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Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover and development of the osteoporosis. The latest data support the correlation of osteoporosis and atherosclerosis, indicating the parallel progression of two tissue destruction processes with increased fatal and nonfatal coronary events, as well as a higher fracture risk. Patients with osteoporosis, have a higher risk of cardiovascular diseases than subjects with normal bone. Many proteins responsible for bone formation and resorption have been identified in the arterial wall. Vascular calcification includes mostly osteogenic and, to a lesser extent chondrogenic differentiation of osteoblasts and osteoclast-like cells. It has been shown that many of the regulators of bone formation and resorption some bone structural proteins, such as osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) are also expressed in the atherosclerotic plaque. When RANKL binds to RANK, osteoclasts are activated and bone resorption occurs and processes of vascular calcification become also activated. OPG, protein homologue to receptor activator of nuclear factor-κB (RANK), can bind to RANKL, blocking the binding of RANKL to RANK, that results in inhibition of differentiation of preosteoclasts to mature osteoclasts, lower osteoclast capacity for resorption of bone mineral matrix, and development vascular calcification. The latest data supports that cathepsin K, a cysteine protease, can efficiently degrade type I and II collagen, both of which are major matrix components of the bone and atherosclerotic plaque. These findings further underscore the potential of cathepsin K as a target for novel molecules to treat osteoporosis and atherosclerosis. Thus, the discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in the process of bone remodeling, vascular calcification and atherosclerosis has made progress in understanding the mechanisms of disease development and possibly to develop new dual therapies. New therapies for osteoporosis and atherosclerosis that may potentially improve or augment existing treatments include the recently approved anti-receptor activator of NF-κB-ligand monoclonal antibody fms (denosumab) and the cathepsin K inhibitor odanacatib, presently in the late stage of clinical development.

Atherosclerosis and osteoporosis are public health problems, with several epidemiological links, and they might be related to each other in terms of pathogenesis and therapeutic agents. The correlation between atherosclerosis and osteoporosis is being established by studies of the underling pathophysiological mechanisms, which seem to coincide in many biochemical pathways, and of the risk factors for vascular disease, which have also been associated with a higher incidence of low bone mineral density. Many experiments showing that the receptor activator of NF-kB (RANK), its ligand (RANKL), and the decoy osteoprotegerin receptor (OPG) are essential, central regulators of bone metabolism were significant turning points in our understanding of bone disease. Moreover, one emerging area in vascular biology involves the RANKL-RANK-OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of vessels calcification process. Animal and human studies results confirm the RANKL-RANK-OPG role in pathogenesis of vascular calcification and osteoporosis. Thus, these molecules may play a central role in regulation the development of vascular calcification coincident with declines in skeletal mineralization. Understanding cellular and molecular mechanisms of vascular calcification and osteoporosis may potentially lead to therapeutic opportunities for treating people with osteoporosis and cardiovascular diseases.