1、Hainan Med J,Jul.2023,Vol.34,No.13海南医学2023年7月第34卷第13期唑来膦酸在骨质疏松性髋部骨折患者术后的应用效果高延伟，杨明智，张文生，王涛延安市人民医院骨科，陕西延安716000【摘要】目的观察唑来膦酸在骨质疏松性髋部骨折患者术后的应用效果。方法选择2018年3月至2021年3月延安市人民医院收治的110例骨质疏松性髋部骨折术后患者为研究对象，按照随机数表法分为研究组和对照组各55例，对照组患者采用阿仑膦酸钠治疗，研究组患者采用唑来膦酸治疗，两组患者疗程均为1年，1年后比较两组患者的骨钙素(BGP)，胰岛素样生长因子(IGF-1)水平，骨代谢指标型胶原
2、交联羧基末端肽(CTX)、脱氧吡啶啉(DPD)、性激素结合球蛋白(SHBG)，血清钙(Ca)、磷(P)水平，骨密度，髋关节功能(Harris)，视觉模拟疼痛量表(VAS)评分。结果治疗后，研究组患者的BGP水平为(12.692.30)ng/mL，明显低于对照组的(13.892.41)ng/mL，差异有统计学意义(P0.05)；研究组患者的IGF-1水平为(231.3638.75)ng/mL，明显高于对照组的(212.8936.27)ng/mL，差异有统计学意义(P0.05)；研究组患者的CTX、DPD、SHBG水平为(381.6069.12)pg/mL，(89.0312.63)ng/mL，(3
3、9.977.86)ng/mL，均明显低于对照组的(426.8175.36)pg/mL、(97.1015.51)ng/mL、(46.069.32)ng/mL，差异均有统计学意义(P0.05)；研究组患者的VAS评分为(4.920.76)分，明显低于对照组的(5.190.65)分，差异有统计学意义(P0.05)。结论唑来膦酸在骨质疏松性髋部骨折患者术后的应用效果比阿仑膦酸钠更具优势，可有效调整骨代谢水平，持续抑制骨吸收，缓解骨疼痛。【关键词】骨质疏松性髋部骨折；唑来膦酸；阿仑膦酸钠；骨代谢；骨密度；髋关节功能【中图分类号】R683.42【文献标识码】A【文章编号】10036350（2023）131
4、86105Effect of zoledronic acid on patients with osteoporotic hip fracture after operation.GAO Yan-wei,YANGMing-zhi,ZHANG Wen-sheng,WANG Tao.Department of Orthopedics,Yanan Peoples Hospital,Yanan 716000,Shaanxi,CHINA【Abstract】ObjectiveTo observe the effect of zoledronic acid on patients with osteopor
5、otic hip fracture afteroperation.MethodsA total of 110 patients with osteoporotic hip fractures after operation who received treatment inYanan Peoples Hospital from March 2018 to March 2021 were selected for this study.According to the simple draw-ing of lots,they were divided into a study group and
6、 a control group,each with 55 cases.Patients in the control groupwere treated with alendronic acid sodium,while those in the study group were treated with zoledronic acid,both for atreatment course of 1 year.After treatment,the levels of osteocalcin(BGP),insulin-like growth factor(IGF-1),bonemetabol
7、ism indexes type I collagen crosslinked carboxy terminal peptide(CTX),deoxypyridinoline(DPD),sex hor-mone binding globulin(SHBG),serum calcium(CA),phosphorus(P),bone mineral density,hip function(Harris),andVisual Analogue Scale score(VAS)were compared between the two groups.ResultsAfter treatment,th
