The main aim of this review was to discuss the literature on ozone intra-articular injection in knee osteoarthritis (OA) patients and to synthesize the available evidence as a meta-analysis.

A systematic review of Pubmed, Google scholar and Cochrane Central Register of Controlled Trials was performed to identify all English-language RCTs that evaluated the efficacy of ozone intra-articular injection versus a control injection for knee OA patients. A Random effect model was used to compare efficacies among trials based on Visual Analogue Scale (VAS) for pain and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire.

From 231 records screened, only 26 one had relevant topics. Among them only five studies satisfied our inclusion criteria. A total of 428 patients were included which 53% of them (n=225) in the treatment group and 47% in the control [HA, hypertonicdextrose and air injection] group (n=203). The mean age of ozone groups was 64.5 years compared with 64.4 years for control group. Females were the majority in both treatment and control group (80% and 77%, respectively). All studies had at least 2 months follow-up. In almost all of them 3–4 weekly rounds of ozone injection were performed, with concentration of 15–30 ug/cm³.

Intra-articular ozone in comparison to HA or hypertonic dextrose injections, may have quietly equal effects in the treatment of mild to moderate knee OA patients throughout short term period; However by 3–6 months after injection, this therapeutic effect would be disappeared, more earlier than other control injections.