Effects of ibuprofen on molecular markers of cartilage and synovium turnover in patients with knee osteoarthritis.
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 After an initial screening visit, patients were withdrawn from their pre-study NSAID and, following a flare of their OA symptoms, were randomised to ibuprofen (2400 mg/day) or placebo.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).


CONCLUSIONS
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.
Gineyts
E
E
INSERM Research Unit 403, Hopital Edouard Herriot, Pavillon F, Place d'Arsonval, 69003 Lyon, France. gineyts@lyon.inserm.fr
Mo
J A
JA
Ko
A
A
Henriksen
D B
DB
Curtis
S P
SP
Gertz
B J
BJ
Garnero
P
P
Delmas
P D
PD
D000208:Acute Disease; D000368:Aged; D000596:Amino Acids / Q000652:urine*; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D002356:Cartilage / Q000276:immunology / Q000378:metabolism; D003094:Collagen / Q000652:urine*; D024042:Collagen Type I; D005260:Female; D005697:Galactosides / Q000652:urine*; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D010455:Peptides / Q000652:urine*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism
D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D024042:Collagen Type I; D005697:Galactosides; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C039434:galactosylpyridinoline; D003094:Collagen; D007052:Ibuprofen