[21] Denosumab is an inhibitor of RANKL (receptor activator of nuclear factor kappa-Β ligand),[19] which works by decreasing the development of osteoclasts, which are cells that break down bone.

Denosumab is a human monoclonal IgG2 antibody that targets the protein RANKL, which is essential for the formation, function and survival of osteoclasts, the cell type responsible for bone resorption.

[24] A 2012 meta-analysis found that denosumab was better than placebo, zoledronic acid, and pamidronate, in reducing the risk of fractures in those with cancer.

[20] It is contraindicated in people with hypocalcemia; sufficient calcium and vitamin D levels must be reached before starting on denosumab therapy.

[29] Denosumab works by lowering the hormonal message that leads to excessive osteoclast-driven bone removal and is active in the body for only six months.

[21] There is an increased risk of infections such as cellulitis, hypocalcemia (low blood calcium), hypersensitivity allergy reactions, osteonecrosis of the jaw, and atypical femur fractures.

[31] It has been proposed that the increase in infections under denosumab treatment might be connected to the role of RANKL in the immune system.

[36] In June 2010, denosumab was approved by the FDA for use in postmenopausal women with risk of osteoporosis[37] under the brand name Prolia,[38] and in November 2010, as Xgeva for the prevention of skeleton-related events in people with bone metastases from solid tumors.

[37] In June 2013, the FDA approved denosumab for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where resection would result in significant morbidity.

[40] In January 2024, the FDA added a black box warning to Prolia because of the risk of severe hypocalcemia in those with advanced kidney disease.

[2][44] In December 2009, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion for denosumab for the treatment of postmenopausal osteoporosis in women and for the treatment of bone loss in men with hormone ablation therapy for prostate cancer.

[18][46] In March 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Jubbonti, intended for the treatment of osteoporosis in women who have been through menopause and in men at increased risk of fractures whose bone loss is linked to hormone ablation or long-term treatment with systemic glucocorticoid.

[7] In December 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Stoboclo, intended for the treatment of osteoporosis in women who have been through menopause, bone loss linked to hormone ablation in men at increased risk of fractures and bone loss associated with long-term treatment with systemic glucocorticoid.

This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response.