title: Potential biomarkers of haemophilic arthropathy: correlations with compatible additive magnetic resonance imaging scores.
abstract: BACKGROUND
  Although biomarkers are useful diagnostic tools to assess joint damage in osteoarthritis and rheumatoid arthritis, few data exist for biomarkers of haemophilic arthropathy.
  
  
  OBJECTIVE
  To evaluate the association between biomarkers and compatible additive magnetic resonance imaging (MRI) scores in patients with severe haemophilia A.
  
  
  METHODS
  Patients aged 12-35 years with no history of factor VIII (FVIII) inhibitors were enrolled in a controlled, cross-sectional, multinational investigation. Patients received primary or secondary prophylaxis or on-demand treatment with FVIII and underwent MRI on four joints (two ankles, two knees). Soluble biomarkers of cartilage and bone degradation, inflammation, and angiogenesis were assessed (serum levels of C-terminal telopeptides of type I collagen [CTX-I], cartilage oligomeric matrix protein [COMP], chondroitin-sulphate aggrecan turnover 846 epitope [CS846], tissue inhibitor of metalloproteinase 1 [TIMP-1]; plasma levels of vascular endothelial growth factor [VEGF], matrix metalloproteinases 3 and 9 [MMP3, MMP9]). Relationships between biomarkers and MRI scores were evaluated using Spearman rank correlation.
  
  
  RESULTS
  Biomarkers were assessed in 117 of 118 per-protocol patients. Mean and median CTX-I, COMP, TIMP-1, MMP3, MMP9, and VEGF values were within normal ranges (reference range not available for CS846 in healthy volunteers). No correlations between biomarkers and MRI scores were found, with the exception of CS846, which showed significant correlation in a subgroup of 22 on-demand patients (r = 0.436; P = 0.04).
  
  
  CONCLUSIONS
  Compatible additive MRI scores showed no clear correlations with any of the potential biomarkers for haemophilic arthropathy in the overall population. CS846 levels were significantly correlated with MRI scores in patients treated on demand.
authors.affiliation: University Clinic Bonn, Bonn, Germany. johannes.oldenburg@ukb.uni-bonn.de.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Kurpfalz Hospital and Haemophilia Centre for Children and Adults, Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Laikon General Hospital, Athens, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Katsarou
authors.affiliation: University of Padua Medical School, Padua, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Zanon
authors.affiliation: Bayer Vital GmbH, Leverkusen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Kellermann
authors.affiliation: Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Lundin
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Ellinghaus
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000000981:diagnostic imaging; D015415:Biomarkers / Q000097:blood*; D002648:Child; D003029:Coagulants / Q000627:therapeutic use; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D005169:Factor VIII / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D010003:Osteoarthritis / Q000175:diagnosis* / Q000000981:diagnostic imaging; D010455:Peptides / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003029:Coagulants; D024042:Collagen Type I; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; C052929:collagen type I trimeric cross-linked peptide; C078147:F8 protein, human; D005169:Factor VIII
keywords: arthropathy; biological markers; haemophilia A; joints; magnetic resonance imaging