Comparative effect of nimesulide and ibuprofen on the urinary levels of collagen type II C-telopeptide degradation products and on the serum levels of hyaluronan and matrix metalloproteinases-3 and -13 in patients with flare-up of osteoarthritis.
OBJECTIVE
Because in vitro studies have shown that nimesulide not only preferentially inhibits COX-2 but also reduces the action/release of pro-inflammatory cytokines, down-regulates the synthesis and/or activity of collagenase(s), and releases reactive oxygen species and other toxic substances from neutrophils, this study investigated whether nimesulide and ibuprofen could affect levels of biochemical markers of joint inflammation and collagen catabolism in patients with flare-up of knee or hip osteoarthritis.


METHODS
Ninety patients were included in this randomised, prospective, single- blind study. They received either nimesulide (n = 45) or ibuprofen (n = 45) for a 4-week treatment period. The following parameters were analysed by ELISA: urinary levels of C-terminal cross-linking telopeptide of type II collagen (CTX-II), a marker of type II collagen breakdown; serum levels of hyaluronan (HA), a marker of synovial inflammation and hyperplasia; and circulating levels of stromelysin-1 (matrix metalloproteinase-3 [MMP-3]), collagenase-1 (MMP-1) and collagenase-3 (MMP-13). Statistical analysis used was ANOVA.


RESULTS
At the end of the treatment period, nimesulide but not ibuprofen markedly reduced the urinary levels of CTX-II (p < 0.001) and the serum levels of HA (p < 0.05), two markers known to prognosticate poor outcome of the osteoarthritis disease process. Nimesulide also reduced the serum levels of both MMP-3 (p < 0.05) and MMP-13 (p < 0.001). Furthermore, in the nimesulide group, the decrease in levels of CTX-II correlated significantly with the decrease in levels of HA and MMP-13.


CONCLUSIONS
Although nonsteroidal anti-inflammatory drugs are effective in improving pain and disability in OA patients, to date it has been unclear to what extent these drugs could affect joint metabolism and hence joint structure. Patients with flare-up of their osteoarthritis disease process exhibit enhanced levels of markers of joint inflammation and cartilage collagen breakdown, which were markedly decreased by nimesulide but not by ibuprofen.
Manicourt
Daniel-Henri
DH
Department of Rheumatology, Université Catholique de Louvain, Saint-Luc University Hospital Saint-Luc, Brussels, Belgium. manicourt@bchm.ucl.ac.be
Bevilacqua
Maurizio
M
Righini
Velella
V
Famaey
Jean-Pierre
JP
Devogelaer
Jean-Pierre
JP
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003094:Collagen / Q000652:urine*; D024042:Collagen Type I; D024043:Collagen Type II / Q000652:urine; D017364:Collagenases / Q000097:blood; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D007052:Ibuprofen / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D015207:Osteoarthritis, Hip / Q000097:blood / Q000188:drug therapy / Q000652:urine; D020370:Osteoarthritis, Knee / Q000097:blood / Q000188:drug therapy / Q000652:urine; D010455:Peptides / Q000652:urine*; D011446:Prospective Studies; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D010455:Peptides; D013449:Sulfonamides; C052929:collagen type I trimeric cross-linked peptide; D006820:Hyaluronic Acid; D003094:Collagen; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; C012655:nimesulide; D007052:Ibuprofen