Paget Disease of Bone - Treatment : Denosumab

Comments:
Denosumab is a human monoclonal antibody that inhibits RANK ligand (RANKL) and prevents development and maturation of osteoclasts. Osteoclast precursors express surface receptors called RANK (receptor activator of nuclear factor-kappa B). RANK is a member of the tumor necrosis factor receptor superfamily. RANK is activated by RANKL which is secreted by osteoblasts. Activation of RANK by RANKL promotes the maturation of osteoclast precursors into osteoclasts via NF-κB signaling pathway.

By binding to and blocking RANKL, denosumab inhibits osteoclast formation, function, and survival. Denosumab mimics the natural action of osteoprotegrin (OPG), an endogenous RANKL inhibitor. Denosumab has been used in patients with Paget disease of bone who are unable to take bisphosphonates, e.g. patients with renal failure.

Reference: Zhang N et al. Pros and Cons of Denosumab Treatment for Osteoporosis and Implication for RANKL Aptamer Therapy. Front. Cell Dev. Biol. May 2020, 8:325. Illustration created with: BioRender.com; adapted from the original image in the reference.