# Current Trends in Adjuvant Therapies for Medication-Related Osteonecrosis of the Jaw
## 3 Results and Discussion
### Hyperbaric Oxygen  
Hyperbaric oxygen (HBO) is a treatment in which patients breathe 100% oxygen in a hyperbaric chamber. The inhaled oxygen dissolves in the blood serum, and its concentration increases in arterial flow and tissues. Therefore, HBO promotes wound healing by maintaining a consistently high oxygen concentration in patients. Elevated oxygen concentration enhances the production of reactive oxygen and nitrogen species, which play important roles in signaling pathways that promote neovascularization, boost matrix formation, and reduce inflammation.  
Numerous indications exist for HBO treatment: embolism, poisoning, myositis, anemia, abscess, necrotizing soft tissue infections, and refractory osteomyelitisitis [47]. [PERSON] et al. reported that HBO has a positive effect on treating necrotizing infections and ulcers [48]. Because HBO treatment promotes wound healing progression, it is considered an effective adjunctive modality in conditions involving impaired bone healing, such as osteoradionecrosis and chronic osteomyelitisitis of the jaw.  
Several studies have investigated the utility of HBO for MRONJ treatment. One case series and one randomized controlled trial reported the effect of HBO in patients with MRONJ [49; 50]. Their findings suggest that HBO is beneficial as an adjunct therapy for MRONJ in combination with a surgical approach and systemic antibiotic treatment. Other studies showed HBO alone is effective in stages 1 and 2 of the disease; however, in advanced stages, it is effective only when combined with surgical treatment [51]. In addition, HBO is successful when used as an adjunct therapy before and after surgery, emphasizing the importance of treatment timing [52]. Recent human studies on HBO therapy for MRONJ are summarized in Table 3.  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Reference** & **Total** & **Medical** & **BP Route** & **Duration** & **Trigger** & **Stage** & **Additional** & \\
**Pt** & **Condition** & **Orig** & **(Tears)** & **Event** & **Stage** & **Adjuvant** & **Outcome** \\ \hline [PERSON] et al. (2012) [44] & 20 & OP/BM & Oral/IV & NA & NA & 3 & None & Favorable \\ [PERSON] et al. (2016) [45] & 1 & OP & Oral & 4 & Ext & 3 & L-PRF & Favorable \\ [PERSON] et al. (2017) [33] & 10 & OP & Oral & 0.5–15 & NA & 2 or 3 & 6 pt (TPTD) & Favorable \\ [PERSON] et al. (2017) [46] & 30 & OP/BM & Oral/IV & 1–15 & Ext/Imp/Period & 1–3 & L-PRF & Favorable \\ [PERSON] et al. (2020) [41] & 16 & OP/BM & Oral & NA & NA & 2 or 3 & None & Favorable \\ [PERSON] et al. (2020) [42] & 3 & OP & Oral/IV & 5 to 10 & Ext/perio & 3 & None & Favorable \\ \hline \hline \end{tabular}  
* Pt, patient; BP, bisphosphonate; Tx, treatment; OP, osteoporosis; TPTD, teriparatide; BM, bone metastasis; NA, not available; IV, intravenous; L-PRF, leukocyte- and platelet-rich fibrin; Spon, spontaneous; Ext, extraction; Imp, implant; Perio, periodontitis.  
\end{table}
Table 2: Human studies of recombinant human bone morphogenetic protein-2(rhBMP-2) administration for MRONJ treatment in the past 10 years.  
Barotrauma, myopia, seizures, and pulmonary edema are minor complications of HBO and generally show minor and reversible symptoms. In rare cases, serious complications, including seizures, congestive heart failure exacerbation, pulmonary edema, and retinal changes, may occur after HBO therapy. As elderly MRONJ patients typically have comorbidities, HBO therapy requires cautious planning. In particular, it should be carefully considered for treating patients who have experienced seizures, hyperthyroidism, or pulmonary disease.