Manicourt Daniel-Henri, Azria Moïse, Mindeholm Linda, Thonar Eugene J-M, Devogelaer Jean-Pierre
St. Luc University Hospital and Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium.
Arthritis Rheum. 2006 Oct;54(10):3205-11. doi: 10.1002/art.22075.
To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis.
In this randomized, double-blind trial, patients received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18) daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX-II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1 [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included nonparametric tests.
A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13.
By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA.
评估口服鲑鱼降钙素(sCT)对膝骨关节炎患者Lequesne algofunctional指数评分及关节代谢生物标志物的影响。
在这项随机双盲试验中,患者连续84天每日接受安慰剂(n = 18)、0.5 mg sCT(n = 17)或1 mg sCT(n = 18)治疗。生物标志物包括II型胶原C末端肽(CTX-II)、II型胶原新表位C2C、胶原酶(基质金属蛋白酶1 [MMP-1]、MMP-8和MMP-13)、基质溶解素(MMP-3)、金属蛋白酶组织抑制剂1和2以及透明质酸。统计分析采用非参数检验。
共有41例患者完成研究(接受0.5 mg sCT组13例,其他两组各14例)。虽然在第84天,安慰剂组和接受1 mg sCT组患者的疼痛评分均显著下降,但仅在两个sCT组中观察到功能评分显著降低。在第84天,安慰剂组生物标志物水平无显著下降,而在两个sCT组中观察到MMP-3和透明质酸水平均显著降低。接受1 mg sCT的患者组中,CTX-II、C2C和MMP-13水平显著下降。
口服1 mg剂量的sCT通过改善功能障碍以及降低被认为可预测关节间隙变窄(进而软骨丢失)的生物标志物水平,可能是治疗人类膝骨关节炎的一种有效药物。