{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:14:32Z","timestamp":1783610072268,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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\u2013ozone therapy. This systematic review aimed to evaluate the efficacy of oxygen\u2013ozone 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\u2013ozone 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\u2013ozone 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\u2013ozone 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\u2013ozone therapy were reported. However, substantial heterogeneity was observed regarding injection protocols, ozone concentrations, number of injections, and follow-up duration. Conclusions: Oxygen\u2013ozone 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\u2013ozone 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\u2013ozone therapy in shoulder rehabilitation.<\/jats:p>","DOI":"10.3390\/jcm15145391","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:17:51Z","timestamp":1783606671000},"page":"5391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Oxygen\u2013Ozone Therapy for Shoulder Disorders: A Systematic Review of Randomized Controlled Trials"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5541-8346","authenticated-orcid":false,"given":"Alessandro","family":"de Sire","sequence":"first","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"},{"name":"Research Center on Musculoskeletal Health, MusculoSkeletalHealth@UMG, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5419-4275","authenticated-orcid":false,"given":"Andrea","family":"Demeco","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"},{"name":"Research Center on Musculoskeletal Health, MusculoSkeletalHealth@UMG, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5932-0116","authenticated-orcid":false,"given":"Andrea","family":"Racinelli","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Agostini","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Histological Sciences, Legal Medicine and Orthopedics Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6394-770X","authenticated-orcid":false,"given":"Angelica","family":"Balena","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-4361","authenticated-orcid":false,"given":"Kristian","family":"Efremov","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, New York University-Langone Winthrop Hospital, Mineola, NY 11501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4063-9821","authenticated-orcid":false,"given":"Umile Giuseppe","family":"Longo","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Via Alvaro del Portillo, 200, 00128 Roma, Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-0681","authenticated-orcid":false,"given":"Marco","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont \u201cA. Avogadro\u201d, 28100 Novara, Italy"},{"name":"Dipartimento Attivit\u00e0 Integrate Ricerca e Innovazione (DAIRI), Translational Medicine, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-7909","authenticated-orcid":false,"given":"Nicola","family":"Marotta","sequence":"additional","affiliation":[{"name":"Research Center on Musculoskeletal Health, MusculoSkeletalHealth@UMG, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"},{"name":"Physical and Rehabilitative Medicine, Department of Experimental and Clinical Medicine, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-2455","authenticated-orcid":false,"given":"Antonio","family":"Ammendolia","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Medical and Surgical Sciences, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"},{"name":"Research Center on Musculoskeletal Health, MusculoSkeletalHealth@UMG, University of Catanzaro \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/03009740310004667","article-title":"Prevalence and Incidence of Shoulder Pain in the General Population; a Systematic Review","volume":"33","author":"Luime","year":"2004","journal-title":"Scand. 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