Predicting Knee Osteoarthritis Progression: Proteomics, Biomarkers, and the Future of Treatment

By Allison Proffitt

June 6, 2023 | What if you could predict the progression of knee osteoarthritis through a simple blood test? That’s the vision of Dr. Virginia Byers Kraus, a professor at Duke University School of Medicine. Knee osteoarthritis (OA) affects 60 million adults in the US and projected to increase to 78 million by 2040, yet we don’t currently have very sensitive tools for diagnosis or disease-modifying drugs or treatments.

Because osteoarthritis is a degenerative joint disease that increases with age and weight gain, it’s viewed as a “wear and tear” disease, almost inevitable as we age. Kraus rejects that idea. In the latest episode of the Scope of Things podcast, Kraus compares it to malaria, a condition that for years was thought to be unavoidable, simply the result of “bad air.”

But of course we know there was more to that story, and Kraus believes our understanding of osteoarthritis will be similarly upended. “We feel strongly that the advent of a biomarker that really depicts what the disease is can really have a substantive impact on the development of drugs—just like finding the malarial parasite under the microscope is what suddenly turned malaria from a ‘bad air’ entity to a disease,” she tells host Deborah Borfitz.

Kraus’s lab is focusing on building a blood-based diagnostic test for knee osteoarthritis based on a proteomic panel of biomarkers that they believe will be able to identify people with active disease long before the evidence is visible on an MRI or X-ray. Ideally, early intervention will find the disease more amenable to treatment. There are no commercial biomarker tests currently available, Kraus says, though there are research-use-only tests.

To identify the proteomic markers, Kraus’s lab looked for blood proteins in four group of patients: ones with no evidence of progressive knee osteoarthritis, patients with pain progression, patients with x-ray progression, and patients with both x-ray as well as pain progression.

“What we found was as few as 11 blood proteins could predict the risk of knee x-ray worsening over the subsequent two to four years. And only 10 were needed to predict pain worsening,” she says.

One protein is of particular interest: cartilage acidic protein 1 (CRTAC1) predicted both x-ray and pain progression. The same protein has been identified as a biomarker for predicting knee and hip replacement, and in longer term studies has predicted the development of x-ray-visible OA within eight years.

Kraus hopes CRTAC1 could be used in patients without progressive pain or x-ray evidence of OA, to distinguish between patients who are likely to experience disease progression and those who have “nuisance symptoms.”

While the outlook is quite promising, Kraus says there is still much work to do. Research interest in osteoarthritis is high right now, but Kraus says the volume of osteoarthritis clinical trials has historically ebbed and flowed. She also emphasized the variability of osteoarthritis in different joints. “Not all cartilage is created equal. There are some tremendous differences across different cartilages in different parts of the body,” she says. “You have different joints doing different jobs.” She predicts that some biomarkers may be specific to OA in the hip or to the ankle, while others might give a general burden of disease score.