用于股骨颈骨折早期干预治疗的新型镁金属支架的生物降解行为及其有限元分析研究
|
摘要
股骨颈骨折是一种临床上常见的骨折，约占全部骨折的3.58%，占股骨近端骨折的50%，其术后的骨折不愈合率和股骨头缺血坏死率较高，这也是其治疗上所面临的主要问题，日益受到临床医生的重视。迄今为止，虽然股骨颈骨折的治疗方法不断完善，但是，由于受多种因素的影响，它的治疗及结果等许多方面仍遗留有许多尚未解决的问题。我院采用一期游离髂骨移植结合三枚空心螺钉固定方法对股骨颈骨折进行早期干预治疗，取得了较好的效果。有限的临床经验证明，此方法具有手术操作简单、创伤小等优点；同时，一期植骨的稳定性好，提高了骨折愈合率，并有助于预防远期股骨头坏死，不失为临床治疗股骨颈骨折的一种有益选择。为了避免手术取骨所造成的损伤和并发症，我们进一步研究使用镁金属支架来代替游离植骨，这种材料能在体内逐渐降解，同时诱导周围新骨生成。为了更好地评价此种支架的腐蚀行为与生物力学特性，为其优化设计和临床应用提供理论依据和必要的参考，本课题系统研究了这种新型的经微弧氧化处理的镁材料在体外模拟生理环境中的降解行为，初步探索了镁离子对成骨细胞生物学行为的影响及其作用机制，并利用有限元分析法建立新型镁支架干预治疗股骨颈骨折的模型，系统研究了金属支架在正常步态周期中的应力变化规律，并与骨移植干预治疗的方法进行了对比分析。
第一部分经微弧氧化处理的新型镁金属材料的体外降解行为和细胞相容性研究
目的：通过在体外模拟生理环境中的电化学试验和浸泡试验，对经表面微弧氧化处理的新型镁材料的腐蚀行为进行系统的研究，并采用拉伸试验对材料在与模拟体液接触过程中的力学性能变化进行检测。此外，对材料在腐蚀过程中的细胞毒性进行评价。
方法：将纯镁试样和经表面微弧氧化处理的镁试样分别浸泡于模拟体液中，用于浸泡的溶液量与试样表面积之比均为30ml/cm2。所有试样在试验前先称重并做记录。实验过程中，温度保持在37±0.5℃，液体的pH值维持在7.4左右。分别在浸泡后的6小时、1天、3天、7天、14天和30天取出试样，利用扫描电镜观察，结合能谱分析和XRD衍射分析对比研究两种试样的腐蚀形貌及其产物成分、降解速度变化和对溶液pH值的影响，并通过电子万能试验机对试样进行拉伸检测，计算材料的抗拉强度，比较不同试样的抗拉强度随腐蚀时间变化的情况。另外，分别以两种试样作为工作电极，利用电化学工作站对样本的电化学阻抗谱（EIS）和动电位极化曲线进行测试，绘制材料的Nyqiust曲线和极化曲线。最后，对Saos-2细胞进行体外培养，利用MTT法、免疫荧光染色技术检测不同材料浸提液对成骨细胞增殖活性和细胞凋亡的影响。使用SAS9.1统计软件对实验数据进行统计学处理，设P＜0.05为差异具有统计学意义。
结果：在模拟体液中，经微弧氧化处理的镁金属的腐蚀速率远低于镁金属（P＜0.05），其对液体pH值的影响也小于镁金属，在72h内从最初的7.4快速上升并稳定在了8.3左右，而镁金属可使溶液的pH值达到约9.1的最高值。两种镁金属表面的腐蚀产物主体成分均为Mg(OH)2和羟基磷灰石。再者，微弧氧化处理可明显降低腐蚀过程中镁金属力学强度的损失，在SBF中浸泡30天后，材料的拉伸强度仍能保持原强度的90%。另外，阻抗频谱和动电位极化曲线也验证了经微弧氧化处理的镁金属的耐腐蚀性要高于镁金属。细胞毒性的分析结果表明，微弧氧化处理前后的镁金属均无明显细胞毒性，具有良好的细胞相容性。
结论：微弧氧化处理可提高镁金属的耐腐蚀性，有利于维持其原有的力学性能，并且材料具有良好的细胞相容性，表面腐蚀产物羟基磷灰石的存在可提高材料的骨结合能力。
第二部分镁离子对成骨细胞生物学行为的影响及其作用机制初探
目的：采用人成骨细胞，研究镁离子对细胞增殖及其主要生物学行为的影响，并对其机制进行初步探讨。
方法：对Saos-2细胞进行体外培养，将1mmol/L、2mmol/L和3mmol/L三种浓度MgSO4作用于成骨细胞，通过MTT法、免疫荧光染色技术检测不同因子对成骨细胞增殖活性和细胞凋亡的影响，并利用ELISA法测定不同因子对成骨细胞ALP活性及骨钙素合成等主要生物学特性的影响。另外，借助ELISA法，测定1mmol/L、2mmol/L和3mmol/L三种浓度MgSO4对成骨细胞Runx2和Fas表达的影响。使用SAS9.1统计软件对各实验的数据进行统计学比较，设P＜0.05为差异具有统计学意义。
结果：不同浓度的镁离子均可促进成骨细胞的增殖（F=44.77，Р＜0.0001），这种刺激作用与镁离子的浓度和作用时间均呈正相关。荧光染色结果显示经镁离子作用后细胞的活性良好。并且，不同浓度的镁离子均可促进成骨细胞的碱性磷酸酶活性和骨钙素合成（Р＜0.05），这种刺激作用也与镁离子的浓度和作用时间均呈正相关。另外，不同浓度的镁离子，在不同时间点均可刺激成骨细胞RUNX2的表达，这种刺激作用与镁离子的浓度和作用时间呈正相关。而镁离子作用组的成骨细胞Fas表达量均明显低于正常对照组（F=16.97，Р＜0.0001），并且，Fas的表达量与镁离子的浓度呈负相关。
结论：镁离子可促进成骨细胞的增殖以及ALP和BGP的合成，其机理可能与调节细胞Runx2和Fas的表达有关，一方面镁离子可通过促进细胞Runx2表达，来刺激成骨细胞的分化和成熟；另一方面，还可通过Fas途径抑制成骨细胞的凋亡，从而维持细胞的增殖与活性。
第三部分镁金属支架干预治疗股骨颈骨折有限元模型的建立及其在正常步态周期中的力学分析研究
目的：建立使用镁金属支架干预治疗股骨颈骨折的有限元模型，研究支架植入后，在正常步态周期中股骨颈部的应力变化规律，为这种新型金属支架的评价和优化提供有益的理论依据，进而指导其临床应用。
方法：选取一名健康成年男性志愿者，对其髋关节及股骨中上段进行CT扫描，获得二维断层图像数据，使用Mimics10.01软件对图像进行处理、提取及重建，得到股骨三维模型，然后将模型导入到Ansys13.0有限元分析软件中，进行体网格划分，生成股骨三维有限元模型，并进一步模拟建立了使用金属支架干预治疗股骨颈骨折的有限元模型。设定边界和载荷条件，对模型进行生物力学分析。使用SAS9.1统计软件对实验数据进行统计学比较，设P＜0.05为差异具有统计学意义。
结果：首先，建立了准确有效的股骨中上段的三维有限元模型以及金属支架干预治疗股骨颈骨折的有限元模型。进一步的分析表明，正常步态周期中骨折固定模型在股骨颈局部的Von Mises应力变化规律与正常股骨模型相似，并且两者的各期应力值以及位移之间均无显著差异（P＞0.05）。分析还表明，正常步态各期中，骨折固定模型在各个方向上的位移变化规律大致相同，均取决于髋关节作用力的大小，各轴向最大位移均出现在髋关节作用力最高的第二期。
结论：本研究建立的股骨三维有限元模型准确有效，为后期的相关实验奠定了基础。另外，松质骨螺钉固定合并金属支架干预治疗股骨颈骨折不仅恢复了骨折部位应力传导的连续性，而且可获得较好的抗压、抗扭转和抗剪切稳定性，对其临床应用具有指导意义。
第四部分镁金属支架和骨移植干预治疗股骨颈骨折生物力学的有限元对比研究
目的：利用有限元法分析镁金属支架和骨移植在股骨颈骨折干预治疗中的应力分布规律，并与临床常用的单独三枚松质骨螺钉固定的方法进行比较。此外，还要对金属支架放置的角度进行研究。通过此实验有助于全面认识这种新型治疗方法的生物力学特点，为其临床应用提供理论指导。
方法：建模的方法和过程以及材料属性同第三部分实验，分别建立镁金属支架和骨移植干预治疗股骨颈骨折的三维有限元模型，将金属支架或骨移植的植入角度分别设置为95°和127°。另外，还建立了单独三枚松质骨螺钉治疗股骨颈骨折的有限元模型。设定边界条件以及426N和2158N两种载荷，对模型进行生物力学分析。使用SAS9.1统计软件对实验数据进行统计学比较，设P＜0.05为差异具有统计学意义。
结果：分析表明，使用金属支架或骨移植对股骨颈骨折进行干预治疗与单纯多枚螺钉固定相比，骨折局部所受的应力水平和产生的位移均无明显差异。另外，对于金属支架或骨移植而言，植入角度的改变并不会对骨折局部的应力产生显著影响，而且使用不同材料的模型之间所受应力和各轴向位移均无显著差异。
结论：可见，松质骨螺钉固定合并金属支架干预治疗股骨颈骨折同样可获得良好的骨折稳定性，而支架的植入角度可根据情况进行适当地调整，再结合镁金属所固有的自身优势，所以它对于股骨颈骨折的干预治疗是一个值得推荐的选择。
The femoral neck fracture is a clinically common skeletal injury,accounting for about3.58%of all fractures and50%of the proximal femurfractures. Nonunion and avascular necrosis of femoral head are the mainproblems in treatment of femoral neck fracture. Up to now, considerableprogress has been made in the treatment of femoral neck fracture, but theguidelines for its management continue to be unsolved and are still evolving.We performed early intervention in femoral neck fracture with the method offree iliac bone graft combined with three cannulated screws fixation, andachieved satisfying clinical result. Based on the limited clinical experience, itwas demonstrated that this method had obvious advantages of simpleoperation, little truma, etc. Meanwhile, one stage bone grafting had reliablestability and improved the rate of fracture healing, helped to prevent theforward avascular necrosis of femoral head. Therefore, this method may be auseful option for the treatment of femoral neck fracture. However, the boneharvesting operation usually caused big surgical trauma and complications. Toavoid the disadvantages of the bone harvesting operation, we introduced anovel metal stent for early intervention in femoral neck fracture to replacebone graft. The novel metal stent is made of magnesium which can graduallydegrade in vivo and induce new bone formation around. In order to betterevaluate the degradation behavior and biomechanical properties of the novelmetal stent and to provide a theoretical basis for its further optimization andclinical application, the degradation behavior of MAO-Mg in simulated bodyfluid was studied systematically, the effects of magnesium ions on the mainbiological actions of osteoblast in vitro and the corresponding mechanismwere preliminarily discussed and disclosed. Additionally, the three-dimensional finite element model of the novel metal stent used for earlyintervention of femoral neck fracture was established to analyze the stresspatterns during a normal gait cycle, and compared with the method using bonegraft for early intervention of femoral neck fracture.
Part1Study of degradation behavior and cytocompatibility for a novelMAO-treated magnesium material
Objective： The degradation behavior of MAO-Mg was studiedsystematically by immersion in simulated body fluid and electrochemical test,and the mechanical performance of MAO-Mg exposed in simulated body fluidwas investigated by tensile test. In addition, the cell toxicity of MAO-Mgduring the corrosion process was evaluated.
Methods：Commercially available pure magnesium and MAO-coated Mgwere used in this study. All the samples were first weighed and recordedbefore the test. Immersion test was performed in a standard simulated bodyfluid (SBF) at a pH value of7.4and the temperature was maintained at37±0.5℃. The ratio of surface area to solution volume was1cm2:30ml. Sampleswere removed after6h,1,3,7,14and30days of immersion, rinsed withdistilled water and dried at room temperature. The surface morphology andcomposition of degradation products for the samples were analyzed byscanning electronic microscope (SEM), energy dispersive spectrometer (EDS)and X-ray diffraction analysis (XRD). The degradation rate, magnesium lossrate and the induced changes in pH were examined. Tension tests were carriedout with a universal testing machine to measure the tensile strength ofdifferent samples over time. In addition, electrochemical measurements wereperformed using a three electrode system, potentiodynamic polarization curvesand electrochemical impedance spectroscopy (EIS) of samples were measured,respectively. Lastly, Saos-2cells were cultured in Dulbecco’s modifiedEagle’s medium (DMEM), supplemented with15%fetal bovine serum (FBS).The effects on osteoblast proliferation and viability in the extraction mediumof the MAO-treated and untreated samples were measured by the MTT assay, and the osteoblastic apoptosis in different media was observed by fluorescentstaining. SAS software (version9.1) was used for the statistical analysis.Statistical significance was assigned to P＜0.05.
