兔骨质疏松模型的快速建立和硫酸钙复合bBMP在椎体强化中的实验研究
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摘要
一、研究背景
骨质疏松症最常见的并发症是椎体压缩骨折，手术治疗包括脊柱内固定和椎体成形术或球囊扩张椎体成形术。椎体成形术是近年来发展起来一种新的脊柱微创手术，该技术已经在临床上取得了很好的效果，在椎体的骨质疏松性骨折及多种良、恶性椎体病变中得到广泛的应用。可以快速缓解疼痛，纠正脊柱畸形，由于椎体成形术创伤小、效果好且疗效快,已成为脊柱微创介入治疗的又一重要方法。临床上现在最常用的椎体成形术的材料为聚甲基丙烯酸甲酯（PMMA）。但PMMA充填材料具有许多缺点：由于PMMA自身具有过高的硬度，导致术后产生的应力集中增加了邻近椎体发生压缩骨折的风险。PMMA的体外聚合温度可达到100多度，术中的发热反应会引起相应周围组织及神经的损伤和坏死；PMMA不能降解，不能融入周围的骨组织并最终被自身骨组织爬行替代，不能促进周围骨的生成和重建，无直接的骨沉积作用；另外PMMA单体还有潜在的全身系统过敏及毒性反应。而且临床越来越要求成形材料能够携带有特殊治疗作用的药物，而PMMA并不能满足这些临床治疗的需要。如何探索一种具有良好生物相容性的成形材料，其在作为固定材料的同时又能成为携带具有特殊治疗作用的药物的载体，是本研究的目的。
二、研究目的
1.探索采用去势法+甲强龙诱导法快速建立兔子骨质疏松模型的方法：通过对去势法+甲强龙诱导后兔骨质疏松模型的皮质骨和松质骨骨结构特性和生物力学特性的改变进行评价，从而探索出一种快速建立兔骨质疏松模型的方法，为骨科领域的相关研究提供新模型。
2.在已经建立的骨质疏松模型体内，采用“二维平面-三维立体-生物力学”的全方位的评价手段，通过对模型的骨结构参数、椎体骨密度以及生物力学参数的检测，评价硫酸钙以及硫酸钙复合BMP对骨质疏松骨结构的改善和强度提高的作用。
三研究内容和方法
第一部分建立兔的骨质疏松模型并进行分析和评价
将20只新西兰大白兔采用随机对照的方法分为：去势（OVX）A组（n=4）、B组（n=8）和假手术组（Sham，n=8）。A组为单纯OVX组，B组为OVX+甲强龙肌注（4周）组。所有动物术前和术后2月均采用双能X线吸收骨密度仪测定腰椎骨密度。术后2个月：①采用DEXA对所有动物的股骨干皮质骨和股骨髁部松质骨的骨密度进行测量。②采用病理组织学切片的方法对骨的二维结构变化进行观察和评价。③采用micro-CT对骨的三维结构改变进行分析和评价。④采用生物力学强度试验，对试验动物的皮质骨和松质骨骨强度变化进行分析评估。
第二部分硫酸钙（calcium sulfate CSC）复合bBMP材料在椎体强化中的实验研究
采用随机对照研究方案，将60只新西兰大白兔随机分为C1组、C2组、C3组、C4组（n=12）和假手术组（Sham，n=12）。C组按照实验一方法建立骨质疏松模型，实验分为假手术对照组（Sham），骨质疏松对照组（C1），注射PMMA组（C2），注射CSC组（C3），注射CSC/bBMP组（C4），通过模拟椎体成形术，分别在每只兔子L2、L4、L6椎体注射材料，每组均于术后24小时，6周、12周各处死4只。①采用病理组织学切片的方法观察和评价松质骨骨小梁的二维结构改变。②采用micro-CT进行分析和评价松质骨骨小梁的三维结构改变。③采用生物力学强度试验分析和评估实验动物松质骨骨小梁的骨强度变化。通过“骨二维平面结构-三维立体结构-生物力学强度”的综合手段，评价硫酸钙和硫酸钙复合bBMP材料对提高骨质疏松椎体强度的作用。
四研究结果
第一部分：Sham、OVX-A及OVX-B各组的腰椎BMD测量值在术前分别为：（266.7±38.58）mg/cm~2、（270.1±25.38）mg/cm~2和（272.8±27.08）mg/cm~2手术2个月后，Sham组、OVX-A组和OVX-B组的BMD分别为（281.8±39.22）mg/cm~2、（248.9±26.14）mg/cm~2和（199.9±30.76）mg/cm~2。OVX-B组的BMD较术前平均下降为26.72％。组织学切片观察发现，去势2个月后，OVX-B组椎体及股骨松质骨骨小梁明显稀疏、变细，局部存在骨小梁骨折及骨缺损;而Sham和OVX-A对照组松质骨具有良好的类圆形或椭圆形的完整骨小梁拱形结构。显微CT结果表明：OVX-B组的骨小梁结构改变与Sham组及OVX-A组相比较有显著差异，表现为骨小梁连续性显著下降，骨小梁柱明显变细，而OVX-A组与Sham组相比骨小梁三维结构无显著变化。生物力学实验结果显示，OVX-B组椎体的抗压缩强度（6.8±2.02MPa）较Sham组（14.5±3.74MPa）和OVX-A组（12.8±3.12MPa）均有显著性降低，而OVX-A组与Sham组无显著性差异。
