Article Text

Download PDFPDF
Extended report
Relationship of serum markers of cartilage metabolism to imaging and clinical outcome measures of knee joint structure
  1. Patricia A Berry1,
  2. Rose A Maciewicz2,
  3. Anita E Wluka1,3,
  4. Mark D Downey-Jones2,
  5. Andrew Forbes1,
  6. Caroline J Hellawell2,
  7. Flavia M Cicuttini1
  1. 1Department of Epidemiology and Preventive Medicine, Monash University Medical School, Alfred Hospital, Prahran, Victoria, Australia
  2. 2Respiratory and Inflammation Research Area, AstraZeneca, Macclesfield, Cheshire, UK
  3. 3Baker Heart Research Institute, Melbourne, Victoria, Australia
  1. Correspondence to Professor Flavia M Cicuttini, Department of Epidemiology and Preventive Medicine, Monash University, Central and Eastern Clinical School, Alfred Hospital, Melbourne, VIC 3004, Australia; flavia.cicuttini{at}


Background Biomarkers of cartilage metabolism have prognostic potential.

Objective To examine whether serum cartilage biomarkers, cartilage oligomeric matrix protein (COMP), N-propeptide of type IIA procollagen (PIIANP), type II collagen breakdown product (collagen type-II cleavage (C2C)) predict cartilage volume loss and knee joint replacement.

Methods 117 subjects with knee osteoarthritis (OA) had MRI at baseline and 2 years. Cartilage biomarkers were measured at baseline. Change in knee cartilage volume over 2 years and knee joint replacement over 4 years was determined. The population was divided into subgroups with high or low cartilage biomarkers (based on biomarker levels greater than or equal to, or less than, the mean, respectively). The relationships between biomarkers and outcome measures were examined in the whole population, and separately in marker subgroups.

Results The relationship between cartilage biomarkers and cartilage volume loss was not linear across the whole population. In the low (regression coefficient B=–9.7, 95% CI –0.01 to 0.003, p=0.01), but not high (B=–0.46, 95% CI –8.9 to 8.0, p=0.92) COMP subgroup, COMP was significantly associated with a reduced rate of medial cartilage volume loss (p for difference between groups=0.05). Similarly, in the low (B=–8.2, 95% CI –12.9 to –3.5, p=0.001) but not high (B=2.6, 95% CI –3.3 to 8.5, p=0.38) PIIANP subgroup, PIIANP was associated with a significantly reduced rate of medial volume cartilage loss (p for difference=0.003). C2C was not significantly associated with rate of cartilage volume loss. PIIANP was associated with a reduced risk of joint replacement (odds ratio (OR)=0.28, 95% CI 0.10 to 0.93, p=0.04).

Conclusion Cartilage biomarkers may be used to identify subgroups among those with clinical knee OA in whom disease progresses at different rates. This may facilitate our understanding of the pathogenesis of disease and allow us to differentiate phenotypes of disease within a heterogeneous knee OA population.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding This work was supported by NHMRC project grant 980914. PAB is the recipient of an Australian postgraduate association scholarship. AEW is the recipient of an NHMRC career development award (545876).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Alfred and Caulfield Hospitals in Melbourne, Australia.

  • Provenance and peer review Not commissioned; externally peer reviewed.