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
Anne-Christine Hick, Michel Malaise, Damien Loeuille, Thierry Conrozier, Yves Maugars, Franz Pelousse, Cédric Tits, Yves Henrotin, Anne-Christine Hick, Michel Malaise, Damien Loeuille, Thierry Conrozier, Yves Maugars, Franz Pelousse, Cédric Tits, Yves Henrotin
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.
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Source: PubMed