The role of the receptor activator of nuclear factor Kappa-B ligand/osteoprotegerin ratio in vascular diseases: a therapeutic approach

Cardiovascular and bone diseases contribute independently to mortality and global health. The exact mechanisms involved in the pathophysiology shared between bone and vascular diseases are not well defined. Endothelial cells and osteoblasts communicate during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. One shared mechanism may involve osteoprotegerin (OPG) and its ligand Receptor Activator of NF-κB Ligand (RANKL). The RANKL/OPG ratio is an important modulator for the skeletal, immunological, and vascular systems. OPG levels are elevated due to either osteogenic causes or inflammatory responses in the vasculature. The data obtained from clinical and in vitro studies support the role of the RANKL/OPG ratio as a potential marker for the progression of endothelial damage. Therefore, determining the therapeutic approaches for the targeting RANKL/OPG ratio and evaluating its usage as a biomarker in cardiovascular and bone pathophysiology are needed. By integrating the protective and disease-causing role of OPG with its ligand, this review outlines the role of the RANKL/OPG ratio at the molecular level. We also consider targeted therapeutic approaches.