EXTENDED REPORT

Urinary levels of type II collagen C-telopeptide crosslink are unrelated to joint space narrowing in patients with knee osteoarthritis

S A Mazzuca¹, K D Brandt², D R Eyre³, B P Katz¹, J Askew³, K A Lane¹

¹ Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
² Department of Medicine and Department of Orthopaedic Surgery, Indiana University School of Medicine
³ Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, USA

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}iupui.edu

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.

Abbreviations: 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

Keywords: knee osteoarthritis; osteoarthritis biomarkers; type II collagen

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