Effect of Once-Weekly Oral Alendronate on Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

A Randomized Trial

20 March 2007 | Volume 146 Issue 6 | Pages 416-424

Background: Androgen deprivation therapy (ADT) in men with prostate cancer is associated with bone loss and fractures.

Objective: To determine whether once-weekly oral bisphosphonate can prevent bone loss and reduce bone turnover in men receiving ADT.

Design: Randomized, double-blind, placebo-controlled, partial crossover trial. First-year, preplanned analysis of a 2-group, parallel-design phase.

Setting: University medical center.

Patients: 112 men with nonmetastatic prostate cancer receiving ADT.

Intervention: Alendronate, 70 mg once weekly, or placebo. All patients received calcium and vitamin D supplementation.

Measurements: Bone mineral density of the spine and hip and markers of bone resorption and formation.

Results: At baseline, 39% of men had osteoporosis and 52% had low bone mass. In men treated with alendronate, bone mineral density increased over 1 year by 3.7% (95% CI, 2.8% to 4.6%; P < 0.001) at the spine and 1.6% (CI, 0.4% to 2.8%; P = 0.008) at the femoral neck. Men in the placebo group had losses of 1.4% (CI, –2.7% to – 0.03%; P = 0.045) at the spine and 0.7% (CI, –1.5% to 0.01%; P = 0.081) at the femoral neck. At 12 months, the difference between the 2 groups was 5.1 percentage points (CI, 3.5 to 6.7 percentage points; P < 0.001) at the spine and was 2.3 percentage points (CI, 1.0 to 3.7 percentage points; P < 0.001) at the femoral neck. Bone turnover statistically significantly decreased with active therapy compared with placebo. The groups did not differ in adverse events.

Limitations: The study was short (1 year) and was not powered to detect differences in the frequency of fractures.

Conclusions: Bone loss that occurred with ADT was prevented and improved with once-weekly oral alendronate. Because most men have low bone mass or osteoporosis, physicians should assess their patients' bone density and provide preventive and therapeutic measures as appropriate.

ClinicalTrials.gov registration number: NCT00048841.

Editors' Notes Context Men who receive androgen deprivation therapy for prostate cancer have an increased risk for bone loss and fractures. Contribution The researchers randomly assigned men receiving androgen deprivation therapy to take alendronate or placebo. After 12 months, men who received alendronate had higher bone mineral density and lower bone turnover than men receiving placebo. Cautions The study was of short duration and was not powered to detect differences in fracture incidence. Implications Alendronate seems to effectively slow bone loss in men with prostate cancer who receive androgen deprivation therapy. —The Editors

 

Author and Article Information

From the University of Pittsburgh, Pittsburgh, Pennsylvania, and Roswell Park Cancer Institute, Buffalo, New York.

Acknowledgments: The authors thank the nursing, professional, laboratory, dietary, administrative, and study staff of the General Clinical Research Center and Osteoporosis Prevention and Treatment Center at the University of Pittsburgh and the members of the data and safety monitoring board for their oversight of the study.

Grant Support: In part by the National Institutes of Health (R01 DK61536), the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK062895), and the General Clinical Research Center of the University of Pittsburgh by the National Institutes of Health and the National Center for Research Resources (M01-RR00056).

Potential Financial Conflicts of Interest: Consultancies: S.L. Greenspan (Merck & Co. Inc.); Honoraria: S.L. Greenspan (Merck & Co. Inc.); Grants received: S.L. Greenspan (Merck & Co. Inc.).

Requests for Single Reprints: Megan Miller, 3471 Fifth Avenue, Suite 1110, Kaufmann Medical Building, Pittsburgh, PA 15213; e-mail, millerm{at}dom.pitt.edu.

Current Author Addresses: Dr. Greenspan: University of Pittsburgh, 3471 Fifth Avenue, Suite 1110, Pittsburgh, PA 15213-3221.

Dr. Nelson: Department of Urology, University of Pittsburgh, 5200 Center Avenue, Suite 209, Pittsburgh, PA 15232.

Dr. Trump: Roswell Park Cancer Institute, Elm and Carlson Streets, Buffalo, NY 14263.

Dr. Resnick: Division of Geriatric Medicine, University of Pittsburgh, Kaufmann Suite 500, 3471 Fifth Avenue, Pittsburgh, PA 15213.

Author Contributions: Conception and design: S.L. Greenspan, N.M. Resnick.

Analysis and interpretation of the data: S.L. Greenspan.

Drafting of the article: S.L. Greenspan.

Critical revision of the article for important intellectual content: S.L. Greenspan, J.B. Nelson, D.L. Trump, N.M. Resnick.

Final approval of the article: S.L. Greenspan, J.B. Nelson, D.L. Trump, N.M. Resnick.

Provision of study materials or patients: S.L. Greenspan, J.B. Nelson, D.L. Trump, N.M. Resnick.

Obtaining of funding: S.L. Greenspan, N.M. Resnick.

Administrative, technical, or logistic support: S.L. Greenspan.

Collection and assembly of data: S.L. Greenspan.

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