Cartilage Biomarkers Coll2-1 and Coll2-1NO2 Are Associated with Knee OA MRI Features and Are Helpful in Identifying Patients at Risk of Disease Worsening

Abstract

Objective: To assess the cross-sectional association between serum levels of Coll2-1 and Coll2-1NO2, two cartilage degradation biomarkers; the burden of magnetic resonance imaging (MRI) features and clinical outcomes; and to evaluate the predictive value of these biomarkers on progression.

Design: A total of 121 subjects with knee osteoarthritis (OA) were followed during 1 year with pain, function, and MRI assessment (PRODIGE study). Type II collagen-specific biomarker Coll2-1 and its nitrated form Coll2-1NO2 were directly measured in serum using immunoassays at baseline and after 3-, 6-, and 12-month follow-up.

Results: Serum Coll2-1 and Coll2-1NO2 were correlated with several baseline knee features quantified with Whole-Organ Magnetic Resonance Imaging Score (WORMS). Coll2-1 was significantly correlated with periarticular cysts/bursitis (ρ = 0.29, P < 0.01), subarticular bone attrition (ρ = 0.25, P = 0.01), subarticular cysts (ρ = 0.24, P = 0.02), and articular cartilage integrity (ρ = 0.23, P = 0.03) WORMS subscores for the whole joint as well as with the medial femorotibial joint sum score (ρ = 0.26, P = 0.01) and medial femorotibial joint cartilage (ρ = 0.23, P = 0.02). Coll2-1NO2 correlated with WORMS total score (ρ = 0.23, P = 0.02), WORMS scores in the patellofemoral (ρ = 0.23, P = 0.02) and medial femorotibial compartments (ρ = 0.21, P = 0.03), with osteophytes scores (ρ = 0.27, P < 0.01), subarticular cysts (ρ = 0.24, P = 0.019), and intraarticular loose bodies (ρ = 0.27, P = 0.007). Baseline Coll2-1NO2 was higher in subjects with a pain worsening (426.4 pg/mL [278.04-566.95]) as compared to non-progressors (306.84 pg/mL [200.37-427.84]) over 1 year (AUC = 0.655, P = 0.015).

Conclusion: Serum cartilage biomarkers Coll2-1 and Coll2-1NO2 are associated with several knee OA features quantified with WORMS. Our study also shows that the baseline value of Coll2-1NO2 is positively associated with pain worsening.

Trial registration: ClinicalTrials.gov NCT02070224.

Keywords: OA progression; articular cartilage; biomarkers; clinical trial; diagnosis; diagnostics; general; osteoarthritis; tissue.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: YH is the founder and the President of ARTIALIS SA, a spin-off company of the University of Liege. He has also received fees from Bepharbel, GSK, KiOmed Pharma SA (formerly Synolyne Pharma SA), Nestle, Genequine, Flexion Therapeutics, IBSA, BioIberica, Laboratoires Expanscience, Royal Canin, MagPharm, LABRHA, Pfizer, Thuasne, and Tilman SA. ACH is employee of ARTIALIS S.A. The other authors have no conflicts of interest to declare.

Figures

Figure 1.

Patient flow diagram of PRODIGE study. A total of 121 subjects suffering from knee osteoarthritis were followed during one year.

Figure 2.

Box and whisker plots illustrate that baseline Coll2-1NO2 is higher in subjects whose VAS pain increases after 1 year (VAS prog., black) compared to subjects with no increase of VAS pain (No prog., white) in general population (all) as well as in polyosteoarthritis subgroup (polyOA) but not in monoosteoarthritis (monoOA) subgroup. prog. = progressors. *P < 0.05, **P < 0.01.

Figure 3.

Box and whisker plots of Coll2-1 change at T3, T6, and T12 as compared to baseline values (T0) for WORMS cartilage progressors (gray) and nonprogressors (white) at 1 year. Coll2-1 ratios are lower in subjects that are progressors according to WORMS cartilage score at T3 and T6 but not at T12. prog. = progressors. *P < 0.05, n.s. (nonsignificant).