Researchers at Duke University developed a blood test that they showed could successfully predict knee osteoarthritis (OA) at least eight years before tell-tale signs of the disease appeared on x-rays (radiographic knee OA; RKOA). In their newly reported study the team validated the blood test, which identifies a panel of osteoarthritis biomarkers, and showed that it could predict development of disease as well as predict disease progression, which the team had demonstrated in earlier work.

The researchers say their work advances the utility of a blood test that would represent an improvement on current diagnostic tools, which often don’t identify the disease until it has caused structural damage to the joint. The new insights could also help scientists better understand the molecular basis of early disease development, and potentially to the development of new disease-modifying drugs for preclinical OA.

“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,” said senior author Virginia Byers Kraus, MD, PhD, a professor in the departments of Medicine, Pathology, and Orthopedic Surgery at Duke University School of Medicine. “What our blood test demonstrates is that it’s possible to detect this disease much earlier than our current diagnostics permit.”

Kraus and colleagues reported on the test in Science Advances, in a paper titled “An osteoarthritis pathophysiological continuum revealed by molecular biomarkers,” in which they stated “… the present study identifies a small number of serum peptides that parsimoniously predicts incident RKOA up to eight years before the appearance of radiographic abnormality. This is important as it provides more evidence for a preradiographic phase of disease.”

Osteoarthritis (OA) is the most common form of arthritis, afflicting an estimated 35 million adults in the US and causing significant economic and societal impacts. While there are currently no cures, the success of potential new therapies could hinge on identifying the disease early and slowing its progression before it becomes debilitating. “Given the growing OA population globally and magnitude of the economic and societal burden, there is a growing interest in a new paradigm—switching from palliation, the traditional focus in OA, to early prevention,” the authors wrote. “Early-stage OA could provide a “window of opportunity” in which to arrest the disease process and restore joint homeostasis.”

Kraus and colleagues have focused on developing molecular biomarkers that can be used for both clinical diagnostic purposes and as a research tool to aid in the development of effective drugs. In previous studies, the team reported on a blood biomarker test demonstrated 74 percent accuracy in predicting knee OA progression and 85% accuracy in diagnosing knee OA.

The current study further honed the biomarker panel’s predictive capabilities. Using a large U.K. database—the Chingford study—the researchers analyzed serum of 200 white women, half diagnosed with OA and the other half without the disease, matched by body mass index and age. “In the current study, we aimed to use serum proteomic biomarkers to predict incident RKOA in a case-control cohort of Chingford study participants selected for low risk of incident RKOA based on traditional risk factors [excluded prior joint injury and any baseline knee OA of Kellgren-Lawrence(KL) grade > 1],” they wrote. “Machine learning techniques were used to select proteomic biomarkers in sera (obtained years two and six) that best predicted RKOA incidence at year 10.”

They found that a small number of biomarkers in the blood test successfully distinguished the women with knee OA from those without it, catching molecular signals of OA eight years before many of the women were diagnosed with the disease by x-ray. “As few as six serum peptides, corresponding to six proteins, reached AUC [area under curve] 77% probability to distinguish those who developed OA from age-matched individuals who did not develop OA up to 8 years later,” the investigators further commented. “Among all 24 protein biomarkers predicting incident knee OA, the majority (58%) also predicted knee OA progression, revealing the existence of a pathophysiological “OA continuum” based on considerable similarity in the molecular pathophysiology of the progression to incident OA and the progression of established OA.”

“This is important because it provides more evidence that there are abnormalities in the joint that can be detected by blood biomarkers well before x-rays can detect OA,” Kraus said. “Early-stage osteoarthritis could provide a ‘window of opportunity’ in which to arrest the disease process and restore joint health.”  Noting limitations of their study, the team further stated, “The value of our study is a panel that, in the absence of clinical factors indicative of high risk of knee OA, has the potential to discriminate individuals at risk of incident RKOA from those not at risk … Our results also provide valuable information for understanding the molecular events of early disease that could inform strategies to develop disease-modifying drugs for preclinical OA.”

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