Last reviewed 2026-04-21 · How we verify

Prolia (DENOSUMAB)

Prolia works by blocking a protein that breaks down bone.

Prolia (Denosumab) is a RANK Ligand Inhibitor developed by AMGEN, targeting tumor necrosis factor ligand superfamily member 11. It is a small molecule modality approved by the FDA in 2010 for the treatment of drug-induced osteoporosis, osteoporosis, and postmenopausal osteoporosis. Prolia is still patented and has a half-life of 25.4 days. Key safety considerations include the risk of osteonecrosis of the jaw and atypical femoral fractures. As a RANK Ligand Inhibitor, Prolia works by blocking the activity of RANKL, a protein that promotes bone resorption.

At a glance

Mechanism of action

Xgeva binds to RANKL, transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption, thereby modulating calcium release from bone. Increased osteoclast activity, stimulated by RANKL, is mediator of bone pathology in solid tumors with osseous metastases. Similarly, giant cell tumors of bone consist of stromal cells expressing RANKL and osteoclast-like giant cells expressing RANK receptor, and signaling through the RANK receptor contributes to osteolysis and tumor growth. Xgeva prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts, their precursors, and osteoclast-like giant cells.

Approved indications

• Drug-induced osteoporosis
• Osteoporosis
• Postmenopausal osteoporosis

Boxed warnings

• WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m 2 ), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following denosumab products administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported [see Warnings and Precautions (5.1) ] . The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients [see Warnings and Precautions (5.1) ] . Prior to initiating Stoboclo in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Stoboclo in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE See full prescribing information for complete boxed warning. Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following denosumab products administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. ( 5.1 ) The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia. ( 5.1 ) Prior to initiating Stoboclo in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Stoboclo in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. ( 2.2 ), ( 5.1 )

Common side effects

• Back pain
• Pain in extremity
• Musculoskeletal pain
• Hypercholesterolemia
• Cystitis
• Vertigo
• Upper respiratory tract infection
• Edema peripheral
• Sciatica
• Bone pain
• Abdominal pain upper
• Anemia

Key clinical trials

• Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma (PHASE3)
• Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Men With Hormone-refractory Prostate Cancer (PHASE3)
• Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium (PHASE2)
• Safety and Efficacy Study of Denosumab in Patients With Recurrent or Unresectable Giant Cell Tumor of Bone (PHASE2)
• Study of Denosumab in Subjects With Giant Cell Tumor of Bone (PHASE2)
• Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma. (PHASE3)
• A Study Comparing Denosumab vs. Zoledronic Acid for the Treatment of Bone Metastases in Breast Cancer Subjects. (PHASE3)
• Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma (PHASE2)

Primary sources

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