TOWARDS THE OPTIMIZATION OF OZONE THERAPY IN KNEE OSTEOARTHRITIS: FACTORS INFLUENCING TREATMENT OUTCOMES

I. Iliakis¹ , E. Iliakis² , V. Demenrios³

¹ PMR Department of Asklepieion, Voulas General Hospital, Voula, Greece
² Ortopaedic surgeon, Ozonaim Clinic, Athens, Greece
³ Biochemistry, Biochemical Analysis and Matrix Pathobiochemistry Research Group, Department of Chemistry, University of Patras, Patras, Greece

Correspondence to:

Journal of Orthopedics 2025 May-August; 17(2): Ahead of Print
https://doi.org/10.69149/orthopedics/2025v7iss2_4

Received: 29 March 2025 Accepted: 16 April 2025

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Abstract

The aim of this study is to determine the optimal ozone concentration for achieving the longest-lasting therapeutic benefits in ozone therapy for osteoarthritic knees. Additionally, we aim to assess the duration of effectiveness following each intra-articular ozone administration and, based on this, determine the appropriate injection frequency. Moreover, investigate whether the therapeutic efficacy of each ozone injection follows the circadian rhythm, which could necessitate selecting a specific time for administration. Methods: The study was conducted in two phases. In the first phase, patients who had undergone intra-articular ozone injections and achieved complete symptomatic relief were categorized into three groups based on the ozone concentration administered. In the second phase, the included patients were divided into four groups based on the time interval after injection at which they reported the maximum therapeutic effect (1-6 days, 7-14 days, 14-21 days, and 21-28 days). We also evaluated whether the ozone concentration influenced the timing of peak efficacy. Additionally, the impact of the administration time on therapeutic outcomes was examined by allocating patients into three different time-of-day groups for ozone injection. Findings from the first phase indicate that an ozone concentration of 30 µg provides the longest-lasting therapeutic effect following intra-articular administration, with a mean duration of 2.17 years. The second phase demonstrated that the optimal therapeutic effect following a single injection occurred at approximately 21 days, regardless of the ozone concentration used. Furthermore, results suggest that the time of day of administration does not significantly affect therapeutic efficacy. Our study suggests that medical ozone therapy provides a longer-lasting therapeutic effect compared to other commonly used intra-articular injection methods for osteoarthritic knees. Despite the fact that ozone, upon contact with biological fluids, ceases to exist as an independent entity within less than a minute, the therapeutic benefits of even a single injection peak around three weeks post-administration. This observation can be explained by ozone’s biochemical and biological mechanisms of action and supports the recommendation of administering treatment every three to four weeks. Although literature suggests that biological factors influenced by ozone may follow a circadian pattern, our study did not confirm this association. Consequently, ozone therapy can be performed at any time of day with consistent therapeutic outcomes.

Keywords: circadian rhythm, intra-articular injections, osteoarthritis, ozone therapy, therapeutic efficacy