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Fracture Risk Following an Atypical Femoral Fracture.

ABSTRACT: Atypical femoral fractures (AFFs) occurring during the course of osteoporosis treatment usually lead to discontinuation of anti-resorptive (AR) drugs. However, the risk of fracture after an AFF is unknown. We conducted a follow-up study of patients with AFF matched 1:3 for age and gender with patients with a peripheral major osteoporotic fracture (pMOF), in the setting of a fracture liaison service, to investigate the incidence of subsequent low-trauma fractures. Fifty-five patients with AFF (95% women, age [mean ± standard deviation] 75 ± 10 years, 89% exposed to AR drugs), followed for 6.2 ± 3.7 years, were compared to 165 matched controls with a pMOF (hip 85%) followed for 4.3 ± 2.6 years. During the follow-up, 38% of patients in the AFF group and 16% in the pMOF group received AR therapies. Continuation of AR drugs after an AFF was associated with contralateral AFF in 27% of subjects. The risks of new low-trauma, major osteoporotic and imminent (within 2 years) fractures, were similar between the two groups: incidence rate ratio (95% confidence interval [CI]) of subsequent fracture following AFF relative to pMOF, 1.30 (95% CI, 0.82-2.04), 1.28 (95% CI, 0.74-2.15), and 1.11 (95% CI, 0.54-2.15), respectively. Moreover, the risk of sustaining multiple fractures per participant was significantly increased among patients with AFF compared to pMOF (hazard ratio 1.48 [95% CI, 1.00-2.19]; p = 0.049). When taking mortality into account, the risk of subsequent fractures tended to be higher in the AFF group (sub-hazard ratio 1.42 [95% CI, 0.95-2.12]). In conclusion, patients who sustained an AFF are at high risk of subsequent fragility fractures, at least equal or even greater to the risk observed after a pMOF. However, continuation of AR drugs increases the risk of contralateral AFF. Therefore, optimal modalities for secondary fracture prevention after AFF require further evaluation. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

SUBMITTER: Begin MJ

PROVIDER: S-EPMC9298806 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Atypical femoral fracture is one of the many complications after the long-term use of bisphosphonates. The American Society for Bone and Mineral Research has officially excluded periprosthetic femoral fractures (PFFs) from the definition of atypical femoral fractures (AFFs). Several case reports found that PFFs can occur with characteristics similar to those of AFFs. The purpose of our study was to evaluate the proportion of atypical fractures among Vancouver type B1 fractures, and to determine the association between the long-term use of bisphosphonates and the occurrence of atypical periprosthetic femoral fractures (APFFs). METHODS:In this retrospective study, we reviewed 41 patients with Vancouver type B1 periprosthetic fractures between January 1, 2011 and December 31, 2018. We classified them into two groups, namely atypical and typical PFFs, based on the fracture morphology. We noted the proportion of atypical periprosthetic fractures among B1 fractures and identified risk factors. RESULTS:Among the 41 PFFs, 5 (13%) fractures were classified as atypical PFF based on the radiological characteristics. The longer duration of bisphosphonate use was probably the only independent risk factor that significantly increases the occurrence of APFF (p?=?0.03, 0.08 (CI 0.008 - 0.16)). There were no significant differences in age, gender, body mass index, comorbidities, corticosteroid use, positioning of the femoral stem, the method of fixation (cemented or cementless) and time lapse from before the primary prosthesis implantation to the PFF in the development of atypical fracture type. CONCLUSIONS:There seems to be a correlation between the long-term intake of bisphosphonates and the atypical periprosthetic fracture. Atypical femoral fracture can also occur in the periprosthetic form. TRIAL REGISTRATION:Study number: 22/2019-SZTE, http://www.klinikaikutatas.hu/hu/kutatasetika/jovahagyott-vizsgalatok-koezerdeku-adatai/category/25-jovahagyott-vizsgalatok-kozerdeku-adatai-rkeb-2019.html?download=985:22-2019 .

Project description:Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate-naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand-searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders (gene): osteogenesis imperfecta (COL1A1/COL1A2), pycnodysostosis (CTSK), hypophosphatasia (ALPL), X-linked osteoporosis (PLS3), osteopetrosis, X-linked hypophosphatemia (PHEX), and osteoporosis pseudoglioma syndrome (LRP5). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate-naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the GGPS1 gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted ALPL gene sequencing, an ALPL heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in ALPL. Targeted sequencing of ALPL, COL1A1, COL1A2, and SOX9 genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs. A large multicenter collaborative study of well-phenotyped AFF cases and controls is needed to understand the role of genetics in this uncommon condition.

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Fracture Risk Following an Atypical Femoral Fracture.

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