FDA not ready to declare link between oral bisphosphonates and atypical subtrochanteric femur fractures

Key Points

On March 10, 2010, FDA announced that its review of data requested in June 2008 from all bisphosphonate drug manufacturers did not suggest an increased risk of subtrochanteric femur fractures (bone breaks just below the hip) in those receiving oral bisphosphonates.

Oral bisphosphonates such as alendronate, ibandronate, and risedronate are commonly used drugs to prevent fractures due to osteoporosis. They inhibit the digestion of bone by osteoclasts and decrease bone turnover. Administration of these drugs in patients at risk for osteoporotic fractures can reduce the incidence of vertebral and hip fractures by as much as 50% over as little as 3 years.

FDA highlighted that recent case reports have raised concerns about whether oral bisphosphonates can increase the risk of this type of fracture in patients with osteoporosis due to excessive suppression of bone turnover. However more recently, Abrahamsen and colleagues reported observational register-based study data on more than 15,000 patients, showing that both those taking (n=5,187) and not taking (n=10,374) alendronate had similar risks of atypical subtrochanteric femur fractures (14% in those receiving alendronate vs 13% in the control group, P=.70), conflicting with the findings of previous case reports. Moreover, those receiving alendronate had similar hazards of developing atypical femur fractures relative to classical osteoporotic hip fractures [(HR=1.46, 95% CI, 0.91-2.35, P=.12) vs (HR=1.45, 95% CI, 1.21-1.74, P<.001), respectively]. The authors surmised that because atypical subtrochanteric femur fractures had similar epidemiology, features, and treatment response when compared with classical osteoporotic hip fractures (including patient age, gender, and trauma mechanism), they should be classified as osteoporotic fractures.

Until then, FDA is recommending that healthcare providers who wish to prescribe an oral bisphosphonate continue to follow the usage guidelines in these products' drug labels. Furthermore, they suggest providers to discuss all the known benefits and potential risks of using an oral bisphosphonates with their patients before the decision to start or alter treatment is made.

SOURCES

1. FDA. FDA Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures. March 10, 2010. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203891.htm. Accessed March 15, 2010.

2. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2010.

3. Abrahamsen B, Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: A register-based national cohort study. J Bone Miner Res. 2009;24(6):1095–1102.