Safety of Intra-Articular Oxygen-Ozone Therapy Compared to Intra-ArticularSodium Hyaluronate in Knee Osteoarthritis: A Randomized Single Blind PilotStudy

Objective: Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease and one of the leading causes of chronic musculoskeletal pain, often affecting the knee. Despite intra-articular (IA) injectable hyaluronan (HA) preparations are widely used in the treatment of this debilitating condition, only a few data about their efficacy have been reported so far. Therefore, the use of HA in OA management is not universally recommend in clinical practice. Oxygen-ozone (O2O3) therapy can be employed in several pain-related conditions and diseases. However, both its efficacy and safety for IA therapy in knee OA have never been explored. Here, we evaluated the reliability of knee IA therapy with O2O3 compared to IA HA in chronic knee OA. Methods: A total of 42 consecutive chronic OA patients with radiological diagnosis of knee OA were prospectively enrolled in this single-blind, controlled study. After randomization, all patients underwent IA therapy with O2O3 or HA (q1wk) for 4 weeks, with additional 4 weeks of follow-up. Examination of the adverse events occurred during the whole study was performed. To measure knee function and pain, visual analogue scale (VAS), Oxford knee questionnaire (OKQ), and 12-item short form survey (SF-12) were administered. EuroQol five dimensions questionnaire (EQ-5D) was used to assess patients’ quality of life. Results: No significant difference in adverse events occurrence was observed. Knee IA treatment with O2O3 showed shorter reduction of pain compared to IA HA. VAS score decreased in both groups during the treatment period (p<0.001), while OKQ score significantly increased (p<0.001). SF-12 and EQ-5D scores were comparable between the two groups of patients. Conclusions: Despite IA administration of O2O3 and hyaluronan are comparable treatments in knee OA both in terms of safety and quality of life improvement, the latter shows longer times of pain reduction.