Bisphosphonates and Atypical subtrochanteric and diaphyseal femoral fractures

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Bisphosphonates and Atypical subtrochanteric and diaphyseal femoral fractures


Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the American Society for Bone and Mineral Research. (Running Title: "Atypical femoral fractures task force report.) J Bone Miner Res 2010; Published online Sept. 14, 2010.


doi  10.1002/jbmr.253




Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the American Society for Bone and Mineral Research



Elizabeth Shane, David Burr, Peter R. Ebeling, Bo Abrahamsen, Robert A. Adler, Thomas D. Brown, Angela M. Cheung, Felicia Cosman, Jeffrey R. Curtis, Richard Dell, David Dempster, Thomas A. Einhorn, Harry K. Genant, Piet Geusens, Klaus Klaushofer, Kenneth Koval, Joseph M. Lane, Fergus McKiernan, Ross McKinney, Alvin Ng, Jeri Nieves, Regis O'Keefe, Socrates Papapoulos, Howe Tet Sen, Marjolein C.H. van der Meulen, Robert S. Weinstein, Michael Whyte




Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a Task Force to address key questions related to this problem.


A multi-disciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as pre?clinical studies that could provide insight into their pathogenesis.


Results and Conclusions

A case definition was developed so that subsequent studies report on the same condition. The Task Force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their associations with cortical thickening, a periosteal reaction of the lateral cortex, a medial spike when the fracture is complete, prodromal pain, bilaterality, co?morbid conditions and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross?linking and maturation, accumulation of microdamage and advanced glycation end?products, mineralization, remodeling, vascularity and angiogenesis, lend biological plausibility to a potential association with long?term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared to the number of vertebral, hip and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure and there is concern that lack of awareness and under?reporting may mask the true incidence of the problem.



Given the relative rarity of atypical femoral fractures, the Task Force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance and additional epidemiological and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopaedic and medical management. 


© 2010 American Society for Bone and Mineral Research