The role of type I collagen fragment C1M in knee osteoarthritis. A longitudinal biomarker study using data from the OA-FNIH consortium

To evaluate the association of neoepitopes from type I and II collagen with knee osteoarthritis (OA) progression phenotypes using data from the OA-FNIH biomarker consortium, with comparison to associations of the other biomarkers assessed in this sample during the consortium's phase 1 analysis. Serum (s) and urinary (u) neoepitopes of type I collagen (sC1M) and type II collagen (sC2M and uCTX-II) were analyzed at baseline, and as time-integrated concentrations over 12 (12 M) and 24 months (24 M) in 600 individuals with knee OA divided into non-progressors (n=200), and three groups of progressors based on joint space loss only (JSL) (n=103), pain only (n=103), and JSL and pain (n=194). Logistic regression models were used to evaluate the relationship between the biomarkers and odds of case status. At all-time points lower levels of sC1M, and higher levels of uCTX-II were associated with JSL progression (sC1M 0 M, OR: 0.43 [0.28, 0.68], 12 M OR: 0.43 [0.27, 0.68], 24 M OR:0.55 [0.35, 0.86]; uCTX-II 0 M, OR: 1.54 [1.01, 2.37], 12 M OR: 1.73 [1.11, 2.7], 24 M OR: 2.05 [1.27,3.29]) CONCLUSIONS: The inverse association of C1M with OA progression compared with the positive association of uCTXII indicates that a reduced concentration of one neoepitope (of type I collagen) and an elevated concentration of another (from type II collagen) are each associated with the risk of OA progression.