Intra-articular ozone therapy versus hyaluronic acid injections for the treatment of knee osteoarthritis: results of a double-blind randomized controlled trial

Ozone therapy (OT) is an innovative approach to treating multiple musculoskeletal disorders. In recent years, increasing interest has been directed towards its properties for the treatment of osteoarthritis (OA). OA is a widespread degenerative disease that causes chronic disability worldwide, for which there are currently no universally approved therapies that can adequately control the symptoms and slow its progression. The aim of this randomized, double-blind, controlled trial was to evaluate the efficacy of intra-articular injections of ozone (O3) versus hyaluronic acid (HA) in relieving pain and reducing disability in patients with knee OA. Patients with knee pain for at least 3 months were included and randomly assigned to receive three intra-articular injections of O3 or HA (once a week). Participants were evaluated at baseline and at 1, 3, 6, and 12 months after treatment for pain, stiffness, and motor function using the following rating scales: WOMAC LK 3.1, NRS, and KOOS. Of the 122 patients assessed for eligibility, 112 participants were admitted to the study and randomly assigned to the two treatment groups. Both groups A and B consisted of 56 patients. During the study, ten patients withdrew. Therefore, a total of 102 patients reached the study endpoints at 12 months. Both groups showed statistically significant improvements over baseline in all outcomes measured from 1 month after treatment. Values remained stable, showing a worsening trend from the sixth month until one year after the intervention, but without returning to baseline values. At short-term observation (1 month), OT-treated patients showed better results in pain control, recovery of motor skills and quality of life than HA-treated patients, although without statistical significance. In contrast, at mid- and long-term follow-ups (3 months to 12 months), the HA-treated group showed statistically significant pain reduction and functional improvement compared to the OT-treated group. In terms of safety, both therapies appeared safe: the few recorded adverse events were mild and self-limiting. In conclusion, due to its anti-inflammatory and analgesic effect, O3 could be considered a potential treatment for OA, particularly to provide a short-term analgesic effect. HA treatment is confirmed to be more effective in the medium and long term.