In our case series, MR-ONJ could be safely managed with denosumab interruption, followed by ozone therapy and surgery
In our case series, MR-ONJ could be safely managed with denosumab interruption, followed by ozone therapy and surgery. THZ1 January 2008 and July 2019. Main outcome measures Incidence, time of onset and clinical features of MR-ONJ. Results 29 patients with locally advanced and/or metastatic GCTB treated with denosumab were identified. At a median follow-up of 70 months (range 1C125), 4 (13.8%) patients experienced MR-ONJ while on treatment, after 125, 119, 85 and 41 months of denosumab, respectively. All patients showed an ongoing tumour stabilisation with denosumab at the MR-ONJ onset and in all cases denosumab was stopped. All four patients were treated with ozone therapy. Two are waiting for surgery, two were already operated on. Both of them experienced disease progression and were thus rechallenged with denosumab. One is still on therapy after 25 months. The other had an MR-ONJ relapse after 39 months and was treated again with ozone therapy and surgery. She is under surveillance, GCTB being currently stable. Conclusion A clinical algorithm of denosumab rechallenge after complete resolution of MR-ONJ in progressing GCTB patients should be prospectively validated. strong class=”kwd-title” Keywords: giant cell tumour of bone, denosumab, osteonecrosis of the jaw, ozono therapy, surgery Key questions What is already known about this subject? The treatment of the very rare unresectable or advanced/metastatic giant cell tumour of bone (GCTB) is usually challenging and the only current available medical option is usually denosumab, an anti-Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) monoclonal antibody inhibiting THZ1 osteolysis. An infrequent but severe and treatment-limiting adverse event of denosumab is the osteonecrosis of the jaw (ONJ). The clinical management of GCTB patients stopping denosumab for medication-related ONJ (MR-ONJ) and the possible reintroduction of denosumab after its resolution are a matter of debate. What does this study add? The cases presented in this series confirm that MR-ONJ is usually a potential severe drug-related treatment-limiting adverse event of denosumab, with a delayed onset, and that it requires an aggressive treatment. Denosumab could be restarted in two patients experiencing GCTB progression after the complete resolution of MR-ONJ, with a prolonged disease control. A clinical algorithm of denosumab rechallenge after complete resolution of MR-ONJ in progressing GCTB patients should be prospectively validated. How might this impact on clinical practice? The rechallenge of denosumab in patients with advanced GCTB after the resolution of MR-ONJ could be considered, even though the validation of a clinical algorithm should be prospectively validated. Introduction Giant cell THZ1 tumour of bone (GCTB) accounts for approximately 5% of bone primitive neoplasms and represents a clinicopathologically defined tumour entity characterised by common radiological, histological and molecular features.1 2 GCTB is endowed with a variable clinical behaviour, that is, a benign or a locally aggressive course with a progressively enlarging bone destroying lesion. Local recurrences may occur in a significant number of cases, while metastatic lesions are extraordinarily rare (2%C3% of cases), mainly to the lung.3 4 GCTB is a tumour predominantly localised in the meta-epiphyseal region of the mature skeleton and is made up of three different cell populations.5 In THZ1 details, stromal cells, giant cell tumour stroma cells (GCTSC), represent the real neoplastic and proliferative component, which recruit blood monocytes thanks to inflammatory cytokines, leading to the fusion of mononuclear histiocytic cells into osteoclast-like multinucleated giant cells (MNGC), able to induce osteolysis. This Hdac11 process is determined by the conversation of Receptor Activator of Nuclear Factor Kappa-B (RANK) and RANK ligand (L), expressed by MNGC and GCTSC, respectively, through macrophage colony-stimulating factor as a cofactor.6 The main treatment of localised GCTB is surgery, but the recurrence rate varies according to the size and location of the tumour, as well as to the extent and the quality of surgery. In addition, in a number of cases, radical surgery is not feasible or is usually.