title: The combination of the biomarkers urinary C-terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathy.
abstract: OBJECTIVE
  Hemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers.
  
  
  METHODS
  Blood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C-terminal telopeptide of type I collagen (CTX-I), urinary CTX-II, serum CTX-I, serum CTX-II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS-846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy.
  
  
  RESULTS
  Urinary CTX-II, serum C1,2C, and serum CS-846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX-II, serum COMP, and serum CS-846. Bone-specific markers (urinary/serum CTX-I and serum C1,2C) did not correlate with specific bone-related items of the Pettersson score (osteoporosis and erosions).
  
  
  CONCLUSIONS
  These results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX-II, serum COMP, and serum CS-846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage.
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands. n.w.d.jansen@umcutrecht.nl
authors.forename: Nathalie W D
authors.initials: NW
authors.lastname: Jansen
authors.forename: Goris
authors.initials: G
authors.lastname: Roosendaal
authors.forename: Björn
authors.initials: B
authors.lastname: Lundin
authors.forename: Lily
authors.initials: L
authors.lastname: Heijnen
authors.forename: Evelien
authors.initials: E
authors.lastname: Mauser-Bunschoten
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Matthias
authors.initials: M
authors.lastname: Theobald
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002356:Cartilage / Q000473:pathology; D064236:Cartilage Oligomeric Matrix Protein; D002809:Chondroitin Sulfates / Q000097:blood*; D024043:Collagen Type II / Q000652:urine*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D006023:Glycoproteins / Q000097:blood*; D006467:Hemophilia A / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002836:Hemophilia B / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007592:Joint Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007596:Joints / Q000473:pathology; D064235:Matrilin Proteins; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D002809:Chondroitin Sulfates