Atypical fractures of the femur and bisphosphonate therapy: A systematic review of case/case series studies.

Atypical fractures of the femur below the lesser trochanter have been reported in patients treated with bisphosphonates. We performed a systematic literature search of case/case series studies to better define the clinical presentation and to identify characteristics that may predispose patients to such fractures. We considered only women treated with a bisphosphonate at a dosing regimen used for the prevention or treatment of osteoporosis and we included also eight own unpublished cases. We identified 141 women with atypical fractures of the femur, mean age of 67.8+/-11.0 years, who were treated with bisphosphonate for 71.5+/-40.0 months (range=3-192 months). The results of this analysis allow identification of patients on bisphosphonate treatment at risk of developing atypical fractures, define fractures better as predominantly insufficiency fractures, illustrate that long-term bisphosphonate treatment is not a prerequisite for their development, recognize the use of glucocorticoids and proton pump inhibitors as important risk factors, but do not provide insights in the pathogenesis of these fractures and raise questions that need to be addressed in properly designed studies.