Blood biomarkers for knee osteoarthritis

Osteoarthritis occurs when tissues in joints break down over time. The disease has become more common worldwide over the past few decades. Diagnosis usually involves finding signs of joint damage on an x-ray. But the disease likely begins long before this damage can be seen.

The early stages of osteoarthritis may offer the best opportunity to stop disease progression and repair joint damage. Thus, there is a need for ways to predict whether people will develop osteoarthritis before damage becomes detectable in medical images.

Earlier, a research team led by Virginia Byers Kraus at Duke University found a set of protein biomarkers in blood serum that could predict the progression of knee osteoarthritis once it appeared in imaging. In a new NIH-funded study, the team looked at whether these proteins could predict the development of osteoarthritis before it could be diagnosed via x-ray. Results appeared in Science Advances on April 26, 2024.

The researchers analyzed serum samples from 200 White women, ages 45-65, who were part of a large study in the United Kingdom. All were at low risk of osteoarthritis based on traditional risk factors. Half of the women were diagnosed with knee osteoarthritis within 10 years, while the other half were not. Women were matched between the groups by age and body mass index (BMI).

As few as six biomarkers in the serum samples could distinguish those who developed knee osteoarthritis from those who did not. Furthermore, they could do so up to 8 years before a clinical diagnosis was made. Predictions using these biomarkers were much more accurate than those based on age and BMI, knee pain, or preexisting osteoarthritis in the hip. Many of the biomarkers the team identified were from proteins involved in acute inflammation.

These results provide evidence that the damage to joint tissue that causes osteoarthritis begins at the molecular level, long before any damage can be seen by imaging. This damage may ultimately result from an acute inflammatory response that fails to shut off.

“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 says. “What our blood test demonstrates is that it’s possible to detect this disease much earlier than our current diagnostics permit.”

More than half of the biomarkers the team identified also predict osteoarthritis progression after diagnosis. Thus, both the initial development and progression of osteoarthritis may share a similar physiological mechanism. Earlier detection could ultimately allow interventions to slow disease development before it becomes debilitating.

—by Brian Doctrow, Ph.D.