Comparative Effectiveness of Low-Dose Intra-Articular Ozone Therapy for Pain and Functional Outcomes in Patients with Knee Osteoarthritis: A Retrospective Cohort Study.

Purpose: Knee osteoarthritis is one of the leading causes of chronic musculoskeletal pain and disability worldwide. Although intra-articular ozone therapy has demonstrated analgesic effects, the optimal concentration for maximizing pain relief while preserving functional improvement remains uncertain. Our aim is to determine whether different low-dose ozone protocols differ in their ability to reduce pain and improve functional performance in patients with knee osteoarthritis. Patients and Methods: This retrospective comparative study included 45 patients aged 40-80 years with Kellgren-Lawrence grade II-III knee osteoarthritis. Patients were retrospectively classified into three groups according to the ozone protocol documented in their medical records: 1 μg/mL, 5 μg/mL, and 10 μg/mL, with 15 patients in each group. All patients received intra-articular ozone injections once weekly for 3 consecutive weeks. Outcomes were assessed at baseline and at week 4 using the Visual Analogue Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the 2-minute walking test. Results: The study included 45 patients, 7 men and 38 women, with a mean age of 59.62 ± 8.08 years. VAS, WOMAC pain, WOMAC physical function, and WOMAC total scores improved significantly in all three groups after treatment. WOMAC stiffness scores improved numerically in all groups but reached statistical significance only in the 5 μg/mL group. No significant between-group differences were found for changes in pain, stiffness, physical function, or total scores. The increase in 2-minute walking test distance was significantly greater in the 1 μg/mL group than in the 10 μg/mL group. No adverse events were documented in any group. Conclusion: Intra-articular ozone therapy was associated with short-term improvements in pain and functional outcomes in patients with knee osteoarthritis, with generally comparable results across the ozone concentrations evaluated. Because of the retrospective design, causal conclusions cannot be drawn, and the difference favoring the lowest concentration in walking distance should be considered exploratory. Prospective studies with larger sample sizes and longer follow-up are needed to confirm these findings.