Alice Goodman

June 12, 2014

PARIS — The presence of 3 specific micro (mi)RNAs in the blood appears to predict the eventual development of severe osteoarthritis, new research shows.

"Ours is the first study to identify these biomarkers in a large population-based cohort," said investigator Christian Beyer, MD, from the University of Erlangen-Nuremberg in Germany.

"Results suggest that, for the first time, we will be able to predict the risk of severe osteoarthritis before the disease starts to take a toll on patients' lives. This will enable us to take preventive action early on to decrease the impact on patients' lives and the socioeconomic burden," he explained.

Currently, miRNAs are being used as biomarkers in many fields, including cancer, diabetes, and cardiovascular disease. "They can persist, remain stable at different temperatures and conditions, and are assessable in the blood," said Dr. Beyer.

He presented the study results here at the European League Against Rheumatism (EULAR) Congress 2014.

The investigators evaluated existing serum samples from patients with osteoarthritis who were part of the Bruneck cohort that was followed from 1995 to 2010. The primary outcome measure was the need for joint replacement surgery of the hip or knee.

During the follow-up period, 67 of the 816 patients underwent at least 1 joint replacement surgery for severe osteoarthritis of the knee or hip. These patients were significantly older than those who did not undergo surgery (P = .053), and they had higher body mass indexes (P = .002).

The existing blood samples were tested for miRNA expression at baseline.

The investigators identified 12 of about 374 miRNAs as candidate biomarkers. On Cox regression analysis, they found that 3 of these miRNAs were associated with the need for hip or knee replacement: miR-454, miR-885-5p, and let-7e.

"The most promising single miRNA was let-7e," Dr. Beyer reported. "The lower the levels of let-7e, the higher the likelihood of needing surgery for osteoarthritis of the knee or hip."

"The study opens many new questions," Dr. Beyer said. "Where do these miRNAs arise? In the diseased joint? Can they affect disease activity? Should we validate these in other cohorts?"

He pointed out that the study cohort consisted of heterogeneous group of people from a small hospital, and noted that these findings need to be confirmed in a larger study.

Currently, several ongoing studies are underway to determine if these biomarkers can be used in clinical practice.

Use in Clinical Practice

One expert thinks that might happen soon.

These biomarkers could come to clinical practice sooner rather than later, said Ulf Müller-Ladner, MD, chair of the Department of Rheumatology at the University of Giessen in Germany and chair of the EULAR scientific program.

"Small miRNA are easily measured. If you pick the right ones, you can predict or diagnose disease," he said. Once these findings are validated in a larger study, they can be used clinically. "Right now, miRNAs are being used in other diseases. They are easily measured and are not affected by temperature," Dr. Müller-Ladner said.

If a patient has a mother in a wheelchair because of osteoarthritis, "you will be able to discuss the predicted course of the disease. If patients appear to have biomarkers for severe disease, you can encourage them to lose weight and exercise and treat them more aggressively," he explained.

Dr. Beyer and Dr. Müller-Ladner have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2014: Abstract OP0003. Presented June 11, 2014.

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