title: Giant cell tumour of bone in the denosumab era.
abstract: Giant cell tumour of bone (GCTB) is an intermediate locally aggressive primary bone tumour, occurring mostly at the meta-epiphysis of long bones. Overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated osteoclast-like giant cells, causing lacunar bone resorption. Preferential treatment is curettage with local adjuvants such as phenol, alcohol or liquid nitrogen. The remaining cavity may be filled with bone graft or polymethylmethacrylate (PMMA) bone cement; benefits of the latter are a lower risk of recurrence, possibility of direct weight bearing and early radiographic detection of recurrences. Reported recurrence rates are comparable for the different local adjuvants (27-31%). Factors increasing the local recurrence risk include soft tissue extension and anatomically difficult localisations such as the sacrum. When joint salvage is impossible, en-bloc resection and endoprosthetic joint replacement may be performed. Local tumour control on the one hand and maintenance of a functional native joint and quality of life on the other hand are the main pillars of surgical treatment for this disease. Current knowledge and development in the fields of imaging, functional biology and systemic therapy are forcing us into a paradigm shift from a purely surgical approach towards a multidisciplinary approach. Systemic therapy with denosumab (RANKL inhibitor) or zoledronic acid (bisphosphonates) blocks, respectively inhibits, bone resorption by osteoclast-like giant cells. After use of zoledronic acid, stabilisation of local and metastatic disease has been reported, although the level of evidence is low. Denosumab is more extensively studied in two prospective trials, and appears effective for the optimisation of surgical treatment. Denosumab should be considered in the standard multidisciplinary treatment of advanced GCTB (e.g. cortical destruction, soft tissue extension, joint involvement or sacral localisation) to facilitate surgery at a later stage, and thereby aiming at immediate local control. Even though several questions concerning optimal treatment dose, duration and interval and drug safety remain unanswered, denosumab is among the most effective drug therapies in oncology.
authors.affiliation: Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lizz
authors.initials: L
authors.lastname: van der Heijden
authors.affiliation: Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: P D Sander
authors.initials: PDS
authors.lastname: Dijkstra
authors.affiliation: Department of Medical Oncology, Centre Leon Berard, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: a.j.gelderblom@lumc.nl.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D000069448:Denosumab / Q000627:therapeutic use*; D052138:Genes, Neoplasm / Q000235:genetics; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D009154:Mutation / Q000235:genetics; D011183:Postoperative Complications / Q000209:etiology
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D000069448:Denosumab
keywords: Denosumab; Giant cell tumour of bone; RANK ligand