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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

机译:尼美舒利和布洛芬对骨关节炎急性发作患者尿液中II型C-四肽胶原降解产物以及透明质酸和基质金属蛋白酶3和-13的影响

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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 col-lagenase(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. 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.
机译:背景与目的:由于体外研究表明尼美舒利不仅能优先抑制COX-2,而且能降低促炎细胞因子的作用/释放,下调胶原酶的合成和/或活性,并且释放中性粒细胞中的活性氧和其他有毒物质,本研究调查了尼美舒利和布洛芬是否会影响膝关节或髋关节骨关节炎发作的患者关节炎症和胶原分解代谢的生化指标。方法:本研究纳入90名患者他们接受了尼美舒利(n = 45)或布洛芬(n = 45)治疗4周的随机,前瞻性,单盲研究.ELISA分析了以下参数:C末端交联尿液水平II型胶原的端肽(CTX-II),II型胶原分解的标志物,透明质酸(HA)的血清水平,滑膜炎症和增生的标志物以及stromelysin-1(ma的循环水平)结果:在治疗期结束时,尼美舒利但不显着增加布洛芬的使用。统计分析为ANOVA。结果:降低了CTX-II的尿水平(p <0.001)和血清HA的水平(p <0.05),这两个已知可预示骨关节炎疾病过程预后不良的标志物。尼美舒利还降低了两种MMP-3的血清水平( p <0.05)和MMP-13(p <0.001)。此外,在尼美舒利组,CTX-II的水平降低与HA和MMP-13的水平显着相关。结论:尽管非甾体类抗炎药可有效改善OA患者的疼痛和残疾,但迄今为止尚不清楚这些药物在多大程度上可影响关节代谢并进而影响关节结构。骨关节炎疾病过程突然发作的患者表现出尼美舒利显着降低了关节炎症和软骨胶原蛋白降解的标志物水平,而布洛芬则未显着降低。

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