Although several studies have shown that high levels of circulating OPG are associated with cardiovascular mortality in elderly women and cardiovascular disease in the general population, vessel wall-derived OPG was also found to protect from atherosclerosis and vascular calcification in apolipoprotein E-deficient (ApoE-/-) mice [54,57,63,64,65,66]. This evidence concerns the gene TNFRSF11B and atherosclerosis.