Asian ethnicity is associated with shorter anti-resorptive exposure prior to atypical femur fracture (AFF): a Transcontinental Atypical Femoral Fracture Consortium (TrAFFiC) cohort study

Osteoporosis prevalence is expected to increase with global ageing. Bisphosphonates and denosumab are effective treatments, but anxiety regarding safety concerns, medication-related osteonecrosis of the jaw and atypical femur fractures (AFFs), have contributed to a decline in bisphosphonate use in recent years. The Transcontinental Atypical Femoral Fracture Consortium (TrAFFiC) was established to identify potential higher risk clinical factors contributing to AFF development. Within TrAFFiC, an AFF registry was established. One hundred and sixty-six patients with AFFs were included. Seventy-seven (46%) patients sustained bilateral AFFs, totalling 243 AFFs (138 complete, 105 incomplete). Sixty-two (37%) individuals were of Asian ethnicity, with 40 (24%) specifically of Southeast Asian ethnicity. Comparisons within this AFF cohort revealed that Asian individuals were shorter and lower weight (152.0 cm vs. 154.6cm, p < 0.038; 57.5kg vs. 66.8 kg, p < 0.001) than non-Asian peers and were less likely to have a history of minimal trauma fractures prior to AFF (53% vs 84%, p < 0.001). Asian ethnicity [OR 2.10 (95% CI 1.06, 4.02), p = 0.034] and Southeast Asian ethnicity [OR 3.25 (95% CI 1.55, 6.8), p = 0.002] were associated with an increased likelihood of "earlier onset" AFF development, that is an AFF sustained following ≤ 5 years of anti-resorptive treatment. Lastly, teriparatide use following incomplete AFF (n=34) did not affect time to healing or pain resolution. In conclusion, Asian individuals sustained AFFs following a shorter duration of anti-resorptive treatment compared with non-Asian AFF peers. In addition, Asian individuals were less likely to sustain additional minimal trauma fractures. Whilst assessment for a drug holiday may be appropriate for patients at lower risk of AFF after five years of oral anti-resorptive treatment, in those with risk factors for "earlier onset" AFF, further research is required to guide whether a lower dose or shorter duration of treatment or prioritisation of bone anabolic treatments should be considered.