Nontraumatic bilateral atypical femoral fractures associated with long-term alendronate therapy

Olayinka A. Ogundipe


Alendronate is a bisphosphonate commonly used in the treatment of post-menopausal and steroid-associated osteoporosis. Bisphosphonates have an evidence base for reducing the occurrence of typical osteoporotic fractures. However, there has been growing recognition of a correlation with the use of long-term therapy with bisphosphonates, and rare occurrence of atypical femoral fractures (AFFs). This report describes a 72-year-old caucasian woman presenting with evolving groin and thigh pains of two weeks duration. Plain X-rays noted features compatible with bilateral impending femoral subtrochanteric fractures. She had been taking oral alendronate 70mg weekly for ten consecutive years as treatment for osteoporosis. Based on the medication history, the absence of preceding trauma or a fall, and the presence of supportive radiological findings, the diagnosis was made of impending bilateral proximal femur fractures secondary to long-term bisphosphonate therapy. The alendronate was discontinued, and the patient managed with two planned successive surgeries involving the insertion of intertrochanteric antegrade nails (inter-TAN) to both femurs. Following a period of rehabilitation, she was successfully discharged home. Some pharmacokinetic and pharmacodynamic considerations of bisphosphonates are discussed. The write-up presents a brief literature review of AFFs. The index report is further reviewed in relation to the American society for bone and mineral research (ASBMR) task force’s recommended case definition of what constitutes AFFs. The discussion concludes with the application of two previously validated causality assessment systems (CAS). In this instance, both CAS indicated a ‘probable’ classification for the adverse drug reaction (ADR) to prolonged usage of oral alendronate.


Adverse drug reaction, Alendronate, Atypical femoral fractures, Bisphosphonates, Causality, Pharmacovigilance

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