[骨保护素基因多态性与绝经后骨质疏松症女性对阿仑膦酸钠的治疗反应]

[Osteoprotegerin gene polymorphism and therapeutic response to alendronate in postmenopausal women with osteoporosis].

作者信息

Wang Chun, He Jin-wei, Qin Yue-juan, Zhang Hao, Hu Wei-wei, Liu Yu-juan, Zhang Zhen-lin

机构信息

Department of Osteoporosis, Metabolic Bone Disease and Genetic Research Unit, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2009 Nov 17;89(42):2958-62.

PMID:20137703

Abstract

OBJECTIVE

To investigate whether the polymorphism of osteoprotegerin (OPG) gene is associated with the change of BMD (bone mineral density) after alendronate therapy in postmenopausal women with osteoporosis and determine the correlation between genotypes and therapeutic effect.

METHODS

Eighty postmenopausal osteoporotic patients were recruited with an average age of (64.2 +/- 7.7) years old. Every patient took oral alendronate (Fosamax) 70 mg weekly and Caltrate 600 mg daily for 12 months. At pre- and post-treatment, BMD was measured at lumbar spine 2 - 4 and hip sites. PCR-RFLP was performed for three polymorphisms at the promoter site of OPG gene (A163G, T245G and T950C).

RESULTS

One-year therapy was accomplished in 67 patients. Patients with G allele (genotype AG and GG) of site A163G, the baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype AA [(0.732 +/- 0.113) g/cm(2) vs (0.819 +/- 0.157) g/cm(2), (0.775 +/- 0.101) g/cm(2) vs (0.843 +/- 0.124) g/cm(2) and (0.667 +/- 0.105) g/cm(2) vs (0.725 +/- 0.091) g/cm(2)]. Patients with G allele (genotype TG and GG) of site T245G, baseline BMD of vertebral L2-4, inter-troche and total hip were lower than genotype TT [(0.723 +/- 0.111) g/cm(2) vs (0.819 +/- 0.155) g/cm(2), (0.776 +/- 0.102) g/cm(2) vs (0.840 +/- 0.124) g/cm(2) and (0.670 +/- 0.109) g/cm(2) vs (0.721 +/- 0.091) g/cm(2)]. After one-year therapy, at site A163G, the percentage of BMD change at inter-troche was higher in genotype AA than in genotypes AG and GG [2.50 (3.47)% vs 0.88% (3.47%)%, P = 0.014]. While at site T245G, the percentage of BMD change at inter-troche and total hip were higher in genotype TT than in genotype TG and GG 2.50% (3.47%) vs 0.61% (3.31%), P = 0.011; 2.72% (2.68%) vs 0.89 (3.01%), P = 0.046].

CONCLUSION

The G allele of sites A163G and T245G may be the risk allele of postmenopausal osteoporosis. Furthermore, patients with genotypes AA (A163G) and (T245G) show a better therapeutic effect to alendronate.

摘要

目的

探讨绝经后骨质疏松症妇女阿仑膦酸钠治疗后骨保护素（OPG）基因多态性与骨密度（BMD）变化的关系，并确定基因型与治疗效果之间的相关性。

方法

招募80例绝经后骨质疏松症患者，平均年龄（64.2±7.7）岁。每位患者每周口服阿仑膦酸钠（福善美）70mg，每日口服钙尔奇600mg，共12个月。治疗前后，测量腰椎2-4和髋部的骨密度。对OPG基因启动子位点的三个多态性（A163G、T245G和T950C）进行聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析。

结果

67例患者完成了一年的治疗。A163G位点具有G等位基因（基因型AG和GG）的患者，L2-4椎体、转子间和全髋的基线骨密度低于基因型AA的患者[（0.732±0.113）g/cm²对（0.819±0.157）g/cm²，（0.775±0.101）g/cm²对（0.843±0.124）g/cm²，（0.667±0.105）g/cm²对（0.725±0.091）g/cm²]。T245G位点具有G等位基因（基因型TG和GG）的患者，L2-4椎体、转子间和全髋的基线骨密度低于基因型TT的患者[（0.723±0.111）g/cm²对（0.819±0.155）g/cm²，（0.776±0.