Skeletal health after continuation, withdrawal, or delay of alendronate in men with prostate cancer undergoing androgen-deprivation therapy

J Clin Oncol. 2008 Sep 20;26(27):4426-34. doi: 10.1200/JCO.2007.15.1233.

Abstract

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.

Publication types

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

MeSH terms

  • Administration, Oral
  • Aged
  • Alendronate / administration & dosage*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage*
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Fractures, Bone / prevention & control*
  • Gonadotropin-Releasing Hormone / agonists*
  • Hormone Antagonists / adverse effects
  • Hormone Antagonists / therapeutic use*
  • Humans
  • Male
  • Osteoporosis / chemically induced
  • Osteoporosis / prevention & control*
  • Prostatic Neoplasms / drug therapy*
  • Risk Assessment

Substances

  • Bone Density Conservation Agents
  • Hormone Antagonists
  • Gonadotropin-Releasing Hormone
  • Alendronate