title: Clusters within a wide spectrum of biochemical markers for osteoarthritis: data from CHECK, a large cohort of individuals with very early symptomatic osteoarthritis.
abstract: OBJECTIVE
  To assess a wide spectrum of biochemical markers (biomarkers) in a large cohort of individuals with (very) early symptomatic knee and/or hip osteoarthritis (OA). Secondly, to investigate associations between biomarkers and between biomarkers and demographics to demonstrate validity of the obtained dataset and further investigate the involvement and/or role of these biomarkers in OA.
  
  
  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 1,002 individuals with early symptomatic knee and/or hip OA.
  
  
  RESULTS
  Quality controls revealed that gathered data were technically reliable. The majority of biomarkers showed relevant associations with demographic variables, which were expectedly different between genders and/or menopausal status for some. Principal component analysis enabled identification of five clusters, consecutively designated as 'bone-CTX-II', 'inflammation', 'synovium', 'C1,2C-adipokines', and 'cartilage synthesis' cluster. Notably, uCTX-II clustered with biomarkers of bone metabolism, while sCOMP clustered with biomarkers of synovial activity.
  
  
  CONCLUSIONS
  The identified clusters extended knowledge on individual biomarkers from mostly smaller studies as did the observed associations between biomarker levels and demographics, from which validity of our data was deduced. uCTX-II may not only reflect articular cartilage but also bone metabolism and sCOMP may reflect synovial rather than cartilage metabolism. Major involvement of adipokines in joint metabolism was not identified.
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. w.e.vanspil@umcutrecht.nl
authors.forename: W E
authors.initials: WE
authors.lastname: van Spil
authors.forename: N W D
authors.initials: NW
authors.lastname: Jansen
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: M
authors.initials: M
authors.lastname: Reijman
authors.forename: J
authors.initials: J
authors.lastname: DeGroot
authors.forename: P M J
authors.initials: PM
authors.lastname: Welsing
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism; D016000:Cluster Analysis; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000175:diagnosis*; D020370:Osteoarthritis, Knee / Q000175:diagnosis*; D025341:Principal Component Analysis; D012737:Sex Factors; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D054392:Adipokines; D015415:Biomarkers