Since the discovery of the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B (RANK)/RANK Ligand (RANKL) signaling pathway, our understanding of the regulation of bone metabolism has advanced considerably. Many factors (eg, PTH, TNF, and IL-1) can lead to bone loss, but they all converge on the OPG/RANK/RANKL pathway. RANKL plays a key role in bone destruction across a range of conditions including osteoporosis, treatment-induced bone loss, rheumatoid arthritis, and fuels a vicious cycle of bone destruction and tumor growth in metastatic disease and multiple myeloma. RANKL is the final common mediator that regulates bone remodeling. Bone resorption is dependent on RANKL, the primary mediator of osteoclast formation, function, and survival. In these disease states, RANKL overwhelms the effects of OPG, causing an imbalance in the bone remodeling process. Current research suggests that RANKL inhibition may provide a new therapeutic approach to limit bone loss in these conditions.1-3
This section provides an overview of various types of bone loss, bone destruction, and current scientific understanding of the role of RANKL in their progression. Choose a topic within this section for additional information about a specific type of bone loss, including prevalence and impact, treatments and guidelines, and the processes involved in bone loss.
For more information about RANKL and OPG, including pathway animations and an interactive illustrated guide to the RANK/RANKL/OPG pathway, visit the section on RANKL inhibition.
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