Suspected Denosumab-Associated Acute Coronary Syndrome

Denosumab, a monoclonal antibody (mAb) targeting receptor activator of nuclear factor-κB ligand (RANKL), is commonly used in managing metabolic bone diseases and giant cell tumors (GCTs) of bone. Growing evidence suggests that RANKL inhibition may influence cardiovascular health by impacting endothelial function, inflammatory pathways, vascular smooth muscle cell behavior, and systemic calcium regulation. We report a case of a 48-year-old Caribbean-South Asian man with recurrent GCTs who received three subcutaneous doses of denosumab and soon thereafter developed an anterior ST-elevation acute coronary syndrome (STE-ACS). The patient had no traditional cardiometabolic risk factors. Coronary angiography revealed thrombotic occlusion of the proximal left anterior descending artery (LAD), which was successfully treated with primary percutaneous coronary intervention (PPCI) and guideline-directed medical therapy (GDMT). Given the lack of modifiable risk factors, a significant family history, and biologically plausible mechanisms linking RANKL inhibition to atherothrombotic events, a denosumab-associated myocardial infarction was considered the most probable cause.