8、e BGP levelof the study group was(12.692.30)ng/mL,which was significantly lower than(13.892.41)ng/mL in the controlgroup(P0.05).The level of IGF-1 in the study group was(231.3638.75)ng/mL,which was significantly higher than(212.8936.27)ng/mL in the control group(P0.05).The levels of CTX,DPD,and SHBG
9、 in the study group were(381.6069.12)pg/mL,(89.0312.63)ng/mL,(39.977.86)ng/mL,which were significantly lower than(426.8175.36)pg/mL,(97.1015.51)ng/mL,(46.069.32)ng/mL in the control group(P0.05).The VAS score of the studygroup was(4.920.76)points,which was significantly lower than(5.190.65)points in
10、 the control group(P0.05)，且具有可比性，见表1。表1两组患者一般资料比较x-s，例(%)Table 1Comparison of general data between the two groups x-s，n(%)组别研究组对照组t/2值P值例数5555男性32(58.18)31(56.36)女性23(41.82)24(43.64)0.0370.847年龄(岁)69.525.1968.935.150.5980.551病程(年)5.181.235.091.260.3790.705左侧37(67.27)35(63.64)右侧18(32.73)20(36.36)0.16
11、10.688患侧性别1.2治疗方法两组患者术后均给予常规口服药物治疗。对照组患者在此基础上给予阿仑膦酸钠(生产厂家：石药集团欧意药业有限公司，规格：70 mg，国药准字：H20061303)治疗，1次/周，70 mg/次。研究组患者在术后1周给予静脉滴注唑来膦酸(生产厂家：正大天晴药业集团股份有限公司，规格，国药准字：H20041346)治疗，5 mg/次，连续治疗12个月。两组患者疗程均为1年。1.3观察指标与评价方法(1)胰岛素样生长因子(insulin like growth factor，IGF-1)和骨钙素(bone-car-boxyglutamic acid-containing
12、protein，BGP)水平：于治疗前及治疗1年后，采集两组患者的静脉血，离心分离血清后等待检测，采用ELISA检测BGP 和IGF-1水平。(2)骨代谢指标：于治疗前及治疗1年后采集患者静脉血，离心分离血清后等待检测，采用ELISA检测型胶原交联羧基末端肽(hydroxy-terminal peptide degra-dation product of type collagen，CTX)、脱氧吡啶啉(deoxypyridinoline，DPD)、性 激素 结 合球 蛋 白(sexhormone-binding globulin，SHBG)水平。(3)血清钙(Ca)、磷(P)水平：于治疗前及
13、治疗1年后，采集患者静脉血，离心分离血清后等待检测，采用全自动生化分析仪(型号：ADVIA1800)检测Ca、P水平。(4)骨密度、髋关节功能 和疼 痛程 度：于 治疗前及 治疗 1 年后采用CHALLENGER双能线骨密度仪测量两组患者的骨密度。患者髋关节功能采用Harris量表评估，分值为100分，70分为差，7079分为可，8089分为良，90分以上为优。患者的疼痛程度评估采用视觉模拟疼痛量表(VAS)评分，分值为010分，分数越高表明疼痛程度越严重。1.4统计学方法应用SPSS18.0统计软件进行数据分析。计数资料比较采用2检验，计量资料以均数标准差(x-s)表示，组间比较采用t检验。
14、以P0.05)；治疗1年后，两组患者BGP水平均明显降低、IGF-1 水平均明显上升，且研究组患者的IGF-1水平明显高于对照组，BGP水平明显低于对照组，差异均有统计学意义(P0.05)，见表2。1862Hainan Med J,Jul.2023,Vol.34,No.13海南医学2023年7月第34卷第13期表2两组患者治疗前后BGP、IGF-1水平比较(x-s，ng/mL)Table 2Comparison of BGP and IGF-1 levels between the twogroups before and after treatment(x-s,ng/mL)组别研究组对照组t
15、值P值例数5555治疗前16.022.8115.852.750.3210.749治疗后12.692.30a13.892.41a2.6710.009治疗前196.0134.90195.8734.670.0210.983治疗后231.3638.75a212.8936.27a2.5810.011BGPIGF-1注：与本组治疗前比较，aP0.05。Note:Compared with that in the same group before treatment,aP0.05)。治疗1年后，两组患者骨密度无明显变化；VAS评分均明显降低，Har-ris评分均明显上升，差异具有统计学意义(P0.05)，
