A biomarker to predict osteoarthritis

Study of large, ethnically diverse population shows strong association between high levels of hyaluronic acid and severe osteoarthritis of the knees and hips

chronic degenerative joint disease, osteoarthritis (OA) is a common cause of pain and disability among older Americans. OA of the knee affects up to 6 percent of the older population, while OA of the hip affects about another 3 percent. While treatments vary, there is hope that early intervention – before joint destruction can be clearly seen and measured on an X-ray image-will improve outcomes.

The need for better ways to assess OA’s activity from its onset has led researchers to investigate possible biomarkers, particularly those related to cartilage and bone turnover. A biomarker is substance found in the blood or joint fluid whose levels can be used to assess the presence or activity of a disease. Among likely candidates for a biomarker for OA is hyaluronic acid, also known as hyaluronan or simply HA. HA is a component of connective tissue that is widely distributed throughout the body and plays an important role in joint function. A recent study, published in the January 2005 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), strongly supports the relationship between increased production of HA and increased risk for OA, specifically of the knees and hips, among ethnically diverse men and women.

Led by Drs. Alan L. Elliott and Joanne M. Jordan of the Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, and Dr. Virginia B. Kraus of Duke University Medical Center, the study drew its subjects from a large, local population of participants in the Johnston County Osteoarthritis Project. The study group comprised 753 subjects, including 120 African American men, 245 African American women, 199 Caucasian men, and 189 Caucasian women. The average age of the participants was just shy of 62 years and the mean body mass index was on the heavy side, just over 30. Of the total subjects, 455 had mild to severe knee OA, confirmed by radiographs. 152 of the subjects with knee OA also had hip OA. In 52 of these individuals with OA, the disease had progressed to both knees and both hips.

The research team obtained a blood sample from every participant and analyzed each for its concentration of HA. Across the board, Caucasians had higher serum HA levels than African Americans and men had higher serum HA levels than women. The most compelling differences in HA levels, however, were between the 298 subjects without any radiographic evidence of OA and the 455 OA participants – especially those with two or more joints affected. As the presence and amount of OA involvement increased, so did the HA levels. On average, the concentration of HA was higher in patients with severe knee OA compared to those in the moderate stages of disease, higher in patients with two diseased knees compared to those with a single diseased knee, and higher in patients with hip OA in addition to knee OA compared to those with knee OA alone. When adjusted for ethnicity, sex, age, and BMI, the associations between elevated HA levels and all definitions of OA status remained statistically significant.

Also significantly, researchers found no independent correlations between elevated levels of HA and other adverse health conditions reported by the subjects, including high blood pressure, diabetes, chronic pulmonary disease, persistent liver, kidney, bladder, and prostate problems, and cancer. Only one condition showed a sustained independent relationship with elevated HA after statistical adjustment: gout, which, like OA, is marked by joint inflammation and damage.

“The results of this study suggest that serum HA measurements are useful for assessing overall OA load,” Dr Elliott notes. “The lack of independent associations of serum HA levels with several comorbid conditions commonly associated with OA further supports its promise in the study of OA.”