Osteoprotegerin as a Predictor of Coronary Artery Disease and Cardiovascular Mortality and Morbidity

Osteoprotegerin (OPG) is a glycoprotein that acts as a decoy receptor for receptor activator of nuclear factor kappa B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand. The OPG/RANKL/receptor activator of nuclear factor kappa B axis plays an important regulatory role in the skeletal, immune, and vascular systems. The protective role of OPG, in animal models, against vascular calcification has not been replicated in human trials; moreover, increased OPG levels have been consistently associated with the incidence and prevalence of coronary artery disease. There seems to be some dichotomy in the role of OPG, RANKL, and tumor necrosis factor-related apoptosis-inducing ligand in atherosclerosis and plaque stability. In this review, we integrate the findings from some of the important studies and try to draw conclusions with a view to gaining some insight into the complex interactions of the OPG/RANKL/receptor activator of nuclear factor kappa B axis and tumor necrosis factor-related apoptosis-inducing ligand in the pathophysiology of atherosclerosis. (J Am Coll Cardiol 2010;55:2049-61) (C) 2010 by the American College of Cardiology Foundation