第二部分：在组织病理学切片二维平面观察中，术后6周和12周，CSC组和CSC/bBMP组骨小梁结构形态的改善明显优于C1对照组。骨小梁的微骨折及缺损处显示新生的骨修复和连接，骨小梁柱体变粗，形态比较规则，连续性显著好于对照组。12周时骨小梁结构已经接近Sham对照组。Micro-CT三维重建显示，6周时, CSC组和CSC/bBMP组骨小梁组的骨小梁三维结构参数明显优于C1对照组(P<0.05)，骨密度值也明显优于C1对照组(P<0.05)；12周时，已与Sham对照组无显著性差别。生物力学实验结果表明，在6周时，CSC组椎体的最大抗压缩强度有增加，但与C1对照组相比无显著性差异，而CSC/bBMP组椎体抗压缩强度在6周时显著高于C1对照组；在12周时，CSC组和CSC/bBMP组椎体最大抗压缩强度均较C1对照组有显著性差异(P<0.05)，与Sham组及PMMA组相比，未见显著性差异(P>0.05)。
五结论
1.通过去势+甲强龙肌注的方法，可以在2个月内快速建立兔的骨质疏松模型。
2.兔骨质疏松模型建成后，二维及三维图像显示椎体松质骨内骨小梁稀疏、变细、断裂，可见明确的骨小梁微骨折及骨缺损，骨的三维结构受到严重损坏，从而伴随相应力学强度的降低。是一种理想实用的骨质疏松动物模型。
3.CSC以及CSC为载体复合bBMP的椎体内注射材料，均具有强大的成骨诱导能力，通过快速地改善骨质疏松椎体内骨小梁的三维结构来提高椎体的结构强度，是具有良好应用价值的骨质疏松椎体内充填材料。
Background
The compression fracture in spine is the most complication of osteoporosis.The primary measures are the medical therapies and braces. The surgicalmeasures include internal fixation, vertebroplasty and kyphoplasty.Vertebroplasty is a minimally invasive surgery in spine developed in recent years.It has got good clinical effects in the therapy of benign or malignant lesions andosteoporosis compression fractures in spine. It has become prevalent inminimally invasive surgery of spine for rapidly relieving the back-pain andcorrecting the deformity. Now, the most commonly used cement ispolymethylmethacrylate (PMMA) in vertebroplasty. Unfortunately, PMMA hasseveral potential disadvantages. PMMA is not bioabsorbable and remainspermanently in the body. Its unreacted monomer is toxic, and its highpolymerization temperature has resulted in temperature readings as much as1220C. The high compressive strength and stiffness of PMMA causes a biomechanical mismatch between treated and untreated vertebral levels whichmay increase the risk of adjacent-level fractures. It has been required that theinjecting materials can carry medicine for special treatments in clinic. So PMMAcan not satisfy these demands. How to explore a biological injecting material，which can not only support the vertebrae but also carry medicine for specialtreatments, is the object of this experiment.
