denoszumab

Denosumab is a human monoclonal antibody that targets RANKL (receptor activator of nuclear factor kappa-B ligand), a protein essential for the formation, function, and survival of osteoclasts. By binding RANKL, denosumab prevents it from activating the RANK receptor on osteoclast precursors, leading to reduced bone resorption and increased bone mineral density in many patients. It is marketed under the brand names Prolia for osteoporosis and Xgeva for cancer-related bone problems and is developed and distributed by Amgen.

Medical uses include the treatment of osteoporosis in postmenopausal women and men at high risk of fracture, and prevention of glucocorticoid-induced osteoporosis. It is also used to reduce skeletal-related events in adults with bone metastases from solid tumors or multiple myeloma, and to treat giant cell tumor of bone in some cases. Denosumab is typically given as a subcutaneous injection, with dosing variations depending on the condition being treated. In osteoporosis, a 60 mg dose is commonly administered every six months, accompanied by calcium and vitamin D supplementation. For cancer-related indications, higher or more frequent dosing may be used as part of a broader treatment plan.

Safety considerations include the risk of hypocalcemia, especially in patients with preexisting calcium abnormalities or advanced kidney disease; therefore assessment of calcium, phosphorus, and magnesium levels and supplementation are important. Other potential adverse effects include osteonecrosis of the jaw, atypical femoral fractures, infections, and dermatologic reactions. Denosumab is not recommended during pregnancy due to potential fetal harm. Discontinuation can lead to rebound increases in bone turnover and fracture risk, so stopping therapy should be managed by a clinician. It is not cleared by hepatic metabolism and does not require dose adjustment for mild to moderate renal impairment, though severe renal impairment increases hypocalcemia risk.