title: Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research.
abstract: 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 multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. 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, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid 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 biologic 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 Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low,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 with 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 underreporting 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 epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management.
authors.affiliation: Columbia University, College of Physicians and Surgeons, PH 8 West 864, 630 West 168th Street, New York, NY 10032, USA. es54@columbia.edu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
authors.forename: David
authors.initials: D
authors.lastname: Burr
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Adler
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Brown
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cheung
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Richard
authors.initials: R
authors.lastname: Dell
authors.forename: David
authors.initials: D
authors.lastname: Dempster
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Einhorn
authors.forename: Harry K
authors.initials: HK
authors.lastname: Genant
authors.forename: Piet
authors.initials: P
authors.lastname: Geusens
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.forename: Kenneth
authors.initials: K
authors.lastname: Koval
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lane
authors.forename: Fergus
authors.initials: F
authors.lastname: McKiernan
authors.forename: Ross
authors.initials: R
authors.lastname: McKinney
authors.forename: Alvin
authors.initials: A
authors.lastname: Ng
authors.forename: Jeri
authors.initials: J
authors.lastname: Nieves
authors.forename: Regis
authors.initials: R
authors.lastname: O'Keefe
authors.forename: Socrates
authors.initials: S
authors.lastname: Papapoulos
authors.forename: Howe Tet
authors.initials: HT
authors.lastname: Sen
authors.forename: Marjolein C H
authors.initials: MC
authors.lastname: van der Meulen
authors.forename: Robert S
authors.initials: RS
authors.lastname: Weinstein
authors.forename: Michael
authors.initials: M
authors.lastname: Whyte
mesh_terms: D026683:Advisory Committees; D003952:Diagnostic Imaging; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D004164:Diphosphonates / Q000009:adverse effects / Q000494:pharmacology; D005264:Femoral Fractures / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000628:therapy; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D006287:Health Planning Guidelines; D006620:Hip Fractures / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008903:Minerals; D011859:Radiography; D012106:Research; D012955:Societies, Medical
chemical_list: D004164:Diphosphonates; D008903:Minerals