【作者】 李晓峰；

【导师】 陈允震；

【作者基本信息】 山东大学 ， 外科学（骨外科）， 2017， 硕士

【摘要】 研究背景:骨质疏松症(Osteoporosis,OP)是一种全身性骨代谢障碍性疾病,其特征是骨密度(BMD)降低及骨组织显微结构的恶化,随之骨的脆性增加及骨折风险比例增高。目前治疗骨质疏松的药物根据其作用机制的不同,主要分为抗骨吸收药物与促骨形成药物。对于处于不同骨转换状态的患者,在抗骨吸收药物与促骨形成药物之间,究竟哪种药会获益更多,目前尚未见到临床研究报道。目的:本研究旨在:积极对比不同作用机理的药物在不同骨转换状态的患者中的疗效,探究骨转换标志物对原发性骨质疏松症药物治疗的指导作用。方法:1.病历资料本次收集的研究对象来自2015年6月至2016年6月,于山东大学齐鲁医院骨科门诊及住院诊治的骨质疏松症患者125例,其中56例符合以下标准纳入本研究,其中男6例,女50例。年龄分布60-78岁之间,平均68.7±6.1岁。2.分组及治疗分组标准:根据骨吸收指标β-crossLaps及骨形成指标PINP测量值进行分组。①低骨转换组:β-crossLaps与PINP均降低(n=30例);②高骨转换组:以β-crossLaps增高为主伴PINP正常或降低(n=26例)。治疗方法:低、高骨转换组,每组随机均分为2种治疗方案,分别给予特立帕肽(PTH 1-34)2(μg/d及唑来膦酸注射液5mg/year。所有入组者均口服骨化三醇胶囊0.5μg/d,钙尔奇D片600mg/d。3观察评价指标3.1骨转换标志物全部入组患者均在治疗前、治疗后1个月、3个月、6个月后,清早空腹收集血样,检测骨形成指标PINP与骨吸收指标β-crossLaps。3.2腰椎与股骨颈骨密度测量采用Hologic QDR双能X线骨密度测量仪,根据统一的国际标准BMD低于同性别、同种族峰值骨量均值的2.5个标准差,即T-Score(T值(?)2.5SD),测量每个入组者治疗前及治疗6个月后腰椎(L1-4)与股骨颈骨密度(BMD)。3.3骨痛评估采用视觉模拟评分(Visual analogue scale,VAS),所有入组者分别与治疗前、治疗3个月后、6个月后,排除外界干扰,患者自身根据视觉模拟疼痛评分标准评估疼痛程度:0分无痛;1-4分轻度疼痛;4-6分中度疼痛:7-10重度疼痛。3.4统计学方法采用Graphpad Prism 5.0数据处理软件及SPSS 19.0统计学软件,对治疗组的数据进行了分析,其中包括所有参与者的基础数据。计量资料采用t检验分析,计数资料以x ±S表示,多组数据采用单因素方差分析,P<0.05为差异有统计学意义。结果:1.在高、低骨转换组中,特立帕肽治疗后P1NP与β-crossLaps均较治疗前浓度升高,唑来膦酸治疗后P1NP与β-crossLaps均较治疗前浓度降低。低骨转换组应用特立帕肽后P1NP与β-crossLaps检测值较唑来膦酸升高明显(P<0.05)。高骨转换组应用唑来膦酸后P1NP与β-crossLaps检测值较特立帕肽显著降低(P<0.05)。2.治疗6个月后,低骨转换组特立帕肽治疗后腰椎BMD升高较唑来膦酸显著(P<0.05);高骨转换组唑来膦酸治疗后股骨颈BMD升高较特立帕肽显著(P<0.05)。3.治疗6个月后,低骨转换组特立帕肽治疗后骨痛缓解优于唑来膦酸(P<0.05),高转换组中两种药物均能缓解骨痛,统计学无显著差异(P>0.05)。结论:1.在骨质疏松症治疗中,骨转换标志物可以作为药物选择的依据。2.低骨转换状态下以促成骨药物为主;高骨转换状态下以抑制骨吸收药物为主。更多还原

