Denosumab — Drug Monograph
Brand names: Xgeva (oncology — 120 mg SC q4w), Prolia (osteoporosis — 60 mg SC q6m; different product — do NOT interchange)
Drug class: Supportive Care Agent
Mechanism of Action
Fully human IgG2 monoclonal antibody that specifically binds RANKL (receptor activator of nuclear factor kappa-B ligand) with high affinity, blocking its interaction with RANK on osteoclast precursors. RANKL is expressed by osteoblasts, bone marrow stromal cells, and tumor cells in the bone microenvironment; it is the principal mediator of osteoclastogenesis, osteoclast activation, and osteoclast survival. By neutralizing RANKL, denosumab prevents osteoclast differentiation from precursors and induces apoptosis of mature osteoclasts, profoundly suppressing bone resorption. Compared to…
FDA Indications
- Prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors (FDA approved 2010; superiority over zoledronic acid in prostate, breast, and solid tumor SRE delay trials)
- Treatment of adults and skeletally mature adolescents with giant cell tumor of bone (GCT) that is unresectable or where surgery is likely to result in severe morbidity (FDA approved 2013)
- Prevention of SREs in patients with multiple myeloma (FDA approved 2018; non-inferior to zoledronic acid; preferred in patients with renal impairment)
Common Side Effects
- Hypocalcemia (more frequent than with bisphosphonates — mandatory calcium and vitamin D supplementation required)
- Fatigue
- Nausea
- Hypophosphatemia
- Extremity and back pain
- Headache
- Peripheral edema
Clinical Pearl
Denosumab's key clinical advantage over zoledronic acid is that it requires NO renal dose adjustment, making it the preferred bone-protective agent in patients with CKD (CrCl <30–60 mL/min) and in multiple myeloma (where renal impairment is common). However, hypocalcemia is more frequent and can be more severe than with bisphosphonates — calcium and vitamin D supplementation is mandatory, not optional. When stopping denosumab after long-term use (especially in adolescents/GCT patients), always…
Related Therapies & Mechanisms
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