title: Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research.
abstract: Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (∼100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs.
authors.affiliation: Author affiliations appear on pp. 15-20.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
authors.forename: David
authors.initials: D
authors.lastname: Burr
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 W
authors.initials: DW
authors.lastname: Dempster
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
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: 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: Tet Sen
authors.initials: TS
authors.lastname: Howe
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 P
authors.initials: MP
authors.lastname: Whyte
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D000069448:Denosumab; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000473:pathology; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging* / Q000453:epidemiology; D015775:Fractures, Stress / Q000000981:diagnostic imaging / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012307:Risk Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab
keywords: BISPHOSPHONATES; DENOSUMAB; FRACTURES; STRESS FRACTURE; SUPPRESSION OF REMODELING