Giant cell tumor of bone (GCT) is a rare, benign tumor characterized by localized bone destruction. GCT is thought to be biphenotypic, comprising a neoplastic stromal cell population and an osteoclast-like giant cell population. Recent studies have established that receptor activator of NF κβ ligand (RANKL) plays an important role in GCT. Although its actions are not fully understood, RANKL acts as an obligate signal for normal osteoclast formation and function. The development of an antagonist

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... to RANKL, denosumab, has led to clinical trials in osteoporosis, bone metastases in cancer, and GCT. Generally well-tolerated, denosumab is an extremely effective inhibitor of osteoclast differentiation and function in humans. A preliminary study of the use of denosumab in patients with advanced or unresectable GCT has suggested considerable activity and clinical benefit. The eventual role of denosumab in GCT is currently the subject of an ongoing clinical trial.