Cross-talk of bone remodeling and cardiac dysfunction; reimagining the bone-heart axis in atherosclerosis pathogenesis

Recent findings detected a dynamic, reciprocal relationship between bone remodeling and cardiac dysfunction, significantly influencing atherosclerosis pathogenesis. The bone-heart axis consists of bidirectional signaling of bone-derived factors and dysregulated mineral metabolism, which directly affect vascular calcification, endothelial function, and myocardial stress. Conversely, cardiac hormones and systemic inflammation modulate osteoclast/osteoblast activity. Critically, shared molecular pathways, like RANKL/RANK/OPG modulate both skeletal turnover and vascular inflammation/calcification. Pathological bone resorption releases calcium and matrix vesicles that nucleate vascular calcification, accelerating atherosclerotic plaque instability. Reimagining this axis emphasizes on osteo-immunological mechanisms with central role in cardiovascular disease progression, suggesting integrated therapeutic targets for atherosclerosis beyond traditional lipid-centric approaches.