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PARIS – Three micro RNAs have been shown to be associated with disease severity in patients with hip or knee osteoarthritis, based on data from a large population-based cohort in Italy*.
The presence of three specific miRNAs are biomarkers that might prove to be useful for predicting OA severity if validated in other cohorts and diverse populations of OA patients, Dr. Christian Beyer reported at a press conference during the annual European Congress of Rheumatology (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204698]).
The miRNAs could also be a first step toward finding new OA therapies, such as approaches that avert cartilage loss, said Dr. Beyer of the University of Erlangen–Nuremberg (Germany).
For the study, serum samples from 816 cohort members who had osteoarthritis and were followed for at least 15 years were analyzed for the presence of any of the 374 miRNAs. A microarray screening identified 12 candidate miRNAs, validated in the entire cohort. Based on a regression analysis, the 67 cohort members who went on to have knee or hip arthroplasty were found to differentially express three of the miRNAs: let-7e, miR-454, and miR-885-5p. The most promising of the markers appears to be let-7e.
Let-7e was a negative predictor for total joint arthroplasty with an adjusted hazard ratio of 0.75 (95% confidence interval, 0.58-0.96; P = .021) when normalized to U6, and 0.76 (95% CI, 0.6-0.97; P = .026) after normalization to the Ct-average. However, miR-454 was inversely correlated with severe knee or hip osteoarthritis with an adjusted HR of 0.77 (95% CI, 0.61-0.97; P = .028) when normalized to U6. This correlation was lost when data were normalized to Ct-average (P = .118). Finally, miR-885-5p showed a trend toward a positive relationship with arthroplasty when normalized to U6 (HR, 1.24; 95% CI, 0.95-1.62; P = .107) or to Ct-average (HR, 1.30; 95% CI, 0.99-1.70; P = .056).
If specific miRNAs prove to be biomarkers to predict OA severity, it would offer the ability to use markers that are found in the peripheral circulation, stable over time, and not sex dependent. Such markers also could prove useful for finding new OA therapies, he said.
Next steps for further study include validation of the miRNA biomarkers in other OA cohorts, Dr. Beyer said. The well-defined Bruneck cohort is a stable community that has been extensively studied similar to the Framingham cohort in the United States. The Bruneck cohort is all white, however, and the results of this study need to be validated in diverse populations.
Dr. Beyer declared having no relevant financial disclosures.
On Twitter@maryjodales
CORRECTION, 6/12/2014: An earlier version of the article misstated the location of the study cohort.
PARIS – Three micro RNAs have been shown to be associated with disease severity in patients with hip or knee osteoarthritis, based on data from a large population-based cohort in Italy*.
The presence of three specific miRNAs are biomarkers that might prove to be useful for predicting OA severity if validated in other cohorts and diverse populations of OA patients, Dr. Christian Beyer reported at a press conference during the annual European Congress of Rheumatology (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204698]).
The miRNAs could also be a first step toward finding new OA therapies, such as approaches that avert cartilage loss, said Dr. Beyer of the University of Erlangen–Nuremberg (Germany).
For the study, serum samples from 816 cohort members who had osteoarthritis and were followed for at least 15 years were analyzed for the presence of any of the 374 miRNAs. A microarray screening identified 12 candidate miRNAs, validated in the entire cohort. Based on a regression analysis, the 67 cohort members who went on to have knee or hip arthroplasty were found to differentially express three of the miRNAs: let-7e, miR-454, and miR-885-5p. The most promising of the markers appears to be let-7e.
Let-7e was a negative predictor for total joint arthroplasty with an adjusted hazard ratio of 0.75 (95% confidence interval, 0.58-0.96; P = .021) when normalized to U6, and 0.76 (95% CI, 0.6-0.97; P = .026) after normalization to the Ct-average. However, miR-454 was inversely correlated with severe knee or hip osteoarthritis with an adjusted HR of 0.77 (95% CI, 0.61-0.97; P = .028) when normalized to U6. This correlation was lost when data were normalized to Ct-average (P = .118). Finally, miR-885-5p showed a trend toward a positive relationship with arthroplasty when normalized to U6 (HR, 1.24; 95% CI, 0.95-1.62; P = .107) or to Ct-average (HR, 1.30; 95% CI, 0.99-1.70; P = .056).
