Of these, the biggest group are the biochemical markers, says Dr. Kraus. Biochemical biomarkers being studied for osteoarthritis fall into the further categories of markers of cartilage and bone degradation and formation, and markers of inflammation.

Every tissue in the body is always undergoing breakdown and repair, explains Dr. Kraus. “We think of osteoarthritis as being an imbalance in the normal amount of breakdown and repair – where you have excessive breakdown compared to the amount of the repair.”

Products of this excessive breakdown – including fragments of joint cartilage proteins such as collagen and aggrecan – can be found in the urine and may serve as markers for active disease. Similarly, high levels of enzymes involved in joint breakdown would be indicative of inflammation and osteoarthritis in a progressive state, she says.

Comparing the Candidates with OAI Database

The researchers are looking at and comparing 12 candidate biomarkers head to head using data and samples from the Osteoarthritis Initiative (OAI)—a multi-center, prospective observational study of knee OA designed to provide a resource for researchers evaluating OA biomarkers.  “We anticipate that a combination of markers from these three categories may all be used together as a panel to try to give the best indication of what the patient status and progression status is.”

A public-private partnership, the OAI established a natural history database for osteoarthritis that includes clinical evaluation data, radiological images and a biospecimen repository from 4,796 men and women between the ages of 45 and 79. Data and images collected through the seven-year project are available to researchers around the world to help speed the identification of OA biomarkers and development of agents to slow or stop OA progression.

Led by Dr. Kraus and  David Hunter, MD, PhD,  at the University of Sydney, Australia, scientists are now using the data to look at baseline and one- and two-year changes in these types of markers to determine if they can predict during the course of one or two years what is happening four years later. To do this, they are comparing markers of 200 people who had worsening of X-rays and symptoms, 100 who had worsening of X-rays only and 100 who had worsening of symptoms only to 200 people who have not experienced worsening.

“If these markers can predict four-year outcomes and they can do that robustly and with great assurance and are truly representative of what is happening, the hope is that down the road the FDA would eventually approve different outcomes for clinical trials,” says Dr. Kraus. “This would facilitate treatment intervention and make it possible for treatment trials to ultimately make difference in the lives of patients.”