title: Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.
abstract: OBJECTIVE
  To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover.
  
  
  METHODS
  Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes.
  
  
  RESULTS
  Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage.
  
  
  CONCLUSIONS
  Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA.
authors.affiliation: Duke University School of Medicine, Durham, North Carolina.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Huebner
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Kim M
authors.initials: KM
authors.lastname: Huffman
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Gary E
authors.initials: GE
authors.lastname: McDaniel
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D016723:Bone Remodeling / Q000502:physiology*; D024042:Collagen Type I / Q000652:urine*; D024043:Collagen Type II / Q000652:urine; D018450:Disease Progression; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000652:urine*; D011859:Radiography
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II