Drugs in R & D

, Volume 6, Issue 5, pp 261–271 | Cite as

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

  • Daniel-Henri Manicourt
  • Maurizio Bevilacqua
  • Velella Righini
  • Jean-Pierre Famaey
  • Jean-Pierre Devogelaer
Original Research Article


Background and aim: 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, singleblind 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.

Conclusion: 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.



There was no external funding for this article, and the authors have no potential conflicts of interest that are directly relevant to the contents of this article.


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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Daniel-Henri Manicourt
    • 1
    • 2
  • Maurizio Bevilacqua
    • 3
  • Velella Righini
    • 3
  • Jean-Pierre Famaey
    • 4
  • Jean-Pierre Devogelaer
    • 1
  1. 1.Department of RheumatologyUniversité Catholique de Louvain, Saint-Luc University Hospital Saint-LucBrusselsBelgium
  2. 2.Christian de Duve Institute of Cellular PathologyUniversité Catholique de LouvainBrusselsBelgium
  3. 3.Department of EndocrinologyLuigi Sacco HospitalMilanItaly
  4. 4.Department of Physical Therapy and RheumatologyFree University of Brussels and Therabel PharmaBrusselsBelgium

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