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Urinary levels of type II collagen C-telopeptide crosslink are unrelated to joint space narrowing in patients with knee osteoarthritis
  1. S A Mazzuca1,
  2. K D Brandt2,
  3. D R Eyre3,
  4. B P Katz1,
  5. J Askew3,
  6. K A Lane1
  1. 1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
  2. 2Department of Medicine and Department of Orthopaedic Surgery, Indiana University School of Medicine
  3. 3Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, USA
  1. Correspondence to:
    Dr Steven A Mazzuca
    Indiana University School of Medicine, Department of Medicine, Rheumatology Division, Long Hospital Room 545, 1110 W Michigan St, Indianapolis, IN 46202-5100, USA; smazzuca{at}


Objective: To determine whether urinary concentrations of the cross linked C-telopeptide of type II collagen (CTx-II) distinguish subjects with progressive radiographic or symptomatic knee osteoarthritis from those with stable disease.

Methods: Subjects were 120 obese women with unilateral knee osteoarthritis who participated in a 30 month, randomised, placebo controlled trial of structure modification by doxycycline, in which a standardised semiflexed anteroposterior view of the knee was obtained at baseline and 30 months. Subjects were selected from a larger sample to permit comparisons of urinary CTx-II levels between 60 progressors and 60 non-progressors with respect to medial joint space narrowing. Each group contained 30 subjects who, across five semi-annual assessments, reported on at least two occasions an increase of ⩾20% in 50 ft walk pain (minimum = 1 cm on a 10 cm visual analogue scale), relative to the previous visit. The remainder reported no increases in knee pain. Urine samples were obtained semi-annually for determination of the CTx-II and creatinine concentrations.

Results: In an analysis of the placebo group only, the frequency of radiographic progressors in the upper and middle tertiles (48% and 60%, respectively) of the baseline CTx-II distribution was not significantly different than that in the lower tertile (64%). These results were unchanged after inclusion of data from subjects in the doxycycline group. Furthermore, serial CTx-II levels did not distinguish subjects with progressive radiographic or symptomatic knee osteoarthritis from those with stable disease.

Conclusions: In this pilot study, urinary CTx-II concentration was not a useful biomarker of osteoarthritis progression.

  • BMI, body mass index
  • CTx-II, type II collagen C-terminal cross linked peptide
  • JSN, joint space narrowing
  • JSW, joint space width
  • RCT, randomised controlled trial
  • uCr, urinary creatinine concentration
  • knee osteoarthritis
  • osteoarthritis biomarkers
  • type II collagen

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  • Published Online First 8 December 2005

  • Supported in part by NIH grants R01 AR43348, R01 AR43370, R01 AR37318, and P60 AR20582.