Results：The corrosion rate of MAO-coated Mg in the SBF was muchlower than that of uncoated Mg, and MAO-coated Mg had lower influence onthe pH value variation of the SBF compared with uncoated Mg, the pH roserapidly from7.4to8.7and basically stabilized in the first72h, while the pHfor pure Mg reached9.1at last. The main components of the surface corrosionproducts on these metal samples were magnesium hydroxide [Mg(OH)2] andhydroxyapatite. Moreover, the MAO treatment slowed down the loss ofmechanical properties of the magnesium metal and maintained the strength ofthe sample at about90%after30days of immersion. The impedancespectroscopy and potentiodynamic polarization curves had also demonstratedthat the corrosion resistance ability of the MAO-coated Mg sample was higherthan that of uncoated magnesium. The cell toxicity experiments showed thattwo kinds of magnesium metal samples had not cytotoxic, and reached a levelof biosafety suitable for the cellular applications.
Conclusion：The MAO coating could enhance the corrosion resistance oftreated Mg metal and help to keep its original mechanical properties. TheMAO-coated Mg material had good cytocompatibility, and the presence ofhydroxyapatite in the surface corrosion products could improve itsbiocompatibility and bone-binding capacity.
Part2Research on the effects of magnesium ions on the biologicalbehaviors of osteoblast and the corresponding mechanism
Objective：The effects of magnesium ions on the main biological actionsof osteoblast in vitro were were investigated and the correspondingmechanism were preliminarily discussed and disclosed.
Methods：Saos-2cells were cultured in Dulbecco’s modified Eagle’smedium (DMEM), supplemented with15%fetal bovine serum (FBS). Theosteoblast was stimulated with MgSO4at a concentration of1,2,3mmol/L and then the effects of different treatment on osteoblast proliferation weremeasured by the MTT assay, and the osteoblastic apoptosis in different factorwas observed by fluorescent staining. The main biological characterizations ofosteoblast including ALP activation and BGP synthesis stimulated by differentfactors were surveyed with ELISA assay. Additionally, the expressions ofRunx2and Fas of the osteoblast under the stimulation of magnesium ions at1,2,3mmol/L were investigated by ELISA assay. SAS software (version9.1)was used for the statistical analysis on experimental data. Statisticalsignificance was assigned to P＜0.05.
Results：The proliferation index (OD value) of the osteoblasts exposed tomagnesium ions at the concentrations of1,2and3mmol/L for24,48and72hours were all significantly higher than those of the blank control group(F=44.77，Р＜0.0001), and the OD value was positively associated with theconcentration of magnesium ions and the time of exposure. The result offluorescent staining showed the osteoblast had good activity under the actionof magnesium ions. In addition, the ALP activity and osteocalcin level ofosteoblasts treated with magnesium ions were stimulated in thedose-dependent and time-dependent manner. Moreover, the expression ofRunx2of the osteoblast under the stimulation of magnesium ions increasedsignificantly, and the expression quantity was positively with theconcentrations of magnesium ions. But the expression of Fas treated withmagnesium ions were significantly lower than that of normal control group(F=16.97，Р＜0.0001), and its expression quantity was inversely associatedwith the concentration of magnesium ions.
Conclusion：The magnesium ions could induce the proliferation of theosteoblasts, and stimulate their ALP activity and osteocalcin synthesis, themechanism may be associated with the regulation of expressions of Runx2andFas. The magnesium ions could promote the differentiation and mature of theosteoblast by stimulating the expression of Runx2, on the other hand, itinhibited the osteoblast apoptosis by decreasing the expression of Fas.
Part3The establishment of three-dimensional finite element model of thenovel metal stent used for early intervention of femoral neckfracture and the stress analysis during a normal gait cycle
Objective：To establish the three-dimensional finite element model of thenovel metal stent used for early intervention of femoral neck fracture, toanalyze the stress patterns during a normal gait cycle, in order to help us tobetter evaluate the design and biomechanical properties of the novel metalstent and to direct its clinical application.
Methods：A normal adult male volunteer was selected for the test. Hiship and proximal femurs were scanned by CT to obtain the two-dimensionalcomputer tomography image data, and reconstruct the three-dimensionalmodel of femur using Mimics10.01software. And then, the model wasimported to the Ansys13.0software and meshed to establish thethree-dimensional finite element model of the proximal femur, furthersimulated and established the three-dimensional finite element model of thenovel metal stent used for early intervention of femoral neck fracture. Next,the boundary and loading condition were set to perform the biomechanicalanalysis on these models. SAS software (version9.1) was used for thestatistical analysis on data. Statistical significance was assigned to P＜0.05.
Results：Firstly, the precise and effective finite element models of theproximal femur and the novel metal stent were established in this study. Andthen the further analysis demonstrated that the model of femoral neck facturefixation had the similar trend for Von Mises stress to the model of normalfemur during a normal gait cycle, and the values of stress and displacementbetween the two models had no significant difference. It was also found thatthe magnitudes of the axial displacement in the model of femoral neck facturefixation increased with the hip joint load, and the maximal displacement waspresented in the second phase of the normal gait cycle.
Conclusion：It was showed that the finite element models of the proximalfemur established in this study was objective and effective, and which laid the foundation for the further related studies. In addition, the method of the novelmetal stent implantation combined with three cannulated screws for earlyintervention of femoral neck fracture could not only recover the stressconduction of femoral neck but also better resist compression, torsion, andshear and increase the stability of fracture. Thus this study had a certainguiding significance to the clinical application of the novel metal stent andprovided a theoretical basis for its further optimization.
Part4The comparative analysis of a novel metal stent against bone graftused for early intervention of femoral neck fracture. A study offinite element analysis
Objective：The purpose of this study was to evaluate the stress patterns ofthe novel metal stent and bone graft used in the early intervention of femoralneck fracture, and to compare with the method of three cannulated screwsfixation commonly used in clinic. Moreover, the implantation angle of thenovel metal stent or bone graft was analyzed. The study contributed tocomprehensively understanding on biomechanical properties of the novelmethod and providing a theoretical guidance for its further clinical application.
Methods：Finite element models of the novel metal stent and bone graftused in the early intervention of femoral neck fracture were created accordingto the same way mentioned in the third test. The implantation angle of thenovel metal stent or bone graft was set95°and127°, respectively. Moreover,the finite element models of three cannulated screws fixation for femoral neckfracture was also established. The boundary condition and two loads of426Nand2158N were set to perform the biomechanical analysis on these models.SAS software (version9.1) was used for the statistical analysis on data.Statistical significance was assigned to P＜0.05.
Results：The finite element analysis demonstrated that the levels of stressand displacement of femoral neck had no significant difference among threekinds of models. In case of the novel metal stent or bone graft, the change ofthe implantation angle from95°to127°did not affect on the stress of femoral neck. And the stress and the axial displacement between the model ofthe novel metal stent and the model of bone graft had also no significantdifference.
Conclusion：It was found that the novel metal stent could also be usedfor the early intervention of femoral neck fracture with good stability offracture compared to using bone graft. The implantation angle of the metalstent could be adjusted as necessary. Based on results of this study and its owninherent advantages, it was concluded that the novel metal stent could be areliable option for the early intervention of femoral neck fracture.
第一部分经微弧氧化处理的新型镁金属材料的体外降解行为和细胞相容性研究
目的：通过在体外模拟生理环境中的电化学试验和浸泡试验，对经表面微弧氧化处理的新型镁材料的腐蚀行为进行系统的研究，并采用拉伸试验对材料在与模拟体液接触过程中的力学性能变化进行检测。此外，对材料在腐蚀过程中的细胞毒性进行评价。
方法：将纯镁试样和经表面微弧氧化处理的镁试样分别浸泡于模拟体液中，用于浸泡的溶液量与试样表面积之比均为30ml/cm2。所有试样在试验前先称重并做记录。实验过程中，温度保持在37±0.5℃，液体的pH值维持在7.4左右。分别在浸泡后的6小时、1天、3天、7天、14天和30天取出试样，利用扫描电镜观察，结合能谱分析和XRD衍射分析对比研究两种试样的腐蚀形貌及其产物成分、降解速度变化和对溶液pH值的影响，并通过电子万能试验机对试样进行拉伸检测，计算材料的抗拉强度，比较不同试样的抗拉强度随腐蚀时间变化的情况。另外，分别以两种试样作为工作电极，利用电化学工作站对样本的电化学阻抗谱（EIS）和动电位极化曲线进行测试，绘制材料的Nyqiust曲线和极化曲线。最后，对Saos-2细胞进行体外培养，利用MTT法、免疫荧光染色技术检测不同材料浸提液对成骨细胞增殖活性和细胞凋亡的影响。使用SAS9.1统计软件对实验数据进行统计学处理，设P＜0.05为差异具有统计学意义。
结果：在模拟体液中，经微弧氧化处理的镁金属的腐蚀速率远低于镁金属（P＜0.05），其对液体pH值的影响也小于镁金属，在72h内从最初的7.4快速上升并稳定在了8.3左右，而镁金属可使溶液的pH值达到约9.1的最高值。两种镁金属表面的腐蚀产物主体成分均为Mg(OH)2和羟基磷灰石。再者，微弧氧化处理可明显降低腐蚀过程中镁金属力学强度的损失，在SBF中浸泡30天后，材料的拉伸强度仍能保持原强度的90%。另外，阻抗频谱和动电位极化曲线也验证了经微弧氧化处理的镁金属的耐腐蚀性要高于镁金属。细胞毒性的分析结果表明，微弧氧化处理前后的镁金属均无明显细胞毒性，具有良好的细胞相容性。
结论：微弧氧化处理可提高镁金属的耐腐蚀性，有利于维持其原有的力学性能，并且材料具有良好的细胞相容性，表面腐蚀产物羟基磷灰石的存在可提高材料的骨结合能力。
第二部分镁离子对成骨细胞生物学行为的影响及其作用机制初探
目的：采用人成骨细胞，研究镁离子对细胞增殖及其主要生物学行为的影响，并对其机制进行初步探讨。
方法：对Saos-2细胞进行体外培养，将1mmol/L、2mmol/L和3mmol/L三种浓度MgSO4作用于成骨细胞，通过MTT法、免疫荧光染色技术检测不同因子对成骨细胞增殖活性和细胞凋亡的影响，并利用ELISA法测定不同因子对成骨细胞ALP活性及骨钙素合成等主要生物学特性的影响。另外，借助ELISA法，测定1mmol/L、2mmol/L和3mmol/L三种浓度MgSO4对成骨细胞Runx2和Fas表达的影响。使用SAS9.1统计软件对各实验的数据进行统计学比较，设P＜0.05为差异具有统计学意义。
结果：不同浓度的镁离子均可促进成骨细胞的增殖（F=44.77，Р＜0.0001），这种刺激作用与镁离子的浓度和作用时间均呈正相关。荧光染色结果显示经镁离子作用后细胞的活性良好。并且，不同浓度的镁离子均可促进成骨细胞的碱性磷酸酶活性和骨钙素合成（Р＜0.05），这种刺激作用也与镁离子的浓度和作用时间均呈正相关。另外，不同浓度的镁离子，在不同时间点均可刺激成骨细胞RUNX2的表达，这种刺激作用与镁离子的浓度和作用时间呈正相关。而镁离子作用组的成骨细胞Fas表达量均明显低于正常对照组（F=16.97，Р＜0.0001），并且，Fas的表达量与镁离子的浓度呈负相关。
结论：镁离子可促进成骨细胞的增殖以及ALP和BGP的合成，其机理可能与调节细胞Runx2和Fas的表达有关，一方面镁离子可通过促进细胞Runx2表达，来刺激成骨细胞的分化和成熟；另一方面，还可通过Fas途径抑制成骨细胞的凋亡，从而维持细胞的增殖与活性。
第三部分镁金属支架干预治疗股骨颈骨折有限元模型的建立及其在正常步态周期中的力学分析研究
目的：建立使用镁金属支架干预治疗股骨颈骨折的有限元模型，研究支架植入后，在正常步态周期中股骨颈部的应力变化规律，为这种新型金属支架的评价和优化提供有益的理论依据，进而指导其临床应用。
方法：选取一名健康成年男性志愿者，对其髋关节及股骨中上段进行CT扫描，获得二维断层图像数据，使用Mimics10.01软件对图像进行处理、提取及重建，得到股骨三维模型，然后将模型导入到Ansys13.0有限元分析软件中，进行体网格划分，生成股骨三维有限元模型，并进一步模拟建立了使用金属支架干预治疗股骨颈骨折的有限元模型。设定边界和载荷条件，对模型进行生物力学分析。使用SAS9.1统计软件对实验数据进行统计学比较，设P＜0.05为差异具有统计学意义。
结果：首先，建立了准确有效的股骨中上段的三维有限元模型以及金属支架干预治疗股骨颈骨折的有限元模型。进一步的分析表明，正常步态周期中骨折固定模型在股骨颈局部的Von Mises应力变化规律与正常股骨模型相似，并且两者的各期应力值以及位移之间均无显著差异（P＞0.05）。分析还表明，正常步态各期中，骨折固定模型在各个方向上的位移变化规律大致相同，均取决于髋关节作用力的大小，各轴向最大位移均出现在髋关节作用力最高的第二期。
结论：本研究建立的股骨三维有限元模型准确有效，为后期的相关实验奠定了基础。另外，松质骨螺钉固定合并金属支架干预治疗股骨颈骨折不仅恢复了骨折部位应力传导的连续性，而且可获得较好的抗压、抗扭转和抗剪切稳定性，对其临床应用具有指导意义。
第四部分镁金属支架和骨移植干预治疗股骨颈骨折生物力学的有限元对比研究
目的：利用有限元法分析镁金属支架和骨移植在股骨颈骨折干预治疗中的应力分布规律，并与临床常用的单独三枚松质骨螺钉固定的方法进行比较。此外，还要对金属支架放置的角度进行研究。通过此实验有助于全面认识这种新型治疗方法的生物力学特点，为其临床应用提供理论指导。
方法：建模的方法和过程以及材料属性同第三部分实验，分别建立镁金属支架和骨移植干预治疗股骨颈骨折的三维有限元模型，将金属支架或骨移植的植入角度分别设置为95°和127°。另外，还建立了单独三枚松质骨螺钉治疗股骨颈骨折的有限元模型。设定边界条件以及426N和2158N两种载荷，对模型进行生物力学分析。使用SAS9.1统计软件对实验数据进行统计学比较，设P＜0.05为差异具有统计学意义。
结果：分析表明，使用金属支架或骨移植对股骨颈骨折进行干预治疗与单纯多枚螺钉固定相比，骨折局部所受的应力水平和产生的位移均无明显差异。另外，对于金属支架或骨移植而言，植入角度的改变并不会对骨折局部的应力产生显著影响，而且使用不同材料的模型之间所受应力和各轴向位移均无显著差异。
结论：可见，松质骨螺钉固定合并金属支架干预治疗股骨颈骨折同样可获得良好的骨折稳定性，而支架的植入角度可根据情况进行适当地调整，再结合镁金属所固有的自身优势，所以它对于股骨颈骨折的干预治疗是一个值得推荐的选择。
The femoral neck fracture is a clinically common skeletal injury,accounting for about3.58%of all fractures and50%of the proximal femurfractures. Nonunion and avascular necrosis of femoral head are the mainproblems in treatment of femoral neck fracture. Up to now, considerableprogress has been made in the treatment of femoral neck fracture, but theguidelines for its management continue to be unsolved and are still evolving.We performed early intervention in femoral neck fracture with the method offree iliac bone graft combined with three cannulated screws fixation, andachieved satisfying clinical result. Based on the limited clinical experience, itwas demonstrated that this method had obvious advantages of simpleoperation, little truma, etc. Meanwhile, one stage bone grafting had reliablestability and improved the rate of fracture healing, helped to prevent theforward avascular necrosis of femoral head. Therefore, this method may be auseful option for the treatment of femoral neck fracture. However, the boneharvesting operation usually caused big surgical trauma and complications. Toavoid the disadvantages of the bone harvesting operation, we introduced anovel metal stent for early intervention in femoral neck fracture to replacebone graft. The novel metal stent is made of magnesium which can graduallydegrade in vivo and induce new bone formation around. In order to betterevaluate the degradation behavior and biomechanical properties of the novelmetal stent and to provide a theoretical basis for its further optimization andclinical application, the degradation behavior of MAO-Mg in simulated bodyfluid was studied systematically, the effects of magnesium ions on the mainbiological actions of osteoblast in vitro and the corresponding mechanismwere preliminarily discussed and disclosed. Additionally, the three-dimensional finite element model of the novel metal stent used for earlyintervention of femoral neck fracture was established to analyze the stresspatterns during a normal gait cycle, and compared with the method using bonegraft for early intervention of femoral neck fracture.
