Kianoush Saberi
1 
, Amir Heidari
2 , Mohammad Rostamzadeh
3 , Abdolmohammad Ranjbar
3 , Faezeh Nesaei
4 , Mohammad Parsa Mahjoob
5 , Iman Zafar Asoodeh
6 , Reza Faramarzzadeh
7 , Shahnaz Sharifi
8* 1 Department of Anesthesiology, Medical Faculty, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
2 Department of Cardiology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Nursing, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5 Prevention of Cardiovascular Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6 Department of Anesthesiology and ICU, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
7 Department of Cardiology, Seyed-al-shohada Cardiology Hospital, Urmia University of Medical Science, Urmia, Iran.
8 Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
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.