Osteoprotegerin (OPG) belongs to the tumor necrosis factor receptor superfamily and acts as a decoy receptor for the receptor activator of NF-kappaB ligand (RANKL), preventing its binding to RANK. Since 1997, the RANKL/RANK/OPG system has been intensively investigated in the fields of bone, immune and cardiovascular system pathophysiology. Specific anti-OPG antibodies have been developed, allowing for the measurement of OPG and, more recently, of soluble RANKL in both physiological and pathological conditions, often yielding unexpected results. When considering circulating OPG measurements, it should be borne in mind that this receptor is ubiquitously expressed, and that circulating levels do reflect the production by a number of tissues. Moreover, strikingly different values of circulating OPG have been reported. The aim of this paper is to summarize the available data on circulating OPG levels in a number of conditions; the pathophysiological significance and potential clinical utility will be emphasized.
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