Alternative Osteoporosis Therapies After Bisphosphonate Associated Atypical Femur Fractures: A Retrospective Analysis

Bisphosphonate medications reduce the risk of osteoporotic fragility fractures; however, prolonged use increases the risk of atypical femur fractures (AFF). As the population ages and the burden of osteoporosis rises, the relative incidence of AFFs is expected to grow. Current expert guidelines recommend discontinuing bisphosphonates and initiating alternative anti-fracture therapies (AFT), such as denosumab, teriparatide, or raloxifene, following an AFF to support skeletal health and reduce future fracture risk. However, it is unclear which patients receive these medications after an AFF. This study aims to identify demographics associated with the initiation of alternate osteoporosis therapies following an AFF.

We conducted a retrospective cohort study using data from the TriNetX Registry to identify patients who were on bisphosphonate therapy that had an AFF. The primary outcome was initiation of teriparatide, denosumab, or raloxifene within one year after AFF. We compared patient demographics and baseline characteristics between those initiated on AFT after an AFF and those who were not. Pairwise comparisons of proportions were performed between the groups using two-proportion Z-tests with Bonferroni correction to account for multiple comparisons.

We identified 784 patients with AFFs following bisphosphonate use. 71 patients (9.5%) were initiated on AFT following the index fracture. Teriparatide (83.1%) was the most commonly prescribed AFT, followed by denosumab (21.9%), then raloxifene (≤14.1%). Patients initiated on AFT were more likely to have a previous fragility fracture (66.2% vs 45.2%, P < 0.001). Other patient demographics assessed did not show any significant differences.

Despite expert recommendations, AFT was initiated in only a small percentage of patients following AFFs. These findings highlight a significant care gap in secondary fracture prevention and underscore the need for a multidisciplinary approach, including coordination between endocrinology, orthopaedics, and primary care, to improve adherence to post-fracture osteoporosis management guidelines.