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. 2021 Apr;19(2):123-130.
doi: 10.1007/s11914-021-00658-y. Epub 2021 Feb 15.

The Genetics of Atypical Femur Fractures-a Systematic Review

Wei Zhou  1 , Jeroen G J van Rooij  1   2 , Peter R Ebeling  3 , Annemieke J M H Verkerk  1 , M Carola Zillikens  4
Affiliations

The Genetics of Atypical Femur Fractures-a Systematic Review

Wei Zhou et al. Curr Osteoporos Rep. 2021 Apr.

Abstract

Purpose of review: Atypical femur fractures (AFFs) are rare subtrochanteric or diaphyseal fractures regarded as side effects of bisphosphonates (BPs), possibly with a genetic background. Here, we summarize the most recent knowledge about genetics of AFFs.

Recent findings: AFF has been reported in 57 patients with seven different monogenic bone disorders including hypophosphatasia and osteogenesis imperfecta; 56.1% had never used BPs, while 17.5% were diagnosed with the disorder only after the AFF. Gene mutation finding in familial and sporadic cases identified possible AFF-related variants in the GGPS1 and ATRAID genes respectively. Functional follow-up studies of mutant proteins showed possible roles in AFF. A recent small genome-wide association study on 51 AFF cases did not identify significant hits associated with AFF. Recent findings have strengthened the hypothesis that AFFs have underlying genetic components but more studies are needed in AFF families and larger cohorts of sporadic cases to confirm previous results and/or find novel gene variants involved in the pathogenesis of AFFs.

Keywords: Atypical femur fractures; Bisphosphonates; Genetics; Osteoporosis.

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Conflict of interest statement

M. Carola Zillikens reports grants from National Health and Medical Research Council of Australia and grants from Jaap Schouten Foundation, the Netherlands during the conduct of the study. Peter R. Ebeling reports grants from National Health and Medical Research Council of Australia during the conduct of the study and grants from Amgen, Eli-Lilly, Alexion outside the submitted work. Jeroen G.J. van Rooij, Annemieke J.M.H. Verkerk, and Wei Zhou declare no conflict of interest.

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