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(6):416-24. doi: 10.7326/0003-4819-146-6-200703200-00006.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alendronate / administration & dosage*
  • Alendronate / adverse effects
  • Androgen Antagonists / adverse effects*
  • Biomarkers / metabolism
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / adverse effects
  • Bone Resorption / chemically induced
  • Bone Resorption / prevention & control*
  • Cross-Over Studies
  • Double-Blind Method
  • Hip
  • Humans
  • Male
  • Middle Aged
  • Prostatic Neoplasms / drug therapy*
  • Risk Factors
  • Spine / metabolism

Substances

  • Androgen Antagonists
  • Biomarkers
  • Bone Density Conservation Agents
  • Alendronate

Associated data

  • ClinicalTrials.gov/NCT00048841