Mechanism of action of denosumab compared to zoledronic acid.
Notes: RANKL is secreted by bone marrow stromal cells and osteoblasts. RANKL binds to the RANK receptor on osteoclasts and promotes osteoclast differentiation and activity. Denosumab is a fully human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts by RANKL. Bisphosphonates (for example, zoledronic acid) bind to bone, enter, and inhibit bone resorption by osteoclasts. See review by Baron et al17 for details.
Abbreviations: RANK, receptor activator of nuclear factor κB; RANKL, RANK ligand.

Mechanism of action of denosumab compared to zoledronic acid. Notes: RANKL is secreted by bone marrow stromal cells and osteoblasts. RANKL binds to the RANK receptor on osteoclasts and promotes osteoclast differentiation and activity. Denosumab is a fully human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts by RANKL. Bisphosphonates (for example, zoledronic acid) bind to bone, enter, and inhibit bone resorption by osteoclasts. See review by Baron et al17 for details. Abbreviations: RANK, receptor activator of nuclear factor κB; RANKL, RANK ligand.

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... Bone-targeted agents such as bisphosphonates and denosumab have become the standard of care for the treatment and prevention of SREs associated with bone metastases from solid tumors (15, 16). However, use of bisphosphonates has the potential risk of adverse effects such as osteonecrosis of the jaw (ONJ), esophageal irritation, and fractures (17); bisphosphonates should be used cautiously in patients with renal insufficiency (17, 18) and the reversible effect after discontinuation of denosumab (19) should be considered. Therefore, it is important to develop new therapies to improve patients' outcomes. ...
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... Denosumab is a monoclonal antibody against RANK-L, blocking binding to RANK and reducing formation, function, and survival of osteoclasts, leading to decreased bone resorption. It is considered safe in patients with impaired renal function, unlike bisphosphonates (85). Otherwise, its side effect profile is similar to bisphosphonates and is usually administered every 4 weeks. ...
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