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Overexpression of receptor activator of nuclear factor \u03baB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%\u201327%) or cryosurgery and PMMA (0%\u201320%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40\u201355 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable.<\/jats:p>","DOI":"10.1634\/theoncologist.2013-0432","type":"journal-article","created":{"date-parts":[[2014,4,10]],"date-time":"2014-04-10T03:27:26Z","timestamp":1397100446000},"page":"550-561","source":"Crossref","is-referenced-by-count":216,"title":["The Clinical Approach Toward Giant Cell Tumor of Bone"],"prefix":"10.1093","volume":"19","author":[{"given":"Lizz","family":"van der Heijden","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.D. Sander","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel A.J.","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith R.","family":"Kroep","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi A.","family":"Nout","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla S.P.","family":"van Rijswijk","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith V.M.G.","family":"Bov\u00e9e","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pancras C.W.","family":"Hogendoorn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Gelderblom","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,9]]},"reference":[{"key":"2021122309081587900_B1","first-page":"321","volume-title":"WHO Classification of Tumours of Soft Tissue and Bone","author":"Athanasou","year":"2013"},{"key":"2021122309081587900_B2","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00432-008-0370-x","article-title":"Giant cell tumor of bone: Treatment and outcome of 214 cases","volume":"134","author":"Balke","year":"2008","journal-title":"J Cancer Res Clin Oncol"},{"key":"2021122309081587900_B3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.2106\/00004623-198769010-00018","article-title":"Giant-cell tumor of bone","volume":"69","author":"Campanacci","year":"1987","journal-title":"J Bone Joint Surg Am"},{"key":"2021122309081587900_B4","first-page":"320","volume-title":"WHO Classification of Tumours of Soft Tissue and Bone","author":"Forsyth","year":"2013"},{"key":"2021122309081587900_B5","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1302\/0301-620X.80B1.0800043","article-title":"Giant-cell tumour of bone metastasising to the lungs. 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