## 1 Introduction  
The term'medication-related osteonecrosis of the jaws' (MRONJ) refers to a potentially serious iatrogenic complication of treatment with medications, such as antiangiogenic or antiresorptive drugs. These drug families are used primarily for the treatment of malignancies (e.g., multiple myeloma or bone metastases) but also have important roles in the management of osteoporosis, Paget's disease and hypercalcemia. The bone targeting agents (BTAs) can reduce the risk of skeletal-related adverse events to protect the skeleton in patients with primary or secondary bone pathology [1; 2]. Since the first reports of bisphosphonate-related osteonecrosis of the jaw in 2003, an increasing number of reports have been published showing similar clinical complications associated with other drugs. New evidence has shown that along with bisphosphonates (BPs), other BTAs such as denosumab also cause osteonecrosis of the jaw bones. In addition, monoclonal antibodies able to bind and selectively inhibit vascular endothelial growth factor-A (VEGF-A), specifically mammalian target of rapamycin (mTOR) inhibitors, can also cause similar lesions [3; 4; 5]. For this reason, the term MRONJ was adopted in the 2014 position paper of the American Association of Oral and Maxillofacial Surgeons (AAOMS) [3]. The medications currently reported to be associated with MRONJ are listed in Table 1 (antiresorptive drugs) and Table 2 (antiangiogenic agents) [6; 7]. The AAOMS position paper states that \"patients may be considered to have MRONJ if all the following characteristics are present: current or previous treatment with antiresorptive or antiangiogenic agents; exposed bone or bone that can be probed through an intraoral or extraoral fistula in the maxillofacial region that has persisted for longer than 8 weeks; and no history of radiation therapy to the jaws or obvious metastatic disease to the jaws\". However, it is accepted that some patients may present with non-specific symptoms and may not have evidence of exposed bone such as those classified as Stage 0 by the AAOMS staging system [8]. The term'stage 0' was first used by [PERSON] et al. to gather suspected MRONJ cases presenting with clinical and radiological signs of disease other than intraoral bone exposure [9]. The AAOMS classification and staging system is based entirely on the intraoral presentation, which they propose should also guide potential treatment. This has been criticised in studies where it was highlighted that radiological findings are an important part of the clinical picture necessary for accurate MRONJ staging (Tables 3 and 4) [6; 8; 10]. The major risk factor for the development of MRONJ is dento-alveolar surgery, with a history of tooth extraction or oral surgery procedure (apicectomy or cystectomy) reported in 52% to 80% of patients with MRONJ [11; 12; 13]. The overall risk of developing MRONJ after dento-alveolar surgery, in patients on IV bisphosphonates ranges from 1.6% to 14.8% in comparison to 0.5% for patients taking oral bisphosphonates [6]. To date, there is no current standard for the treatment of MRONJ associated with antiresorptive or antiangiogenic drug therapy. Several treatment options have been described, with the earlier stages of MRONJ reportedly responding well to conservative management such as topical or systemic antibiotics, or limited bone debridement, although this still remains controversial [14; 15]. Ozone therapy (OT) and hyperbaric oxygen therapy (HBO) have been reported as effective adjunctive therapies in situations where normal bony wound healing is impaired, such as osteoradionecrosis and chronic osteomyelitisitis of the jaw [16; 17; 18].