Cardiovascular Safety of Romosozumab vs PTH Analogues for Osteoporosis Treatment: A Propensity-Score-Matched Cohort Study

Abstract

Abstract 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.