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Osteoblasts produce both osteoprotegerin (OPG) and Receptor Activator for Nuclear Factor B Ligand (RANKL), members of the tumor necrosis factor (TNF) super family that compete for the same receptor - RANK - expressed at the surface of osteoclasts, to play important roles in bone remodeling by controlling differentiation, activation and apoptosis of osteoclasts. Osteoprotegerin is secreted at different other sites such as endothelial and vascular smooth muscle cells, pulmonary or renal tissue, or the immune system. Hormones, cytokines and transcription factors, with osteotropic hormones playing a key role, control OPG synthesis. Thyroid hormones regulate bone turnover, as evidenced by important changes in bone turnover found in patients with thyroid dysfunction. In thyroid hormones excess, the increase in serum OPG is, probably, due to enhanced bone turnover, to compensate for excessive bone resorption. In hypothyroidism, the mechanisms are less clear, either cardiovascular changes or the low OPG kidney clearance or the increased TSH level being involved. In addition, OPG is held responsible for the development of endothelial dysfunction, an early stage of atherosclerosis progression, thyroid dysfunction being associated to increased cardiovascular risk. [ABSTRACT FROM AUTHOR]