Part1Study of degradation behavior and cytocompatibility for a novelMAO-treated magnesium material
Objective： The degradation behavior of MAO-Mg was studiedsystematically by immersion in simulated body fluid and electrochemical test,and the mechanical performance of MAO-Mg exposed in simulated body fluidwas investigated by tensile test. In addition, the cell toxicity of MAO-Mgduring the corrosion process was evaluated.
Methods：Commercially available pure magnesium and MAO-coated Mgwere used in this study. All the samples were first weighed and recordedbefore the test. Immersion test was performed in a standard simulated bodyfluid (SBF) at a pH value of7.4and the temperature was maintained at37±0.5℃. The ratio of surface area to solution volume was1cm2:30ml. Sampleswere removed after6h,1,3,7,14and30days of immersion, rinsed withdistilled water and dried at room temperature. The surface morphology andcomposition of degradation products for the samples were analyzed byscanning electronic microscope (SEM), energy dispersive spectrometer (EDS)and X-ray diffraction analysis (XRD). The degradation rate, magnesium lossrate and the induced changes in pH were examined. Tension tests were carriedout with a universal testing machine to measure the tensile strength ofdifferent samples over time. In addition, electrochemical measurements wereperformed using a three electrode system, potentiodynamic polarization curvesand electrochemical impedance spectroscopy (EIS) of samples were measured,respectively. Lastly, Saos-2cells were cultured in Dulbecco’s modifiedEagle’s medium (DMEM), supplemented with15%fetal bovine serum (FBS).The effects on osteoblast proliferation and viability in the extraction mediumof the MAO-treated and untreated samples were measured by the MTT assay, and the osteoblastic apoptosis in different media was observed by fluorescentstaining. SAS software (version9.1) was used for the statistical analysis.Statistical significance was assigned to P＜0.05.
Results：The corrosion rate of MAO-coated Mg in the SBF was muchlower than that of uncoated Mg, and MAO-coated Mg had lower influence onthe pH value variation of the SBF compared with uncoated Mg, the pH roserapidly from7.4to8.7and basically stabilized in the first72h, while the pHfor pure Mg reached9.1at last. The main components of the surface corrosionproducts on these metal samples were magnesium hydroxide [Mg(OH)2] andhydroxyapatite. Moreover, the MAO treatment slowed down the loss ofmechanical properties of the magnesium metal and maintained the strength ofthe sample at about90%after30days of immersion. The impedancespectroscopy and potentiodynamic polarization curves had also demonstratedthat the corrosion resistance ability of the MAO-coated Mg sample was higherthan that of uncoated magnesium. The cell toxicity experiments showed thattwo kinds of magnesium metal samples had not cytotoxic, and reached a levelof biosafety suitable for the cellular applications.
Conclusion：The MAO coating could enhance the corrosion resistance oftreated Mg metal and help to keep its original mechanical properties. TheMAO-coated Mg material had good cytocompatibility, and the presence ofhydroxyapatite in the surface corrosion products could improve itsbiocompatibility and bone-binding capacity.
Part2Research on the effects of magnesium ions on the biologicalbehaviors of osteoblast and the corresponding mechanism
Objective：The effects of magnesium ions on the main biological actionsof osteoblast in vitro were were investigated and the correspondingmechanism were preliminarily discussed and disclosed.
Methods：Saos-2cells were cultured in Dulbecco’s modified Eagle’smedium (DMEM), supplemented with15%fetal bovine serum (FBS). Theosteoblast was stimulated with MgSO4at a concentration of1,2,3mmol/L and then the effects of different treatment on osteoblast proliferation weremeasured by the MTT assay, and the osteoblastic apoptosis in different factorwas observed by fluorescent staining. The main biological characterizations ofosteoblast including ALP activation and BGP synthesis stimulated by differentfactors were surveyed with ELISA assay. Additionally, the expressions ofRunx2and Fas of the osteoblast under the stimulation of magnesium ions at1,2,3mmol/L were investigated by ELISA assay. SAS software (version9.1)was used for the statistical analysis on experimental data. Statisticalsignificance was assigned to P＜0.05.
Results：The proliferation index (OD value) of the osteoblasts exposed tomagnesium ions at the concentrations of1,2and3mmol/L for24,48and72hours were all significantly higher than those of the blank control group(F=44.77，Р＜0.0001), and the OD value was positively associated with theconcentration of magnesium ions and the time of exposure. The result offluorescent staining showed the osteoblast had good activity under the actionof magnesium ions. In addition, the ALP activity and osteocalcin level ofosteoblasts treated with magnesium ions were stimulated in thedose-dependent and time-dependent manner. Moreover, the expression ofRunx2of the osteoblast under the stimulation of magnesium ions increasedsignificantly, and the expression quantity was positively with theconcentrations of magnesium ions. But the expression of Fas treated withmagnesium ions were significantly lower than that of normal control group(F=16.97，Р＜0.0001), and its expression quantity was inversely associatedwith the concentration of magnesium ions.
Conclusion：The magnesium ions could induce the proliferation of theosteoblasts, and stimulate their ALP activity and osteocalcin synthesis, themechanism may be associated with the regulation of expressions of Runx2andFas. The magnesium ions could promote the differentiation and mature of theosteoblast by stimulating the expression of Runx2, on the other hand, itinhibited the osteoblast apoptosis by decreasing the expression of Fas.
Part3The establishment of three-dimensional finite element model of thenovel metal stent used for early intervention of femoral neckfracture and the stress analysis during a normal gait cycle
Objective：To establish the three-dimensional finite element model of thenovel metal stent used for early intervention of femoral neck fracture, toanalyze the stress patterns during a normal gait cycle, in order to help us tobetter evaluate the design and biomechanical properties of the novel metalstent and to direct its clinical application.
Methods：A normal adult male volunteer was selected for the test. Hiship and proximal femurs were scanned by CT to obtain the two-dimensionalcomputer tomography image data, and reconstruct the three-dimensionalmodel of femur using Mimics10.01software. And then, the model wasimported to the Ansys13.0software and meshed to establish thethree-dimensional finite element model of the proximal femur, furthersimulated and established the three-dimensional finite element model of thenovel metal stent used for early intervention of femoral neck fracture. Next,the boundary and loading condition were set to perform the biomechanicalanalysis on these models. SAS software (version9.1) was used for thestatistical analysis on data. Statistical significance was assigned to P＜0.05.
Results：Firstly, the precise and effective finite element models of theproximal femur and the novel metal stent were established in this study. Andthen the further analysis demonstrated that the model of femoral neck facturefixation had the similar trend for Von Mises stress to the model of normalfemur during a normal gait cycle, and the values of stress and displacementbetween the two models had no significant difference. It was also found thatthe magnitudes of the axial displacement in the model of femoral neck facturefixation increased with the hip joint load, and the maximal displacement waspresented in the second phase of the normal gait cycle.
Conclusion：It was showed that the finite element models of the proximalfemur established in this study was objective and effective, and which laid the foundation for the further related studies. In addition, the method of the novelmetal stent implantation combined with three cannulated screws for earlyintervention of femoral neck fracture could not only recover the stressconduction of femoral neck but also better resist compression, torsion, andshear and increase the stability of fracture. Thus this study had a certainguiding significance to the clinical application of the novel metal stent andprovided a theoretical basis for its further optimization.
Part4The comparative analysis of a novel metal stent against bone graftused for early intervention of femoral neck fracture. A study offinite element analysis
Objective：The purpose of this study was to evaluate the stress patterns ofthe novel metal stent and bone graft used in the early intervention of femoralneck fracture, and to compare with the method of three cannulated screwsfixation commonly used in clinic. Moreover, the implantation angle of thenovel metal stent or bone graft was analyzed. The study contributed tocomprehensively understanding on biomechanical properties of the novelmethod and providing a theoretical guidance for its further clinical application.
Methods：Finite element models of the novel metal stent and bone graftused in the early intervention of femoral neck fracture were created accordingto the same way mentioned in the third test. The implantation angle of thenovel metal stent or bone graft was set95°and127°, respectively. Moreover,the finite element models of three cannulated screws fixation for femoral neckfracture was also established. The boundary condition and two loads of426Nand2158N were set to perform the biomechanical analysis on these models.SAS software (version9.1) was used for the statistical analysis on data.Statistical significance was assigned to P＜0.05.
Results：The finite element analysis demonstrated that the levels of stressand displacement of femoral neck had no significant difference among threekinds of models. In case of the novel metal stent or bone graft, the change ofthe implantation angle from95°to127°did not affect on the stress of femoral neck. And the stress and the axial displacement between the model ofthe novel metal stent and the model of bone graft had also no significantdifference.
Conclusion：It was found that the novel metal stent could also be usedfor the early intervention of femoral neck fracture with good stability offracture compared to using bone graft. The implantation angle of the metalstent could be adjusted as necessary. Based on results of this study and its owninherent advantages, it was concluded that the novel metal stent could be areliable option for the early intervention of femoral neck fracture.
