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

Lucy Collins; Cat Shore-Lorenti; Colin Chen; Frances Milat; Shoshana Sztal-Mazer; Vivian Grill; Christopher Yates; Cherie Chiang; Christian M Girgis; Aasis Unnanuntana; Richard Dell; Roderick Clifton-Bligh; Peter R Ebeling; Hanh H Nguyen

doi:10.1093/jbmr/zjag070

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

J Bone Miner Res. 2026 Apr 16:zjag070. doi: 10.1093/jbmr/zjag070. Online ahead of print.

Authors

Lucy Collins^{1

2

3}, Cat Shore-Lorenti¹, Colin Chen¹, Frances Milat^{1

2

4}, Shoshana Sztal-Mazer^{5

6}, Vivian Grill^{3

7}, Christopher Yates^{3

8}, Cherie Chiang^{7

8

9}, Christian M Girgis^{10

11

12}, Aasis Unnanuntana¹³, Richard Dell¹⁴, Roderick Clifton-Bligh^{10

12}, Peter R Ebeling^{1

2}, Hanh H Nguyen^{1

2

3

7}

Affiliations

¹ Department of Medicine, School of Clinical Sciences, Monash University, Victoria, Australia.
² Department of Endocrinology, Monash Health, Victoria, Australia.
³ Department of Endocrinology and Diabetes, Western Health, Victoria, Australia.
⁴ Hudson Institute of Medical Research, Victoria, Australia.
⁵ Department of Endocrinology and Diabetes, Alfred Health, Victoria, Australia.
⁶ Department of Public Health and Preventative Medicine, Monash University, Victoria, Australia.
⁷ Department of Medicine, The University of Melbourne, Victoria, Australia.
⁸ Department of Endocrinology and Diabetes, The Royal Melbourne Hospital, Victoria, Australia.
⁹ Department of Endocrinology, Austin Health, Victoria, Australia.
¹⁰ Department of Endocrinology, Royal North Shore Hospital, New South Wales, Australia.
¹¹ Department of Diabetes and Endocrinology, Westmead Hospital, New South Wales, Australia.
¹² Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.
¹³ Department of Orthopaedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
¹⁴ Department of Orthopaedics, Southern California Permanente Medical Group, California, United States of America.

PMID: 41989128
DOI: 10.1093/jbmr/zjag070

Abstract

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.

Keywords: Anti-resorptives; Asian ethnicity; Atypical femur fracture; Bisphosphonates; Ethnicity; Fragility fracture.

Plain language summary

Atypical femur fractures (AFFs) are a rare safety concern of medications used to treat osteoporosis. Fear of AFFs has led to a decline in treatment of osteoporosis. We analysed data from 166 patients with AFFs. We found that individuals of Asian and Southeast Asian ethnicity tended to sustain AFFs after a shorter duration of treatment compared to non-Asian individuals. These findings may help guide more individualised discussions about osteoporosis treatment duration.