How Safe Are Oxygen-Ozone Therapy Procedures for Spine Disc Herniation? The SIOOT Protocols for Treating Spine Disorders
Franzini M, Chirumbolo S, Vaiano F, Valdenassi L, et al. Journal of Imaging, 2025.
- Study type
- Other
- Population
- Seven studies of intramuscular or intradiscal oxygen-ozone for disc herniation, pooled in a meta-analysis, plus CT scans of one 49-year-old man after an intramuscular injection
- Published
- 2025, Journal of Imaging
- Identifiers
- PMID 41440568, DOI 10.3390/jimaging11120428
What the authors reported
CT of one man showed gas in a lumbar disc minutes after a paravertebral intramuscular oxygen-ozone injection, which the authors attribute to diffusion. A meta-analysis of seven studies gave pain effect sizes of g = -1.55 (intramuscular) and 2.87 (intradiscal), and the authors put severe adverse events at 6.57 times as likely with intradiscal procedures (number needed to harm about 1180).
What limits this result
Nine of the 13 authors are from SIOOT, whose intramuscular protocol the paper recommends. The imaging is one patient, and the intradiscal estimate comes from uncontrolled cohorts. The abstract's 120 patients conflicts with Table 1, the text gives intradiscal complication rates of 9.52% and about 0.1%, and the intramuscular rate behind the NNH was back-calculated from the 6.57 ratio.
Harms reported after ozone therapy, and studies of how ozone exposure affects health. One study rarely settles a medical question; our guides weigh each paper against the rest of the evidence.
How the study was done
- Design
- Mixed-method study: CT imaging of one patient, biophysical diffusion modelling, and a meta-analysis of clinical studies
This mixed-method study combined computed tomography (CT) imaging, biophysical diffusion modelling, and a meta-analysis of clinical trials to evaluate whether intramuscular O2-O3 therapy can achieve disc penetration and therapeutic efficacy comparable to intradiscal nucleolysis, while minimizing procedural risk.
- Setting
- Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT), Gorle, Italy (affiliation of 9 of the 13 authors)
- Read from
- Read from the full text of the paper. Read on October 2, 2026.
Source: Abstract on PubMed
Study arms
| Group | Participants | What they received |
|---|---|---|
| Imaging case | Not reported | 49-year-old man with L5-S1 herniation; 20 mL oxygen-ozone at 15 µg/mL by the paravertebral intramuscular approach, with CT at 0, 3, 7, and 12 minutes |
| Studies in the meta-analysis | 7 | Intramuscular oxygen-ozone (three RCTs, against placebo or steroid) or intradiscal oxygen-ozone (cohort studies, and one RCT against surgery) |
Source: Full text on PubMed Central
Procedure as reported
- Ozone concentration
- 15 µg/mL (imaging case, 20 mL paravertebral intramuscular injection)
- Sessions
- Imaging case: CT after six sessions of intramuscular/paravertebral injection
following six sessions of intramuscular/paravertebral injections of a 20 mL oxygen–ozone mixture (ozone at 15 µg/mL)
In the paper's own units, not converted.
Source: Full text on PubMed Central
What it measured
- CT after intramuscular injection (one patient)
- Gas appeared in the intervertebral disc within minutes, which the authors read as diffusion through annular micro-fissures
- Pooled pain effect, all seven studies
- Hedges' g -2.42 (95% CI -3.384 to -1.456); I2 99.3%
resulted in −2.42 pooled Hedges’ g (where CI 95 = [−3.384, −1.456], τ 2 = 6.176, I 2 = 99.3% ( p < 0.0001), Q-statistic = 860.57
- Intramuscular subgroup (three RCTs)
- Hedges' g -1.55 (95% CI -2.10 to -1.00) for pain, against placebo or steroid injection
The pooled effect size for intramuscular delivery, based on three randomized controlled trials (RCTs), was Hedges’ g = −1.55 [95% CI: −2.10, −1.00], indicating a large and statistically significant reduction in pain relative to placebo or steroid injection.
- Intradiscal subgroup (three cohort studies)
- Hedges' g +2.87 (95% CI +1.79 to +3.95), a pre-post improvement
In contrast, intradiscal delivery, based on three cohort studies, yielded a pooled Hedges’ g = +2.87 [95% CI: +1.79, +3.95], reflecting a very large pre-post treatment improvement.
- Risk of serious complications by route
- 9.52% for intradiscal and 1.45% for intramuscular
The analysis shows that the risk (probability) of complications for the intradiscal approach is 9.52%, while for the intramuscular approach it is only 1.45%.
- Relative risk of severe adverse events, intradiscal versus intramuscular
- 6.57 times higher for intradiscal procedures; number needed to harm about 1180
- Intramuscular baseline used for the number needed to harm
- 0.015%, back-calculated from the 6.57:1 risk ratio (0.10% divided by 6.57)
- Authors' conclusion
- Oxygen-ozone therapy offers a safer, effective alternative to intradiscal injection; they support its adoption as a first-line strategy for lumbar disc herniation
Safety as reported
The authors list discitis, infection, bleeding, nerve injury, and damage to the annulus fibrosus as risks of the intradiscal route; no adverse event is described for the imaging patientAlthough generally considered safe when performed by experienced practitioners, the intradiscal route carries risks such as discitis, infection, bleeding, nerve injury, and potential damage to the annulus fibrosus, which may compromise disc integrity or provoke an exacerbated inflammatory response
Source: Full text on PubMed Central
Funding and conflicts
No external funding; one author was employed by Tirelli Medical Group, and the others declare no commercial or financial relationships
Source: Full text on PubMed Central
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