引文
1Sen RK, Tripathy SK, Goyal T, et al. Osteosynthesis of femoral-necknonunion with angle blade plate and autogenous fibular graft. Int Orthop,2012,36:827~832
2Tripathy SK, Goyal T, Sen RK. Revision internal fixation and nonvascularfibular graft for femoral neck nonunion. J Trauma,2011,71:270~271
3Zhenyu P, Aixi Y, Guo-Rong Y, et al. Treatment of serious femoral neckfractures with the transposition of vascularized greater trochanter bone flapin young adults. J Reconstr Microsurg,2011,27:303~308
4Davidovitch RI, Jordan CJ, Egol KA, et al. Challenges in the treatment offemoral neck fractures in the nonelderly adult. J Trauma,2010,68:236~242
5Jun X, Chang-Qing Z, Kai-Gang Z, et al. Modified free vascularizedfibular grafting for the treatment of femoral neck nonunion. J OrthopTrauma,2010,24:230~235
6Kannan MB, Raman RK. In vitro degradation and mechanical integrity ofcalcium-containing magnesium alloys in modified-simulated body fluid.Biomaterials,2008,29(15):2306~2314
7Robert SB. Magnesium Products Design. New York: Marcle Dekker,1987
8王德云,东青,陈传忠,等.微弧氧化技术进展.硅酸盐学报,2005,33(9):1133~1137
9蒋百灵,吴建国,张淑芬,等.镁合金微弧氧化生长过程及微观结构的研究.材料热处理学报,2002,23(1):5~8
10Sergei VG, Oleg SP, Vitalyi SS. Unseeded precipitation of calcium andmagnesium phosphates from modified seawater solutions. J of CrystGrowth,1999,205(3):354~360
11Kuwahara H, Al-Abdullat Y, Mazaki N, et al. Precipitation of magnesiumapatite on pure magnesium surface during immersing in Hank’s solution.Mater Trans,2001,42(7):1317~1321
12宋光铃.镁合金的腐蚀与防护.北京：化学工业出版社,2004
13Staiger MP, Pietak AM, Huadmai J, et al. Magnesium and its alloys asorthopedic biomaterials: A review. Biomaterials,2006,27(9):1728~1734
1Hartwig A. Role of magnesium in genomic stability. Mutat Res/Fund MolMech Mutagen,2001,475(1-2):113~121
2Okuma T. Magnesium and bone strength. Nutrition,2001,17(7-8):679~680
3De Valk H. Magnesium in diabetes mellitus. The Netherlands journal ofmedicine,1999,54(4):139
4Saris N, Mervaala E, Karppanen H, et al. Magnesium an update onphysiological, clinical and analytical aspects. Clinica chimica acta,2000,294(1-2):1~26
5Okuma T. Magnesium and bone strength. Nutrition,2001,17(7-8):679~680
6Fatemi S, Ryzen E, Flores J, et al. Effect of experimental humanmagnesium depletion on parathyroid hormone secretion and1,25-dihydroxyvitamin D metabolism. J Clin Endocrinol Metab,1991,73:1067~1072
7Risco F, Traba ML. Influence of magnesium on the in vitro synthesis of24,25-dihydroxyvitamin D3and1-α,25-dihydroxyvitamin D3. MagnesiumRes,1992,5:5~14
8Rude RK, Kirchen ME, Gruber HE, et al. Magnesium deficiency-inducedosteoporosis in the rat: Uncoupling of bone formation and bone resorption.Magnes Res,1999,12:257~267
9Leidi M, Dellera F, Mariotti M, et al. High magnesium inhibits humanosteoblast differentiation in vitro. Magnes Res,2011,24:1~6
10孟昭亭.骨钙素及其临床意义.中华内分泌代谢杂志,1992,8:41
11Sun YQ, Ashhurst DE. Osteogenic growth peptide enhances the rate offracture healing in rabbits. Cell Biol Int,1998,22:313
12Lerner UH. The role of skeletal nerve fibers in bone metabolism.Endocrinologist,2000,10:377~382
13McIntosh TK. Novel pharmacologic therapies in the treatment ofexperimental traumatic brain injury: A review. J Am Chem Soc,1993,89:2719~2725
14Rude RK, Gruber HE, Norton HJ, et al. Reduction of dietary magnesiumby only50%in the rat disrupts bone and mineral metabolism. OsteoporosisInt,2006,17:1022~1032
15Robert RK, Gruber HE, Norton HJ, et al. Dietary magnesium reduction to25%of nutrient requirement disrupts bone and mineral metabolism in therat. Bone,2005,37:211~219
16Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and magnesium in the stimulation of osteoblast proliferationand migration by platelet-derived growth factor. Am J Physiol Cell Physiol,2009,297:C360~368
17Crespi R, Mariani E, Benasciutti E, et al. Magnesium-enrichedhydroxyapatite versus autologous bone in maxillary sinus grafting:combining histomorphometry with osteoblast gene expression profiles exvivo. J Periodontol,2009,80:586~593
18Park JW, Kim YJ, Jang JH, et al. Osteoblast response to magnesiumion-incorporated nanoporous titanium oxide surfaces. Clin Oral ImplantsRes,2010,21(11):1278~1287
19Jilka RL, Weistein T, Bellido AM, et al. Osteoblast programmed cell death:modulation by growth faetors and cytokines. J Bone Miner Res,1998,13(3):793~802
20Wang Y, Toury R, Hauehecorne M, et al. Expression of Bcl-2protein inthe epiphyseal plate cartilage and trabecular bone of growing rats.Histochem Cell Biol,1997,108:45~55
21Steller H. Mechanisms and genes of celluar suicid. Science,1995,267:1445~1448
22Kawakami A, Nakane PK, Matsuka N, et al. Fas and Fas ligand interaetionis necessary for human osteoblast apoptosis. J Bone Miner Res,1997,12(10):1637~1646
23Komori T, et al. Regulation of bone development and maintenance byRunx2. Front Biosci,2008,1(13):898~903
24Komori T. Regulation of osteoblast differentiation by transcription factors.J Cell Biochem,2006,99(5):1233~1239
25Kato M，Patel MS，Levasseur R，et al. Cbfa1-independent decrease inosteoblast proliferation， osteopenia， and persistent embryonic eyevascularization in mice deficient in Lrp5，a Wnt coreceptor. J Cell Biol,2002,157:303~314
26Gilbert L, He X, Farmer P, et al. Expression of the osteoblastdifferentiation factor RUNX2(Cbfa1/AML3/Pebp2alpha A) is inhibited bytumor necrosis factor2alpha. Biol Chem,2002,277(4):2695~2701
27Ding J, Ghali O, Lencel P, et al. TNF-alpha and IL-1beta inhibit RUNX2and collagen expression but increase alkaline phosphatase activity andmineralization in human mesenchymal stem cells. Life Sci,2009,84(15-16):499~504
1张英泽.临床创伤骨科学[M].河北:河北科学技术出版社,2004:414.
2Bergmann G, Graichen F, Rohimann A. Instrumentation of a hip jointprosthesis. In: Implantable Telemetry in Orthopaedics,1990, pp:35~63
3Brekelmans WA, Poort HW, Sbooff TJ. A new method to analyse themechanical behaviour of skeletal parts. Acta Orthop Scand,1972,93(5):301~317
4Vasue R, Carter DR, Harris HW. Stress distribution of in the acetabularregion-Ι, before and after total joint replacement. J Biomethanics,1982,15:155~164
5Rapperport DJ, Carter DR, Schurman DJ. Cantact finite element stressanalysis of the hip joint. J Orthop Res,1985,3:435~446
6Goel VK, Valliappan S, Svensson NL. Stresses in the normal pelvis.Comput Biol Med,1978,8:91~104
7Koeneman JB, Hansen TM, Beris K. Three dimentional finite elementsanalysis of the hip joint. Trans ORS,1989,14:223
8Namba RS, Keyak JH, Kim AS, et al. Cementless implant composition andfemoral stress. A finite elements analysis. Clin Orthop Relat Res,1998,347:261~267
9Bucholz RW, Ross SE, Lawrence KL. Fatigue fractures of the intellockingnail in the treatment of the distal part of the femoral shaft. J Bone JointSurg Am,1987,69(9):139
10Cheung G, Zalzal P, Bhandari M, et al. Finite elements analysis of afemoral retrograde intramedullary nail subject to gait loading. Med EngPhys,2004,26(2):93~108
11徐遄,吴勇,贾克斌.数字医学影像与通信的重要标准-DICOM.标准中国医学影像技术,2002,18:76
12Jang SH, Kim WY. Defining a new annotation object for DICOM image: apractical approach. Comput Med Imaging Graph,2004,28(7):371~375
13Escott EJ, Rubinstein D. Free. DICOM image viewing and processingsoftware for your desktop computer: what’s available and what it can dofor you. Radiographics,2003,23(5):1341~1357
14Kling PT, Rydmark M. Modeling and modification of medical3D objects:The benefit of using a haptic modeling tool. Stud Health Technol Inform,2000,70:162~167
15Durand LG, Garcia D, Sakr F, et al. A new flow model for Dopplerultrasound study of prosthetic heart valves. J Heart Valve Dis,1999,8(1):85~95
16Taylor WR, Roland E, Ploeg H, et al. Determination of orthotropic boneelastic constants using FEA and modal analysis. J Biomech,2002,35(6):767~773
17Merz B, Niederer P, Muller R, et al. Automated finite element analysis ofexcised human femora based on precision-QCT. J Biomech Eng,1996,118(3):387~390
18Cattaneo PM, Dalstra M, Frich LH. A three-dimensional finite elementmodel from computed tomography data: a semi-automated method. ProcInst Mech Eng H,2001,215(2):203~213
19Marom SA, Linden MJ. Computer aided stress analysis of long bonesutilizing computed tomography. J Biomech,1990,23(5):399~404
20Zannoni C, Mantovani R, Viceconti M. Material properties assignment tofinite element models of bone structures: a new method. Med Eng Phys,1998,20(10):735~740
21Rho JY, Hobatho MC, Ashman RB. Relations of mechanical properties todensity and CT numbers in human bone. Med Eng Phys,1995,17(5):347~355
22Esses SI, Lotz JC, Hayes WC. Biomechanical properties of the proximalfemur determined in vitro by single-energy quantitative computedtomography. J Bone Miner Res,1989,4(5):715~722
23Peng L, Bai J, Zeng X, et al. Comparison of isotropic and orthotropicmaterial property assignments on femoral finite element models under twoloading conditions. Med Eng Phys,2006,28(3):227~233
24Baca V, Horak Z, Mikulenka P, et al. Comparison of an inhomogeneousorthotropic and isotropic material models used for FE analyses. Med EngPhys,2008,30(7):924~930
25Crowninshield RD, Brand RA. A physiologically based criterion of muscleforce prediction in locomotion. J Biomechanics,1981,14:793~801
26Dalstra M, Huiskes R. Load transfer across the pelvic bone. JBiomechanics,1995,28(6):715~724
27Antekeier SB, Burden RL Jr, Voor MJ, et al. Mechanical study of the safedistance between distal femoral fracture site and distal locking screws inantegrade intramedullary nailing. J Orthop Trauma,2005,19(10):693~697
28Taylor ME, Tanner KE, Freeman MA, et al. Stress and strain distributionwithin the intact femur: compression or bending? Med Eng Phys,1996,18(2):122~131
29Bergmann G, Graichen F, Rohimann A. Five month in vivo measurement ofhip joint forces. Proc Congr Int Soc Biomech,1989,12:43
1Jun X, Chang-Qing Z, Kai-Gang Z, et al. Modified free vascularizedfibular grafting for the treatment of femoral neck nonunion. J OrthopTrauma,2010,24(4):230~235
2Sen RK, Tripathy SK, Goyal T, et al. Osteosynthesis of femoral-necknonunion with angle blade plate and autogenous fibular graft. Int Orthop,2012,36(4):827~832
3Bhuyan BK. Augmented osteosynthesis with tensor fascia latae musclepedicle bone grafting in neglected femoral neck fracture. Indian J Orthop,2012,46(4):439~446
4Singh MP, Aggarwal AN, Arora A, et al. Unstable recent intracapsularfemoral neck fractures in young adults: osteosynthesis and primary valgusosteotomy using broad dynamic compression plate. Indian J Orthop,2008,42(1):43~48
5Goldberg VM. Selection of bone grafts for revision total hip arthroplasty.Clin Orthop,2000,381:68~76
6Bramfeldt H, Sabra G, Centis V, et al. Scaffold vascularization: a challengefor three-dimensional tissue engineering. Curr Med Chem,2010,17(33):3944~3967
7Wang Y, Huang YC, Gertzman AA, et al. Endogenous regeneration ofcritical-size chondral defects in immunocompromised rat xiphoid cartilageusing decellularized human bone matrix scaffolds. Tissue Eng Part A,2012,18(21-22):2332~2342
8Schwartz Z, Hyzy SL, Moore MA, et al. Osteoinductivity of demineralizedbone matrix is independent of donor bisphosphonate use. J Bone JointSurg Am,2011,93(24):2278~2286
9Kirk JF, Ritter G, Waters C, et al. Osteoconductivity and osteoinductivityof NanoFUSE() DBM. Cell Tissue Bank,2013,14(1):33~44
1Staiger MP, Pietak AM, Huadmai J, et al. Magnesium and its alloys asorthopedic biomaterials: A review. Biomaterials,2006,27:1728~1734
