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Associations Between Joint Space Narrowing and Molecular Markers of Collagen and Proteoglycan Turnover in Patients with Knee Osteoarthritis
STEVEN A. MAZZUCA, A. ROBIN POOLE, KENNETH D. BRANDT, BARRY P. KATZ, KATHLEEN A. LANE, and TATIANA LOBANOK ABSTRACT. Objective. We examined whether plasma concentrations of biomarkers of the collagenase cleavage of type II collagen (C2C), types I and II collagens (C1,2C), type II collagen synthesis (CPII), proteoglycan aggrecan turnover (CS846), and the ratio C2C:CPII would distinguish subjects with progressive radiographic osteoarthritis (OA) from those with stable disease. Methods. Subjects were 120 obese middle-aged women with unilateral knee OA who participated in a 30-month clinical trial of structure modification with doxycycline, in which a standardized semiflexed anteroposterior view of the knee was obtained at baseline, 16 months, and 30 months. Subjects were selected from a larger sample to permit a priori comparisons between 60 OA progressors and 60 nonprogressors, as defined by joint space narrowing (JSN) in the medial tibiofemoral compartment. Each group contained 30 subjects who exhibited clinically significant increases in knee pain over 30 months and 30 who did not. Plasma samples were obtained every 6 months for determination of C2C, CPII, CS846, and C1,2C. Results. None of the biomarkers was a significant predictor of progression of JSN. Over the interval from baseline to 16 months, the mean and the maximum of the intercurrent CS846 values were significantly associated with JSN (i.e., 0.12–0.14 mm of JSN per SD decrease in mean or maximum CS846; p < 0.01). The mean of serial CS846 levels was related to JSN also during the interval between months 16 and 30. Conclusion. Markers of type II collagen synthesis/degradation and of proteoglycan aggrecan turnover were not predictive of JSN in knee OA in this pilot study. However, serial concentrations of proteoglycan aggrecan epitope CS846 were associated with JSN during both the intervals studied. (First Release May 1 2006; J Rheumatol 2006;33:1147–51) Key Indexing Terms:
KNEE OSTEOARTHRITIS
From the Department of Medicine and Department of Orthopaedic Surgery, Indiana University School of Medicine (IUSM), Indianapolis, Indiana, USA; and the Joint Diseases Laboratory, Shriners Hospitals for Children, McGill University, Montreal, Quebec, Canada. Supported in part by grants from National Institutes of Health (R01 AR43348, R01 AR43370, P60 AR20582) and Shriners Hospitals for Children. S.A. Mazzuca, PhD; B.P. Katz, PhD; K.A. Lane, MS, Department of Medicine; K.D. Brandt, MD, Department of Medicine and Department of Orthopaedic Surgery, Indiana University School of Medicine; A.R. Poole, PhD, DSc; T. Lobanok, BSc, Joint Diseases Laboratory, Shriners Hospitals for Children, McGill University. Address reprint requests to Dr. S.A. Mazzuca, Rheumatology Division, Long Hospital, Room 545, 1110 West Michigan Street, Indianapolis, IN 46202-5100. E-mail: smazzuca@iupui.edu Accepted for publication January 11, 2006.
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