Oxygen-Based Adjunct Therapies in Periodontitis: A Systematic Review and Meta-Analysis Within the Framework of Hypoxia and Inflammation

<b>Background/Aim:</b> This systematic review and meta-analysis aimed to evaluate the clinical efficacy of oxygen-based adjunct therapies in patients with periodontitis, including ozone therapy, hyperbaric oxygen therapy, and local oxygen delivery, as adjuncts to subgingival instrumentation. These interventions have been proposed to counteract tissue hypoxia and inflammation, which sustain an environment favorable to anaerobic pathogens in periodontitis. <b>Methods:</b> An electronic search was conducted in MEDLINE PubMed, the Cochrane Library, the Cochrane Central Register of Controlled Trials, and SciELO. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Standardized mean difference was calculated for gains in clinical attachment level, and a random effects model was applied due to high variability. <b>Results:</b> The meta-analysis of adjunct ozone therapies presented a pooled standardized mean difference of 0.53 (95% CI [-0.14, 1.19]), indicating a clinically relevant medium effect in favor of ozone therapies, though this effect was not statistically significant and substantial heterogeneity was observed (I² = 70%, <i>p</i> < 0.01). Meta-analysis was restricted to adjunct ozone therapies due to the limited availability of qualifying studies for hyperbaric oxygen therapy and local oxygen therapies. <b>Conclusions:</b> While the medium effect size in favor of ozone therapies could be clinically relevant, the statistical non-significance underscores the need for more evidence before widespread adoption. Individual studies reported significant benefits for adjunct HBOT and ozonated olive oil, but comparison between oxygen delivery modes was not possible due to heterogeneous protocols.