Intra-articular ozone or hyaluronic acid injection: Which one is superior in patients with knee osteoarthritis? A 6-month randomized clinical trial

Purpose: Knee osteoarthritis (OA) is a common disease, imposing a great burden through pain and decreased function. There are many therapeutic modalities including non-pharmacologic choices and oral, topical, and intra-articular medications. New studies have shown promising results for ozone application in knee OA. Our aim was to compare the effects of ozone therapy versus hyaluronic acid (HA) intra-articular injection in knee OA patients. Methods: In this randomized clinical trial, a total of 174 patients with more than 3 months of chronic pain or swelling in the knee joints along with consistent imaging findings were enrolled and randomly allocated into two groups of HA and ozone, which were planned to undergo 3 weekly injections of HA (Hyalgan (R)) and 10 mL of a 30 mu g/mL ozone solution, respectively. Patients were evaluated at baseline and 6 months after the last injection for pain, stiffness, and function using the visual analog scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Results: No major adverse events were detected in this study. Total WOMAC score decreased from 40.8 +/- 9.8 to 20.4 +/- 4.9 (p<0.01) in the ozone group and from 38.5 +/- 7.9 to 17.1 +/- 4.2 (p<0.01) in the HA group. A similar trend was observed in pain improvement according to VAS. Pain, stiffness, and function significantly improved in both the groups, but no between-group difference was found. Conclusion: Although both ozone and HA can be effectively used for improving function and reducing pain in selected knee OA patients, neither of the two showed any superiority at 6-month follow-up.