OA Progression as Seen in a Biomarker Panel

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There are better ways to predict knee osteoarthritis (OA) progression, according to a Duke University physician scientist reporting at OARSI 2016 World Congress.

There are better ways to predict knee osteoarthritis (OA) progression, according to a Duke University physician scientist reporting at OARSI 2016 World Congress.

Currently, most physicians rely on poor predictors, such as age, sex, body mass index, knee pain, general bone mineral content and joint space width, but osteoarthritis comes in phases, reported Virginia Kraus, M.D., Ph.D., of the Duke Molecular Physiology Institute.

Osteoarthritis is a disease associated with periods of inactivity with no more than 30 percent of individuals affected by the progression of knee OA at any one time. These periods of quiescence effect clinical trials - the majority of which in OA suffer from “low power” due to an inability to identify progressors, Dr. Kraus reported.

During an April 1 presentation at OARSI 2016 in Amsterdam earlier this month, Dr. Kraus reported that serum biomarkers may offer a more accurate measure of osteoarthritis progression.  [[{"type":"media","view_mode":"media_crop","fid":"47323","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3600058145930","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5557","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]]

“We developed a method of predicting OA progression based on a panel of mass spectrometry and ELISA based biomarkers. Markers predicting osteophyte progression were distinctly different from those predicting JSN progression. These results suggest that a select set of biomarkers identified from targeted and non-targeted analyses could significantly improve prediction of knee OA progression and could be useful for enriching knee OA clinical trials for progressors,” she reported.

The Kraus study pulled participant data from the Prediction of Osteoarthritis Progression cohort and Genetics of Generalized OA studies. Kraus’s team ran a mass spectrometry analysis to create a Multiple Reaction Monitoring (MRM) panel on 146 peptides (99 proteins) in serum that included synovial fluid (n=23), urine (n=45), and serum (n=40) from knee osteoarthritis radiographic progressors and non-progressors.

Dr. Kraus and colleagues found that MRM or ELISA-based biomarkers, in combination with clinical parameters, significantly improved the prediction of OA progression (all definitions) over clinical variables alone achieving AUCs ranging from 0.84-0.97.

Of the subject population, 82 percent were female with a mean age of 64 and mean BMI of 28. The percentage of each sample meeting the knee OA progress definition was:  75 percent ANY, 52 percent JSN, 66 percent osteophyte, and 29 percent KL progression. Age, gender, and BMI were only significant in predicting osteophyte progression.  

Knee osteoarthritis progression was defined as any knee osteoarthritis  progression or osteophyte, joint space narrowing (JSN) or Kellgren Lawrence (KL) grade progression within four years. Any progression was predicted by 10 MRM markers; osteophyte progression by 7 MRM markers; JSN progression by 6 ELISA markers; and KL progression by 1 ELISA marker.

 

 

References:

“Development of a Serum Biomarker Panel Highly Predictive of Knee Osteoarthritis Progression,” Virginia Kraus, Friday, April 1, OARSI 2016.

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