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. Summary: 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.
Bibliographical noteAcknowledgements: The authors are grateful for the support from the
Jaap Schouten Foundation, Rotterdam, the Netherlands, and the
National Health and Medical Research Council of Australia. The authors
also wish to thank Maarten F.M. Engel from the Erasmus MC Medical
Library for developing and updating the search strategies.
Publisher Copyright: © 2021, The Author(s).