Is intra-articular injection of high-concentration ozone (O2–O3) more effective in treating knee osteoarthritis?

Knee osteoarthritis is a prevalent joint disorder globally, resulting in pain and disability, with various treatment options available. Intra-articular ozone (O ₂ –O ₃ ) administrations are an efficient therapeutic approach commonly employed in this condition. With this study, we aimed to compare the effect of varying ozone concentrations on treatment outcomes. This multicenter retrospective cohort study was conducted at 2 distinct university hospitals between May 2023 and September 2024. Medical records of patients who underwent intra-articular knee ozone injections were retrospectively reviewed and divided into 2 groups as 15 μg/mL (group A) and 25 μg/mL ozone (group B). Participants’ pain scores were measured by Numeric Rating Scale, functional status by Western Ontario and McMaster Universities Osteoarthritis Index and quality of life by 12-item Short Form Health Survey before and at 1 and 3 months following ozone therapy. A total of 190 patients were screened; 159 patients (105 females, 54 males) were included in the study, with 77 patients in group A and 82 patients in group B. Both groups demonstrated significant improvements in all outcomes during follow-up. After adjustment for multiple comparisons, between-group differences in Numeric Rating Scale scores were not statistically significant at either 1 or 3 months. Group B had significantly better Western Ontario and McMaster Universities Osteoarthritis Index, 12-item Short Form Health Survey physical component summary, and 12-item Short Form Health Survey mental component summary scores at both follow-up assessments (all Holm-adjusted P  < .001). The 25 μg/mL concentration was associated with more favorable short-term functional and quality-of-life outcomes and a trend toward greater pain improvement. These findings should be considered exploratory and require confirmation in prospective randomized studies.