title: The ability of systemic biochemical markers to reflect presence, incidence, and progression of early-stage radiographic knee and hip osteoarthritis: data from CHECK.
abstract: OBJECTIVE
  To relate systemic biochemical markers of joint metabolism to presence, incidence, and progression of early-stage radiographic knee and/or hip osteoarthritis (OA).
  
  
  METHODS
  The cartilage markers uCTX-II, sCOMP, sPIIANP, and sCS846, bone markers uCTX-I, uNTX-I, sPINP, and sOC, and synovial markers sHA and sPIIINP were assessed by enzyme-linked immunosorbent assay or radioactive immunoassay in baseline samples of CHECK (Cohort Hip and Cohort Knee), a cohort study of early-stage symptomatic knee and/or hip OA. Knee and hip radiographs were obtained at baseline and 5-year follow-up. Presence of OA at baseline was defined as Kellgren and Lawrence (K&L) = 1 (maximum observed). Incidence of OA was defined as K&L = 0 at baseline and K&L ≥ 1 at 5-year follow-up. Progression of OA was defined as K&L = 1 at baseline and K&L ≥ 2 at 5-year follow-up.
  
  
  RESULTS
  Data were available for 801 subjects at baseline and for 723 subjects at both baseline and 5-year follow-up. Multiple cartilage and synovial markers showed positive associations with presence and progression of knee and hip OA and with incidence of hip OA, except for negative associations of uCTX-II and sCOMP with incidence of knee OA. uCTX-II and sCOMP showed multiple interactions with other biomarkers in their associations with knee and hip OA. Bone markers were positively associated with presence of radiographic knee OA, but negatively associated with progression of radiographic hip OA.
  
  
  CONCLUSIONS
  Especially metabolism in cartilage and synovial matrix appear to be of relevance in knee and hip OA. The role of bone metabolism appears to differ between knee and hip OA.
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: w.e.vanspil@umcutrecht.nl.
authors.forename: W E
authors.initials: WE
authors.lastname: Van Spil
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: p.m.j.welsing@umcutrecht.nl.
authors.forename: P M J
authors.initials: PM
authors.lastname: Welsing
authors.affiliation: Department of General Practice, Department of Orthopaedics, University Medical Center Rotterdam - Erasmus Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Electronic address: s.bierma-zeinstra@erasmusmc.nl.
authors.forename: S M A
authors.initials: SM
authors.lastname: Bierma-Zeinstra
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: j.w.j.bijlsma@umcutrecht.nl.
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Amsterdam Rehabilitation Research Center, Reade, PO Box 58271, 1040 HG, Amsterdam, The Netherlands. Electronic address: l.roorda@reade.nl.
authors.forename: L D
authors.initials: LD
authors.lastname: Roorda
authors.affiliation: Sint Maartenskliniek, PO Box 9011, 6500 GM, Nijmegen, The Netherlands. Electronic address: h.cats@maartenskliniek.nl.
authors.forename: H A
authors.initials: HA
authors.lastname: Cats
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: f.lafeber@umcutrecht.nl.
authors.forename: F P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein / Q000378:metabolism; D002358:Cartilage, Articular / Q000000981:diagnostic imaging; D002809:Chondroitin Sulfates / Q000378:metabolism; D015331:Cohort Studies; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000000981:diagnostic imaging* / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D011859:Radiography; D013583:Synovial Membrane / Q000000981:diagnostic imaging
chemical_list: D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D024042:Collagen Type I; D024043:Collagen Type II; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates
keywords: Biomarkers; Hip osteoarthritis; Knee osteoarthritis; Radiography