SAT-803 Bone Gains and Heart Strains: Romosozumab and Cardiovascular Safety

Abstract Disclosure: M.J. Barnett: None. J.R. Lam: None. C. Casipit: None. A. Rivadeneira: None. Introduction: Romosozumab, a monoclonal antibody for the management of osteoporosis, was approved by the Food and Drug Administration in 2019. It has a unique mechanism of action, functioning as a dual anti-resorptive/anabolic agent, targeting sclerostin. Treatment involves monthly subcutaneous injections for one year followed by rapid transition to anti-resorptive therapy to prevent rapid bone loss. Currently, there is a black box warning for a heightened risk of cardiovascular events. Objective: Due to the mixed findings from previous studies, the primary purpose of this study is to assess major adverse cardiovascular events in osteoporotic patients receiving romosozumab compared to those receiving anabolic agents (teriparatide or abaloparatide). Methods: Data was acquired through TrinNetX, a globally de-identified collation of networks. Cohorts were defined based on osteoporosis and romosozumab (n = 14,760) or osteoporosis and an anabolic agent (teriparatide or abaloparatide) (n = 45,302). Following propensity scoring, a balanced cohort of n = 14,406 was achieved. There was no age limit for this study, and all genders were included. Furthermore, there was no time restriction, with data analyzed from one day after receiving medication onward. Key outcomes included cerebrovascular accidents, ischemic heart disease, acute myocardial infarction and acute heart failure; those with such outcomes previously were excluded. Cohorts were balanced for age, gender, race, A1c, tobacco use, hypertension, chronic kidney disease, ischemic heart disease, cerebrovascular disease, diabetes mellitus, hyperlipidemia, and family history of ischemic heart disease. Results: After matching, the mean age at index was 70.5 +/- 9.4 years, with 94% being female and 71% white. The risk of cerebrovascular accidents demonstrated a trend towards a reduction (albeit not significant; Relative Risk 0.601, 95% CI: 0.345-1.047, p = 0.0692). Ischemic heart disease (including acute) was lower in the romosozumab compared to the anabolic agent cohort (Relative Risk 0.848, 95% CI: 0.764-0.94, p = 0.0017). Similarly, the risk of an acute myocardial infarction was lower in the romosozumab cohort (Relative Risk 0.654; 95% CI: 0.534-0.801, p < 0.0001). Finally, acute heart failure (either systolic or diastolic) was significantly lower in the romosozumab cohort (Relative Risk 0.664; 95% CI: 0.506-0.871, p = 0.0029). Conclusion: These findings suggest there is no heightened risk for major adverse cardiovascular events in patients with osteoporosis treated with romosozumab compared to anabolic agents (teriparatide or abaloparatide). Further observational data is required to concur such findings, which may lead to a discontinuation of the black-box warning. Presentation: Saturday, July 12, 2025