ab22102

Osteoarthritic patients with high cartilage turnover show increased responsiveness to the cartilage protecting effects of glucosamine sulphate

S. Christgau¹, Y. Henrotin², L.B. Tankó³, L.C. Rovati⁴, J. Collette², O. Bruyere², R. Deroisy², J.-Y. Reginster^2,5

¹Nordic Bioscience A/S, Herlev, Denmark; ²Bone and Cartilage Metabolism Unit, University of Liège, Liège, Belgium; ³Centre for Clinical and Basic Research, Ballerup, Denmark; ⁴Department of Clinical Pharmacology, Rotta Research Laboratory, Monza, Italy; 5WHO Collaborating Centre for Public Health Aspects of Osteoarticular Disorders.

ABSTRACT
Objective
Glucosamine sulphate has been shown in a large double-blind, placebo-controlled clinical trial to prevent structural damage and improve clinical symptoms of osteoarthritis (OA). We investigated whether early response in a newly developed biochemical marker of collagen type II degradation (CTX-II, CartiLaps ELISA) could reflect the long-term preservation of hyaline cartilage.

Methods
Study subjects comprised 212 knee OA patients participating in a clinical trial of the effects of glucosamine sulphate. Disease symptoms were assessed quarterly by WOMAC scoring and X-ray analysis was performed at baseline and after 3 years. Urine samples were obtained at baseline and after 1, 2 and 3 years for measurement in the CartiLaps assay. The measurements were corrected for creatinine.

Results
At baseline the patients had an average concentration of urinary CTX-II of 222.4±159.5 ng/mmol creatinine. This was significantly above the CTX-II levels measured in urine samples from 415 healthy controls (169.1±92.3 ng/mmol, p<0.0001). There was no significant difference in the CTX-II response in the placebo group and the glucosamine treated group. However, those with high cartilage turnover presented a significant decrease in CTX-II after 12-month glucosamine treatment. Thus, thee group with CTX II concentrations above normal average + 1SD decreased 15.5 % after 12-month therapy. The 12 months change in CTX-II in OA patients with elevated CTX-II at baseline correlated with the change in average joint space width observed after 36 months (R=0.43, p<0.05). Increased baseline levels of CTX-II were associated with a worsening of the WOMAC index (p<0.01).

Conclusion
The data indicate that measurement of urinary collagen type II C-telopeptide fragments enables the identification of OA patients with high cartilage turnover who at the same time are most responsive to therapy with structure modifying drugs.

Key words
Osteoarthritis, glucosamine sulphate, collagen type II, biochemical marker.

Please address correspondence to: Dr. Stephan Christgau, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, Denmark.
E-mail: sc@nordicbioscience.com