VANCOUVER, BC, Canada—Biomarkers associated with collagen degradation can differentiate patients with knee pain due to knee osteoarthritis (OA) from those whose knee pain is not related to OA, and can differentiate patients whose OA is radiographically detectable from those with very early-stage damage. Some of these markers can be readily measured in urine as well as in serum, raising the possibility that a quick screen of urinary biomarkers might help clinicians intervene early enough to prevent joint damage.

”Our study did not include an asymptomatic control group. However, the utility of biomarkers to differentiate symptomatic subjects without OA from those with early OA is more important clinically, since subjects with joint pain are those likely to present to the health care professional,” wrote Jolanda Cibere, MD, MPH, FRCPC, PhD, in Arthritis & Rheumatism.¹ Dr. Cibere is The J.W. McConnell Family Foundation Scholar and is also Assistant Professor in the Division of Rheumatology at the University of British Columbia and the Arthritis Research Centre of Canada. This was the first study to measure a range of biomarkers in subjects with imaging-proven OA.

Biomarkers studied in patients with no OA, pre-radiographic OA, and fully developed OA

Dr. Cibere and colleagues studied 10 collagen-related biomarkers in a population-based cohort of patients who had undergone magnetic resonance imaging (MRI) of painful joints. These 201 subjects were classified into OA subgroups according to MRI-based cartilage score and Kellgren/Lawrence grades of radiographic severity. Subgroups were defined as:

• no OA: (MRC score 0, K/L grade <2)
• pre-radiographic OA (pre-ROA): MCR score ≥1, K/L grade <2)
• radiographic OA (ROA): MRC score ≥1, K/L grade ≥2

Analysis of urinary and serum biomarkers showed that the risk of ROA (versus no OA) increased with increasing levels of urinary CTX-II (C-telopeptide of type II collagen), urinary C2C (collagen cleavage neoepitope type II, and urinary C1,2C (types I and II collagen cleavage neoepitopes).

Radiographic OA risk was reduced in patients with high levels of sCPII (serum C-propeptide of type II procollagen).

Finally, patients with knee pain who had increasing levels of uC2C and uC1,2C were twice as likely to have pre-ROA as to have no OA. Ratios of collagen markers to collagen synthesis markers were even better at differentiating subjects with no OA from those with pre-ROA or ROA.

“Different cartilage degradation markers are associated with pre-ROA than are associated with ROA, indicating that their use as diagnostic markers depends on the stage of OA. Biomarker ratios contrasting cartilage degradation with cartilage synthesis are better able to differentiate OA stages compared with levels of the individual markers,” the authors write.

“Our study thus shows that different type II collagen degradation markers are associated with pre-ROA versus ROA. This will be important for future evaluation of biomarkers as diagnostic tools,” Dr. Cibere said.

Reference

1. Cibere J, Zhang H, Garnero P, et al. Association of biomarkers with pre-radiographically defined and radiographically defined knee osteoarthritis in a population-based study. Arthritis Rheum. 2009;60:1372-1380.