阿仑膦酸钠治疗绝经后骨质疏松的效果及与低密度脂蛋白受体相关蛋白5基因N740N多态性的关系研究

摘要

目的 通过分析阿仑膦酸钠治疗绝经后骨质疏松患者骨密度变化及与低密度脂蛋白受体相关蛋白5(LRP5)基因N740N位点多态性的关系,明确该多态性与疗效的关系.方法 本研究为自身前后对照研究,共入选67例绝经后骨质疏松患者,平均年龄(64.2±7.7)岁,口服阿仑膦酸钠70 mg,1次/周,钙尔奇D 600 mg/次,1 次/d,治疗1年.治疗前后分别使用双能X线吸收仪检测第2~4腰椎以及左股骨近端各部位骨密度,利用PCR和琼脂糖凝胶电泳检测LRP5基因N740N多态性.结果 共63例患者完成阿仑膦酸钠1年治疗,第2~4腰椎骨密度上升(4.05±3.39)%、股骨颈骨密度上升(1.05±2.63)%、大转子区骨密度上升(2.00±2.89)%、转子间骨密度上升(2.17±2.62)%、总髋部骨密度上升(1.79±2.29)%;治疗前与治疗后各部位骨密度比较,差异有统计学意义(P＜0.01).本研究人群中LRP5基因N740N位点CC基因型和CT基因型频率分别为65.1%和34.9%.TT基因型未检出,符合Hardy-Weinberg定律.治疗前后大转子区骨密度变化百分比,CC基因型上升(2.53±3.77)%,CT基因型上升(6.35±6.43)%;总髋部骨密度变化百分比,CC基因型上升(1.93±2.33)%,而CT基因型上升(3.79±4.15)%.CC基因型和CT基因型患者治疗前后各部位骨密度比较,差异有统计学意义(P＜0.05).结论 阿仑膦酸钠对于绝经后骨质疏松患者骨密度的提高有显著疗效,腰椎骨密度升高超过髋部,而对于LRP5基因N740N多态性为位点各基因型之间骨密度的分析,发现CT基因型治疗前后大转子和总髋部骨密度变化百分比高于CC基因型,故此基因型疗效较好,提示该基因型与阿仑膦酸钠疗效相关.可进一步扩大样本量并对该基因型多个多态性位点予以证实.%Objective To investigate whether the change of bone mineral density ( BMD ) after one - year alendronate treatment in postmenopausal patients with osteoporosis associates with the N740N polymorphism of low density lipoprotein receptor related protein 5 ( LRP5 ) gene and determine the correlation between genotypes and the therapeutic effect. Methods Totally 67 postmenopausal osteoporotic patients aged ( 64. 2 ±7.7 ) years were recruited. Each patient took oral alendronate ( Forsamax ) 70 mg weekly and caltrate 600 mg daily for 12 months. Bone mass density was measured at lumbar spine 2-4 and left hip sites before and after treatment. PCR - RELP was performed for the N740N polymorphism of low density lipoprotein receptor related protein 5 ( LRP5 ) gene. Results One -year therapy was accomplished in 63 patients. Compared with the baseline level, the post - treatment BMD increased significantly at all sites: BMD increased by ( 4. 05 ± 3. 39 )% at the lumer spine 2 ~4, by ( 1. 05 ± 2. 63 )% at femoral neck, by ( 2. 00 ±2. 89 )% at the torch, by ( 2. 17 ±2. 62 )% at inter - torch, and by ( 1. 79 ±2. 29 )% at total hip ( allP <0. 01 ). In all the 63 patients, the frequencies of CC and CT genotypes were 65. 1% and 34. 9% . TT genotype was not found. The distribution followed the Hardy - Weinberg equilibrium. For the greater trochanter bone density change per- centage after treatment, CC genotype increased by ( 2. 53 ± 3. 77 )% and CT genotype by ( 6. 35 ± 6. 43 )% ; similarly, for the total hip bone mineral density change percentage, CC genotype increased by ( 1. 93 ± 2. 33 )% and CT genotype by ( 3. 79 ± 4. 15 )% . The two genotypes were significantly associated with the percentage of BMD at lumer spine L2 ~4, femoral neck, and inter - torch. Conclusion The BMD increases more remarkably at lumbar spine than at hip sites in postmenopausal osteoporotic Chinese women after one - year alendronate therapy. CT gene type shows a better correlation with alendronate treatment than CC gene type, which should be further validated.