Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI

Osteoarthritis Cartilage. 2009 Mar;17(3):384-9. doi: 10.1016/j.joca.2008.07.009. Epub 2008 Sep 3.


Objective: Osteoarthritis (OA) is characterized by increased bone and cartilage metabolism leading to joint damage. The urinary excretion of C-telopeptides of type II collagen (CTX-II) has earlier predicted progression in radiographic OA (ROA)--useful for participant selection in clinical studies of potential disease modifying OA drugs (DMOADs). We investigated the longitudinal interrelationship between CTX-II and knee cartilage volume quantified from magnetic resonance imaging (MRI).

Methods: We followed 158 subjects [48% females, 36 with knee ROA at baseline (BL)] for 21 months. The Kellgren and Lawrence (KL) index and joint space width were assessed from radiographs (acquired load-bearing, semi-flexed). MRI scans were acquired from a 0.18 T Esaote scanner (40 degrees flip angle (FA), TR 50 ms, TE 16 ms, scan time 10 min, resolution 0.7 mm x 0.7 mm x 0.8 mm) and medial tibial and femoral cartilage volume was quantified. Radiographs and MRI were acquired at BL and follow-up. Fasting morning urine samples (second void) were collected for BL CTX-II measurement.

Results: CTX-II was 56% higher in ROA subjects (P=0.0001). In addition, elevated BL CTX-II was associated with radiographic progression (by KL or joint space narrowing) although not statistically significant. Contrarily, elevated BL CTX-II predicted longitudinal cartilage loss by MRI (middle/high tertiles had odds ratios 4.0/3.9, P<0.01) corresponding to 3.1% increased yearly cartilage loss.

Conclusion: Prognostic markers in study selection criteria must ensure that placebo-treated participants progress to enable efficacy demonstration. And efficacy markers must allow progression detection within the study period. Our results support applying CTX-II for selection of high risk subjects and applying the fully automatic MRI-based framework for quantification of cartilage loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / urine
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology*
  • Collagen Type II / urine*
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / pathology
  • Osteoarthritis, Knee / urine*
  • Peptides / urine*
  • Predictive Value of Tests
  • Radiography


  • Biomarkers
  • Collagen Type II
  • Peptides