Aromatase inhibitors therapy and major osteoporotic fracture risk in postmenopausal breast cancer patients: a nationwide real-world cohort study

The increased risk of fractures associated with aromatase inhibitors (AIs) therapy has been well established in clinical trials; however, data on Asian populations remain limited. Furthermore, the impact of AIs on fracture risk across different age groups and breast cancer stages has not been thoroughly investigated. This study aimed to assess the association between AIs therapy and major osteoporotic fractures (MOFs) in postmenopausal Taiwanese women with breast cancer using real-world data. We used Taiwan’s National Health Insurance and Cancer Registry databases to identify women aged ≥ 50 years with newly diagnosed breast cancer who received continuous AIs (N = 1,835) or tamoxifen (TAM) (N = 1,868) treatment. MOFs requiring hospitalization were tracked through 2019. The mean follow-up duration was 47.49 months (SD = 29.73) for the AIs group and 72.49 months (SD = 37.22) for the TAM group. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). MOFs incidence in AIs users compared to TAM users, with secondary outcomes including fractures of the spine, hip, humerus, and forearm. AIs users had a higher incidence of MOFs than TAM users. After adjustment, AIs therapy significantly increased forearm fracture risk [adjusted hazard ratios (aHR) = 2.16, 95% CI = 1.24–3.76)]. In age-stratified analyses, women aged 50–65 years had a notably higher risk of hip fractures (aHR = 5.65, 95% CI: 1.55–20.68) and forearm fractures (aHR = 3.14, 95% CI: 1.55–6.36) compared with TAM users, while no significant difference was observed in women over 65 years. Among early-stage (0–1) patients, AIs use was associated with a higher risk of hip fractures (aHR = 3.14, 95% CI: 1.10–8.97). In later-stage (2–3) patients, AIs use was linked to a higher risk of forearm fractures (aHR = 2.41, 95% CI: 1.11–5.20). Additionally, even among low-risk groups, AIs users had a significantly higher fracture risk than TAM users (p = 0.040). AIs therapy significantly increased the risk of hip and forearm fractures compared to TAM, particularly in women aged 50–65 years and in specific cancer stages. Regular bone mineral density monitoring and personalized bone-protective strategies are recommended.