Laird Harrison

November 13, 2015

SAN FRANCISCO — An ozone injection into the knee can soothe pain and improve quality of life for people with knee osteoarthritis, a randomized controlled trial suggests.

"When I saw the results I was very surprised," said Virginia Fernandes Moça Trevisani, PhD, from the Federal University of Sao Paulo, who presented the finding here at the American College of Rheumatology (ACR) 2015 Annual Meeting.

Ozone appears to inhibit prostaglandins and cytokines and reduce oxidative stress, she told Medscape Medical News.

It has been used in Europe for many years in the treatment of cancer, AIDS, caries, rheumatoid arthritis, and a variety of other ailments. However, it is not approved for clinical use in Brazil or in the United States, and the only studies in osteoarthritis have been case reports, Dr Trevisani explained.

She said she was skeptical when she read the literature. "It seemed too good to be true."

To test the claims, Dr Trevisani and her colleagues recruited 98 people 60 to 85 years of age who met the ACR criteria for knee osteoarthritis.

The researchers randomized 63 patients to an injection of ozone gas 10 mL once a week for 8 weeks, and randomized 35 patients, who served as the control group, to injections of air.

The team used a specially designed device to inject the gases. It is important to follow correct procedures because ozone can be toxic if inhaled, Dr Trevisani explained.

At baseline, age, sex, pain joint stiffness, physical activity, functional activity, and emotional aspects were similar in the ozone and control groups.

At 16 weeks, pain, function, overall health, and quality of life were significantly better in the ozone group than in the control group.

"It has great results," Dr Trevisani said.

Differences emerged in the first week for some tests and by the fourth week for most tests.

However, the WOMAC stiffness score was only significant at week 8. And there was no difference between the ozone and control groups on the Timed Up and Go test, which evaluates the time it takes a participant to stand up, walk a set distance, return, and sit. In addition to pain and stiffness, this test evaluates balance and strength, which might explain the lack of difference between the groups, she explained.

Table. Measures of Pain and Functioning at 16 Weeks

Test Ozone Group Control Group P Value
Visual analog scale for pain 1.67 2.59 <.001
Geriatric Pain Measure 20.48 43.59 .002
Lequesne Index 5.91 5.30 .001
Timed Up and Go test 12.40 12.81 .498
   Pain score 13.61 31.57 <.001
   Stiffness score 4.51 8.21 .128
36-Item Short Form Health Survey      
   Physical limitations score 69.80 58.60 <.001
   Emotional limitations score 91.20 64.80 <.001


The only adverse events were puncture accidents, two of which occurred in the ozone group and one of which occurred in the control group. Two patients in the ozone group did not complete the study.

I'm always looking for something I can inject into a joint to make it feel better.

The results are surprising, said James Udell, MD, from the Arthritis Group in Philadelphia, who moderated the press conference that was held after an ACR team flagged the study as one of the most interesting abstracts being presented.

"We know that ozone can be anti-inflammatory and an antioxidant, but we weren't sure how they were injecting it," he said. "I'm always looking for something I can inject into a joint to make it feel better."

Dr Trevisani reported that she and her colleagues are now using MRI to see if the ozone has an effect on cartilage.

Dr Trevisani and Dr Udell have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2015 Annual Meeting: Abstract 311. Presented November 8, 2015.


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