Association between androgen deprivation therapy and fracture risk: A population-based cohort study in men with non-metastatic prostate cancer

Abstract

4507 Background: Androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist decreases bone mineral density in men with prostate cancer. Small retrospective studies have suggested that GnRH agonists increase fracture risk. We conducted a population-based cohort study to better characterize the association between GnRH agonist treatment and clinical fractures. Methods: Using 1991–2001 medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group (N=3887) of men with non-metastatic prostate cancer who initiated GnRH agonist treatment in 1992–94. A comparison group (N=7,774) of men with non-metastatic prostate cancer who did not receive GnRH agonist treatment during the study period was randomly matched on a 1:2 ratio based on age, race and Charlson co-morbidity index. We analyzed their inpatient, outpatient, and physician claims to identify clinical fractures between 1994–2001. Results: One third of the men who received GnRH agonist treatment experienced one or more fractures. When adjusted for survival, the fracture incidence rates during the final year of the analysis were 83% for the study group versus 56% for control group. Men in the study group were significantly more likely to develop fractures over the study period than men in control group (hazard ratio 1.4; 95% CI 1.16–1.70; P<0.001). Longer-term (>3 years) treatment with a GnRH agonist was associated with a marked increase in fracture risk compared to shorter term use (< 1year) (hazard ratio 1.5; 95% CI 1.17–1.93; P<0.001). Conclusion: Non-metastatic prostate cancer patients receiving GnRH agonist treatment were 40% more likely to develop a clinical fracture over the study period relative to those not receiving this treatment. Long-term treatment is associated with higher fracture risk. These results highlight the importance of diagnosis and management of skeletal complications in this population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceutical Corp. Novartis Oncology Novartis Oncology