Osteoporosis therapies and coronary risk: insights from vascular calcification biology and sclerostin signaling

Osteoporosis therapies have become increasingly relevant to cardiovascular medicine because the bone-vascular interface links skeletal remodeling to vascular calcification biology. This narrative review examines whether anti-osteoporosis therapies truly modify coronary biology or risk, or whether the current literature more often reflects heterogeneous vascular end points, indirect coronary inference, and incomplete translation from mechanistic plausibility to clinical outcomes. We summarize the biologic pathways connecting bone remodeling to vascular calcification, including osteogenic transdifferentiation of vascular smooth muscle cells, matrix vesicle-mediated mineralization, the OPG/RANKL axis, and Wnt-sclerostin signaling. We then reassess current evidence for antiresorptive and osteoanabolic therapies while distinguishing coronary-specific data from broader vascular, renal-mineral, pharmacovigilance, and genetic evidence. Bisphosphonates and denosumab remain biologically relevant to vascular calcification, but based on currently available evidence, current studies do not support a reproducible or clinically decisive effect on coronary-specific outcomes. By contrast, romosozumab has sharpened the debate because it combines robust anti-fracture efficacy with unresolved cardiovascular safety questions linked to sclerostin inhibition, whose mechanistic, genetic, and clinical signals are not fully concordant. We further discuss why the literature remains conflicted, emphasizing end point heterogeneity, differences between calcification burden and plaque vulnerability, population-specific mineral stress, and the limitations of fracture trials for coronary inference. Overall, current evidence does not support a uniform cardiovascular class effect of osteoporosis therapies; instead, vascular consequences appear drug-specific, context-dependent, and highly sensitive to phenotype, baseline risk, and time horizon.