Biomarkers of type II collagen synthesis and degradation may predict rapid progression among patients with knee osteoarthritis (OA), according to a 5-year longitudinal study presented recently at the 10th World Congress of the Osteoarthritis Research Society International (OARSI) in Boston, Massachusetts.¹

In the new 5-year study of 84 patients with persistent knee pain for more than 3 months in one or both knees, researchers found a mean 1.6% increase of N-propeptide of collagen type IIA (PIIANP), whereas urinary crosslinked C-telopeptide (CTX-II) remained stable. Moreover, both PIIANP and CTX-II were higher throughout the study among the 24 patients whose disease progressed, compared with the 60 whose OA remained stable over the 5-year study. In fact, patients in the highest quartile of mean 5-year levels of PIIANP and the two highest quartiles of mean 5-year levels of CTX-II were among the most likely to show disease progression, the study showed.

"In early knee OA, disease progression is associated with increases of both synthesis and degradation of CTX II," conclude the researchers, led by Patrick Garnero, PhD, vice president and general manager of molecular marker services for Synarc in Lyon, France. "Combination of serum PIIANP and urinary CTX-II may be useful to improve the identification of patients with early knee OA at high risk for rapid progression."

Researchers used specific ELISA techniques at baseline and at 2-,  3-, and 5-year marks to measure PIIANP and CTX-II. Patients had knee x-rays at baseline and at 5 years. Disease progression was defined as a reduction in tibiofemoral joint space by at least 2 mm or total knee arthroplasty in either knee during the 5-year follow-up period.

Lee Simon, MD, a rheumatologist and associate clinical professor of medicine at Harvard Medical School in Boston, Massachusetts, tells CIAOMed that while preliminary, the findings have interesting utility. The new assays, however, do not reflect destroyed or altered type II collagen, he says.

"We have a long way to go for this to be a surrogate, but it will help," Dr. Simon says. "The problem in developing a disease-modifying drug and studying it is in the recruitment of patients who would have progressive disease within the window of a therapeutic trial."

Reference

1. Garnero P, Sharif, M, Charni, N, et al. Biochemical markers of Type II collagen synthesis and degradation predict disease progression in early knee osteoarthritis: A 5-year longitudinal study. Presented at: 10th World Congress on Osteoarthritis; December 8-11, 2005; Boston, Mass. Presentation A6.