The Effect of Ozone (O3) versus Hyaluronic Acid on Pain and Function in Patients with Knee Osteoarthritis: A Systematic Review and Meta-Analysis

Abstract

Background: Of the pharmacological modalities for knee osteoarthritis (OA), intra-articular injections including ozone<br />(O3) and hyaluronic acid (HA) are commonly used for reducing pain and improving function. In this systematic review<br />and meta-analysis, we aimed to compare the effect of O3 versus HA in reducing pain and increasing function in patients<br />with knee OA.<br />Methods: After searching databases, we included 6 randomized controlled trials on patients with knee OA that<br />compared the effects of intra-articular injection of ozone versus HA. The primary outcome was visual analogue scale<br />(VAS) of pain. The secondary outcome was Western Ontario and McMaster Universities Arthritis Index (WOMAC)<br />score.<br />Results: There was a total of 237 patients in the HA group and 230 patients in the Ozone group. Of 6 studies, 4 were<br />in English, 1 was in Persian, and 1 was in German language. The overall Standardized Mean Difference (SMD) for VAS<br />pain did not show a significant difference between the groups although it favored HA injection (1.27 [95%CI: (-0.12)-<br />2.66]). Total WOMAC score showed a significant difference over the time favoring HA injection (4.5 [95%CI: 1.1-8]).<br />However, no single time point showed any significant difference between groups.<br />Conclusion: This meta-analysis showed no significant difference between HA and ozone in reducing pain and<br />improving function in patients with knee OA, although the overall results favored HA over ozone. Since previous studies<br />have shown comparable results between HA and placebo, ozone seems to fall in the same category with more placebo<br />effect rather than a real disease-modifier.<br />Level of evidence: I