Background The actual value of biochemical markers (biomarkers) for osteoarthritis (OA) remains doubtful, partly because available studies are mostly small and focus on late rather than the more relevant early OA stages.
Objectives Firstly, to assess a wide spectrum of biochemical markers in a large cohort of individuals with symptoms of (very) early OA, as opposed to literature mainly reporting on small studies of individual or limited numbers of biomarkers in more advanced OA. Secondly, to investigate interrelationships between these biomarkers and with demographics to demonstrate validity of the obtained dataset and extend hypotheses on the backgrounds of these biomarkers.
Methods Fourteen biomarkers (uCTX-II, uCTX-I, uNTX-I, sCOMP, sPIIANP, sCS846, sC1,2C, sOC, sPINP, sHA, sPIIINP, pLeptin, pAdiponectin, pResistin) were assessed by ELISA or RIA in CHECK (Cohort Hip and Cohort Knee), a 10-year prospective cohort of 1002 individuals with symptoms of early knee and/or hip OA. Associations between biomarkers and demographics were investigated through multiple linear regression analysis. Clusters of interrelated biomarkers within the assessed biomarker spectrum were identified through principal component analysis.
Results Quality controls revealed that gathered data were technically reliable. Principal component analysis identified six clusters, consecutively designated as “bone-CTX-II”, “inflammation”, “synovium”, “C1,2C-adipokines”, “PIIANP”, and “CS846” cluster. Notably, uCTX-II clustered with biomarkers of bone metabolism, while sCOMP clustered with biomarkers of synovial activity. Furthermore, pResistin and pAdiponectin contributed inversely to one cluster together with sC1,2C. All biomarkers, except for sCS846, were statistically significantly associated with demographics.
Conclusions This is the first time that a wide spectrum of biomarkers was assessed in such a large longitudinal cohort of early-OA subjects followed in detail for 10 years. Data were generally considered of good technical quality. Associations between biomarkers and demographics were conform hypotheses based on established OA risk factors and literature data. sCOMP was mainly associated with (markers of) synovial activity. Indeed, sCOMP is (also) produced by synoviocytes, is present in synovial tissue, and has been associated with clinical and ultrasonographically detected signs of synovitis and/or effusion. Furthermore, uCTX-II was mainly associated with (markers of) bone metabolism. Other authors have also suggested this association and uCTX-II has been linked to osteoclastic resorption of calcified cartilage by some. In summary, our unique biomarker data were considered valid since exploratory analysis of our data extended knowledge on individual or limited numbers of biomarkers from, mostly, smaller cohorts.
Acknowledgements This study was funded by CHECK, an initiative of the Dutch Arthritis Association.
Disclosure of Interest None Declared
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