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Cartilage degradation in knee osteoarthrithis patients with elevated levels of urinary collagen type II C-Telopeptide fragments.


Stephan Christgau: 1, Yves Henrotin: 2, Dennis Henriksen: 1, Lucio Rovati: 3, Julien Collette: 2, Rita Deroisy: 2, Claus Christiansen: 4, Jean-Yves Reginster: 2

1)Osteometer BioTech, Herlev, Denmark

2)Bone and Cartilage Metabolism, University of Liège, Liège, Belgium

3)Rotta Research Laboratories, Monza, Italy

4)Center for Clinical and Basic Research, Ballerup, Denmark

Fragments of collagen type II were measured in urine samples from 212 patients suffering from knee osteoarthritis (OA). The measurements were performed with a new ELISA, specific for a fragment from the C-telopeptide of collagen type II (CartiLaps,CL). The patients were participating in a double blind placebo controlled prospective study assessing the effects of glucosamine sulphate (GAS) on OA symptoms and joint structure. Study subjects were sampled for biochemical assessment at baseline and after 12 months of therapy. Clinical as well as radiological examinations were carried out at baseline and after 36 months for determination of WOMAC score as well as knee joint space width. At baseline the patients had an average concentration of urinary collagen type II C-telopeptide fragments (CL)of 0.22 ±0.16 nM/mmol creatinine.

This was significantly above the CL concentration measured in urine samples from 659 age and sex matched controls (0.17 ±0.1 nM/mmol,p<0.0001). Baseline CL concentration n the patient group varied from 0.01 to 1.3 nM/mmol. There was no significant difference in the CL response in the placebo group and the GAS treated group among the complete study cohort. However, when the patients were divided according baseline CL concentration, individuals with CL concentration above normal average +1SD showed a significant decrease in CL after 12 months GAS treatment of 15.5% compared with the placebo treated group which showed an increase in CL concentration of 17.7%. The 12 months change in CL in this group correlated with the change in average joint space width observed after 36 months (R=0.36,p=0.014). Increased baseline levels of CL were associated with a worsening of the WOMAC pain scoring index (p=0.0023).

In conclusion, the data indicate that measurement of urinary Collagen type II C-telopeptide fragments by the newly developed CartiLaps assay enables an assessment of the current status of cartilage degradation in the individual. OA patients with elevated baseline CL levels showed a significant response to the GAS therapy compared to patients with low baseline CL concentration and to placebo treated women. Furthermore the response correlated with the long-term radiological progression in the patients.