2Witte F, Hort N, Vogt C, et al. Degradable biomaterials based onmagnesium corrosion. Curr Opin Solid State Mater Sci,2008,12:63~72
3Hort N, Huang Y, Fechner D, et al. Magnesium alloys as implantmaterials–Principles of property design for Mg-RE alloys. ActaBiomaterialia,2010,6:1714~1725
4Pollock TM. Weight loss with magnesium alloys. Science,2010,328:986~987
5Erbel R, Di Mario C, Bartunek J, et al. Temporary scaffolding ofcoronary arteries with bioabsorbable magnesium stents: a prospective,non-randomised multicentre trial. Lancet,2007,369:1869~1875
6Witte F. The history of biodegradable magnesium implants: A review.Acta Biomaterialia,2010,6:1680~1692
7Rose IA. The state of magnesium in cells as estimated from the adenylatekinase equilibrium. Proc Natl Acad Sci USA,1968,61:1079~1086
8Witte F, Feyerabend F, Maier P, et al. Biodegradablemagnesium-hydroxyapatite metal matrix composites. Biomaterials,2007,28:2163~2174
9Lambotte A. L’utilisation du magnesium comme materiel perdu dansl’osteosynthese. Bull Mem Soc Nat Chir,1932,28:1325~1334
10Troitskii VV, Tsitrin DN. The resorbing metallic alloy ‘Osteosinthezit’ asmaterial for fastening broken bone. Khirurgiia,1944,8:41~44
11Znamenskii MS. Metallic osteosynthesis by means of an apparatus madeof resorbing metal. Khirurgiia,1945,12:60~63
12McBride ED. Absorbable metal in bone surgery. J Am Med Assoc,1938,111:2464~2467
13Troganov GB, Savitsky E, Mikhailovich T, et al. Magnesium-base alloysfor use in bone surgery. US Patent no.3,1972,687:135
14Serre CM, Papillard M, Chavassieux P, et al. Influence of magnesiumsubstitution on a collagen-apatite biomaterial on the production of acalcifying matrix by human osteoblasts. J Biomed Mater Res,1998,42:626~633
15Zeng RC, Dietzel W, Witte F, et al. Progress and challenge formagnesium alloys as biomaterials. Adv Eng Mater,2008,10: B3~B14
16Gu X, Zheng Y, Cheng Y, et al. In vitro corrosion and biocompatibility ofbinary magnesium alloys. Biomaterials,2009,30:484~498
17Witte F, Fischer J, Nellesen J, et al. In vitro and in vivo corrosionmeasurements of magnesium alloys. Biomaterials,2006,27:1013~1018
18Witte F, Kaese V, Haferkamp H, et al. In vivo corrosion of fourmagnesium alloys and the associated bone response. Biomaterials,2005,26:3557~3563
19Kannan MB, Raman RK. In vitro degradation and mechanical integrity ofcalcium-containing magnesium alloys in modified-simulated body fluid.Biomaterials,2008,29:2306~2314
20Li Z, Gu X, Lou S, et al. The development of binary Mg-Ca alloys for useas biodegradable materials within bone. Biomaterials,2008,29:1329~1344
21Zhang S, Zhang X, Zhao C, et al. Research on an Mg-Zn alloy as adegradable biomaterial. Acta Biomater,2010,6:626~640
22Wong HM, Yeung KW, Lam KO, et al. A biodegradable polymer-basedcoating to control the performance of magnesium alloy orthopaedicimplants. Biomaterials,2010,31:2084~2096
23Xin Y, Jiang J, Huo K, et al. Corrosion resistance and cytocompatibilityof biodegradable surgical magnesium alloy coated with hydrogenatedamorphous silicon,2009,89:717~726
24Xu L, Zhang E, Yang K. Phosphating treatment and corrosion propertiesof Mg-Mn-Zn alloy for biomedical application. J Mater Sci Mater Med,2009,20:859~867
25Zberg B, Uggowitzer PJ, L ffler JF. Mg-Zn-Ca glasses without clinicallyobservable hydrogen evolution for biodegradable implants. Nat Mater,2009,8:887~891
26Domingo JL. Aluminum and other metals in Alzheimer’s disease: Areview of potential therapy with chelating agents. J Alzheimer’s Dis,2006,10:331~341
27Yun YH, Dong ZY, Lee N, et al. Revolutionizing biodegradable metals.Mater Today,2009,12:22~32
28Atiyeh BS, Costagliola M, Hayek SN, et al. Effect of silver on burnwound infection control and healing: Review of the literature. Burns,2007,33:139~148
29Tie D, Feyerabend F, Müller WD, et al. Antibacterial biodegradableMg-Ag alloys. Eur Cell Mater,2013,25:284~298
30Paton BE, Kaleko DM, Koval YM, et al. Influence of alloying with silverand tantalum on features of medical-purpose Ti-Ni alloy. Metallofiz NovTekhnol-Met Phys Adv Techn,2010,32:1691~1703
31Necula BS, Apachitei I, Tichelaar FD, et al. An electron microscopicalstudy on the growth of TiO2-Ag antibacterial coatings on Ti6Al7Nbbiomedical alloy. Acta Biomaterialia,2011,7:2751~2757
32Bosetti M, Massè A, Tobin E, et al. Silver coated materials for externalfixation devices: in vitro biocompatibility and genotoxicity. Biomaterials,2002,23:887~892
33Hardes J, Streitburger A, Ahrens H, et al. The influence of elementarysilver versus titanium on osteoblast behaviour in vitro using humanosteosarcoma cell lines. Sarcoma,2007,265:39
34Drake PL, Hazelwood KJ. Exposure-related health effects of silver andsilver compounds: A review. Ann Occup Hyg,2005,49:575~585
35Willumeit R, Fischer J, Feyerabend F, et al. Chemical surface alterationof biodegradable magnesium exposed to corrosion media. Acta Biomater,2011,7:2704~2715
36Feyerabend F, Drücker H, Laipple D, et al. Ion release from magnesiummaterials in physiological solutions under different oxygen tensions. JMater Sci Mater Med,2012,23:9~24
37Jang Y, Collins B, Sankar J, et al. Effect of biologically relevant ions onthe corrosion products formed on alloy AZ31B: An improvedunderstanding of magnesium corrosion. Acta Biomater,2013,9(10):8761~8770
38Rude RK, Shils ME. Magnesium. In Shils ME (ed):“Modern Nutrition inHealth and Disease.” Philadelphia, PA: Lippincott, Williams and Wilkins,2006, pp223~247
39Rude RK. Magnesium deficiency: a heterogeneous cause of disease inhumans. J Bone Miner Res,1998,13:749~758
40Standing Committee on the Scientific Evaluation of Dietary ReferenceIntakes, Food and Nutrition Board, Institute of Medicine:“DietaryReference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, andFluoride.” Washington, DC: National Academy Press,1997, pp190~249
41Mountokalakis T, Singhellakis P, Alevizaki C, et al. Relationshipbetween degree of renal failure and impairment of intestinal magnesiumabsorption. In Seelig MS (ed):“Magnesium in Health and Disease.” NewYork: Spectrum Publications, Inc,1980, pp453~458
42Martin BJ. The magnesium load test: experience in elderly subjects.Aging,1990,2:291~296
43Rubin H. Central roles of Mg2+and of MgATP2-in the regulation ofprotein synthesis and cell proliferation: significance for neoplastictransformation. Adv Cancer Res,2005,93:1~58
44Rubin H. Magnesium: The missing element in molecular views of cellproliferation control. Bioessays,2005,27:311~320
45Rubin H, Terasaki M, Sanui H. Major intracellular cations and growthcontrol: Correspondence among magnesium content, protein synthesis,and the onset of DNA synthesis in Balb/c3T3cells. Proc Natl Acad SciUSA,1979,76:3917~3921
46Rubin H, Terasaki M, Sanui H. Magnesium reverses inhibitory effects ofcalcium deprivation on coordinate response of3T3cells to serum. ProcNatl Acad Sci USA,1978,75:4379~4383
47Schreier MH, Staehelin T. Initiation of mammalian protein synthesis: theimportance of ribosome and initiation factor quality for the efficiency ofin vitro systems. J Mol Biol,1973,73:329~349
48Terasaki M, Rubin H. Evidence that intracellular magnesium is present incells at a regulatory concentration for protein synthesis. Proc Natl AcadSci USA,1985,82:7324~7326
49Vidair C, Rubin H. Mg2+as activator of uridine phosphorylation and othercellular responses to growth factors. Proc Natl Acad Sci USA,2005,102:662~666
50Dennis PB, Jaeschke A, Saitoh M, et al. Mammalian TOR: a homeostaticATP sensor. Science,2001,294:1102~1105
51Lau YT, Yassin RR, Horowitz SB. Potassium salt microinjection intoXenopus oocytes mimics gonadotropin treatment. Science,1988,240:1231~1233
52Achs MJ, Garfinkel D. Computer simulation of energy metabolism inanoxic perfused rat heart. Am J Physiol,1982,232:R164~174
53Grubbs RD. Effect of epidermal growth factor on Mg2+homeostasis inBC3H-1myocytes. Am J Physiol,1991,260:C1158~1164
54Ishijima S, Sonoda T, Tatibana M. Mitogen-induced early increase incytosolic free Mg2+concentration in single Swiss3T3fibroblasts. Am JPhysiol,1991,261:C1074~1080
55Trzeciakiewicz A, Opolski A, Mazur A. TRPM7: a protein responsiblefor magnesium homeostasis in a cell. Postepy Hig Med Dosw (Online),2005,59:496~502
56Touyz RM. Transient receptor potential melastatin6and7channels,magnesium transport, and vascular biology: implications in hypertension.Am J Physiol Heart Circ Physiol,2008,294:H1103~1118
57Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and cations (magnesium, calcium) in human osteoblast-likecell proliferation. Cell Prolif,2007,40:849~865
58Chubanov V, Gudermann T, Schlingmann KP. Essential role for TRPM6in epithelial magnesium transport and body magnesium homeostasis.Pflugers Arch,2005,451:228~234
59He Y, Yao G, Savoia C, et al. Transient receptor potential melastatin7ionchannels regulate magnesium homeostasis in vascular smooth musclecells: role of angiotensin II. Circ Res,2005,96:207~215
60Clapham DE, Runnels LW, Strubing C. The TRP ion channel family. NatRev Neurosci,2001,2:387~396
61Harteneck C, Plant TD, Schultz G. From worm to man: three subfamiliesof TRP channels. Trends Neurosci,2000,23:159~166
62Minke B, Cook B. TRP channel proteins and signal transduction. PhysiolRev,2002,82:429~472
63Montell C, Birnbaumer L, Flockerzi V. The TRP channels, a remarkablyfunctional family. Cell,2002,108:595~598
64Harteneck C. Function and pharmacology of TRPM cation channels.Naunyn Schmiedebergs Arch Pharmacol,2005,371:307~314
65Fleig A, Penner R. The TRPM ion channel subfamily: molecular,biophysical and functional features. Trends Pharmacol Sci,2004,25:633~639
66Nadler MJ, Hermosura MC, Inabe K, et al. LTRPC7is aMg.ATP-regulated divalent cation channel required for cell viability.Nature,2001,411:590~595
67Schmitz C, Dorovkov MV, Zhao X, et al. The channel kinases TRPM6and TRPM7are functionally nonredundant. J Biol Chem,2005,280:37763~37771
68Chubanov V, Waldegger S, Schnitzler M, et al. Disruption ofTRPM6/TRPM7complex formation by a mutation in the TRPM6genecauses hypomagnesemia with secondary hypocalcemia. Proc Natl AcadSci USA,2004,101:2894~2899
69Baserga R. In: The Biology of Cell Reproduction. Boston: Harvard Univ.Press,1985,138~140
70Wallach S. Effects of magnesium on skeletal metabolism. Magnes TraceElem,1990,9:1~14
71Rude RK, Kirchen ME, Gruber HE, et al. Magnesium deficiency-inducedosteoporosis in the rat: Uncoupling of bone formation and boneresorption. Magnes Res,1999,12:257~267
72Leidi M, Dellera F, Mariotti M, et al. High magnesium inhibits humanosteoblast differentiation in vitro. Magnes Res,2011,24:1~6
73Yun Y, Dong Z, Tan Z, et al. Development of an electrode cellimpedance method to measure osteoblast cell activity inmagnesium-conditioned media. Anal Bioanal Chem,2010,396:3009~3015
74Rude RK. Magnesium homeostasis. In Bilezikian JB, Raisz L, Rodan G(eds):“Principles of Bone Biology,”3rd ed. San Diego, CA: AcademicPress,2008, pp487~513
75Fatemi S, Ryzen E, Flores J, et al. Effect of experimental humanmagnesium depletion on parathyroid hormone secretion and1,25-dihydroxyvitamin D metabolism. J Clin Endocrinol Metab,1991,73:1067~1072
76Litosch I. G protein regulation of phospholipase C activity in amembrane-solubilized system occurs through an Mg2+-andtime-dependent mechanism. J Bio Chem,1991,266:4764~4771
