Frank Traub1, Janith Singh1, Brendan C Dickson2, Stephanie Leung3, Rakesh Mohankumar3, Martin E Blackstein4, Albiruni R Razak4, Anthony M Griffin1, Peter C Ferguson5, Jay S Wunder6. 1. University Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada. 2. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada. 3. Musculoskeletal Division, Department of Medical Imaging, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada. 4. Department of Medical Oncology, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada. 5. 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. 6. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: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: Robert Koucheki; Aaron Gazendam; Jonathan Perera; Anthony Griffin; Peter Ferguson; Jay Wunder; Kim Tsoi Journal: Eur J Orthop Surg Traumatol Date: 2022-03-30