## 1 Introduction
\begin{table}
\begin{tabular}{c c} \hline \hline
**Stage** & **MRONJ Clinical Findings** \\ \hline At risk category & No apparent necrotic bone in patients who have been treated with either oral or IV bisphosphonates \\ \hline Stage 0 & No clinical evidence of necrotic bone, but non-specific clinical findings, radiographic changes and symptoms \\ \hline Stage 1 & Exposed and necrotic bone, or fistulae that probes to bone, in patients who are asymptomatic and have no evidence of infection \\ \hline Stage 2 & Exposed and necrotic bone, or fistulae that probes to bone, associated with infection as evidenced by pain and erythema in the region of the exposed bone with or without purulent drainage \\ \hline Stage 3 & Exposed and necrotic bone or a fistula that probes to bone in patients with pain, infection, and one or more of the following: exposed and necrotic bone extending beyond the region of alveolar bone,(i.e., inferior border and ramus in the mandible, maxillary sinus and zygoma in the maxilla) resulting in pathologic fracture, extra-oral fistula, oral \\  & &HBO increases local concentrations of reactive nitrogen species (RNS) and reactive oxygen species (ROS) by providing substrates (oxygen and L-arginine) for nitric oxide synthase, as well as by the generation of superoxide [19; 20]. ROS and RNS influence osteoclast (OC) differentiation and activity and participate in the regulation of various aspects of bone metabolism [21; 22; 23]. Nitric oxide (NO) is constitutively synthesised by both OCs and osteoblasts (OBs) and has contrasting biphasic effects. At lower levels, NO decreases bone resorption and stimulates its turnover; whereas at higher concentrations, NO promotes inflammatory processes and inhibits bone formation [24]. Indeed, ROS stimulate the expression of receptor activator of nuclear factor kappa-B ligand (RANKL), changing the RANKL/osteoprotegerin ratio and favouring OC differentiation, and avoiding osteopterosis in animal models [22; 25]. Authors have also suggested that HBO-generated ROS could induce suppression of OC activity and promote bone healing [21; 23]. Recent research has shown that HBO-generated ROS and RNS induce stem cell mobilisation, vasculogenesis, mitochondrial biogenesis and preconditioning [26; 27; 28; 29]. Ozone dissolves physically in biological water (physiological saline, plasma, lymph, urine). All these reagents act as donor electrons and are oxidisable, and participate in the ozonation process and the consequent formation of ROSs and lipid oxidation products (LOPs). These molecules are responsible for the biochemical actions of ozone and function as biochemical regulators of inflammation at distinct times and physiological concentrations [30; 31]. Through interactions with cellular components and depending on the concentration of ozone in the tissue, these molecules can trigger biological effects that are either therapeutic or detrimental to health [30; 31]. During normal metabolism, osteoclasts, platelets, lymphocytes, neutrophils, monocytes and fibroblasts can induce the formation of ROS [32; 33]. When in excess, these ROSs can trigger damage to cellular constituents, extracellular components and affect the metabolism of the cells responsible for extracellular matrix synthesis--fundamental in tissue repair--which leads to apoptosis and cellular necrosis [34; 35]. The aim of this review is to analyse all available evidence and evaluate the reported outcome of oxygen therapy as treatment for patients affected by MRONJ.