Giant-cell tumor of bone (GCTB) primarily occurs in young adults between the ages of 20 and 40 years and comprises approximately 5% of primary bone tumors.1 Pediatric cases of GCT are even less frequent and are believed to comprise only 1.7% of all cases of GCTB.2 Although usually a benign tumor, GCTB frequently recurs locally after surgical resection.1,3,4 Approximately 3% of GCTB metastasize, primarily to the lungs5; metastatic disease at presentation is uncommon. Histologically, GCTB has two cellular components: neoplastic mononuclear cells that are evenly scattered among osteoclast precursors and osteoclast-like giant cells.3,6 Radiographically, these tumors usually appear as lytic destructive lesions, often in the proximal femur or distal tibia.3,6 Clinically, patients present with pain and often have deformities at the tumor site, without constitutional symptoms. About two decades ago, the receptor activator of NF-kappaB ligand (RANKL) signaling pathway was discovered, and its importance in the regulation of bone growth and turnover became apparent. For instance, RANKL knockout mice (with absence of the ligand) demonstrate osteopetrotic bone changes as a result of impaired osteoclast differentiation and subsequent decreased bone resorption. Because denosumab inhibits RANKL (and therefore osteoclast activity), it is used in the treatment of postmenopausal osteoporosis, in which there is a state of increased bone resorption. Furthermore, RANKL is thought to participate in the growth of the tumor cells, possibly as a result of production of growth factors by osteoclast-like giant cells through a paracrine loop.7 Recently, a phase II study in adults with GCTs has demonstrated significant clinical response to the anti-RANKL monoclonal antibody denosumab.6 There is also histologic confirmation of the treatment effects of denosumab on GCTs.8 However, we are unaware of published data regarding the safety and efficacy of this drug in pediatric patients and the impact it may have on bone growth and health.



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