Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis

Arthritis Res Ther. 2006;8(1):R31. doi: 10.1186/ar1882. Epub 2006 Jan 10.


Introduction: The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA).

Methods: Clinical and radiographic data of 87 RA patients were recorded 1 year after disease onset and then annually up to four years. Serum concentrations of four cartilage biomarkers were determined at these time points: a neoepitope formed by collagenase cleavage of type II collagen (C2C), a neoepitope formed by collagenase cleavage of type II collagen as well as type I collagen (C1,2C), a carboxy propeptide of type II procollagen formed during synthesis (CPII), and a cartilage proteoglycan aggrecan turnover epitope (CS846-epitope). Biomarker concentrations between patients with rapid radiographic progression (>7.3 Sharp/van der Heijde units per year) and those with slow radiographic progression (<2.3 units per year) were compared. In addition, we evaluated the long-term and short-term predictive value of each biomarker for progression of radiographic damage.

Results: Patients with rapid radiographic progression had higher C2C, higher C1,2C, and higher CS846-epitope levels than slow progressors. CPII levels showed no differences. Most importantly, the long-term radiographic progression for C2C, for C1,2C, and for CS846-epitope can be predicted by the biomarker value at year 1 after disease onset. C2C was also a predictor for joint space narrowing and annual radiographic damage during the subsequent year.

Conclusion: This study shows that the concentration of serum biomarkers of cartilage collagen breakdown and proteoglycan turnover, but not of collagen synthesis, are related to joint destruction in RA. The use of these biomarkers may be of value when studying progression of joint damage in patients with RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aggrecans
  • Arthritis, Rheumatoid / diagnostic imaging*
  • Arthritis, Rheumatoid / physiopathology*
  • Arthrography*
  • Biomarkers / blood*
  • Cartilage / physiopathology*
  • Chondroitin Sulfate Proteoglycans / immunology
  • Collagen Type I / immunology
  • Collagen Type I / metabolism
  • Collagen Type II / blood
  • Collagen Type II / immunology
  • Collagen Type II / metabolism
  • Collagenases / metabolism
  • Disease Progression
  • Epitopes / blood
  • Extracellular Matrix Proteins / immunology
  • Female
  • Humans
  • Lectins, C-Type / immunology
  • Male
  • Middle Aged
  • Peptide Fragments / blood
  • Predictive Value of Tests
  • Time Factors


  • Aggrecans
  • Biomarkers
  • Chondroitin Sulfate Proteoglycans
  • Collagen Type I
  • Collagen Type II
  • Epitopes
  • Extracellular Matrix Proteins
  • Lectins, C-Type
  • Peptide Fragments
  • Collagenases