title: Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.
abstract: BACKGROUND
  We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.
  
  
  METHODS
  Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).
  
  
  RESULTS
  sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.
  
  
  CONCLUSIONS
  These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.
authors.affiliation: Department of Medicine for Motor Organ, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. ishijima@juntendo.ac.jp
authors.forename: Muneaki
authors.initials: M
authors.lastname: Ishijima
authors.forename: Taiji
authors.initials: T
authors.lastname: Watari
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Naito
authors.forename: Haruka
authors.initials: H
authors.lastname: Kaneko
authors.forename: Ippei
authors.initials: I
authors.lastname: Futami
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshimura-Ishida
authors.forename: Akihito
authors.initials: A
authors.lastname: Tomonaga
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kurosawa
authors.forename: Robin A
authors.initials: RA
authors.lastname: Poole
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002356:Cartilage / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020370:Osteoarthritis, Knee / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D010146:Pain / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D011859:Radiography; D013583:Synovial Membrane / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D015415:Biomarkers