Biomarkers of incident radiographic knee osteoarthritis: do they vary by chronic knee symptoms?

Arthritis Rheum. 2011 Aug;63(8):2276-83. doi: 10.1002/art.30412.


Objective: To explore the ability of osteoarthritis (OA)-related biomarkers to predict incident radiographic knee OA in a large sample of African American and Caucasian men and women.

Methods: Baseline levels of serum cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high-sensitivity C-reactive protein (hsCRP), and keratan sulfate (KS) and baseline and followup radiographs were available for 353 knees without baseline osteophyte formation and for 446 knees without baseline joint space narrowing (JSN). Cox models estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for incident knee OA for a 1-unit increase in the ln of each biomarker, with adjustment for age, race, sex, body mass index, and knee OA of the contralateral limb. Report of chronic knee symptoms was explored as a modifier of the association.

Results: The hazard of incident knee osteophytes (HR 2.16 [95% CI 1.39-3.37]) and incident JSN (HR 1.82 [95% CI 1.15-2.89]) increased with higher baseline ln(COMP) levels. The hazard of incident knee JSN increased with higher ln(HA) levels (HR 1.46 [95% CI 1.14-1.87]). Baseline ln(hsCRP) and ln(KS) did not predict incident knee outcomes. HRs per unit increase in ln(COMP), ln(HA), and ln(KS) were higher among knees with chronic symptoms than among those without symptoms.

Conclusion: Higher baseline ln(COMP) and ln(HA) levels were associated with incident knee OA over an average followup period of 6.3 years. These results represent detection of a molecular stage of OA prior to radiographic manifestations. Further exploration is needed to determine how chronic knee symptoms modify the biomarker-incident knee OA association.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Cartilage Oligomeric Matrix Protein
  • Extracellular Matrix Proteins / blood*
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood*
  • Humans
  • Hyaluronic Acid / blood*
  • Keratan Sulfate / blood*
  • Knee Joint / diagnostic imaging
  • Male
  • Matrilin Proteins
  • Middle Aged
  • Osteoarthritis, Knee / blood*
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteophyte / diagnostic imaging
  • Radiography


  • Biomarkers
  • Cartilage Oligomeric Matrix Protein
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Matrilin Proteins
  • TSP5 protein, human
  • Hyaluronic Acid
  • C-Reactive Protein
  • Keratan Sulfate