77Volpe P, Alderson-Lang BH, Nickols GA. Regulation of inositol1,4,5-trisphosphate-induced Ca2+release. I. Effect of Mg2+. Am J Physiol,1990,258:C1077~C1085
78Northup JK, Smigel MD, Gilman AG. The guanine nucleotide activatingsite of the regulatory component of adenylate cyclase: Identification byligand binding. J Biol Chem,1982,257:11416~11423
79Rude RK, Adams JS, Ryzen E, et al. Low serum concentrations of1,25-dihydroxyvitamin D in human magnesium deficiency. J ClinEndocrinol Metab,1985,61:933~940
80Risco F, Traba ML. Influence of magnesium on the in vitro synthesis of24,25-dihydroxyvitamin D3and1-α,25-dihydroxyvitamin D3.Magnesium Res,1992,5:5~14
81Saggese G, Federico G, Bertelloni S, et al. Hypomagnesemia and theparathyroid hormone-vitamin D endocrine system in children withinsulin-dependent diabetes mellitus: effect of magnesium administration.J Pediatr,1991,118:220~225
82Welsh JJ, Weaver VM. Adaptation to low dietary calcium inmagnesium-deficient rats. J Nutr,1988,118:729~734
83Christiansen P. The skeleton in primary hyperparathyroidism: a reviewfocusing on bone remodeling, structure, mass, and fracture. APMIS Suppl,2001,102:1~52
84Gruber HE, Rude RK, Wei L, et al. Magnesium deficiency: effect onbone mineral density in the mouse appendicular skeleton. BMCMusculoskelet Disord,2003,17:4~7
85Mackie EJ. Osteoblasts: novel roles in orchestration of skeletalarchitecture. Int J Biochem Cell Biol,2003,35:1301~1305
86Park JW, Kim YJ, Jang JH, et al. Osteoblast response to magnesiumion-incorporated nanoporous titanium oxide surfaces. Clin Oral ImplantsRes,2010,21(11):1278~1287
87Park JW, An CH, Jeong SH, et al. Osseointegration of commercialmicrostructured titanium implants incorporating magnesium: ahistomorphometric study in rabbit cancellous bone. Clin Oral ImplantsRes,2012,23(3):294~300
88Jeon SH, Kim SJ, Kim JS, et al. Immunosuppressant FK506decreases theintracellular magnesium in the human osteoblast cell by inhibiting theERK1/2pathway. Life Sci,2009,84:23~27
89Jeon SH, Lee MY, Kim SJ, et al. Taurine increases cell proliferation andgenerates an increase in [Mg2+]i accompanied by ERK1/2activation inhuman osteoblast cells. FEBS Lett,2007,22:581:5929~5934
90Lerner UH. The role of skeletal nerve fibers in bone metabolism.Endocrinologist,2000,10:377~382
91McIntosh TK. Novel pharmacologic therapies in the treatment ofexperimental traumatic brain injury: A review. J Am Chem Soc,1993,89:2719~2725
92Weglicki WB, Dickens BF, Wagner TL, et al. Immunoregulation byneuropeptides in magnesium deficiency: Ex vivo effect of enhancedsubstance P production on circulation T lymphocytes frommagnesium-deficient mice. Magnes Res,1996,9:3~11
93Kramer JH, Phillips TM, Weglicki WB. Magnesium-deficiency-enhancedpost-ischemic myocardial injury is reduced by substance P receptorblockade. J Mol Cell Cardiol,1997,29:97~110
94Malpuech-Brugere C, Nowacki W, Rock E, et al. Enhanced tumornecrosis factor-a production following endotoxin challenge in rats is anearly event during magnesium deficiency. Biochimica et Biophysica Acta,1999,1453:35~40
95Nakagawa M, Oono H, Nishio A. Enhanced productrion of IL-1β andIL-6following endotoxin challenge in rats with dietary magnesiumdeficiency. J Vet Med Sci,2001,6:467~469
96Malpuech-Brugere C, Nowacki W, Daveau M, et al. Inflammatoryresponse following acute magnesium deficiency in the rat. BiochimicaBiophysica Acta,2000,1501:91~98
97Rameshwar P, Ganea D, Gascon P. Induction of IL-3andgranulocyte-macrophage colony stimulating factor by substance P inbone marrow cells in partially mediated through the release of IL-1andIL-6. J Immunol,1994,152:4044~4054
98Miyaura C, Kusano K, Masuzawa T, et al. Endogenous bone-resorbingfactors in estrogen deficiency: cooperative effect of IL-1β and IL-6. JBone Miner Res,1995,10:1365~1373
99Nanes MS. Tumor necrosis factor-a: molecular and cellular mechanism inskeletal pathology. Gene,2003,321:1~15
100Rude RK, Gruber HE, Wei LY, et al. Magnesium deficiency: effect onbone and mineral metabolism in the mouse. Calcif Tiss Int,2003,72:32~41
101Rude RK, Gruber HE, Norton HJ, et al. Reduction of dietary magnesiumby only50%in the rat disrupts bone and mineral metabolism.Osteoporosis Int,2006,17:1022~1032
102Rude RK, Gruber HE, Norton HJ, et al. Bone loss induced by dietarymagnesium reduction to10%Nutrient Requirement in rats is associatedwith increase release of substance P and tumor necrosis factor-a. J Nutr,2004,134:79~85
103Robert RK, Gruber HE, Norton HJ, et al. Dietary magnesium reduction to25%of nutrient requirement disrupts bone and mineral metabolism in therat. Bone,2005,37:211~219
104Hofbauer LC, Heufelder AE. The role of receptor activator of nuclearfactor-kB ligand and osteoprotegerin in the pathogenesis and treatment ofmetabolic bone diseases. J Clin Endocrinol Metab,2000,85:2355~2363
105Manolagas SC. Birth and death of bone cells: basic regulatorymechanisms and implications for the pathogenesis and treatment ofosteoporosis. Endocr Rev,2000,21:115~137
106Rude RK, Gruber HE, Wei LY, et al. Immunolocalization of RANKL isincreased and OPG decreased during dietary magnesium deficiency in therat. Nutr Met,2005,2:1~8
107Crespi R, Mariani E, Benasciutti E, et al. Magnesium-enrichedhydroxyapatite versus autologous bone in maxillary sinus grafting:combining histomorphometry with osteoblast gene expression profiles exvivo. J Periodontol,2009,80:586~593
108Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and magnesium in the stimulation of osteoblast proliferationand migration by platelet-derived growth factor. Am J Physiol CellPhysiol,2009,297:C360~368
109Abed E, Labelle D, Martineau C, et al. Expression of transient receptorpotential (TRP) channels in human and murine osteoblast-like cells. MolMembr Biol,2009,26:146~158
110Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and cations (magnesium, calcium) in human osteoblast-likecell proliferation. Cell Prolif,2007,40:849~865
2Tripathy SK, Goyal T, Sen RK. Revision internal fixation and nonvascularfibular graft for femoral neck nonunion. J Trauma,2011,71:270~271
3Zhenyu P, Aixi Y, Guo-Rong Y, et al. Treatment of serious femoral neckfractures with the transposition of vascularized greater trochanter bone flapin young adults. J Reconstr Microsurg,2011,27:303~308
4Davidovitch RI, Jordan CJ, Egol KA, et al. Challenges in the treatment offemoral neck fractures in the nonelderly adult. J Trauma,2010,68:236~242
5Jun X, Chang-Qing Z, Kai-Gang Z, et al. Modified free vascularizedfibular grafting for the treatment of femoral neck nonunion. J OrthopTrauma,2010,24:230~235
6Kannan MB, Raman RK. In vitro degradation and mechanical integrity ofcalcium-containing magnesium alloys in modified-simulated body fluid.Biomaterials,2008,29(15):2306~2314
7Robert SB. Magnesium Products Design. New York: Marcle Dekker,1987
8王德云,东青,陈传忠,等.微弧氧化技术进展.硅酸盐学报,2005,33(9):1133~1137
9蒋百灵,吴建国,张淑芬,等.镁合金微弧氧化生长过程及微观结构的研究.材料热处理学报,2002,23(1):5~8
10Sergei VG, Oleg SP, Vitalyi SS. Unseeded precipitation of calcium andmagnesium phosphates from modified seawater solutions. J of CrystGrowth,1999,205(3):354~360
11Kuwahara H, Al-Abdullat Y, Mazaki N, et al. Precipitation of magnesiumapatite on pure magnesium surface during immersing in Hank’s solution.Mater Trans,2001,42(7):1317~1321
12宋光铃.镁合金的腐蚀与防护.北京：化学工业出版社,2004
13Staiger MP, Pietak AM, Huadmai J, et al. Magnesium and its alloys asorthopedic biomaterials: A review. Biomaterials,2006,27(9):1728~1734
1Hartwig A. Role of magnesium in genomic stability. Mutat Res/Fund MolMech Mutagen,2001,475(1-2):113~121
2Okuma T. Magnesium and bone strength. Nutrition,2001,17(7-8):679~680
3De Valk H. Magnesium in diabetes mellitus. The Netherlands journal ofmedicine,1999,54(4):139
4Saris N, Mervaala E, Karppanen H, et al. Magnesium an update onphysiological, clinical and analytical aspects. Clinica chimica acta,2000,294(1-2):1~26
5Okuma T. Magnesium and bone strength. Nutrition,2001,17(7-8):679~680
6Fatemi S, Ryzen E, Flores J, et al. Effect of experimental humanmagnesium depletion on parathyroid hormone secretion and1,25-dihydroxyvitamin D metabolism. J Clin Endocrinol Metab,1991,73:1067~1072
7Risco F, Traba ML. Influence of magnesium on the in vitro synthesis of24,25-dihydroxyvitamin D3and1-α,25-dihydroxyvitamin D3. MagnesiumRes,1992,5:5~14
8Rude RK, Kirchen ME, Gruber HE, et al. Magnesium deficiency-inducedosteoporosis in the rat: Uncoupling of bone formation and bone resorption.Magnes Res,1999,12:257~267
9Leidi M, Dellera F, Mariotti M, et al. High magnesium inhibits humanosteoblast differentiation in vitro. Magnes Res,2011,24:1~6
10孟昭亭.骨钙素及其临床意义.中华内分泌代谢杂志,1992,8:41
11Sun YQ, Ashhurst DE. Osteogenic growth peptide enhances the rate offracture healing in rabbits. Cell Biol Int,1998,22:313
12Lerner UH. The role of skeletal nerve fibers in bone metabolism.Endocrinologist,2000,10:377~382
13McIntosh TK. Novel pharmacologic therapies in the treatment ofexperimental traumatic brain injury: A review. J Am Chem Soc,1993,89:2719~2725
14Rude RK, Gruber HE, Norton HJ, et al. Reduction of dietary magnesiumby only50%in the rat disrupts bone and mineral metabolism. OsteoporosisInt,2006,17:1022~1032
15Robert RK, Gruber HE, Norton HJ, et al. Dietary magnesium reduction to25%of nutrient requirement disrupts bone and mineral metabolism in therat. Bone,2005,37:211~219
16Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and magnesium in the stimulation of osteoblast proliferationand migration by platelet-derived growth factor. Am J Physiol Cell Physiol,2009,297:C360~368
17Crespi R, Mariani E, Benasciutti E, et al. Magnesium-enrichedhydroxyapatite versus autologous bone in maxillary sinus grafting:combining histomorphometry with osteoblast gene expression profiles exvivo. J Periodontol,2009,80:586~593
18Park JW, Kim YJ, Jang JH, et al. Osteoblast response to magnesiumion-incorporated nanoporous titanium oxide surfaces. Clin Oral ImplantsRes,2010,21(11):1278~1287
19Jilka RL, Weistein T, Bellido AM, et al. Osteoblast programmed cell death:modulation by growth faetors and cytokines. J Bone Miner Res,1998,13(3):793~802
20Wang Y, Toury R, Hauehecorne M, et al. Expression of Bcl-2protein inthe epiphyseal plate cartilage and trabecular bone of growing rats.Histochem Cell Biol,1997,108:45~55
21Steller H. Mechanisms and genes of celluar suicid. Science,1995,267:1445~1448
22Kawakami A, Nakane PK, Matsuka N, et al. Fas and Fas ligand interaetionis necessary for human osteoblast apoptosis. J Bone Miner Res,1997,12(10):1637~1646
23Komori T, et al. Regulation of bone development and maintenance byRunx2. Front Biosci,2008,1(13):898~903
24Komori T. Regulation of osteoblast differentiation by transcription factors.J Cell Biochem,2006,99(5):1233~1239
25Kato M，Patel MS，Levasseur R，et al. Cbfa1-independent decrease inosteoblast proliferation， osteopenia， and persistent embryonic eyevascularization in mice deficient in Lrp5，a Wnt coreceptor. J Cell Biol,2002,157:303~314
26Gilbert L, He X, Farmer P, et al. Expression of the osteoblastdifferentiation factor RUNX2(Cbfa1/AML3/Pebp2alpha A) is inhibited bytumor necrosis factor2alpha. Biol Chem,2002,277(4):2695~2701
27Ding J, Ghali O, Lencel P, et al. TNF-alpha and IL-1beta inhibit RUNX2and collagen expression but increase alkaline phosphatase activity andmineralization in human mesenchymal stem cells. Life Sci,2009,84(15-16):499~504
1张英泽.临床创伤骨科学[M].河北:河北科学技术出版社,2004:414.
