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Blood-Based Protein Markers Help Predict Who Will Develop Knee Osteoarthritis

NEW YORK – A team from the US and the UK has uncovered blood-based protein markers that were able to predict osteoarthritis risk — particularly knee osteoarthritis — up to eight years before the disease developed in patients.

The study, published in Science Advances on Friday, offers "valuable information for understanding the molecular events of early disease that could inform strategies to develop disease-modifying drugs for preclinical [osteoarthritis]," first and corresponding author Virginia Byers Kraus, a researcher affiliated with Duke University and the Duke University School of Medicine, and her colleagues wrote.

Using a quantitative liquid chromatography-multiple reaction monitoring (LC-MRM) mass spectrometry approach, along with machine learning-informed analyses, researchers at Duke and the University of Oxford assessed protein profiles in blood serum samples from 200 age- and body mass index (BMI)-matched female participants of European ancestry from the UK who were 45 to 65 years old when the study began. While all of the women were osteoarthritis-free at baseline, 100 participants went on to develop osteoarthritis within a decade.

Along with blood samples collected two years and six years after baseline, the team had access to knee radiographs taken at baseline, after five years, and at the 10-year mark. Together, the data led to two dozen protein biomarkers that coincided with eventual knee osteoarthritis development.

"Currently, you've got to have an abnormal X-ray to show clear evidence of knee osteoarthritis, and by the time it shows up on X-ray, your disease has been progressing for some time," Kraus said in a statement. "What our blood test demonstrates is that it’s possible to detect this disease much earlier than our current diagnostics permit."

From their initial set, the researchers focused in on six proteins that could predict future osteoarthritis with 77 percent accuracy, compared to the prediction accuracy of conventional approaches based on age and BMI or knee pain, which had 51 percent and 57 percent accuracy, respectively.

"The value of our study is a panel that, in the absence of clinical factors indicative of high risk of knee [osteoarthritis], has the potential to discriminate individuals at risk of incident [established radiographic knee osteoarthritis] from those not at risk," the authors reported.

Along with yielding early clinical markers for knee osteoarthritis, the researchers explained, the analyses offered clues to the biological processes that contribute to the way the disease develops and its propensity for progression.

"The results are important because they contribute more evidence that there are abnormalities in the joint that can be detected by blood biomarkers well before X-rays can detect [osteoarthritis]," Kraus said. "Early-stage osteoarthritis could provide a 'window of opportunity' in which to arrest the disease process and restore joint health."