Objective
1. In order to study a rapid osteoporosis animal model which can be used inthe orthopaedic research, the rabbit model is established by ovariectomy (OVX)and injecting solu-medrol. After OVX, it is evaluated by surveying themicro-architectural and biomechanical changes of cancellous and cortical bone.
2. To evaluate the effects of calcium sulfate cement (CSC) and CSCcombined with bovine bone morphogenetic protein (bBMP) on osteoporoticrabbit’s vertebral micro-architecture and biomechanical properties in vivo.
Material and methods
Part1Establishment and evaluation of an osteoporosis rabbit model.
20adult rabbits were divided into three groups randomly, includingsham-operated group (n=8), OVX-A group (n=4) and OVX-B (n=8) group.OVX-B group was started to inject solu-medrol for4consecutive weeks after2weeks late of OVX. Sham group and OVX-A group were control groups. Beforeand2months after the operation, the measure of dual energy x-rayabsorptiometry (DEXA) was done on all the rabbits’ lumbar vertebrae twice.2months after the operation, the rabbits were sacrificed and the femoral condyle andshaft and the spines were harvested. The cortical bone (femoral shaft) andtrabecular bone(spine and femoral condyle) were measured by DEXA andreconstructed by micro-CT. The strength of vertebral bodies was determined by compressive mechanical measurment of vertebra cancellous bone. Themechanical properties of cortical bone (femur shaft) were evaluated bythree-point-bending tests.
Part2the study on the vertebrae augmentaion in osteoporotic rabbitvertebrae with calcium sulfate (CSC)/bBMP composite.
60adult rabbits were were divided into five groups randomly, includingsham-operated group (n=12), C1group (n=12), C2group (n=12), C3group (n=12)and C4group (n=12). C groups were estabilished osteoporotic rabbit modelsaccording to the methods of part1experiments. Sham group and C1group werecontrol groups.0.1-0.2ml PMMA (Group C2), CSC (Group C3) and CSC/bBMP(Group C4) were injected into L2, L4and L6vertebra of every rabbits.4rabbitswere killed respectively from every group in24hours,6weeks and12weeksafter PVP. The changes of trabecular architecture were reviewedhistomorphologically. Micro-architecture changes of vertebrae were measured bymicro-CT after the rabbits were killed. The vetebral specimens’ strength wasevaluated by axial compression tests.
Result
Part1: The lumbar spine BMD of pre-OVX in Sham group, OVX-A andOVX-B group were （266.7±38.58）mg/cm~2、（270.1±25.38）mg/cm~2and（272.8±27.08）mg/cm~2respectively.2months later, the BMD of post-OVX inSham group, OVX-A and OVX-B group were （281.8±39.22） mg/cm~2、（248.9±26.14）mg/cm~2and（199.9±30.76）mg/cm~2respectively. BMD in OVX-Bdecreased by26.72%compared with the pre-OVX BMD. Compared with that insham group and OVX-A group, trabecular bone reduced significantly in OVX-Bgroup, histomorphologically. The microfracture and microdefect of trabecularbone could be seen in OVX-B. The parameters of trabecular bone had significantly difference compared with control groups (p<0.05). In mechanicaltesting, the maximum compression strength of vertebrae decreased significantlyin OVX-B compared with that in the other two groups. In3-point bending test ofcortical bone, no difference was observed between three groups.
Part2: Histomorphologically, compared with that in C1group, theconnectivity in group C3and C4was better respectively at6th week and12thweek. The shape of trabecular bone was also better.The architecture of trabecularbone was same as that in sham group. Microfractures and microdefects were alsoless than that in the C1group. After the injection of CSC or CSC/bBMP, theMicro-CT reconstruction analysis showed that the BMD in group C3and C4were significantly higher than that in group C1respectively at6th week and12thweek(P<0.05). In group C3and C4, the trabecular connectivity, thickness andbone fraction were significantly higher than that in C1group and were as good asthe sham group in12th week. The results of the vertebrae maximum compressionstrength in C4was higher significantly than that in C1group in6th week(P<0.05). It was also higher significantly in both C3and C4than that in C1andhad no significantly difference compared with that in sham group and C2groupin12th week.
