Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study

OBJECTIVE: The aim of the trial was to determine the effectiveness of oxygen-ozone injections on knee osteoarthritis concerning pain reduction, joint functional improvement, and quality of life. METHODS: In this randomized, double-blinded, placebo controlled clinical trial, 98 patients with symptomatic knee osteoarthritis (OA) were randomized into two groups receiving intra-articular 20 μg/ml of ozone (OZ) or placebo (PBO) for 8 weeks. The efficacy outcomes for knee OA were the Visual Analogue Scale (VAS), Lequesne Index, Timed Up and Go Test (TUG Test), SF-36, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Geriatric Pain Measure (GPM). RESULTS: After 8 weeks of treatment, ozone was more effective than the placebo: VAS [mean difference (MD) = 2.16, p < 0.003 (CI 95% 0.42–3.89)], GPM [MD = 18.94, p < 0.004 (CI 95% 3.43–34.44)], LEQ [MD = 4.05, p < 0.001 (CI 95% 1.10–7.00)], WOMAC (P) [median of diff = 9.999, p = 0.019 (CI 95% 0.000–15.000)], WOMAC (JS) [median of diff = 12.499, p < 0.001 (CI 95% 0.000–12.500)], WOMAC (PF) = [median of diff = 11.760, p = 0.003 (CI 95% 4.409–19.119)], TUG (no statistical difference) and SF-36 (FC) [(MD = -25.82, p < 0.001 (CI 95% 33.65–17.99)], SF-36 (PH) [MD = -40.82, p < 0.001 (CI 95% -54.48–27.17)], SF-36 (GSH) [MD = -3.38, p < 0.001 (CI 95% -4.83–1.93)], SF-36 (SA) [MD = 2.17, p < 0.001 (CI 95% -19.67–8.24), SF-36 (EA) [MD = -35.37, p < 0.001 (CI 95% -48.86–21.89)]. Adverse events occurred in 3 patients (2 in the placebo group and 1 in the ozone group) and included only puncture accidents. CONCLUSIONS: The study confirms the efficacy of ozone concerning pain relief, functional improvement, and quality of life in patients with knee osteoarthritis. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register ISRCTNR55861167