2Bergmann G, Graichen F, Rohimann A. Instrumentation of a hip jointprosthesis. In: Implantable Telemetry in Orthopaedics,1990, pp:35~63
3Brekelmans WA, Poort HW, Sbooff TJ. A new method to analyse themechanical behaviour of skeletal parts. Acta Orthop Scand,1972,93(5):301~317
4Vasue R, Carter DR, Harris HW. Stress distribution of in the acetabularregion-Ι, before and after total joint replacement. J Biomethanics,1982,15:155~164
5Rapperport DJ, Carter DR, Schurman DJ. Cantact finite element stressanalysis of the hip joint. J Orthop Res,1985,3:435~446
6Goel VK, Valliappan S, Svensson NL. Stresses in the normal pelvis.Comput Biol Med,1978,8:91~104
7Koeneman JB, Hansen TM, Beris K. Three dimentional finite elementsanalysis of the hip joint. Trans ORS,1989,14:223
8Namba RS, Keyak JH, Kim AS, et al. Cementless implant composition andfemoral stress. A finite elements analysis. Clin Orthop Relat Res,1998,347:261~267
9Bucholz RW, Ross SE, Lawrence KL. Fatigue fractures of the intellockingnail in the treatment of the distal part of the femoral shaft. J Bone JointSurg Am,1987,69(9):139
10Cheung G, Zalzal P, Bhandari M, et al. Finite elements analysis of afemoral retrograde intramedullary nail subject to gait loading. Med EngPhys,2004,26(2):93~108
11徐遄,吴勇,贾克斌.数字医学影像与通信的重要标准-DICOM.标准中国医学影像技术,2002,18:76
12Jang SH, Kim WY. Defining a new annotation object for DICOM image: apractical approach. Comput Med Imaging Graph,2004,28(7):371~375
13Escott EJ, Rubinstein D. Free. DICOM image viewing and processingsoftware for your desktop computer: what’s available and what it can dofor you. Radiographics,2003,23(5):1341~1357
14Kling PT, Rydmark M. Modeling and modification of medical3D objects:The benefit of using a haptic modeling tool. Stud Health Technol Inform,2000,70:162~167
15Durand LG, Garcia D, Sakr F, et al. A new flow model for Dopplerultrasound study of prosthetic heart valves. J Heart Valve Dis,1999,8(1):85~95
16Taylor WR, Roland E, Ploeg H, et al. Determination of orthotropic boneelastic constants using FEA and modal analysis. J Biomech,2002,35(6):767~773
17Merz B, Niederer P, Muller R, et al. Automated finite element analysis ofexcised human femora based on precision-QCT. J Biomech Eng,1996,118(3):387~390
18Cattaneo PM, Dalstra M, Frich LH. A three-dimensional finite elementmodel from computed tomography data: a semi-automated method. ProcInst Mech Eng H,2001,215(2):203~213
19Marom SA, Linden MJ. Computer aided stress analysis of long bonesutilizing computed tomography. J Biomech,1990,23(5):399~404
20Zannoni C, Mantovani R, Viceconti M. Material properties assignment tofinite element models of bone structures: a new method. Med Eng Phys,1998,20(10):735~740
21Rho JY, Hobatho MC, Ashman RB. Relations of mechanical properties todensity and CT numbers in human bone. Med Eng Phys,1995,17(5):347~355
22Esses SI, Lotz JC, Hayes WC. Biomechanical properties of the proximalfemur determined in vitro by single-energy quantitative computedtomography. J Bone Miner Res,1989,4(5):715~722
23Peng L, Bai J, Zeng X, et al. Comparison of isotropic and orthotropicmaterial property assignments on femoral finite element models under twoloading conditions. Med Eng Phys,2006,28(3):227~233
24Baca V, Horak Z, Mikulenka P, et al. Comparison of an inhomogeneousorthotropic and isotropic material models used for FE analyses. Med EngPhys,2008,30(7):924~930
25Crowninshield RD, Brand RA. A physiologically based criterion of muscleforce prediction in locomotion. J Biomechanics,1981,14:793~801
26Dalstra M, Huiskes R. Load transfer across the pelvic bone. JBiomechanics,1995,28(6):715~724
27Antekeier SB, Burden RL Jr, Voor MJ, et al. Mechanical study of the safedistance between distal femoral fracture site and distal locking screws inantegrade intramedullary nailing. J Orthop Trauma,2005,19(10):693~697
28Taylor ME, Tanner KE, Freeman MA, et al. Stress and strain distributionwithin the intact femur: compression or bending? Med Eng Phys,1996,18(2):122~131
29Bergmann G, Graichen F, Rohimann A. Five month in vivo measurement ofhip joint forces. Proc Congr Int Soc Biomech,1989,12:43
1Jun X, Chang-Qing Z, Kai-Gang Z, et al. Modified free vascularizedfibular grafting for the treatment of femoral neck nonunion. J OrthopTrauma,2010,24(4):230~235
2Sen RK, Tripathy SK, Goyal T, et al. Osteosynthesis of femoral-necknonunion with angle blade plate and autogenous fibular graft. Int Orthop,2012,36(4):827~832
3Bhuyan BK. Augmented osteosynthesis with tensor fascia latae musclepedicle bone grafting in neglected femoral neck fracture. Indian J Orthop,2012,46(4):439~446
4Singh MP, Aggarwal AN, Arora A, et al. Unstable recent intracapsularfemoral neck fractures in young adults: osteosynthesis and primary valgusosteotomy using broad dynamic compression plate. Indian J Orthop,2008,42(1):43~48
5Goldberg VM. Selection of bone grafts for revision total hip arthroplasty.Clin Orthop,2000,381:68~76
6Bramfeldt H, Sabra G, Centis V, et al. Scaffold vascularization: a challengefor three-dimensional tissue engineering. Curr Med Chem,2010,17(33):3944~3967
7Wang Y, Huang YC, Gertzman AA, et al. Endogenous regeneration ofcritical-size chondral defects in immunocompromised rat xiphoid cartilageusing decellularized human bone matrix scaffolds. Tissue Eng Part A,2012,18(21-22):2332~2342
8Schwartz Z, Hyzy SL, Moore MA, et al. Osteoinductivity of demineralizedbone matrix is independent of donor bisphosphonate use. J Bone JointSurg Am,2011,93(24):2278~2286
9Kirk JF, Ritter G, Waters C, et al. Osteoconductivity and osteoinductivityof NanoFUSE() DBM. Cell Tissue Bank,2013,14(1):33~44
1Staiger MP, Pietak AM, Huadmai J, et al. Magnesium and its alloys asorthopedic biomaterials: A review. Biomaterials,2006,27:1728~1734
2Witte F, Hort N, Vogt C, et al. Degradable biomaterials based onmagnesium corrosion. Curr Opin Solid State Mater Sci,2008,12:63~72
3Hort N, Huang Y, Fechner D, et al. Magnesium alloys as implantmaterials–Principles of property design for Mg-RE alloys. ActaBiomaterialia,2010,6:1714~1725
4Pollock TM. Weight loss with magnesium alloys. Science,2010,328:986~987
5Erbel R, Di Mario C, Bartunek J, et al. Temporary scaffolding ofcoronary arteries with bioabsorbable magnesium stents: a prospective,non-randomised multicentre trial. Lancet,2007,369:1869~1875
6Witte F. The history of biodegradable magnesium implants: A review.Acta Biomaterialia,2010,6:1680~1692
7Rose IA. The state of magnesium in cells as estimated from the adenylatekinase equilibrium. Proc Natl Acad Sci USA,1968,61:1079~1086
8Witte F, Feyerabend F, Maier P, et al. Biodegradablemagnesium-hydroxyapatite metal matrix composites. Biomaterials,2007,28:2163~2174
9Lambotte A. L’utilisation du magnesium comme materiel perdu dansl’osteosynthese. Bull Mem Soc Nat Chir,1932,28:1325~1334
10Troitskii VV, Tsitrin DN. The resorbing metallic alloy ‘Osteosinthezit’ asmaterial for fastening broken bone. Khirurgiia,1944,8:41~44
11Znamenskii MS. Metallic osteosynthesis by means of an apparatus madeof resorbing metal. Khirurgiia,1945,12:60~63
12McBride ED. Absorbable metal in bone surgery. J Am Med Assoc,1938,111:2464~2467
13Troganov GB, Savitsky E, Mikhailovich T, et al. Magnesium-base alloysfor use in bone surgery. US Patent no.3,1972,687:135
14Serre CM, Papillard M, Chavassieux P, et al. Influence of magnesiumsubstitution on a collagen-apatite biomaterial on the production of acalcifying matrix by human osteoblasts. J Biomed Mater Res,1998,42:626~633
15Zeng RC, Dietzel W, Witte F, et al. Progress and challenge formagnesium alloys as biomaterials. Adv Eng Mater,2008,10: B3~B14
16Gu X, Zheng Y, Cheng Y, et al. In vitro corrosion and biocompatibility ofbinary magnesium alloys. Biomaterials,2009,30:484~498
17Witte F, Fischer J, Nellesen J, et al. In vitro and in vivo corrosionmeasurements of magnesium alloys. Biomaterials,2006,27:1013~1018
18Witte F, Kaese V, Haferkamp H, et al. In vivo corrosion of fourmagnesium alloys and the associated bone response. Biomaterials,2005,26:3557~3563
19Kannan MB, Raman RK. In vitro degradation and mechanical integrity ofcalcium-containing magnesium alloys in modified-simulated body fluid.Biomaterials,2008,29:2306~2314
20Li Z, Gu X, Lou S, et al. The development of binary Mg-Ca alloys for useas biodegradable materials within bone. Biomaterials,2008,29:1329~1344
21Zhang S, Zhang X, Zhao C, et al. Research on an Mg-Zn alloy as adegradable biomaterial. Acta Biomater,2010,6:626~640
22Wong HM, Yeung KW, Lam KO, et al. A biodegradable polymer-basedcoating to control the performance of magnesium alloy orthopaedicimplants. Biomaterials,2010,31:2084~2096
23Xin Y, Jiang J, Huo K, et al. Corrosion resistance and cytocompatibilityof biodegradable surgical magnesium alloy coated with hydrogenatedamorphous silicon,2009,89:717~726
24Xu L, Zhang E, Yang K. Phosphating treatment and corrosion propertiesof Mg-Mn-Zn alloy for biomedical application. J Mater Sci Mater Med,2009,20:859~867
25Zberg B, Uggowitzer PJ, L ffler JF. Mg-Zn-Ca glasses without clinicallyobservable hydrogen evolution for biodegradable implants. Nat Mater,2009,8:887~891
26Domingo JL. Aluminum and other metals in Alzheimer’s disease: Areview of potential therapy with chelating agents. J Alzheimer’s Dis,2006,10:331~341
27Yun YH, Dong ZY, Lee N, et al. Revolutionizing biodegradable metals.Mater Today,2009,12:22~32
28Atiyeh BS, Costagliola M, Hayek SN, et al. Effect of silver on burnwound infection control and healing: Review of the literature. Burns,2007,33:139~148
29Tie D, Feyerabend F, Müller WD, et al. Antibacterial biodegradableMg-Ag alloys. Eur Cell Mater,2013,25:284~298
30Paton BE, Kaleko DM, Koval YM, et al. Influence of alloying with silverand tantalum on features of medical-purpose Ti-Ni alloy. Metallofiz NovTekhnol-Met Phys Adv Techn,2010,32:1691~1703
31Necula BS, Apachitei I, Tichelaar FD, et al. An electron microscopicalstudy on the growth of TiO2-Ag antibacterial coatings on Ti6Al7Nbbiomedical alloy. Acta Biomaterialia,2011,7:2751~2757
32Bosetti M, Massè A, Tobin E, et al. Silver coated materials for externalfixation devices: in vitro biocompatibility and genotoxicity. Biomaterials,2002,23:887~892
33Hardes J, Streitburger A, Ahrens H, et al. The influence of elementarysilver versus titanium on osteoblast behaviour in vitro using humanosteosarcoma cell lines. Sarcoma,2007,265:39
34Drake PL, Hazelwood KJ. Exposure-related health effects of silver andsilver compounds: A review. Ann Occup Hyg,2005,49:575~585
35Willumeit R, Fischer J, Feyerabend F, et al. Chemical surface alterationof biodegradable magnesium exposed to corrosion media. Acta Biomater,2011,7:2704~2715
36Feyerabend F, Drücker H, Laipple D, et al. Ion release from magnesiummaterials in physiological solutions under different oxygen tensions. JMater Sci Mater Med,2012,23:9~24
37Jang Y, Collins B, Sankar J, et al. Effect of biologically relevant ions onthe corrosion products formed on alloy AZ31B: An improvedunderstanding of magnesium corrosion. Acta Biomater,2013,9(10):8761~8770
38Rude RK, Shils ME. Magnesium. In Shils ME (ed):“Modern Nutrition inHealth and Disease.” Philadelphia, PA: Lippincott, Williams and Wilkins,2006, pp223~247
39Rude RK. Magnesium deficiency: a heterogeneous cause of disease inhumans. J Bone Miner Res,1998,13:749~758
40Standing Committee on the Scientific Evaluation of Dietary ReferenceIntakes, Food and Nutrition Board, Institute of Medicine:“DietaryReference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, andFluoride.” Washington, DC: National Academy Press,1997, pp190~249
