RANKL, denosumab, and giant cell tumor of bone

Purpose of review Giant cell tumor (GCT) of bone is a benign, osteolytic neoplasm of bone. The receptor activator of NF-KB ligand (RANKL) pathway has recently been shown to play a key role in the pathogenesis of GCT. Recent findings Treatment for refractory, recurrent, or metastatic GCT remains challenging. The recent development of a monoclonal antibody to RANKL, denosumab, offers promise in the management of these patients. A recent phase 2 study suggested denosumab offers disease and symptom control for patients with advanced or refractory disease. In this population, denosumab appears to be well tolerated. There are key questions which remain to be addressed, including patient selection, optimal scheduling, use as an adjuvant, and application to other giant cell-rich disorders. Summary Denosumab offers a new treatment option for a subset of patients with previously untreatable GCT. The role of denosumab in curative treatment is the subject of ongoing studies.