If specific miRNAs prove to be biomarkers to predict OA severity, it would offer the ability to use markers that are found in the peripheral circulation, stable over time, and not sex dependent. Such markers also could prove useful for finding new OA therapies, he said.
Next steps for further study include validation of the miRNA biomarkers in other OA cohorts, Dr. Beyer said. The well-defined Bruneck cohort is a stable community that has been extensively studied similar to the Framingham cohort in the United States. The Bruneck cohort is all white, however, and the results of this study need to be validated in diverse populations.
Dr. Beyer declared having no relevant financial disclosures.
On Twitter@maryjodales
CORRECTION, 6/12/2014: An earlier version of the article misstated the location of the study cohort.
PARIS – Three micro RNAs have been shown to be associated with disease severity in patients with hip or knee osteoarthritis, based on data from a large population-based cohort in Italy*.
The presence of three specific miRNAs are biomarkers that might prove to be useful for predicting OA severity if validated in other cohorts and diverse populations of OA patients, Dr. Christian Beyer reported at a press conference during the annual European Congress of Rheumatology (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204698]).
The miRNAs could also be a first step toward finding new OA therapies, such as approaches that avert cartilage loss, said Dr. Beyer of the University of Erlangen–Nuremberg (Germany).
For the study, serum samples from 816 cohort members who had osteoarthritis and were followed for at least 15 years were analyzed for the presence of any of the 374 miRNAs. A microarray screening identified 12 candidate miRNAs, validated in the entire cohort. Based on a regression analysis, the 67 cohort members who went on to have knee or hip arthroplasty were found to differentially express three of the miRNAs: let-7e, miR-454, and miR-885-5p. The most promising of the markers appears to be let-7e.
Let-7e was a negative predictor for total joint arthroplasty with an adjusted hazard ratio of 0.75 (95% confidence interval, 0.58-0.96; P = .021) when normalized to U6, and 0.76 (95% CI, 0.6-0.97; P = .026) after normalization to the Ct-average. However, miR-454 was inversely correlated with severe knee or hip osteoarthritis with an adjusted HR of 0.77 (95% CI, 0.61-0.97; P = .028) when normalized to U6. This correlation was lost when data were normalized to Ct-average (P = .118). Finally, miR-885-5p showed a trend toward a positive relationship with arthroplasty when normalized to U6 (HR, 1.24; 95% CI, 0.95-1.62; P = .107) or to Ct-average (HR, 1.30; 95% CI, 0.99-1.70; P = .056).
If specific miRNAs prove to be biomarkers to predict OA severity, it would offer the ability to use markers that are found in the peripheral circulation, stable over time, and not sex dependent. Such markers also could prove useful for finding new OA therapies, he said.
Next steps for further study include validation of the miRNA biomarkers in other OA cohorts, Dr. Beyer said. The well-defined Bruneck cohort is a stable community that has been extensively studied similar to the Framingham cohort in the United States. The Bruneck cohort is all white, however, and the results of this study need to be validated in diverse populations.
Dr. Beyer declared having no relevant financial disclosures.
On Twitter@maryjodales
CORRECTION, 6/12/2014: An earlier version of the article misstated the location of the study cohort.
AT THE EULAR CONGRESS 2014
Key clinical point: Biomarkers may allow early interventions to limit osteoarthritis risks, such as cartilage damage.
Major finding: Let-7e was a negative predictor for total joint arthroplasty with an adjusted HR of 0.75 (95% CI, 0.58-0.96; P = .021) when normalized to U6, and 0.76 (95% CI, 0.6-0.97; P = .026) after normalization to the Ct-average.
Data source: The large population-based Bruneck cohort in Italy.
Disclosures: Dr. Beyer had no relevant financial disclosures.