41Mountokalakis T, Singhellakis P, Alevizaki C, et al. Relationshipbetween degree of renal failure and impairment of intestinal magnesiumabsorption. In Seelig MS (ed):“Magnesium in Health and Disease.” NewYork: Spectrum Publications, Inc,1980, pp453~458
42Martin BJ. The magnesium load test: experience in elderly subjects.Aging,1990,2:291~296
43Rubin H. Central roles of Mg2+and of MgATP2-in the regulation ofprotein synthesis and cell proliferation: significance for neoplastictransformation. Adv Cancer Res,2005,93:1~58
44Rubin H. Magnesium: The missing element in molecular views of cellproliferation control. Bioessays,2005,27:311~320
45Rubin H, Terasaki M, Sanui H. Major intracellular cations and growthcontrol: Correspondence among magnesium content, protein synthesis,and the onset of DNA synthesis in Balb/c3T3cells. Proc Natl Acad SciUSA,1979,76:3917~3921
46Rubin H, Terasaki M, Sanui H. Magnesium reverses inhibitory effects ofcalcium deprivation on coordinate response of3T3cells to serum. ProcNatl Acad Sci USA,1978,75:4379~4383
47Schreier MH, Staehelin T. Initiation of mammalian protein synthesis: theimportance of ribosome and initiation factor quality for the efficiency ofin vitro systems. J Mol Biol,1973,73:329~349
48Terasaki M, Rubin H. Evidence that intracellular magnesium is present incells at a regulatory concentration for protein synthesis. Proc Natl AcadSci USA,1985,82:7324~7326
49Vidair C, Rubin H. Mg2+as activator of uridine phosphorylation and othercellular responses to growth factors. Proc Natl Acad Sci USA,2005,102:662~666
50Dennis PB, Jaeschke A, Saitoh M, et al. Mammalian TOR: a homeostaticATP sensor. Science,2001,294:1102~1105
51Lau YT, Yassin RR, Horowitz SB. Potassium salt microinjection intoXenopus oocytes mimics gonadotropin treatment. Science,1988,240:1231~1233
52Achs MJ, Garfinkel D. Computer simulation of energy metabolism inanoxic perfused rat heart. Am J Physiol,1982,232:R164~174
53Grubbs RD. Effect of epidermal growth factor on Mg2+homeostasis inBC3H-1myocytes. Am J Physiol,1991,260:C1158~1164
54Ishijima S, Sonoda T, Tatibana M. Mitogen-induced early increase incytosolic free Mg2+concentration in single Swiss3T3fibroblasts. Am JPhysiol,1991,261:C1074~1080
55Trzeciakiewicz A, Opolski A, Mazur A. TRPM7: a protein responsiblefor magnesium homeostasis in a cell. Postepy Hig Med Dosw (Online),2005,59:496~502
56Touyz RM. Transient receptor potential melastatin6and7channels,magnesium transport, and vascular biology: implications in hypertension.Am J Physiol Heart Circ Physiol,2008,294:H1103~1118
57Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and cations (magnesium, calcium) in human osteoblast-likecell proliferation. Cell Prolif,2007,40:849~865
58Chubanov V, Gudermann T, Schlingmann KP. Essential role for TRPM6in epithelial magnesium transport and body magnesium homeostasis.Pflugers Arch,2005,451:228~234
59He Y, Yao G, Savoia C, et al. Transient receptor potential melastatin7ionchannels regulate magnesium homeostasis in vascular smooth musclecells: role of angiotensin II. Circ Res,2005,96:207~215
60Clapham DE, Runnels LW, Strubing C. The TRP ion channel family. NatRev Neurosci,2001,2:387~396
61Harteneck C, Plant TD, Schultz G. From worm to man: three subfamiliesof TRP channels. Trends Neurosci,2000,23:159~166
62Minke B, Cook B. TRP channel proteins and signal transduction. PhysiolRev,2002,82:429~472
63Montell C, Birnbaumer L, Flockerzi V. The TRP channels, a remarkablyfunctional family. Cell,2002,108:595~598
64Harteneck C. Function and pharmacology of TRPM cation channels.Naunyn Schmiedebergs Arch Pharmacol,2005,371:307~314
65Fleig A, Penner R. The TRPM ion channel subfamily: molecular,biophysical and functional features. Trends Pharmacol Sci,2004,25:633~639
66Nadler MJ, Hermosura MC, Inabe K, et al. LTRPC7is aMg.ATP-regulated divalent cation channel required for cell viability.Nature,2001,411:590~595
67Schmitz C, Dorovkov MV, Zhao X, et al. The channel kinases TRPM6and TRPM7are functionally nonredundant. J Biol Chem,2005,280:37763~37771
68Chubanov V, Waldegger S, Schnitzler M, et al. Disruption ofTRPM6/TRPM7complex formation by a mutation in the TRPM6genecauses hypomagnesemia with secondary hypocalcemia. Proc Natl AcadSci USA,2004,101:2894~2899
69Baserga R. In: The Biology of Cell Reproduction. Boston: Harvard Univ.Press,1985,138~140
70Wallach S. Effects of magnesium on skeletal metabolism. Magnes TraceElem,1990,9:1~14
71Rude RK, Kirchen ME, Gruber HE, et al. Magnesium deficiency-inducedosteoporosis in the rat: Uncoupling of bone formation and boneresorption. Magnes Res,1999,12:257~267
72Leidi M, Dellera F, Mariotti M, et al. High magnesium inhibits humanosteoblast differentiation in vitro. Magnes Res,2011,24:1~6
73Yun Y, Dong Z, Tan Z, et al. Development of an electrode cellimpedance method to measure osteoblast cell activity inmagnesium-conditioned media. Anal Bioanal Chem,2010,396:3009~3015
74Rude RK. Magnesium homeostasis. In Bilezikian JB, Raisz L, Rodan G(eds):“Principles of Bone Biology,”3rd ed. San Diego, CA: AcademicPress,2008, pp487~513
75Fatemi S, Ryzen E, Flores J, et al. Effect of experimental humanmagnesium depletion on parathyroid hormone secretion and1,25-dihydroxyvitamin D metabolism. J Clin Endocrinol Metab,1991,73:1067~1072
76Litosch I. G protein regulation of phospholipase C activity in amembrane-solubilized system occurs through an Mg2+-andtime-dependent mechanism. J Bio Chem,1991,266:4764~4771
77Volpe P, Alderson-Lang BH, Nickols GA. Regulation of inositol1,4,5-trisphosphate-induced Ca2+release. I. Effect of Mg2+. Am J Physiol,1990,258:C1077~C1085
78Northup JK, Smigel MD, Gilman AG. The guanine nucleotide activatingsite of the regulatory component of adenylate cyclase: Identification byligand binding. J Biol Chem,1982,257:11416~11423
79Rude RK, Adams JS, Ryzen E, et al. Low serum concentrations of1,25-dihydroxyvitamin D in human magnesium deficiency. J ClinEndocrinol Metab,1985,61:933~940
80Risco F, Traba ML. Influence of magnesium on the in vitro synthesis of24,25-dihydroxyvitamin D3and1-α,25-dihydroxyvitamin D3.Magnesium Res,1992,5:5~14
81Saggese G, Federico G, Bertelloni S, et al. Hypomagnesemia and theparathyroid hormone-vitamin D endocrine system in children withinsulin-dependent diabetes mellitus: effect of magnesium administration.J Pediatr,1991,118:220~225
82Welsh JJ, Weaver VM. Adaptation to low dietary calcium inmagnesium-deficient rats. J Nutr,1988,118:729~734
83Christiansen P. The skeleton in primary hyperparathyroidism: a reviewfocusing on bone remodeling, structure, mass, and fracture. APMIS Suppl,2001,102:1~52
84Gruber HE, Rude RK, Wei L, et al. Magnesium deficiency: effect onbone mineral density in the mouse appendicular skeleton. BMCMusculoskelet Disord,2003,17:4~7
85Mackie EJ. Osteoblasts: novel roles in orchestration of skeletalarchitecture. Int J Biochem Cell Biol,2003,35:1301~1305
86Park JW, Kim YJ, Jang JH, et al. Osteoblast response to magnesiumion-incorporated nanoporous titanium oxide surfaces. Clin Oral ImplantsRes,2010,21(11):1278~1287
87Park JW, An CH, Jeong SH, et al. Osseointegration of commercialmicrostructured titanium implants incorporating magnesium: ahistomorphometric study in rabbit cancellous bone. Clin Oral ImplantsRes,2012,23(3):294~300
88Jeon SH, Kim SJ, Kim JS, et al. Immunosuppressant FK506decreases theintracellular magnesium in the human osteoblast cell by inhibiting theERK1/2pathway. Life Sci,2009,84:23~27
89Jeon SH, Lee MY, Kim SJ, et al. Taurine increases cell proliferation andgenerates an increase in [Mg2+]i accompanied by ERK1/2activation inhuman osteoblast cells. FEBS Lett,2007,22:581:5929~5934
90Lerner UH. The role of skeletal nerve fibers in bone metabolism.Endocrinologist,2000,10:377~382
91McIntosh TK. Novel pharmacologic therapies in the treatment ofexperimental traumatic brain injury: A review. J Am Chem Soc,1993,89:2719~2725
92Weglicki WB, Dickens BF, Wagner TL, et al. Immunoregulation byneuropeptides in magnesium deficiency: Ex vivo effect of enhancedsubstance P production on circulation T lymphocytes frommagnesium-deficient mice. Magnes Res,1996,9:3~11
93Kramer JH, Phillips TM, Weglicki WB. Magnesium-deficiency-enhancedpost-ischemic myocardial injury is reduced by substance P receptorblockade. J Mol Cell Cardiol,1997,29:97~110
94Malpuech-Brugere C, Nowacki W, Rock E, et al. Enhanced tumornecrosis factor-a production following endotoxin challenge in rats is anearly event during magnesium deficiency. Biochimica et Biophysica Acta,1999,1453:35~40
95Nakagawa M, Oono H, Nishio A. Enhanced productrion of IL-1β andIL-6following endotoxin challenge in rats with dietary magnesiumdeficiency. J Vet Med Sci,2001,6:467~469
96Malpuech-Brugere C, Nowacki W, Daveau M, et al. Inflammatoryresponse following acute magnesium deficiency in the rat. BiochimicaBiophysica Acta,2000,1501:91~98
97Rameshwar P, Ganea D, Gascon P. Induction of IL-3andgranulocyte-macrophage colony stimulating factor by substance P inbone marrow cells in partially mediated through the release of IL-1andIL-6. J Immunol,1994,152:4044~4054
98Miyaura C, Kusano K, Masuzawa T, et al. Endogenous bone-resorbingfactors in estrogen deficiency: cooperative effect of IL-1β and IL-6. JBone Miner Res,1995,10:1365~1373
99Nanes MS. Tumor necrosis factor-a: molecular and cellular mechanism inskeletal pathology. Gene,2003,321:1~15
100Rude RK, Gruber HE, Wei LY, et al. Magnesium deficiency: effect onbone and mineral metabolism in the mouse. Calcif Tiss Int,2003,72:32~41
101Rude RK, Gruber HE, Norton HJ, et al. Reduction of dietary magnesiumby only50%in the rat disrupts bone and mineral metabolism.Osteoporosis Int,2006,17:1022~1032
102Rude RK, Gruber HE, Norton HJ, et al. Bone loss induced by dietarymagnesium reduction to10%Nutrient Requirement in rats is associatedwith increase release of substance P and tumor necrosis factor-a. J Nutr,2004,134:79~85
103Robert RK, Gruber HE, Norton HJ, et al. Dietary magnesium reduction to25%of nutrient requirement disrupts bone and mineral metabolism in therat. Bone,2005,37:211~219
104Hofbauer LC, Heufelder AE. The role of receptor activator of nuclearfactor-kB ligand and osteoprotegerin in the pathogenesis and treatment ofmetabolic bone diseases. J Clin Endocrinol Metab,2000,85:2355~2363
105Manolagas SC. Birth and death of bone cells: basic regulatorymechanisms and implications for the pathogenesis and treatment ofosteoporosis. Endocr Rev,2000,21:115~137
106Rude RK, Gruber HE, Wei LY, et al. Immunolocalization of RANKL isincreased and OPG decreased during dietary magnesium deficiency in therat. Nutr Met,2005,2:1~8
107Crespi R, Mariani E, Benasciutti E, et al. Magnesium-enrichedhydroxyapatite versus autologous bone in maxillary sinus grafting:combining histomorphometry with osteoblast gene expression profiles exvivo. J Periodontol,2009,80:586~593
108Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and magnesium in the stimulation of osteoblast proliferationand migration by platelet-derived growth factor. Am J Physiol CellPhysiol,2009,297:C360~368
109Abed E, Labelle D, Martineau C, et al. Expression of transient receptorpotential (TRP) channels in human and murine osteoblast-like cells. MolMembr Biol,2009,26:146~158
110Abed E, Moreau R. Importance of melastatin-like transient receptorpotential7and cations (magnesium, calcium) in human osteoblast-likecell proliferation. Cell Prolif,2007,40:849~865
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |