Sclerostin and Cardiovascular Risk: Evaluating the Cardiovascular Safety of Romosozumab in Osteoporosis Treatment

Abstract

Background/Objectives: Osteoporosis and cardiovascular disease (CVD) share common risk factors and pathophysiological mechanisms, raising concerns about the cardiovascular implications of sclerostin inhibition. Romosozumab, a monoclonal antibody that targets sclerostin, is effective in increasing bone mineral density (BMD) and reducing fracture risk. However, evidence suggests that sclerostin inhibition may adversely affect vascular calcification, potentially increasing the risk of myocardial infarction (MI) and stroke. Methods: This review synthesizes data from clinical trials, such as ARCH, BRIDGE, and FRAME, alongside genetic studies and observational analyses, to evaluate the cardiovascular safety of romosozumab. PubMed was searched for relevant studies published within the last five years. Studies addressing the relationship between romosozumab and cardiovascular outcomes were included, emphasizing both its efficacy in osteoporosis management and potential cardiovascular risks. Results: Romosozumab significantly improves BMD and reduces fracture risk in postmenopausal women and men with osteoporosis. However, clinical trials report an increased incidence of major adverse cardiovascular events (MACE), particularly in patients with pre-existing cardiovascular conditions such as chronic kidney disease (CKD), diabetes, or prior CVD. Genetic studies indicate that SOST gene variants may also influence cardiovascular outcomes. Conclusions: While romosozumab is an effective treatment for osteoporosis, careful cardiovascular risk assessment is crucial before initiating therapy, especially for high-risk populations. Long-term studies are needed to evaluate chronic safety. Future therapeutic strategies should aim to maintain bone health while minimizing cardiovascular risks, ensuring a balance between efficacy and safety in osteoporosis treatment.