Timing of androgen deprivation therapy use and fracture risk among elderly men with prostate cancer in the United States

Pharmacoepidemiol Drug Saf. 2012 Jan;21(1):70-8. doi: 10.1002/pds.2258. Epub 2011 Nov 24.

Abstract

Purpose: Fractures are a recognized consequence of androgen deprivation therapy (ADT); however, less is known about the incidence of fracture in relation to the timing of ADT use or the impact of fracture on mortality in men with prostate cancer.

Methods: Using data from the Surveillance, Epidemiology, and End Results-Medicare linked database, we estimated adjusted hazard ratios (aHRs) using time-dependent Cox regression for fracture incidence related to the recency of exposure and dose among prostate cancer patients on gonadotropin-releasing hormone (GnRH) agonists, as well as mortality associated with fractures.

Results: In our cohort of 80 844 patients, ADT was associated with an increased rate of fracture in both non-metastatic patients (aHR = 1.34; 95% confidence interval [CI] = 1.29-1.39) and metastatic patients (aHR = 1.51; 95%CI = 1.36-1.67). Fracture rates increased with increasing cumulative GnRH dose but decreased with increasing number of months since last use in each dose category. The mortality rate doubled for men experiencing a fracture after their diagnosis compared with that for men who did not experience a fracture (aHR = 2.05; 95%CI = 1.98-2.12).

Conclusions: ADT in elderly men with prostate cancer increased the incidence of fractures, and the effect appears to diminish with increasing time since the last dose of a GnRH agonist. Experiencing a fracture after the diagnosis of prostate cancer was associated with decreased survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / adverse effects*
  • Androgen Antagonists / therapeutic use
  • Dose-Response Relationship, Drug
  • Fractures, Bone / epidemiology*
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Incidence
  • Male
  • Medicare
  • Neoplasm Metastasis
  • Proportional Hazards Models
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • SEER Program
  • Survival Rate
  • Time Factors
  • United States / epidemiology

Substances

  • Androgen Antagonists
  • Gonadotropin-Releasing Hormone