Bisphosphonates not associated with femoral fractures, study suggests

Bisphosphonates do not appear to be associated with atypical fractures of the femur, even after long-term use, according to a new study.

Findings from case reports and case series have indicated that the risk for atypical femoral fractures may be increased in patients taking bisphosphonates. To further investigate this possible association, researchers performed secondary analyses of data from three large randomized trials of bisphosphonate use: the Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX), and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial (PFT). They determined the relative hazards for fractures of the subtrochanteric or diaphyseal femur. The industry-funded study was published online March 24 by the New England Journal of Medicine.

Of 284 hip or femur fractures among 14,195 women in the three randomized trials, 12 fractures in 10 patients involved the subtrochanteric or diaphyseal femur. Relative hazards were 1.03 (95% CI, 0.06 to 16.46) for alendronate use in FIT, 1.50 (95% CI, 0.25 to 9.00) for zoledronic acid use in HORIZON-FIT, and 1.33 (95% CI, 0.12 to 14.67) for ongoing alendronate use in FLEX. The combined fracture rate was 2.3 per 10,000 patient-years.

The authors acknowledged that they were not able to examine patients' radiographs, that the number of events examined was small, and that their study “was underpowered for definitive conclusions.” However, they wrote, their findings indicate that femoral fractures occur rarely in patients taking bisphosphonates, even after long-term use, and that the drugs were not associated with a significant increase in femoral fracture risk.

An accompanying editorial noted that physicians should not stop prescribing bisphosphonates because of concern about atypical femoral fracture risk. “However, they should reevaluate patients who are receiving long-term bisphosphonate therapy in the context of contemporary guidelines for treatment initiation, progress while receiving therapy, current bone mineral density measurements, and risk factors for fracture,” the editorialist wrote.