Developing Biomarkers to Monitor Progression of Osteoarthritis
March 23, 2004
By Stephanie Riesenman for Knee1
Osteoarthritis is a disease that progresses at a rate specific to the individual afflicted, so researchers are hoping to develop tests through the use of biological markers that can assess pain and predict how quickly a patient’s joints will degenerate, allowing them to select the best choice for treatment.
New research is finding that the body produces specific chemicals or biomarkers when joints become osteoarthritic, and these biomarkers may be the key to monitoring disease progression and to developing therapies to stop or even reverse the disease. Biomarkers reflect quantitative changes in joint tissue that are produced when joint tissue is broken down, and when new tissue is produced to replace that which is lost.
Currently, doctors diagnose osteoarthritis using medical and physical exams and X-rays — which show areas where the joint space has narrowed or where bone has become abnormal. But how quickly a patient’s arthritis will become worse is not easy to predict with a standard X-ray. In fact, some people with terrible pain may show very little joint space narrowing, whereas some with progressive narrowing may experience little pain. Biomarkers may be able to help doctors diagnose osteoarthritis during the pre-X-ray stages.
Because biomarkers reflect the active processes in arthritic joints, some doctors believe biomarkers will provide more reliable predictors of joint destruction. The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health, has formed a national Osteoarthritis Biomarkers Network to discover and coordinate the evaluation of biomarkers for earlier detection of osteoarthritis and for the assessment of risk and response to treatments.
Research has focused on detecting biomarkers in serum, urine, and joint fluid. The largest body of research focuses on collagen—the principle structural component of cartilage. Osteoarthritis is characterized by the degeneration of articular cartilage. In osteoarthritic joints collagen is broken down into smaller molecules, which can be detected through a sampling of various body fluids in the joints. The presence of specific molecules may reflect different stages of disease progression.
There is also increasing evidence of a correlation between severity of synovitus—inflammation of the tissue surrounding the joint—and progression of joint destruction. With synovitus, there is increased production of a chemical called hyaluronan. Measuring levels of this chemical may help doctors predict which patients will experience more rapid osteoarthritis progression.
Researchers are also studying the application of the systemic inflammatory marker, C-reactive protein, as a biomarker for progression of osteoarthritis.
One of the lead researchers in the Osteoarthritis Biomarker Network is Dr. Steven Abramson, from the NYU Hospital for Joint Diseases in New York. His team is focusing on genetic biomarkers of osteoarthritis, and finding genes that are turned on in joints that are osteoarthritic. A test that would look for the presence of these genes could be used as a predictor of disease progression.
In addition to identifying which patients are prone to rapid progression of osteoarthritis, researchers are hoping biologic markers will have the ability to provide early information on the efficacy of a disease-modifying therapy. One drawback of current studies on potential new drugs is the long period of time it takes to prove or disprove a drug’s ability to treat osteoarthritis. The current method involves waiting years to demonstrate on X-ray that a drug has prevented or had no effect on the progression of joint space narrowing. Instead, doctors could give patients a drug then measure the levels of molecules associated with arthritis to see if the drug was effective in slowing progression of the disease—as would be evidenced by the levels of the osteoarthritis molecules.
In addition to the potential biomarkers already discovered, NIAMS researchers are hoping to discover more biological indicators of disease progression, which could be developed into simple tests for osteoarthritis.