title: Systemic biochemical markers of joint metabolism and inflammation in relation to radiographic parameters and pain of the knee: data from CHECK, a cohort of early-osteoarthritis subjects.
abstract: OBJECTIVE
  To investigate associations of biochemical markers of joint metabolism and inflammation with minimum joint space width (JSW) and osteophyte area (OP area) of knees showing no or doubtful radiographic osteoarthritis (OA) and to investigate whether these differed between painful and non-painful knees.
  
  
  METHODS
  Serum (s-) and urinary (u-) levels of the cartilage markers uCTX-II, sCOMP, sPIIANP, and sCS846, bone markers uCTX-I, uNTX-I, sPINP, and sOC, synovial markers sPIIINP and sHA, and inflammation markers hsCRP and erythrocyte sedimentation rate (ESR) were assessed in subjects from CHECK (Cohort Hip and Cohort Knee) demonstrating Kellgren and Lawrence grade ≤1 OA on knee radiographs. Minimum JSW and OP area of these knees were quantified in detail using Knee Images Digital Analysis (KIDA).
  
  
  RESULTS
  uCTX-II levels showed negative associations with minimum JSW and positive associations with OP area. sCOMP and sHA levels showed positive associations with OP area, but not with minimum JSW. uCTX-I and uNTX-I levels showed negative associations with minimum JSW and OP area. Associations of biochemical marker levels with minimum JSW were similar between painful and non-painful knees, associations of uCTX-II, sCOMP, and sHA with OP area were only observed in painful knees.
  
  
  CONCLUSIONS
  In these subjects with no or doubtful radiographic knee OA, uCTX-II might not only reflect articular cartilage degradation but also endochondral ossification in osteophytes. Furthermore, sCOMP and sHA relate to osteophytes, maybe because synovitis drives osteophyte development. High bone turnover may aggravate articular cartilage loss. Metabolic activity in osteophytes and synovial tissue, but not in articular cartilage may be related to knee pain.
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: s.c.nair@umcutrecht.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Nair
authors.affiliation: Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: m.b.kinds@umcutrecht.nl.
authors.forename: M B
authors.initials: MB
authors.lastname: Kinds
authors.affiliation: Department of Orthopaedic Surgery, Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. Electronic address: Pj.Emans@maastrichtuniversity.nl.
authors.forename: P J
authors.initials: PJ
authors.lastname: Emans
authors.affiliation: Allied Health Care Center for Rheumatology and Rehabilitation Groningen, Helpermolenstraat 25, 9721 BT, Groningen, The Netherlands. Electronic address: info@PCRR.nl.
authors.forename: W K H A
authors.initials: WK
authors.lastname: Hilberdink
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 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; D018771:Arthralgia / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011859:Radiography
chemical_list: D015415:Biomarkers
keywords: Biochemical markers; Inflammation; Joint space width; Osteoarthritis; Osteophytes