Giant cell tumor of bone (GCTB) is an osteolytic, usually benign neoplasm 
characterized by infiltration with osteoclast-like giant cells, and the 
osteoclast differentiation factor receptor activator of nuclear factor kappa-B 
ligand (RANKL) is heavily involved in its pathogenesis. Denosumab belongs to a 
new class of drugs that inhibit RANKL. Prior to denosumab, multimodality 
treatment in refractory, recurrent and metastatic GCTB has shown variable 
results. Recent phase II data have demonstrated denosumab's activity with regard 
to disease and symptom control, without significant adverse effects. On the 
basis of this data, the FDA approved denosumab for the treatment of patients 
whose GCTB is unresectable, or when surgery is likely to result in severe 
morbidity. Ongoing questions remain, including the optimal scheduling, patient 
selection, use in the adjuvant setting and long-term toxicity concerns.