Risk Assessment of the Progression of Early Knee Osteoarthritis by Collagen Neoepitope C2C: A Longitudinal Study of an Estonian Middle-Aged Cohort

One of the unmet needs to be addressed is prognostic biomarkers for early knee osteoarthritis (kOA). We aimed to study the association of urinary collagen type-II C-terminal cleavage neoepitope (uC2C) with the emergence and progression of kOA. The longitudinal data of 330 subjects (aged 32–60 years) from an Estonian population-based cohort were used. The radiographic progression was evaluated by the grading system of Nagaosa et al. of knee compartments at baseline and three years later. The emerging kOA consisted of subjects with developing osteophytes or joint space narrowing, whereas kOA progressors showed aggravation of radiographic grade. Baseline uC2C levels were measured by the IBEX-uC2C assay. At baseline, the subjects were middle-aged (mean age, 47.6 years) and overweight (mean BMI, 28.0 kg/m(2)), and the majority of them (51.2%) had a diagnosis of kOA grade 1. Multiple logistic regression models adjusted for sex, age, and BMI were used for risk calculations. We demonstrate that increased uC2C accurately predicted the risk of emerging of kOA (OR = 5.87 (1.71–20.22); AUC = 0.79) compared with controls without radiographic kOA over 12 years. However, the most accurate prediction of progression by the biomarker was found in women (OR = 23.0 (2.2–245), AUC = 0.91). In conclusion, uC2C may be a promising candidate as a prognostic biomarker for kOA progression, particularly of emerging kOA in women.