老年女性骨质疏松患者血清IGF-1和ET-1水平变化的意义

孙 建, 房义辉, 柳 达

·临床论著·

老年女性骨质疏松患者血清IGF-1和ET-1水平变化的意义

孙 建1, 房义辉1, 柳 达2

目的 探讨老年女性骨质疏松患者血清胰岛素样生长因子-1(IGF-1)和内皮素-1(ET-1)水平变化的意义。方法 选取93例老年女性骨质疏松患者作为病例组,并选取同期50例老年女性健康者作为对照组。采用ELISA法检测血清IGF-1和ET-1水平及骨代谢指标；采用双能X线骨密度(BMD)测量仪对每位研究对象L1～4椎体处和股骨颈的BMD进行检测。采用Pearson相关分析对变量间相关关系进行分析。结果 病例组IGF-1、骨钙素(BGP)、骨碱性磷酸酶(BAP)和BMD水平均低于对照组,而ET-1、Ⅰ型胶原交联羧基端肽(CTX-1)和抗酒石酸酸性磷酸酶5b(TRACP-5b)水平均高于对照组,差异均有统计学意义(P<0.001)。Pearson相关分析显示,病例组血清IGF-1水平与ET-1、CTX-1和TRACP-5b呈负相关(P<0.05),而与BGP、BAP和BMD呈正相关(P<0.05)；病例组血清ET-1水平与BGP、BAP和BMD呈负相关(P<0.05),而与CTX-1和TRACP-5b呈正相关(P<0.05)。结论 老年女性骨质疏松患者血清IGF-1水平降低而ET-1水平升高,且与BMD和骨代谢指标密切相关,可能共同参与了骨质疏松发病过程。

老年人;女性;骨质疏松;胰岛素样生长因子-1;内皮素-1

随着我国人口老龄化加剧,骨质疏松的患病率呈逐年上升趋势;骨质疏松成为患者骨折甚至死亡的重要原因,其中老年女性占了绝大部分,这严重影响老年女性的健康[1]。目前,老年女性发生骨质疏松的发病机制尚未研究清楚。胰岛素样生长因子-1(IGF-1)作为骨骼中含量较多的生长因子,在调控破骨细胞增殖和分化、骨细胞功能、骨代谢等方面发挥重要作用[2],研究表明[3]IGF-1可能与骨质疏松发生过程密切相关。内皮素-1(ET-1)作为缩血管多肽,与血管内皮细胞增殖密切相关[4],研究表明[5]雌激素水平可影响ET-1生物活性而导致微循环血管功能紊乱。笔者选取2013年2月～2015年3月在我院就诊的93例老年女性骨质疏松患者作为研究对象,分析患者血清中IGF-1和ET-1水平变化,探讨两者与骨代谢指标之间的关系,报道如下。

1 材料与方法

1.1 病例与对照资料 病例组93例,年龄65～79(70.4±5.3)岁。患者均符合WHO推荐的骨质疏松诊断标准。排除标准:① 甲状腺、甲状旁腺、糖尿病等内分泌系统疾病者；② 心、肝、肾等重要脏器功能障碍者；③ 恶性肿瘤者；④ 6个月内有服用钙剂、Vit D、肝素及激素类药物者。同期,招募在我院进行健康体检≥65岁的老年女性健康志愿者,均排除骨质疏松及其他骨科疾病,其他排除标准同病例组,最终入选50例作为对照组,年龄65～81(71.2±5.7)岁。本研究通过医院伦理委员会批准,病例组和对照组人员均知情同意。

1.2 方法

1.2.1 血清IGF-1和ET-1水平及骨代谢指标检测 研究对象均抽取晨起空腹静脉血6 ml,3 500 r/min离心15 min,留取血清,保存于-70℃冰箱备检。采用ST-360自动多功能酶标仪(上海科华公司),ELISA法检测血清IGF-1和ET-1水平,以及骨代谢指标骨钙素(BGP)、骨碱性磷酸酶(BAP)、Ⅰ型胶原交联羧基端肽(CTX-1)和抗酒石酸酸性磷酸酶5b(TRACP-5b)指标。人IGF-1和ET-1检测试剂盒均购自上海常斤生物科技有限公司,BGP、BAP、CTX-1和TRACP-5b检测试剂盒均购自上海研生生化试剂有限公司。实验均在标准条件下按照试剂盒操作说明进行。

1.2.2 骨密度(BMD)检测 用双能X线BMD测量仪(美国GE公司)对每位研究对象L1～4椎体处和股骨颈(左侧)的BMD进行检测。参照WHO的标准,骨量正常:T值>-1.0 SD；骨量减少:-2.5 SD

2 结果

2.1 两组一般资料比较 见表1。年龄、绝经时间、体重、体重指数和高血压比例两组比较差异无统计学意义(P>0.05)。

2.2 两组血清IGF-1和ET-1水平及骨代谢指标比较 见表2。IGF-1、BGP、BAP和BMD病例组水平均低于对照组,ET-1、CTX-1和TRACP-5b水平病例组均高于对照组,各项比较差异均有统计学意义(P<0.001)。

2.3 病例组血清IGF-1和ET-1水平与骨代谢指标相关性 见表3。Pearson相关分析显示,病例组血清IGF-1水平与ET-1、CTX-1和TRACP-5b呈负相关(P<0.05),而与BGP、BAP和BMD呈正相关(P<0.05)；病例组血清ET-1水平与BGP、BAP和BMD呈负相关(P<0.05),而与CTX-1和TRACP-5b呈正相关(P<0.05)。

