title: Clinical and pathological results of denosumab treatment for giant cell tumors of bone: Prospective study of 14 cases.
abstract: OBJECTIVE
  Giant cell tumor of bone (GCT) is a primary, osteolytic, benign tumor of the bone. Surgery is the commonly used treatment; however, recurrence remains a problem. Receptor activator of nuclear factor kappa B (RANKL) is responsible for the formation of osteoclastic cells. Discovery of RANKL and its human monoclonal antibody, denosumab, led to use of denosumab for treatment of GCT. The aim of this study was to evaluate clinical and pathological results of treatment of GCT with denosumab and to assess adverse effect profile and recurrence rate.
  
  
  METHODS
  Thirteen patients with 14 lesions were enrolled in the study. Mean age was 38.3 years. Patients were given subcutaneous injections of denosumab (120 mg) every 4 weeks (with additional doses on days 0, 8 and 15 in cycle 1 only) and were radiologically evaluated for tumor response. Pain and functional status were measured using Visual Analog Score (VAS) and Musculoskeletal Tumor Society Score (MSTS). Adverse effects were analyzed after each cycle.
  
  
  RESULTS
  Participants were 5 men and 8 women. Mean follow-up was 17 months. One lesion was Campanacci grade I, 8 were grade II, and 5 were grade III. Eight lesions were recurrent, and remaining were primary lesions. After average of 9 cycles (range: 4-17 cycles), all tumors underwent radiological regression. Ten lesions were removed surgically. More than 90% of giant cells were found to have regressed in all pathological specimens. On last follow-up, average VAS was 1 and MSTS was 87%. Fatigue and joint and muscle pain after injections was reported by 46% of patients, and mild hypocalcaemia was seen in 1 patient.
  
  
  CONCLUSIONS
  Denosumab has been shown to be a successful drug in treatment of GCT. Denosumab can be used as neoadjuvant for all recurrent lesions, grade II lesions with high surgical risk, grade III lesions, and metastatic cases of GCT.
  
  
  METHODS
  Level IV, Therapeutic study.
authors: Çukurova University Faculty of Medicine, Department of Orthopedics and Traumatology, Adana, Turkey. Electronic address: drmehmetali@hotmail.com.
authors: Mehmet Ali
authors: MA
authors: Deveci
authors: Çukurova University Faculty of Medicine, Department of Medical Oncology, Adana, Turkey.
authors: Semra
authors: S
authors: Paydaş
authors: Çukurova University Faculty of Medicine, Department of Pathology, Adana, Turkey.
authors: Gülfiliz
authors: G
authors: Gönlüşen
authors: Çukurova University Faculty of Medicine, Department of Orthopedics and Traumatology, Adana, Turkey.
authors: Cenk
authors: C
authors: Özkan
authors: Çukurova University Faculty of Medicine, Department of Orthopedics and Traumatology, Adana, Turkey.
authors: Ömer Sunkar
authors: ÖS
authors: Biçer
authors: Çukurova University Faculty of Medicine, Department of Orthopedics and Traumatology, Adana, Turkey.
authors: Mustafa
authors: M
authors: Tekin
mesh_terms: D000328:Adult; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D000069448:Denosumab / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D059352:Musculoskeletal Pain / Q000175:diagnosis / Q000209:etiology; D060787:Neoplasm Grading; D010147:Pain Measurement / Q000379:methods; D011446:Prospective Studies; D053245:RANK Ligand / Q000378:metabolism; D011859:Radiography / Q000379:methods; D020127:Recovery of Function / Q000187:drug effects; D055502:Secondary Prevention / Q000379:methods; D016896:Treatment Outcome; D014421:Turkey
chemical_list: D050071:Bone Density Conservation Agents; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab
keywords: Denosumab; Giant cell tumor; Recurrence