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Alendronate’s Effect on Bone Loss in Men Treated with Hormonal Therapy for Prostate Cancer

Compared with placebo, an oral bisphosphonate significantly improved BMD and lessened bone turnover in men who were receiving ADT.

Androgen-deprivation therapy (ADT) for patients with prostate cancer has risen dramatically during the past decade in the U.S., primarily because it is now used in patients with nonmetastatic disease (i.e., rising prostate-specific antigen [PSA]-only disease). Men with metastatic disease survived for about 2 to 4 years after diagnosis, and short-term therapy-related complications were minimal, giving ADT a good risk-benefit ratio. However, in men without overt metastatic disease, the typical natural history is substantially longer, and long-term exposure to ADT is common. Compelling evidence shows that men who receive ADT exhibit bone loss and increased fracture risk compared with men who do not receive ADT.

To investigate whether cotherapy with the bisphosphonate alendronate, which has proven ability to retard or reverse osteoporosis, would slow bone loss or improve bone mass, 112 men (age, 85) with nonmetastatic prostate cancer were enrolled in a randomized double-blind trial at a single center in Pennsylvania. At baseline, 39% of men had osteoporosis, and 52% had low bone mass. Median ADT duration was 14 months. Oral alendronate (70 mg once weekly) or placebo was administered for 1 year; all patients received vitamin D and calcium supplementation. Patients underwent assessment of bone-mineral density (BMD) of the spine and hip and of markers of bone resorption and formation at baseline and at 1 year.

In the alendronate group, BMD increased significantly from baseline, by 3.7% (P<0.001) in the spine and by 1.6% in the femoral neck (P=0.008). In the placebo group, losses of 1.4% and 0.7%, respectively, were recorded. Bone turnover significantly decreased from baseline in alendronate patients only. No between-group differences in adverse events were observed. The study was not powered to evaluate differences in fracture rates.

Comment: Evidence is accumulating to show that ADT exerts substantial adverse effects, including diminishing BMD, worsening obesity, and enhancing risk for diabetes and cardiovascular disease, in men who are being treated for prostate cancer. These researchers showed that once weekly alendronate can increase BMD and decrease bone turnover in such men, but the substantial increase in ADT courses that are administered for nonmetastatic prostate cancer remains largely unsupported by prospective evidence. Preventing bone loss in men who, in fact, might not need ADT in the first place remains an issue for consideration.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology April 2, 2007

Citation(s):

Greenspan SL et al. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: A randomized trial. Ann Intern Med 2007 Mar 20; 146:416-24.

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