Recent advances in the crosstalk between bone and vascular system: from mechanism to therapy.

Osteoporosis and cardiovascular disease are prevalent health concerns, particularly among the elderly. Recent studies have increasingly demonstrated that osteoporosis is consistently associated with vascular calcification, drawing attention to the interactions between bones and blood vessels, and giving rise to the concept of the bone-vascular axis. The bone vascular axis involves several factors, including osteokines such as FABP3, PDGF-BB, MYGDF, and Aging Bone-Derived Extracellular Vesicles (AB-EVs), which influence vascular calcification. Simultaneously, calcified blood vessels secrete sclerostin, Dickkopf1 (Dkk-1), Activin-A, and frizzled-related protein (SFRP), further affecting bone metabolism. The bone-vascular axis is characterized by reciprocal regulation and influence between the skeletal and vascular systems, and is crucial for maintaining bone metabolic homeostasis and preventing cardiovascular disease. However, the causal relationship between these two systems, as well as the specific regulatory mechanisms and targets, remains unclear. Therefore, this review aims to explore the mechanisms underlying the crosstalk between bone and blood vessels from both the skeletal and vascular perspectives, as well as their common pathways, and to provide an overview of current therapeutic agents, with the goal of enhancing understanding of the bone-vascular association and offering new insights and approaches for clinical treatment.