Fracture Risk in Women with Breast Cancer Initiating Aromatase Inhibitor Therapy: A Registry-Based Cohort Study

Background Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. Materials and Methods Using a population-based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure (n = 1,775), women with breast cancer not receiving AIs (n = 1,016), and women from the general population (n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users). Results At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. Conclusion Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures. Implications for Practice In a population-based observational registry that included 1,775 patients initiating long-term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure.