阿仑膦酸钠对绝经后骨质疏松疗效及与雌激素β受体基因AluⅠ多态性的关系

The therapeutic response to Alendronate in Chinese postmenopausal women with osteoporosis and the Alu Ⅰ polymorphism of estrogen receptor β gene

目的通过分析绝经后骨质疏松患者阿仑膦酸钠治疗前后骨密度变化及与雌激素β受体(ESR2)基因Alu I多态位点的关系,明确是否存在与疗效有关的基因型。方法为前瞻性研究,入选80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70mg每周一次及钙尔奇D 600mg每天一次治疗一年。治疗前后分别使用双能X线吸收仪检测腰椎2-4及左股骨近端各部位骨密度,利用PCR-RFLP检测ESR2基因Alu I多态性。结果 67例患者完成阿仑膦酸钠一年治疗,患者腰椎2-4和髋部的骨密度均有显著上升。其中腰椎2-4上升(5.48±4.68)%、股骨颈上升(1.77±4.72)%、大转子区上升(3.81±5.10)%、转子间上升(2.60±3.14)%、总髋部上升(2.50±3.14)%(P值均<0.01);在本研究人群中未发现E3R2基因Alu I位点的AA基因型,Aa基因型和aa基因型频率分别为10.4%和89.6%。治疗前后腰椎和左髋各部位骨密度变化百分比在aa和Aa基因型之间差异均无统计学意义。结论阿仑膦酸钠提高绝经后骨质疏松患者的骨密度疗效显著,腰椎骨密度的升高超过髋部,但骨密度的变化与ESR2基因Alu I多态性不相关,不存在与疗效有关的基因型。可进一步扩大样本量并对该基因多个多态位点进行研究。

Objective To investigate whether the change of BMD after one-year alendronate treatment in postmenapausal women with osteoporosis associates with the Alu Ⅰ polymorphism of estrogen receptor 13 gene （ ESR2 ） and determine the correlation between genotypes and the therapeutic effect. Methods Eighty postmenopausal osteoporosis patients were recruited with the average age of （64. 2 ± 7. 7） years. Every patient took oral Alendronate （Forsamax） 70mg weekly and Caltrate 600mg daily for 12 months. Pre- and post-treatment, bone mass density was measured at lumbar spine 2-4 and left hip sites. PCR-RFLP was performed for the Alu Ⅰ pelymorphism of ESR2 gene. Results One year therapy was accomplished in 67 patients. Compared with the baseline BMD, the post-treatment BMD was increased significantly at all sites. The BMD of lumbar spine 2-4 was increased （5.48 ± 4. 68 ） %, while the BMD of femoral neck was increased （ 1.77 ± 4.72） %, the BMD of troch was increased （3.81 ± 5.10） %, the BMD of inter-troch was increased （2. 60 ± 3.14） % and the BMD of total hip was increased （2. 50±3.14） % （ P 〈0.01 ）. In all 67 patients, no AA genotype was detected. The frequency of Aa and aa genotypes were 10. 4% and 89. 6%. Between Aa and aa genotypes, no significant differences of the base line BMD, the post-treatment BMD and the percentage of BMD changing were found. Conclusion The BMD of lumbar spine was increased more significantly than the BMD of hip sites in Chinese postmenopausal osteoperosis women after one-year alendronate therapy. But there is no correlation between the therapeutic response and the Alu Ⅰ polymorphism of ESR2 gene. Larger sample studies are needed to confirm these results.