Efficacy of Oxygen-Ozone Therapy for Shoulder Disorders: A Systematic Review of Randomized Controlled Trials

Background: Shoulder disorders are among the leading causes of musculoskeletal pain and disability worldwide. Despite the widespread use of corticosteroid injections, concerns regarding their short-term efficacy and potential adverse effects have encouraged research into alternative therapies such as oxygen-ozone therapy. This systematic review aimed to evaluate the efficacy of oxygen-ozone therapy in the management of shoulder disorders. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted up to 16 March 2026, according to PRISMA guidelines. Randomized controlled trials investigating localized oxygen-ozone injections for shoulder disorders were included. Pain scores and shoulder function were the main outcomes considered. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Results: Five randomized controlled trials involving 263 participants with shoulder impingement syndrome, adhesive capsulitis, or chronic rotator cuff syndrome were included. Given the heterogeneity of the included studies, we only performed a qualitative synthesis. Oxygen-ozone therapy demonstrated significant improvement in pain and shoulder function across all of the included studies. Corticosteroid injections generally showed superior short-term pain relief, whereas oxygen-ozone therapy demonstrated more persistent clinical improvements during medium-to-long follow-up periods. Studies employing multiple ozone injection protocols reported more stable outcomes when compared with single-injection approaches. No major adverse events related to oxygen-ozone therapy were reported. However, substantial heterogeneity was observed regarding injection protocols, ozone concentrations, number of injections, and follow-up duration. Conclusions: Oxygen-ozone therapy appeared to be a potentially effective treatment option for shoulder disorders, particularly in patients with contraindications to corticosteroids or chronic degenerative conditions. While corticosteroid injection might provide short-term symptom relief, repeated oxygen-ozone injection protocols seemed to offer sustained clinical benefits over time. Further high-quality randomized controlled trials with standardized protocols and longer follow-ups are needed to better define the role of oxygen-ozone therapy in shoulder rehabilitation.