The Genetics of Atypical Femur Fractures—a Systematic Review
Open Access
- 15 February 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Current Osteoporosis Reports
- Vol. 19 (2), 123-130
- https://doi.org/10.1007/s11914-021-00658-y
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. 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.Keywords
Funding Information
- The National Health and Medical Research Council of Australia
- The Jaap Schouten Foundation, Rotterdam, the Netherlands
This publication has 57 references indexed in Scilit:
- Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fracturesJournal of Bone and Mineral Research, 2011
- Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral ResearchJournal of Bone and Mineral Research, 2010
- Trends in Incidence of Subtrochanteric Fragility Fractures and Bisphosphonate Use Among the US Elderly, 1996–2007Journal of Bone and Mineral Research, 2010
- The molecular basis of oral‐facial‐digital syndrome, type 1Seminars in Medical Genetics, Part C of the American Journal of Medical Genetics, 2009
- Incidence of stress fractures of the femoral shaft in women treated with bisphosphonateActa Orthopaedica, 2009
- Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control studyOsteoporosis International, 2008
- Collagen maturity, glycation induced-pentosidine, and mineralization are increased following 3-year treatment with incadronate in dogsOsteoporosis International, 2008
- Effects of non-enzymatic glycation on cancellous bone fragilityBone, 2007
- Subtrochanteric insufficiency fractures in patients on alendronate therapyThe Journal of Bone and Joint Surgery. British volume, 2007
- Corticosteroid-induced osteoporosis prevention: longitudinal practice patterns in The Netherlands 2001–2005Osteoporosis International, 2007