Miheller Pál, Muzes Györgyi, Zágoni Tamás, Tóth Miklós, Rácz Károly, Tulassay Zsolt
Semmelweis Egyetem, Altalános Orvostudományi Kar, II. Belgyógyászati Klinika, Budapest.
Orv Hetil. 2005 Jul 10;146(28):1477-80.
Osteoporosis has received increasing attention as a potential complication of Crohn's disease. Among cytokines tumor necrosis factor-alpha plays a pivotal role in the pathogenesis of inflammatory bowel diseases by inducing a wide variety of inflammatory responses, including bone resorption. Only few data are present about the effect of infliximab on bone metabolism.
The authors evaluated the effect of infliximab on bone metabolism in patients with Crohn's disease.
Twenty seven patients (17 females, 10 males, mean age 32.58 yrs) with refractory fistulizing Crohn's disease were treated with a series of three infusions of 5 mg infliximab per kg at weeks 0, 2, and 6. Biochemical markers of bone formation (osteocalcin) and bone resorption (beta-CrossLaps) were measured before administration of each infliximab infusion. 54 patients were studied with inactive Crohn's disease (Crohn's disease activity index < 150) as a control.
There were significant differences in beta-CrossLaps concentrations (ng/ml) between the day 0 and 14 (0.57 +/- 0.32 vs. 0.46 +/- 0.29, p < 0.01) and the day 0 and 42 (0.57 +/- 0.32 vs. 0.45 +/- 0.26, p < 0.05). The osteocalcin levels significantly increased from day 0 to day 42 (21.31 +/- 12.14 vs. 25.64 +/- 16.97, p < 0.05). The serum beta-CrossLaps and osteocalcin levels were 0.47 +/- 0.24, 27.2 +/- 8.44 in the control group respectively. These results differed from the serum levels of active patients before the treatment, but there were no notable differences at the day 42.
Infliximab therapy in Crohn's disease patients displayed a rapid influence on bone metabolism by enhancing bone formation and decreasing bone resorption. In addition to its mucosal effect affecting the bone homeostasis, indicate a further rationale usage of tumor necrosis factor-alpha blockade in the therapy of inflammatory bowel diseases.
骨质疏松作为克罗恩病的一种潜在并发症日益受到关注。在细胞因子中,肿瘤坏死因子-α通过引发包括骨吸收在内的多种炎症反应,在炎症性肠病的发病机制中起关键作用。关于英夫利昔单抗对骨代谢的影响,目前仅有少量数据。
作者评估了英夫利昔单抗对克罗恩病患者骨代谢的影响。
27例(17例女性,10例男性,平均年龄32.58岁)难治性瘘管型克罗恩病患者在第0、2和6周接受了3次每千克5毫克英夫利昔单抗的输注治疗。在每次输注英夫利昔单抗前,测量骨形成(骨钙素)和骨吸收(β-交联C端肽)的生化标志物。54例非活动期克罗恩病患者(克罗恩病活动指数<150)作为对照进行研究。
第0天和第14天之间β-交联C端肽浓度(纳克/毫升)存在显著差异(0.57±0.32对0.46±0.29,p<0.01),第0天和第42天之间也有显著差异(0.57±0.32对0.45±0.26,p<0.05)。骨钙素水平从第0天到第42天显著升高(21.31±12.14对25.64±16.97,p<0.05)。对照组血清β-交联C端肽和骨钙素水平分别为0.47±0.24、27.2±8.44。这些结果与治疗前活动期患者的血清水平不同,但在第42天时无显著差异。
克罗恩病患者接受英夫利昔单抗治疗通过增强骨形成和减少骨吸收对骨代谢产生快速影响。除了其影响骨稳态的黏膜效应外,这表明肿瘤坏死因子-α拮抗剂在炎症性肠病治疗中有进一步合理应用的依据。