Effects of ibuprofen on molecular markers of cartilage and synovium turnover in patients with knee osteoarthritis.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the effect of ibuprofen on the urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) and urinary glucosyl galactosyl pyridinoline (Glc-Gal-PYD), two new molecular markers of cartilage and synovial tissue metabolism, respectively, in patients with knee osteoarthritis (OA).

METHODS:

We studied 201 patients with knee pain and radiographic evidence of knee OA who were on treatment with non-steroidal anti-inflammatory drugs (NSAIDs) prior to study initiation. After an initial screening visit, patients were withdrawn from their pre-study NSAID and, following a flare of their OA symptoms, were randomised to ibuprofen (2400 mg/day) or placebo. Urinary CTX-II and Glc-Gal-PYD levels were measured at time of randomisation (baseline) and after 4-6 weeks of treatment.

RESULTS:

After 4 to 6 weeks, urinary CTX-II (+17%, p = 0.023) and Glc-Gal-PYD (+10%, p = 0.020) increased significantly from baseline in the placebo group whereas marginal or no increase was observed in the ibuprofen group (CTX-II +2%, NS and Glc-Gal-PYD +4%, p = 0.045). For urinary CTX-II, the difference in the change from baseline between placebo and ibuprofen treated groups was significant (13%, p = 0.017). At baseline, urinary levels of CTX-II and Glc-Gal-PYD were higher in patients with knee swelling (n = 127) than in those without (n = 74) (p<0.02 for both markers). When patients were stratified according to presence or absence of knee swelling at baseline, the increases over 4-6 weeks of urinary CTX-II and Glc-Gal-PYD in the placebo group were restricted to patients with knee swelling (+22% from baseline, p = 0.001 and +12%, p = 0.011, for urinary CTX-II and Glc-Gal-PYD respectively). In patients with knee swelling who were treated with ibuprofen this increase was not observed and the difference from placebo was significant for urinary CTX-II (p = 0.014).

CONCLUSION:

In patients with a flare of knee OA, specifically in patients with evidence of joint inflammation documented by knee swelling, there was a significant increase in markers reflecting cartilage and synovium metabolism that could partly be prevented by high doses of ibuprofen. These data suggest that patients with a flare of knee OA are characterised by increased cartilage and synovial tissue degradation, which may be partly prevented by high doses of NSAIDs.

• Authors: E Gineyts, J A Mo, A Ko, D B Henriksen, S P Curtis, B J Gertz, P Garnero, P D Delmas
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 63 Issue 7 Pg. 857-61 (Jul 2004) ISSN: 0003-4967 [Print] England
• PMID: 15194584 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Amino Acids
• Anti-Inflammatory Agents, Non-Steroidal
• Biomarkers
• Collagen Type I
• Galactosides
• Peptides
• collagen type I trimeric cross-linked peptide
• galactosylpyridinoline
• Collagen
• Ibuprofen

Topics

• Acute Disease
• Aged
• Amino Acids (urine)
• Analysis of Variance
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Biomarkers (urine)
• Cartilage (immunology, metabolism)
• Collagen (urine)
• Collagen Type I
• Female
• Galactosides (urine)
• Humans
• Ibuprofen (therapeutic use)
• Male
• Middle Aged
• Osteoarthritis, Knee (blood, drug therapy, immunology)
• Peptides (urine)
• Synovial Membrane (immunology, metabolism)