Osteoprotegerin: A Biomarker With Many Faces

Abstract

Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is a soluble decoy receptor for the osteoclast differentiation factor receptor-activator of nuclear factor κB ligand (RANKL) that inhibits interaction between RANKL and its membrane-bound receptor RANK (Figure).1 The RANKL/OPG/RANK axis has been shown to regulate bone remodeling2,3 and was more recently found to be involved in carcinogenesis as well as central thermoregulation.4,5 This system has also been linked to the development of atherosclerosis and plaque destabilization.6,7 RANKL exhibits several properties with relevance to atherogenesis, such as promotion of inflammatory responses in T cells and dendritic cells, induction of chemotactic properties in monocytes, induction of matrix metalloproteinase (MMP) activity in vascular smooth muscle cells (SMC), and RANKL has also been found to have prothrombotic properties.2,8 In observational studies, elevated circulating OPG levels have been associated with prevalence and severity of coronary artery disease, cerebrovascular disease, and peripheral vascular disease.2,8 Circulating OPG levels are increased in patients with acute coronary syndrome,9 and enhanced expression has been found within symptomatic carotid plaques.10 Elevated OPG levels have also been associated with the degree of coronary calcification in the general population as a marker of coronary atherosclerosis.11 OPG has been reported to predict survival in patients with heart failure after acute myocardial infarction,12 to predict heart failure hospitalization and mortality in patients with acute coronary syndrome,9 and to be associated with long-term mortality in patients with ischemic stroke.13 There are also a few …