title: Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.
abstract: OBJECTIVE
  We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA).
  
  
  METHODS
  Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured.
  
  
  RESULTS
  Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels.
  
  
  CONCLUSIONS
  Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA.
authors.affiliation: INSERM Research Unit 831, Université de Lyon, Lyon, France. jean-charles.rousseau@inserm.fr
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Rousseau
authors.forename: Guillaume
authors.initials: G
authors.lastname: Chevrel
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Schott
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D010013:Osteogenesis Imperfecta / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II