【Abstract】 Background:Osteoporosis(Osteoporosis,OP)is a kind of systemic bone metabolic disorder characterized by reduced bone mineral density(BMD)and deterioration of bone tissue microstructure,increases the bone brittleness and increased fracture risk ratio.The treatment of osteoporosis drugs according to its mechanism of action,mainly divides into the bone absorption of drugs and promote bone formation.For patients in different bone transformation,promote bone formation in bone resorption drug resistance and drug,what kind of medicine will benefit more,has yet to meet clinical study reports.Objective:Positive contrast promote bone formation drugs and inhibiting bone resorption under the different bone metabolism in patients,analysis of bone metabolic changes,to explore an accurate and effective treatment way for osteoporosis drug treatment.Methods:1 The Medical RecordsThe research object of this collected from June 2015 to June 2016,in shandong university qilu hospital orthopaedic outpatient and hospitalization diagnosis and treatment of 125 patients with osteoporosis,56 cases meet the following criteria included in this study,6 cases of male,female 50 cases.Age distribution between the ages of 60-78,an average of 68.7 +/-6.1 years old.2 Group and the TreatmentGroup standard:according to the β-crossLaps bone absorption index and bone formation index PINP measurements grouping.(1)low bone transform group:β-crossLaps and PINP decreases(n = 30);(2)high bone transform group:give priority to with higher β-crossLaps with PINP normal or reduce(n = 26).Treatment:low and high bone transformation group,each group randomly were divided into two kinds of treatments,respectively Teriparatide(PTH 1-34)20μg/d and Azole phosphonic acid injection 5 mg/year.All the groups of oral capsule of calcitriol 0.5 μg/day,calcium he D 600 mg/day.3 Observe the Evaluation Indicators3.1 Bone turnover markersAll treatment before and after treatment in patients with 1 month,3 months,6 months later,in the morning on an empty stomach blood collection,test bone formation index of PINP and bone absorption index of P-crossLaps.3.2 Lumbar spine and Femoral neck BMD assessmentIn the trial,BMD at Lumbar spine(L1-L4)and Femoral neck was assessed by dual-energy X-ray absorptiometry(DXA,Hologic QDR).Measurements were performed at baseline and 6 month after the beginning of the treatment.3.3 Back Pain VAS Score AssessmentPatients assess their back pain at baseline,at 3 and 6 months,using the VAS score for pain:0 painless;1-4 mild;4 to 6 moderate;7-10 severe pain.3.4 Statistical AnalysisStatistics were calculated with GraphPad Prism 5.0 and the Statistical Package for Social Science for Windows(SPSS)19.Mean and standard deviation(SD)were calculated for continuous variables.Measurement data using t-test analysis and multiple sets of data using one-way ANOVA.A p-value<0.05 was considered statistically significant.Results:1.In both group,the level of PINP and β-crossLaps were significantly increased from baseline during the therapy with teriparatide;the level of P1NP and P-crossLaps were significantly reduced from baseline during the therapy with zoledronic acid.In low bone turnover group,the measurements of PINP and β-crossLaps increasing faster treated with teriparatide than zoledronic acid(P<0.05).In low bone turnover group,the measured value of P1NP and β-crossLaps decreased more significantly treated with teriparatide compared with zoledronic acid(P<0.05).2.6 month later,In low bone turnover group,lumbar spine BMD increments were higher with teriparatide versus zoledronic acid(P<0.05);In high bone turnover group,femoral neck BMD increments were higher with zoledronic acid versus teriparatide(P<0.05).3.6 month later,the bone pain relief better treated with teriparatide than zoledronic acid in low bone turnover group(P<0.05),In high bone turnover group,there was no significant statistically difference between the two drugs(P>0.05).Conclusion:In the treatment of primary osteoporosis,bone turnover markers can be used as the basis for drug selection:low bone turnover state should be applied to anti-resorptive drugs and high bone turnover state use bone-forming drugs.Result:1.In the treatment of primary osteoporosis,bone turnover markers can be used as the basis for drug selection.2.In low bone turnover state should mainly applied to anti-resorptive drugs;In high bone turnover state should mainly use bone-forming drugs.更多还原