CONTEXT: Romosozumab, a monoclonal sclerostin antibody, is a recently approved highly potent antiosteoporotic agent with osteoanabolic properties. Clinical use of romosozumab is hindered by the fear of adverse cardiovascular (CV) events raised following the pivotal ARCH trial. OBJECTIVE: This work aimed to assess real-world CV safety of romosozumab vs alternative osteoanabolic therapies used for treatment of severe osteoporosis. METHODS: Data were obtained from TriNetX, a global federated health research network including real-time electronic medical records from 113 health care organizations with 136 460 930 patients across 16 countries at time of analysis. Inclusion criteria were age 40 years or older, a diagnosis of osteoporosis and prescription of romosozumab or a parathyroid hormone (PTH) analogue (teriparatide/abaloparatide) during August 2019 through August 2022. Propensity-score-matched cohorts were created 1:1 using demographic variables, comorbidities, and medications. Kaplan-Meier analysis was used to estimate the probability of the outcomes. Outcome measures included incident 3-point major adverse CV event or death (3P-MACE) during 1-year of follow-up after the initial prescription. RESULTS: A total of 5626 and 15 986 patients met the criteria for romosozumab and PTH analogue cohorts, respectively, with 5610 patients per group following propensity score matching. 3P-MACE was significantly less frequent in the romosozumab vs PTH analogue cohort (158 vs 211 patients with an outcome
P = .003) with reductions in the individual components of the composite outcome: myocardial ischemic events (31 vs 58
P = .003)
cerebrovascular events 56 vs 79
P = .037
deaths (83 vs 104
P = .099). CONCLUSION: In a diverse, real-world setting, prescription of romosozumab for osteoporosis is associated with fewer adverse CV events when compared to PTH analogue therapy.