Atypical femur fracture (AFF) occurs after a shorter duration of antiresorptive therapy in Asians compared to non-Asians: a transcontinental atypical femoral fracture consortium (TRAFFIC) study.

Abstract

Purpose Antiresorptive drugs are effective osteoporosis therapies, but fear of AFFs, a rare side effect, have led to faltering treatment rates. TrAFFiC is an international multisite AFF registry established to systemically characteristic clinical, radiographic, bone densitometric, microarchitectural and genetic profiles of patients with AFF. Herein, we present the cohort's baseline phenotypic data. Methods AFF cases were referred from study sites in Australia and Thailand, and radiographs were reviewed by a single orthopaedic surgeon (RD) to verify cases fulfilling the ASBMR AFF case definition. Patients completed a standardized questionnaire regarding demographic data, comorbidities, medication/antiresorptive history and AFF details, including AFF healing and treatment. Pathology, bone densitometric and femur radiographs at the time of AFF were collected. All participants provided blood samples for biobanking, and a subgroup consented to high resolution pQCT. Descriptive data are displayed as counts [n(%)], mean (SD) or median (IQR). Mann-Whitney U test (non-parametric variables), independent t-test (parametric variables) and Chi-square tests (categorical variables) were used. Statistical significance was defined as a p value <= 0.05. Results 166 patients were recruited (Table 1), of which 72 (43.4%) sustained bilateral AFFs, totalling 238 AFFs. The median age at first AFF was 73 years (IQR 66-79). Bilateral AFF cases were younger than those who sustained unilateral AFF (71 versus 75 years, p=0.002). Majority were female (95%) and independently ambulating prior to sustaining an AFF (74%). Sixty (36%) individuals were of Asian ethnicity. Five patients had a known rare bone disease. AFFs were sustained following minimal trauma (90%) and prodromal pain recorded in 53%. Antiresorptive therapy was recorded in 93%, and median duration of use prior to first AFF was 9 years (IQR 5-12). Prior corticosteroid use was documented in 44 (26.5%). In Asians with AFF, <= 5 years of antiresorptive use prior to the first AFF was more common compared with non-Asians with AFF (40% vs 25.7%, p=0.05), and duration of use was shorter [median 8 years (IQR 4-11) vs 9 years (IQR 5-14), p=0.028]. Treatment involved surgical fixation in the majority (91%). Teriparatide was utilised in 10% of cases. No biochemical abnormalities were noted. Conclusions Baseline phenotypic data from this large international AFF registry suggests Asian ethnicity is associated with AFF following a shorter duration of antiresorptive therapy than in their non-Asian peers. Further work is under way to evaluate the bone microstructure, radiographic and genetic risk factors underlying this difference.