Bisphosphonates and atypical fractures

Atypical fractures of the femur have been linked with bisphosphonate therapy in several recent news stories. A recent industry-sponsored study looks to quell these concerns. Secondary analysis from three large randomized bisphosphonate trials with more than 14,000 women showed that among 284 hip or femur fractures recorded, a total of 12 fractures in 10 patients were classified as occurring in the subtrochanteric or diaphyseal femur, a combined rate of 2.3 per 10,000 patient years. As compared with placebo, the relative hazard ratio for the three trials did not meet statistical significance, although confidence intervals were wide. The authors conclude that the occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had been treated with bisphosphonates for as long as 10 years (N Engl J Med; published on-line March 24, 2010). An accompanying editorial published on-line at the same time by Elizabeth Shane, MD, Columbia University, acknowledges that despite excellent safety profiles, bisphosphonates have been associated with "atypical" fractures of the femur that occur with minimal or no trauma, generally affecting the proximal third of the femoral shaft. Most of these fractures have occurred in women on long-term alendronate therapy, occasionally taken together with other antiresorptive drugs, corticosteroids, or proton pump inhibitors. Shane points out that while these fractures represent concern, they are uncommon and actually occur more frequently in patients who are not on bisphosphonates. The results of this study "provide assurance that subtrochanteric fractures are extremely rare" and many more hip fractures are "prevented by bisphosphonates than are potentially caused by the drugs." Treatment with bisphosphonates up to 10 years is more effective than shorter-term treatment in preventing new vertebral fractures and nonvertebral fractures, but she also suggests that patients should be considered for "drug holidays with careful observation" if they have been on long-term therapy.