Summary of Clinical Use

Prolia® was initially approved (FDA 2010) to treat bone loss in postmenopausal osteoporosis, men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. In May 2018 the FDA approval for Prolia® was expanded to include treatment of glucocorticoid-induced osteoporosis in males and females who are at high risk of fracture. In early 2024 the FDA issued a warning of Prolia®-induced severe hypocalcemia in patients with advanced chronic kidney disease, and this resulted in revised prescribing information aimed to reduce the risk of this potentially life-threatening adverse effect. Xgeva® (FDA approval 2011) is used for the prevention of skeletal-related events in patients with bone metastases from solid tumours. In December 2014 Xgeva® approval was expanded to include treatment of hypercalcemia of malignancy (HCM) which is refractory to traditional bisphosphonate therapy. HCM symptoms arise from cancer-driven increases in bone resorption. Untreated HCM can lead to renal failure, progressive mental impairment, coma and death [2,4].

Mechanism Of Action and Pharmacodynamic Effects

Denosumab is a high-affinity, selective inhibitor of receptor activator of nuclear factor-kappaB ligand (RANKL). Inhibition of RANKL-mediated RANK activation on pre-osteoclasts reduces their maturation to osteoclasts, thus protecting bone from degradation [3] and shifting the equilibrium of bone re-modelling towards bone formation.

External links

For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA)