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Glucosamine Sulfate and Cartilage Type II Collagen Degradation in Patients with Knee Osteoarthritis: Randomized Discontinuation Trial Results Employing Biomarkers
JOLANDA CIBERE, ANONA THORNE, JACEK A. KOPEC, JOEL SINGER, JANICE CANVIN, DAVID B. ROBINSON, JANET POPE, PAUL HONG, ERIC GRANT, TATIANA LOBANOK, MIRELA IONESCU, A. ROBIN POOLE, and JOHN M. ESDAILE
ABSTRACT.
Methods. A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose. Treatment was continued to Week 24 or disease flare, whichever occurred first. Serum and urine samples were collected at Weeks 0, 4, 12, and 24 or flare visit. Samples were analyzed in triplicate for 2 type II collagen degradation biomarkers: C2C epitope (COL2-3/4Clong) and C1,2C epitope (COL2-3/4Cshort). The primary outcome was the mean change in serum and urine C1,2C/C2C ratio in the glucosamine and placebo groups from baseline to final (flare or Week 24) visit. Linear regression analyses were conducted to adjust for potential confounders. Due to non-normal distributions, the data were log-transformed (lnC1,2C/C2C). Secondary outcomes included comparison of mean change scores at final visit compared to baseline for serum and urine C1,2C and C2C in the 2 treatment groups and in Flare versus No-Flare groups. Results. Baseline and final visit samples were available in 130 subjects for serum analysis and 126 subjects for urinalysis. No significant difference was seen between placebo and glucosamine groups in the serum C1,2C/C2C ratio, with a mean (SD) change from baseline to final visit of 0.8 (27.8) and –0.1 (1.8), respectively (mean difference 0.9; 95% CI –6.0, 7.7, p = 0.80). Similarly, no differences between treatment groups were seen for mean change in urine C1,2C/C2C (p = 0.82), or for mean change in C2C or C1,2C. In linear regression analysis, after adjustment for sex, radiographic severity, baseline lnC1,2C/C2C ratio, WOMAC function, and flare status, treatment was not a significant predictor of final serum or urine lnC1,2C/C2C ratio. When those who experienced flare were contrasted with those without flare, there was a nonsignificant trend toward a difference in mean baseline to final visit change score for serum C1,2C/C2C ratio (p = 0.12). In addition, in the multivariable linear regression analysis, flare status showed a borderline association with final visit serum lnC1,2C/C2C ratio (p = 0.16). Conclusion. No statistically significant effect of glucosamine sulfate on type II collagen fragment levels in serum or urine was observed for knee OA over 6 months. Further research is necessary to elucidate which biopathologic systems, if any, are affected by glucosamine treatment. While collagen degradation products may be of value in predicting progression, at least as defined by clinical flare, a larger dataset would be needed to prove this. (J Rheumatol 2005;32:896-902) Key Indexing Terms:
OSTEOARTHRITIS
From the Arthritis Research Centre of Canada and the Canadian HIV Trials Network, Vancouver, British Columbia; Departments of Medicine and Health Care and Epidemiology, University of British Columbia (UBC), Vancouver, British Columbia; University of Manitoba Arthritis Center, Winnipeg, Manitoba; Department of Medicine, University of Western Ontario, London, Ontario; Department of Medicine, Saint John Campus of Dalhousie University, Saint John, New Brunswick; and Joint Diseases Laboratory, Shriners Hospitals for Children, and Departments of Surgery and Medicine, McGill University, Montreal, Quebec, Canada. Supported by the Mary Pack Research Fund, Vancouver, BC, Canada, the Doris Alma Mary Anderson Fund for Geriatric Research, London, ON, Canada, and the Canadian Arthritis Network. Dr. Cibere was supported by a Canadian Institutes of Health Research Clinician Scientist Award, a Michael Smith Foundation for Health Research Postdoctoral Fellowship Award, the J.W. McConnell Family Foundation Arthritis Scholarship, and the Department of Medicine Academic Enhancement Fund, Departmental Scholar Award. J. Cibere, MD, PhD, Assistant Professor, Department of Medicine, UBC, Research Scientist, Arthritis Research Centre of Canada; A. Thorne, MSc, Senior Biostatistician, Canadian HIV Trials Network, Department of Health Care and Epidemiology, UBC; J.A. Kopec, MD, PhD, Assistant Professor, Department of Health Care and Epidemiology, UBC, Research Scientist, Arthritis Research Centre of Canada; J. Singer, PhD, Professor, Department of Health Care and Epidemiology, UBC, Centre for Health Evaluation and Outcome Sciences; J. Canvin, MD, Associate Professor of Medicine, University of Manitoba, Medical Director, Disease Area Clinical Expert, R & D, AstraZeneca, Charnwood, UK; D.B. Robinson, MD, MSc, Assistant Professor of Medicine, University of Manitoba; J. Pope, MD, MPH, Associate Professor, Department of Medicine and Department of Epidemiology and Biostatistics, University of Western Ontario, St. Joseph's Health Care London, London, ON; P. Hong, BSc, Medical Student, University of Ottawa; E. Grant, MD, Assistant Professor of Medicine, Saint John Campus of Dalhousie University; T. Lobanok, MSc; M. Ionescu, MSc, Joint Diseases Laboratory, Shriners Hospitals for Children, McGill University; A.R. Poole, PhD, DSc, Professor, Departments of Surgery and Medicine, Director, Joint Diseases Laboratory, Shriners Hospitals for Children, McGill University; J.M. Esdaile, MD, MPH, Professor of Medicine, University of British Columbia, Scientific Director, Arthritis Research Centre of Canada. Address reprint requests to Dr. J. Cibere, Arthritis Research Centre of Canada, 895 West 10th Avenue, Vancouver, BC V5Z 1L7, Canada. E-mail: jcibere@arthritisresearch.ca Accepted for publication January 24, 2005. |