e12502 Background: Aromatase inhibitors (AIs) have been associated with increased bone loss and a higher risk of fractures compared to tamoxifen. This disparity is primarily attributed to differences in their mechanisms of action: in postmenopausal women, tamoxifen exhibits partial estrogen agonist effects on bone, which can lead to preservation or even improvement of bone mineral density (BMD). In contrast, AIs cause profound estrogen depletion, which accelerates bone resorption and turnover, ultimately resulting in reduced BMD and heightened fracture risk. In this study, we leveraged real-world data from the TriNetX network to compare the incidence of osteopenia, osteoporosis, and pathological fracture among patients receiving either aromatase inhibitors or tamoxifen. Methods: This TriNetX study utilized a retrospective matched cohort design using data from 157 healthcare organizations worldwide. Adult patients with breast cancer were separated into two groups: those starting tamoxifen and those starting any aromatase inhibitor (AI: anastrozole, exemestane, letrozole, or fadrozole), with the index date being the first instance of each medication after cancer diagnosis. Outcomes (osteopenia, osteoporosis, pathological fracture) were measured starting 365 days post-medication initiation. Propensity score matching ensured demographic and diagnostic balance between groups (n=120,341 per cohort). Outcomes were analyzed using association measures and Kaplan-Meier survival functions, including all patients regardless of preexisting bone conditions. Results: After matching, tamoxifen showed lower osteopenia risk (17.0% vs. 21.8%; OR 0.738, RR 0.783, p<0.0001) and pathological fracture risk (2.1% vs. 2.2%; OR 0.944, RR 0.946, p = 0.0416) compared with AIs. However, osteoporosis risk was similar between cohorts (13.8% vs. 14.0%; OR 0.986, RR 0.988, p = 0.236). Ultimately, tamoxifen showed longer bone health survival overall compared to AIs (HR=0.607, p<0001). These data are consistent with tamoxifen showing lower risk of BMD decreases and pathological fractures compared to AIs. Conclusions: Our large real-world cohort analysis supports other previously published evidence and meta-analyses showing a statistically significantly increased risk of osteopenia and pathological fractures with AIs when compared to tamoxifen. This reiterates the importance of bone density monitoring and addressing osteopenia before progression, especially in patients receiving endocrine therapy.
Karthikeyan et al. (Thu,) studied this question.