Abstract

gender and BMI (stand betas 0.113, P1⁄40.003 and 0.129, P1⁄40.000, respectively). Only cartilage marker combinations showed stronger associations with baseline summed K&L grades than individual biomarkers (stand beta 0.150, P1⁄40.000 for uCTX-II+sCOMP+PIIANP+CS846 combination, after adjustment). Associations with AUC of the summed K&L score were statistically significant for uCTX-II, sCOMP, sPIIANP, and sCS846 (stand betas 0.089-0.133, P<0.018) and persisted after adjustment for age, gender, BMI, and baseline summed K&L score for sCOMP only (stand beta 0.105, P1⁄40.005). Stronger associations were observed for cartilage and synovial combinations (stand beta 0.128, P1⁄40.001 for uCTXII+sCOMP+sPIIANP+sCS846, and stand beta 0.110, P1⁄40.003 for sCOMP+sPIIINP). Conclusions: Associations with burden and progression of (very) early knee and hip OAwere observed for cartilage and synovial biomarkers. The low grade of the associations may be due to limitations of biomarkers as well as radiography in reflecting disease in OA, especially in early-stage disease. Associations may be stronger at 10-year follow-up and/or when using more sensitive measures of individual radiographic OA features (e.g. osteophytes, joint space narrowing, etc). Nevertheless, together with literature data these results indicate that the search for biomarkers for (very) early OA should be primarily aimed at (combinations of) cartilage and synovial metabolism. This study was funded by CHECK (Cohort Hip & Cohort Knee), an initiative of the Dutch Arthritis Association.

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