Intra-articular ozone may provide pain relief, functional improvement, and gains in quality of life (QoL) in patients with knee osteoarthritis (OA), according to a study recently published in PLoS One.1
The intervention, which was conducted by a team of Brazilian researchers affiliated with the Sao Paulo Federal University in Brazil, was shown to be safe and effective. “Although many clinical series reports have been accomplished, no randomized, double-blind, placebo-controlled clinical trial had been accomplished until now,” said lead investigator Carlos César Lopes de Jesus, MD, in an interview with Clinical Pain Advisor.
A total of 98 patients with symptomatic knee OA were enrolled in the trial and randomly assigned to receive intra-articular injections of ozone (20 μg/mL; n=63), or air (10 mL; n=35) once weekly for 8 weeks. Efficacy measures included the Visual Analogue Scale (VAS); Lequesne Index, in which patients with knee OA rate pain and function on a 0 to 24-point scale; Timed Up and Go Test, which evaluates balance and fall risk; SF-36 Health Survey Instrument, which evaluates QoL on a scale of 0 to 100 (0 =worst health); Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); and the Geriatric Pain Measure (GPM).
After 8 weeks of treatment, statistically significant differences favoring ozone were seen in several efficacy measures. A significant reduction in pain as measured by VAS, GPM, and WOMAC scores was seen in the ozone group compared with the placebo group (P <.001). Differences in WOMAC scores, particularly toward the end of the treatment course, also indicated a significant improvement in joint stiffness and engagement in physical activities (P <.001). Lequesne Index measures also indicated a significant reduction in pain and improvement in function (P < .001), and QoL in relation to function, pain, and general physical and mental health was also statistically superior in the ozone group compared with the placebo group (P <.001). No significant differences were observed between groups in relation to the Timed Up and Go Test.
The study investigators reminded clinicians that symptomatic knee OA affects more than 9.3 million US adults and is a leading cause of disability. Agents to slow progression are lacking. Ozone therapy has been used as an alternative therapy in some chronic conditions such as rheumatic and osteoarthritic disease.
“In my opinion, ozone injections are more effective than the use of corticosteroids and nonsteroidal anti-inflammatory agents [NSAIDs] for the treatment of knee OA,” said Dr Lopes de Jesus. He explained that ozone has a significantly broader mechanism of action than NSAIDs and corticosteroids, providing anti-inflammatory and antioxidant effects and the ability to deter antalgic gait.2 “Ozone activates the cellular metabolism, reduces prostaglandin synthesis, makes the redox system function properly by reducing oxidative stress through induction of the synthesis of antioxidant enzymes, and ameliorates tissue oxygen supply through hemorheologic action, vasodilatation, and angiogenic stimulation.“ Dr Lopes de Jesus added that ozone has been reported to have a restorative effect once it mobilizes bone marrow, mesenchymal, and endothelial stem cells, but no study had demonstrated this until now.
Puncture accidents, which occurred in 2 patients in the placebo group and 1 in the ozone group, were the only reported adverse events in this study. Adverse events are rare and comprise acute and transitory pain in the knee at the moment of ozone application, said Dr Lopes de Jesus.
The investigators concluded that their results are encouraging and warrant further study.
Summary and Clinical Applicability
The value of intra-articular ozone for pain relief and functional improvement in patients with knee osteoarthritis was confirmed in a randomized double-blind placebo-controlled clinical trial.
Limitations and Disclosures
According to Dr Lopes de Jesus, the main limitation of the current study was the lack of imaging examination control to evaluate the impact of treatment.
- Lopes de Jesus CC, Dos Santos FC, de Jesus LMOB, et al. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. PLoS One. 2017;12(7):e0179185
- Bocci VA. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res. 2006;37(4):425-435.