Bisphosphonate-Associated Fractures of the Femur: Pathophysiology and Treatment

Bisphosphonates have improved the treatment of osteoporosis and millions of patients have benefited from their therapeutic effects. However, there is strong evidence that in a small number of patients, they are associated with the development of atypical femur fractures. These fractures most likely occur as a result of impaired bone remodeling. In some patients who are not exposed to bisphosphonates, the development of atypical femur fractures may be due to inherent subclinical bone remodeling abnormalities. Nevertheless, the majority of these fractures seem to be associated with bisphosphonate use and the accumulation of a bisphosphonate at specific skeletal sites may lead to insufficient repair of microcracks, the development of stress fractures, and ultimate failure of the femur. Whether or not these effects will be observed or as prevalent with the more recently developed antiresorptive drugs, including those that do not focally accumulate such as monocloncal antibodies against Receptor Activator of NFkappaB ligand, or inhibitors of cathepsin K, remains unknown at this time. Once there are skeletal changes associated with the development of atypical femur fractures such as cortical thickening or a visible stress fracture, bisphosphonate treatment should be discontinued and appropriate management instituted. This could range from use of ambulatory assistive devices and careful observation to prophylactic internal fixation. Operative intervention would be indicated in patients who have prodromal pain that is unresponsive to rest and unloading. Complete fractures are best treated by intramedullary nail fixation though the rate of healing may be delayed and in some cases impaired. However, it must be emphasized that the use of bisphosphonates to treat patients with osteoporosis represents a major step forward. Further investigation is required to understand the safety of prolonged use, to determine if bisphosphonates should be discontinued after a certain period of time in all patients, and possibly to identify subsets of patients whose skeletons are more sensitive to pharmacological suppression of bone remodeling who may not be candidates for bisphosphonate treatment. Copyright © 2014 by Lippincott Williams & Wilkins.