osteoprotegerine

Osteoprotegerin, abbreviated OPG and also known by its gene name TNFRSF11B, is a secreted glycoprotein in the tumor necrosis factor receptor superfamily. It functions as a decoy receptor for receptor activator of nuclear factor kappa-Β ligand (RANKL) and, to a lesser extent, for TRAIL. OPG is produced by osteoblasts and other cell types, including osteocytes, endothelial cells, and vascular smooth muscle cells.

OPG exerts its primary effect by binding RANKL with high affinity, preventing RANKL from interacting with its receptor RANK on osteoclast precursors. This action inhibits osteoclast differentiation, activation, and survival, thereby reducing bone resorption. Through this mechanism, OPG plays a central role in bone remodeling and calcium homeostasis, balancing bone formation and resorption in response to physiological needs.

Beyond bone, OPG expression occurs in various tissues and is regulated by mechanical loading, hormonal signals (such as estrogen and glucocorticoids), and inflammatory cytokines. Its levels can reflect changes in bone turnover and are influenced by metabolic, hormonal, and inflammatory states.

Clinical relevance of OPG centers on its involvement in diseases of bone and mineral metabolism. Altered OPG concentrations or imbalances in the RANKL/OPG axis are associated with osteoporosis, osteolytic lesions in cancer, and inflammatory conditions such as rheumatoid arthritis and periodontitis. While OPG itself is not a standard therapy, its pathway is targeted by anti-RANKL therapies (for example, denosumab) that mimic the anti-resorptive effect of the RANKL/OPG balance. OPG is also studied as a biomarker of bone turnover and vascular health in research settings.