Abstract
Denosumab is a fully human monoclonal antibody, the first RANKL inhibitor to be approved by the FDA, now available for the treatment of osteoporosis, treatment-induced bone loss, bone metastases, multiple myeloma and giant cell tumour of bone. Precursors of osteoclasts, called pre-osteoclasts, express the surface receptor RANK (receptor activator of nuclear factor kappa B), a member of the tumour necrosis factor receptor (TNFR) family. RANK is activated by the ligand RANKL, which are cell surface molecules on osteoblasts. Activation of RANK by RANKL promotes the differentiation of pre-osteoclasts to active osteoclasts. Denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL. This reaction mimics the natural action of osteoprotegerin (OPG) and protects bone from resorption.
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