Introduction: Giant cell tumor of bone (GCTB) is a locally aggressive tumor with low metastatic potential. Giant cells express RANK ligand (RANKL), contributing to osteolytic destruction. Denosumab, a monoclonal antibody against RANKL, inhibits osteoclast activity.

Aims & Objectives: To evaluate the role of denosumab in GCTB management and assess its risks and benefits.

Methods: Fifteen patients (aged ≥12 years, weight ≥45 kg) with Campanacci grade 2/3 GCTB received denosumab (120 mg SC monthly for 3–4 months, with loading doses on days 8 and 15). Calcium (500 mg) and vitamin D (400 IU) were supplemented. Assessments included clinical, radiological (X-ray, CT, MRI), and biochemical (CBC, calcium, phosphate) monitoring every 4 weeks.

Results: Denosumab showed high tumor response rates, improved quality of life, reduced pain, and decreased need for extensive surgery. Toxicity was acceptable.

Conclusion: Denosumab is effective as adjunct therapy in advanced GCTB, though complications (hypocalcemia, ONJ, atypical fractures, recurrence) require monitoring.