16、且研究组VAS评分更低，差异具有统计学意义(P0.05)，见表5。表4两组患者治疗前后的Ca、P水平比较(x-s，nmol/L)Table 4Comparison of Ca and P levels between the two groupsbefore and after treatment(x-s,nmol/L)组别研究组对照组t值P值治疗前2.180.162.200.170.6350.527治疗后2.300.232.270.220.6990.486例数5555治疗前1.560.291.570.300.1780.859治疗后1.510.261.470.230.8550.395CaP表3
17、两组患者治疗前后的骨代谢指标比较(x-s)Table 3Comparison of bone metabolism indexes between two groups before and after treatment(x-s)组别研究组对照组t值P值例数5555治疗前523.9890.21522.8990.130.0630.950治疗后381.6069.12a426.8175.36a3.2790.001治疗前108.9718.26109.2318.300.0750.941治疗后89.0312.63a97.1015.51a2.9920.003治疗前53.1010.6253.2910.570
18、.0940.925治疗后39.977.86a46.069.32a3.7040.001CTX(pg/mL)DPD(ng/mL)SHBG(ng/mL)注：与本组治疗前比较，aP0.05。Note:Compared with that in the same group before treatment,aP0.05.表5两组患者治疗前后的骨密度、髋关节功能和疼痛程度比较(x-s)Table 5 Comparison of bone density,hip joint function,and pain level between the two groups before and after tr
19、eatment(x-s)组别研究组对照组t值P值治疗前1.570.281.600.300.5420.589治疗后1.420.261.390.230.6410.523例数5555治疗前42.915.3142.865.290.0490.961治疗后65.297.0364.076.890.9190.360骨密度(g/cm2)Harris(分)治疗前6.610.806.630.820.1290.897治疗后4.920.76a5.190.65a2.0020.048VAS(分)注：与本组治疗前比较，aP0.05。Note:Compared with that in the same group befor
20、e treatment,aP0.05)；治疗 1 年后，两组患者的 CTX、DPD、SHBG水平均明显降低，且研究组患者的CTX、DPD、SHBG水平明显低于对照组，差异均有统计学意义(P0.05)，见表4。1863海南医学2023年7月第34卷第13期Hainan Med J,Jul.2023,Vol.34,No.13类药物后，降低破骨细胞功能，减弱骨破坏作用，从而能够保留更多的骨骼，减少过多的骨质溶解，减少骨质疏松17-18。药理学表明，阿仑膦酸能够密切地接触骨骼，当破骨细胞逐渐融骨时，会对破骨细胞产生作用19。阿仑膦酸钠为口服用药，口服生物利用度低，持久性较弱20。研究表明，唑来膦酸属于
21、双膦酸盐，在药动力学方面，唑来膦酸为静脉用药，具有较高的生物利用度，其抑骨吸收活性分别为第一、二代双膦酸盐类药物的2 000倍和100倍，可使其与骨表面羟磷灰石具有更强的结合力，能够增强抑破骨细胞能力，较其他的双膦酸盐可减少用药频次21-22。唑来膦酸可减少合成破骨细胞内微小结构蛋白，导致破骨细胞丧失或凋亡23。BGP能够稳定且不受骨吸收影响，通过该指标可了解成骨细胞，常作为反映成骨活性的特异性指标。IGF-1是一组具有促进生长作用的多肽类物质，广泛分布于人体的各器官组织中，是一类广谱性的促生长因子，是骨生成的强刺激因子，具有增强成骨细胞活性、刺激型胶原的合成和骨骼细胞的有丝分裂、抑制骨胶原降
22、解的作用，可有效维持骨量24-25。本研究结果显示，研究组患者的BGP、IGF-1改善情况明显优于对照组，差异有统计学意义(P0.05)，说明唑来膦酸在改善患者术后骨质疏松方面效果更好。本研究结果还显示，研究组患者CTX、DPD、SHBG水平明显低于对照组，差异有统计学意义(P0.05)，说明唑来膦酸能够缓解患者术后骨丢失，且不会对髋关节功能恢复造成影响。研究组患者VAS评分明显低于对照组，差异有统计学意义(P0.05)，说明唑来膦酸在缓解患者疼痛方面优于阿仑膦酸钠。综上所述，唑来膦酸在骨质疏松性髋部骨折患者术后应用可有效改善患者的骨代谢，缓解骨密度下降，且对髋关节功能恢复无影响。但由于本研究
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