Association Between Endocrine Therapy and Fracture Risk in Women with Breast Cancer in Germany—A Retrospective Cohort Study

Background: Aromatase inhibitors (AIs) are widely used in hormone receptor-positive breast cancer but may adversely affect bone health. Evidence on their independent association with fracture risk compared with tamoxifen (TAM) remains inconsistent. Methods: In this retrospective cohort study, women with an initial prescription of TAM or AIs between 2016 and 2024 were identified in the IQVIA Longitudinal Prescription (LRx) database. Their prescription histories were combined with records from the IQVIA Disease Analyzer (DA) database using a validated co-therapy-based approach. Patients were then followed for up to five years. Kaplan–Meier analyses estimated cumulative fracture incidence, and Cox regression models assessed associations in unadjusted, age-adjusted, and fully adjusted analyses. Results: The study included 8938 TAM users and 14,594 AI users. Five-year cumulative incidence of all fractures was higher in the AI group than in the TAM group (14.8% vs. 9.2%). In fully adjusted primary analyses, AI therapy was not significantly associated with overall fracture risk (HR 1.10, 95% CI 0.99–1.23). A modest association persisted for major osteoporotic fractures (HR 1.24, 95% CI 1.05–1.46). Secondary exploratory analyses (age-stratified and fracture-type-specific models) showed patterns consistent with the primary results but were not powered or corrected for confirmatory inference. Conclusions: Aromatase inhibitor therapy was associated with a higher fracture incidence than tamoxifen, but much of this difference was explained by age and comorbidities. Both treatment-related effects and underlying patient characteristics contribute to fracture risk, underscoring the importance of individualized bone health assessment and targeted preventive strategies in women receiving endocrine therapy.