Three-dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture

BACKGROUND: Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown. METHODS: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992-2004 were identified. By using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall-related fracture outside the radiation field. RESULTS: After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR, 1.76; 95% confidence interval [CI, 1.38-2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56-1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88-3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17-1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97-2.10). The number needed to treat to result in 1 hip fracture during a 10-year period was 51 patients (95% CI, 31-103). CONCLUSIONS: In men with prostate cancer, pelvic 3-D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT must be site-specific as there was no increase in the risk of fall-related fractures in bones that were outside the radiation field.