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VBCR - August 2014, Volume 3, No 4 - Osteoarthritis
Phoebe Starr

Paris, France—Three biomarkers have been identified that may be used to determine disease severity in osteo­arthritis (OA), according to data presented at the 2014 European League Against Rheumatism (EULAR) Congress. The miRNAs—miR 454, miR 885-5p, and miR let-7e—may predict the development of severe OA in patients with early disease.

If validated in future studies, these specific miRNAs could play a role in decision-making for treatment of early OA, targeting aggressive treatment for patients who need it the most. “Ours is the first study to identify these biomarkers for people at risk of severe OA in a large population-based cohort. Results suggest that for the first time, we will be able to predict the severity before the disease starts to impact patients’ lives,” said Christian Beyer, MD, from the University of Erlangen-Nuremberg, Germany. “We will be able to take preventive action early on to decrease the impact of disease on patients’ lives and the socioeconomic burden of the disease.”

Predicting Disease Severity
The study was based on an analysis of serum samples from 816 patients with OA who were part of the Bruneck cohort and who were followed from 1995 to 2010. The need for hip or knee joint replacement surgery was used as the outcome that correlated with disease severity.

During the 15-year follow-up period, 67 patients underwent at least 1 hip or knee replacement surgery for severe OA. Factors that were significantly correlated with the need for a joint replacement include older age (P = .053) and higher body mass in­dex (P = .002), compared with patients who did not undergo surgery.

Identifying miRNA Signatures
Identifying miRNAs in existing blood samples of the patient population was a 2-step process. Approximately 374 miRNAs were tested and a panel of 12 candidate miRNAs was identified. A Cox regression analysis further identified 3 miRNAs associated with the need for hip or knee replacement surgery: miR 454, miR 885-5p, and miR let-7e. Dr Beyer said the strongest predictor of joint replacement surgery among these 3 biomarkers was let-7e.

The signature of miRNA in individuals with OA was then compared with controls to validate that the signature was specific to OA.

Validating the Data
This was a single-center study, and the findings need to be validated in a larger population. Ongoing studies are planned to establish the clinical utility of these markers. According to EULAR Scientific Program Chair Ulf Müller-Ladner, MD, these small mi­RNAs hold great promise for predicting OA severity. MiRNAs are already being used as biomarkers in cancer, diabetes, and cardiovascular disease. They have attractive properties for testing, because they can persist, are stable under different temperatures and conditions, and can be measured in the blood, Dr Müller-Ladner added.

If these findings are validated, then the information can be used to counsel patients about how to manage their OA more aggressively if the markers are present and less aggressively if not, according to the investigators.

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