A new study has found radiographic OA to be associated with changes in the serum proteins implicated in matrix degradation, cellular activation, and inflammation—changes that can occur years before radiographic detection of the disease, suggesting a role for these biomarkers in predicting the development of OA, according to results from a small pilot study¹ presented in December at the 10th World Congress of the Osteoarthritis Research Society International (OARSI) in Boston, Massachusetts.

In the nested case-control study, serum samples were drawn from participants in the Baltimore Longitudinal Study of Aging. Individuals who were not found to have significant OA on the initial knee and hand x-rays obtained between 1984 and 1991 were later classified as OA cases (n = 19) or OA-free controls (n = 66) by follow-up x-rays performed between 1995 and 1998. These were then matched by age, sex, and body mass index. Samples obtained both at the time of x-ray classification and 10 years prior were applied to a proprietary protein chip.

The pattern of proteins predictive of future OA was found to be different from that associated with current OA, according to the study authors, led by Shari Ling, MD, a staff clinician at the Clinical Research Branch of the National Institute on Aging in Baltimore, Maryland. While sixteen proteins implicated in matrix degradation, cellular activation, and inflammation were associated with OA in both the current and decade-old samples, four of these proteins (metalloproteinase-7, interleukin-15, plasminogen activating inhibitor-1, and soluble vascular adhesion protein-1) were found to be differentially expressed in the decade-old samples, and six additional proteins were only associated with subsequent, but not established, OA.

New biomarkers need validation

The new biomarkers need validation, however. "Assays are being performed to confirm and further quantitate the differentially expressed proteins along with cartilage turnover products," Dr. Ling tells CIAOMed. "Hopefully we can do this all within a few months," she says, adding that the study's results should be confirmed using other populations.
"This study is one of many striving to identify people at risk of developing disease at a time amenable to early intervention," Dr. Ling asserts. "At this time we can only speculate that the protein signatures identified in this study will be of therapeutic relevance as prognostic indicators or predictors of therapeutic response."

Reference

1. Ling SM, Patel DD, Zhan M, et al. Osteoarthritis is associated with changes in serum proteins that precede radiographic detection by years. Presented at: 10th World Congress of the Osteoarthritis Research Society International (OARSI); December 8–11, 2005; Boston, Mass. Abstract P51.