3 讨论

3.1 骨代谢指标与骨质疏松相关性 骨质疏松是由于骨密度降低和骨微结构破坏而导致骨强度降低及骨折风险增加的全身性疾病。骨质疏松发病因素较为复杂,与肥胖、内分泌、遗传、酗酒等多种因素有关[6],但具体机制尚未研究清楚。研究表明[7]绝经后女性骨质疏松发病率显著升高。本研究中病例组与对照组一般资料比较差异无统计学意义,排除了一般情况对研究结果的影响。BGP作为骨基质中主要的非胶原蛋白,是骨形成的特异性标志物[8]；BAP作为非单一的同工酶,可反映人体成骨细胞活性,骨质疏松患者血清水平显著降低；BMD是反映骨质破坏程度的直接指标[8]；CTX-1作为反映破骨细胞活性及骨吸收的指标,是骨转换标志物中首选的风险评估指标[9],TRACP-5b是反映骨吸收及破骨细胞功能的指标[10]。本研究显示,病例组BGP、BAP和BMD水平均低于对照组,而CTX-1和TRACP-5b水平均高于对照组,说明病例组患者骨代谢指标发生了一系列改变,骨形成与骨吸收平衡被打破,从而导致BMD降低,发生骨质疏松。

表1 两组一般资料比较±s)

表2 两组血清IGF-1和ET-1水平及骨代谢指标比较

表3 病例组血清IGF-1和ET-1水平与骨代谢指标相关性

注:*P<0.05

3.2 IGF-1参与骨质疏松发病过程 IGF-1作为骨骼中含量最为丰富的细胞因子,在骨细胞增殖、骨代谢等方能发挥重要作用,研究表明[11]IGF-1可抑制骨吸收并促进骨形成。同时,IGF-1亦可通过促进血管生成因子(VEGF)在成骨细胞中分泌而促进血管新生,为骨生长提高保障[12]。本研究显示,病例组IGF-1水平均低于对照组,说明血清IGF-1水平改变与骨质疏松发病有关,Pearson相关分析显示病例组血清IGF-1水平与CTX-1和TRACP-5b呈负相关(P<0.05),而与BGP、BAP和BMD呈正相关(P<0.05),说明IGF-1参与了骨质疏松发病过程。有研究指出[13],IGF-1参与调控骨代谢取决于机体内雌激素水平。由于绝经后老年女性体内雌激素水平降低,从而影响和干扰了IGF-1分泌,进而影响骨质代谢而促进骨质疏松的发生。

3.3 ET-1参与骨质疏松发病过程 ET-1存在于骨细胞、成骨细胞和破骨细胞,与微循环血管收缩功能密切相关[14]。本研究中病例组ET-1水平高于对照组,Pearson相关分析显示,病例组血清ET-1水平与BGP、BAP和BMD呈负相关(P<0.05),而与CTX-1和TRACP-5b呈正相关(P<0.05),说明ET-1亦参与了骨质疏松发病过程。我们推测,高水平ET-1可对骨组织微循环产生影响,通过破坏血管内皮及改变血流,使血液中的各种微量元素及营养物质无法正常进入骨骼组织，导致骨营养代谢障碍,从而加速骨质疏松病程。

亦有研究指出[15],IGF-1与ET-1在冠心病患者血浆中呈负相关,参与冠心病发病过程。本研究亦发现,病例组血清IGF-1水平与ET-1呈负相关,提示IGF-1和ET-1可能相互影响而参与了骨质疏松发病过程,具体机制尚待进一步研究。

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(接收日期：2016-11-15)

Values of changes of serum IGF-1 and ET-1 levels in aged women with osteoporosis

SUNJian,FANGYi-hui,LIUDa

(DeptofBoneTrauma,ChineseMedicineHospitalofLiaochengCity,Liaocheng,Shandong252000,China)

Objective To investigate the values of changes of serum IGF-1 and ET-1 levels in aged women with osteoporosis. Methods Ninty-three cases of aged women with osteoporosis seemed as the case group and 50 cases of healthy older women seemed as the control group were selected. The serum IGF-1 and ET-1 levels and bone metabolism indexes were detected by using ELISA method. The bone mineral density(BMD) of each subject at the L1～4vertebrae and femoral neck were tested by using dual-energy X-ray absorptiometry measuring instrument. The correlations among variables were analyzed by using pearson correlation analysis. Results The serum levels of IGF-1,BGP, BAP and BMD in case group were lower than the control group, and the serum levels of ET-1, CTX-1 and TRACP-5b were higher than the control group, the differences were statistically significant (P<0.001). Pearson correlation analysis showed that serum levels of IGF-1 in case group were negatively correlated with ET-1, CTX-1 and TRACP-5b (P<0.05), while were positively correlated with BGP, BAP and BMD (P<0.05). The serum levels of ET-1 in case group were negatively correlated with BGP, BAP and BMD (P<0.05), while were positively correlated with CTX-1 and TRACP-5b (P<0.05). Conclusions The serum level of IGF-1 in aged women with osteoporosis is reduced, while the serum level of ET-1 is elevated, and they are closely related with BMD and bone metabolism indexes. They might be involved in the pathogenesis of osteoporosis.

aged;women;osteoporosis;insulin-like growth factor-1;endothelin-1

10.3969/j.issn.1008-0287.2017.01.019

辽宁省自然科学基金(编号:2013021054)

1聊城市中医医院骨创伤科,山东 聊城 2520002中国医科大学第四医院骨科,辽宁 沈阳 110000

孙 建,男,主治医师,主要从事代谢性骨病研究,E-mail:176572191@qq.com

R 681；R 446.112

A

1008-0287(2017)01-0042-04