Intra-Articular Injection of Medical Ozone Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials .

Medical ozone has emerged as a potential intra-articular therapy for knee osteoarthritis, yet its comparative efficacy against hyaluronic acid (HA) remains unclear. This systematic review and meta-analysis synthesizes data from five RCTs involving 555 patients, covering pain and function outcomes at 1, 2, 6, and 12 months. While a few short-term results at 2 months favored ozone, most meaningful outcomes actually favored HA, especially by 6 and 12 months. Safety looked similar between the two treatments. However, the overall evidence was very weak—most outcomes were rated very low quality due to bias, inconsistency, and small sample sizes. Because of this, no firm conclusions about ozone’s effectiveness compared with HA can be made.