{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T15:39:09Z","timestamp":1764776349109,"version":"3.46.0"},"reference-count":64,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Imaging"],"abstract":"<jats:p>Oxygen\u2013ozone (O2\u2013O3) therapy is widely used for treating lumbar disc herniation. However, controversy remains regarding the safest and most effective route of administration. While intradiscal injection is purported to show clinical efficacy, it has also been associated with serious complications. In contrast, the intramuscular route can exhibit a more favourable safety profile and comparable pain outcomes, suggesting its potential as a safer alternative in selected patient populations. This mixed-method study combined computed tomography (CT) imaging, biophysical diffusion modelling, and a meta-analysis of clinical trials to evaluate whether intramuscular O2\u2013O3 therapy can achieve disc penetration and therapeutic efficacy comparable to intradiscal nucleolysis, while minimizing procedural risk. Literature searches across PubMed, Scopus, and Cochrane databases identified seven eligible studies (four randomized controlled trials and three cohort studies), encompassing a total of 120 patients. Statistical analyses included Hedges\u2019 g, odds ratios, and number needed to harm (NNH). CT imaging demonstrated gas migration into the intervertebral disc within minutes after intramuscular injection, confirming the plausibility of diffusion through annular micro-fissures. The meta-analysis revealed substantial pain reduction with intramuscular therapy (Hedges\u2019 g = \u22121.55) and very high efficacy with intradiscal treatment (g = 2.87), though the latter was associated with significantly greater heterogeneity and higher complication rates. The relative risk of severe adverse events was 6.57 times higher for intradiscal procedures (NNH \u2248 1180). O2\u2013O3 therapy offers a biologically plausible, safer, and effective alternative to intradiscal injection, supporting its adoption as a first-line, minimally invasive strategy for managing lumbar disc herniation.<\/jats:p>","DOI":"10.3390\/jimaging11120428","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T15:02:48Z","timestamp":1764774168000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How Safe Are Oxygen\u2013Ozone Therapy Procedures for Spine Disc Herniation? The SIOOT Protocols for Treating Spine Disorders"],"prefix":"10.3390","volume":"11","author":[{"given":"Marianno","family":"Franzini","sequence":"first","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-8307","authenticated-orcid":false,"given":"Salvatore","family":"Chirumbolo","sequence":"additional","affiliation":[{"name":"Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy"}]},{"given":"Francesco","family":"Vaiano","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Luigi","family":"Valdenassi","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Francesca","family":"Giannetti","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Marianna","family":"Chierchia","sequence":"additional","affiliation":[{"name":"Unit of Orthopaedics, University Luigi Vanvitelli, 81100 Caserta, Italy"}]},{"given":"Umberto","family":"Tirelli","sequence":"additional","affiliation":[{"name":"Tirelli Medical Group, 33170 Pordenone, Italy"}]},{"given":"Paolo","family":"Bonacina","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Gianluca","family":"Poggi","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Aniello","family":"Langella","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Edoardo Maria","family":"Pieracci","sequence":"additional","affiliation":[{"name":"USL Centro Toscana, Health Clinical Service, Piazza Santa Maria 1, 50122 Firenze, Italy"}]},{"given":"Christian","family":"Giannetti","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]},{"given":"Roberto Antonio","family":"Giannetti","sequence":"additional","affiliation":[{"name":"Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), 24020 Gorle, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00062-025-01510-x","article-title":"Neurological Adverse Effects Associated with Ozone Therapy","volume":"35","author":"Rouhi","year":"2025","journal-title":"Clin. 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