ◽

Penelope Coates ◽

Susan M. Sereika ◽

Joel B. Nelson ◽

Donald L. Trump ◽

...

Keyword(s):

Prostate Cancer ◽

Body Composition ◽

Bone Density ◽

Bone Loss ◽

Bone Turnover ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Healthy Controls ◽

Mineral Density ◽

Total Body

Context: Although androgen deprivation therapy (ADT) for prostate cancer is associated with bone loss, little is known about when this bone loss occurs. Objective: We postulated that men on ADT would experience the greatest bone loss acutely after initiation of ADT. Design and Setting: We conducted a 12-month prospective study at an academic medical center. Patients or Other Participants: We studied 152 men with prostate cancer (30 with acute ADT, <6 months; 50 with chronic ADT, ≥6 months; and 72 with no ADT) and 43 healthy age-matched controls. Main Outcome Measures: We assessed bone mineral density (BMD) of the hip, wrist, total body, and spine; body composition; and markers of bone turnover. Results: After 12 months, men receiving acute ADT had a significant reduction in BMD of 2.5 ± 0.6% at the total hip, 2.4 ± 1.0% at the trochanter, 2.6 ± 0.5% at the total radius, 3.3 ± 0.5% at the total body, and 4.0 ± 1.5% at the posteroanterior spine (all P < 0.05). Men with chronic ADT had a 2.0 ± 0.6% reduction in BMD at the total radius (P < 0.05). Healthy controls and men with prostate cancer not receiving ADT had no significant reduction in BMD. Both use and duration of ADT were associated with change in bone mass at the hip (P < 0.05). Men receiving acute ADT had a 10.4 ± 1.7% increase in total body fat and a 3.5 ± 0.5% reduction in total body lean mass at 12 months, whereas body composition did not change in men with prostate cancer on chronic ADT or in healthy controls (P < 0.05). Markers of bone formation and resorption were elevated in men receiving acute ADT after 6 and 12 months compared with the other men with prostate cancer and controls (P < 0.05). Men in the highest tertile of bone turnover markers at 6 months had the greatest loss of bone density at 12 months. Conclusions: Men with prostate cancer who are initiating ADT have a 5- to 10-fold increased loss of bone density at multiple skeletal sites compared with either healthy controls or men with prostate cancer who are not on ADT, placing them at increased risk of fracture. Bone loss is maximal in the first year after initiation of ADT, suggesting initiation of early preventive therapy.

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Oral bisphosphonates fail to prevent bone loss from androgen deprivation therapy in men with prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14643 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14643-14643 ◽

Cited By ~ 1

Author(s):

R. Y. Lam ◽

M. Scholz ◽

B. Guess ◽

T. Trilling

Keyword(s):

Prostate Cancer ◽

Bone Density ◽

Bone Loss ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Phase Iii ◽

Oral Bisphosphonates ◽

Prevent Bone Loss ◽

Bone Mineral Densitometry

14643 Background: Androgen deprivation therapy (ADT) is a widely administered treatment for prostate cancer. However, ADT is associated with accelerated bone loss, osteoporosis, and fractures (Shahinian, NEJM 2005; 352:154). According to Smith et al, annual bone loss on ADT approaches 9% (Smith, NEJM 2001;345:948), using QCT densitometry, a highly sensitive test for the detection of osteoporosis in men. Intravenous bisphosphonates (pamidronate, zolendronate) have been shown to prevent ADT-related bone loss in randomized phase III trials. We performed a retrospective analysis to determine if oral bisphosphonates effectively prevent bone loss in men receiving ADT. Methods: Twenty two men, ages 60–80, were placed on alendronate or risendronate at the initiation of ADT. Baseline and follow-up bone mineral densitometry (BMD) studies were performed with QCT densitometry. Repeat BMD was performed 12- 27 months (mean = 17mo) after the baseline BMD. Percentage change in bone density was annualized. Within each treatment group, the hypothesis of no mean change from baseline was analyzed using a paired t test. Results: Mean baseline bone density was 122.6mg/cc. Mean follow-up bone density was 112.7mg/cc. For the whole group, the annualized mean change in BMD was negative 7.77%/yr (p = 0.0003). Of note, 9/22 men maintained or gained bone density (-1.26% to +5.95%). 13/22 men lost at least 6.03% (-6.03% to -23.2%). There was no unexpected toxicity or fractures. Conclusions: In this retrospective study, prophylactic oral bisphosphonates do not protect against accelerated ADT-induced bone loss in men with prostate cancer. No significant financial relationships to disclose.

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