Denosumab is a fully human monoclonal antibody for the treatment of osteoporosis, treatment induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma and giant cell tumor of bone.

Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal. In many bone loss conditions, RANKL overwhelms the body’s natural defense against bone destruction.

It was approved by U.S. Food and Drug Administration (FDA) for use in postmenopausal women with risk of osteoporosis in June 2010, under the trade name Prolia and for the prevention of skeletal-related events in patients with bone metastases from solid tumors in November 2010, making it the first RANKL inhibitor to be approved by the FDA. 

Mechanism of action

Bone remodeling is the process by which the body continuously builds new bone and removes old bone material. It is driven by various types of cells, most notably osteoblasts, which secrete new bone, and osteoclasts, which break it down.
Precursors to osteoclasts, called pre-osteoclasts, express a receptor on their surfaces called RANK, short for receptor activator of nuclear factor-kappa B. RANK is a member of the tumor necrosis factor receptor superfamily. RANK is activated by RANKL (the RANK-Ligand), which is produced by osteoblasts. Activation of RANK promotes the maturation of pre-osteoclasts into osteoclasts.

Denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL. This protects bone from degradation and helps counter the progression of osteoporosis. The drug therefore mimics the endogenous effects of osteoprotegerin, another receptor produced by osteoblasts which can bind RANKL, thus reducing its effect on RANK and helping to modulate bone production.

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