title: Efficacy of denosumab in joint preservation for patients with giant cell tumour of the bone.
abstract: Giant cell tumour of the bone (GCTB) is an aggressive osteolytic primary tumour. GCTB is rich in osteoclast-like giant cells and contains mononuclear cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. The potential therapeutic effect of denosumab was investigated with special reference to its role in joint preservation.
  
  
  
  In this prospective non-randomised study patients with GCTB received denosumab for 6-11 months preoperatively. Serial radiographs and biopsy and resection tumour specimens were used to monitor response to denosumab.
  
  
  
  All 20 patients experienced pain relief in the first month of treatment. All patients demonstrated a positive radiographic response with improved subchondral and cortical bone which allowed intralesional tumour resection and preservation of the joint and articular surface in 18 cases. Histological examination following denosumab revealed rarely detectable osteoclast-like giant cells. There was an obvious increase in osteoid matrix and woven bone which showed rare RANK staining amongst the mononuclear cells and only focal RANKL positivity. At median 30 months follow-up after resection, local tumour recurrence occurred in three patients.
  
  
  
  Denosumab provides favourable and consistent clinical, radiographic and pathologic responses which facilitates less aggressive surgical treatment, especially joint preservation. However, the local recurrence rate for GCTB following resection does not seem to be affected by denosumab and remains a concern.
authors.affiliation: University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Traub
authors.affiliation: University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Janith
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Dickson
authors.affiliation: Musculoskeletal Division, Department of Medical Imaging, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Leung
authors.affiliation: Musculoskeletal Division, Department of Medical Imaging, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Mohankumar
authors.affiliation: Department of Medical Oncology, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Blackstein
authors.affiliation: Department of Medical Oncology, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Albiruni R
authors.initials: AR
authors.lastname: Razak
authors.affiliation: University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Griffin
authors.affiliation: University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada; Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto M5G 1X5, ON, Canada.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Ferguson
authors.affiliation: University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada; Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto M5G 1X5, ON, Canada. Electronic address: jwunder@mtsinai.on.ca.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Wunder
mesh_terms: D000293:Adolescent; D000328:Adult; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D000069448:Denosumab / Q000627:therapeutic use*; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007592:Joint Diseases / Q000188:drug therapy* / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D011300:Preoperative Care; D011446:Prospective Studies; D053245:RANK Ligand / Q000378:metabolism; D016059:Range of Motion, Articular / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D000069448:Denosumab
keywords: Denosumab; Giant cell tumour of the bone; Histopathological findings; Joint preservation; Radiological effects