Conclusion
1. Osteoporosis rabbit model can be rapidly establisher by ovariectomy andinjecting solu-medrol in2months.
2. In the induced rabbit model, the trabecular bone becomes sparsely andthinning. Microfractures and microdefects occur in trabecular and lead to thedeterioration of bone mechanical properties. It is an ideal osteoporosis model forexperiments.
3. CSC and CSC/bBMP injecting in osteoporosis vertebrae can reinforce the
bone quality significantly by repairing the microfractures and microdefects oftrabecular bone. CSC and CSC/bBMP can be applied in the treatment of vertebralosteoporosis.
骨质疏松症最常见的并发症是椎体压缩骨折，手术治疗包括脊柱内固定和椎体成形术或球囊扩张椎体成形术。椎体成形术是近年来发展起来一种新的脊柱微创手术，该技术已经在临床上取得了很好的效果，在椎体的骨质疏松性骨折及多种良、恶性椎体病变中得到广泛的应用。可以快速缓解疼痛，纠正脊柱畸形，由于椎体成形术创伤小、效果好且疗效快,已成为脊柱微创介入治疗的又一重要方法。临床上现在最常用的椎体成形术的材料为聚甲基丙烯酸甲酯（PMMA）。但PMMA充填材料具有许多缺点：由于PMMA自身具有过高的硬度，导致术后产生的应力集中增加了邻近椎体发生压缩骨折的风险。PMMA的体外聚合温度可达到100多度，术中的发热反应会引起相应周围组织及神经的损伤和坏死；PMMA不能降解，不能融入周围的骨组织并最终被自身骨组织爬行替代，不能促进周围骨的生成和重建，无直接的骨沉积作用；另外PMMA单体还有潜在的全身系统过敏及毒性反应。而且临床越来越要求成形材料能够携带有特殊治疗作用的药物，而PMMA并不能满足这些临床治疗的需要。如何探索一种具有良好生物相容性的成形材料，其在作为固定材料的同时又能成为携带具有特殊治疗作用的药物的载体，是本研究的目的。
二、研究目的
1.探索采用去势法+甲强龙诱导法快速建立兔子骨质疏松模型的方法：通过对去势法+甲强龙诱导后兔骨质疏松模型的皮质骨和松质骨骨结构特性和生物力学特性的改变进行评价，从而探索出一种快速建立兔骨质疏松模型的方法，为骨科领域的相关研究提供新模型。
2.在已经建立的骨质疏松模型体内，采用“二维平面-三维立体-生物力学”的全方位的评价手段，通过对模型的骨结构参数、椎体骨密度以及生物力学参数的检测，评价硫酸钙以及硫酸钙复合BMP对骨质疏松骨结构的改善和强度提高的作用。
三研究内容和方法
第一部分建立兔的骨质疏松模型并进行分析和评价
将20只新西兰大白兔采用随机对照的方法分为：去势（OVX）A组（n=4）、B组（n=8）和假手术组（Sham，n=8）。A组为单纯OVX组，B组为OVX+甲强龙肌注（4周）组。所有动物术前和术后2月均采用双能X线吸收骨密度仪测定腰椎骨密度。术后2个月：①采用DEXA对所有动物的股骨干皮质骨和股骨髁部松质骨的骨密度进行测量。②采用病理组织学切片的方法对骨的二维结构变化进行观察和评价。③采用micro-CT对骨的三维结构改变进行分析和评价。④采用生物力学强度试验，对试验动物的皮质骨和松质骨骨强度变化进行分析评估。
第二部分硫酸钙（calcium sulfate CSC）复合bBMP材料在椎体强化中的实验研究
采用随机对照研究方案，将60只新西兰大白兔随机分为C1组、C2组、C3组、C4组（n=12）和假手术组（Sham，n=12）。C组按照实验一方法建立骨质疏松模型，实验分为假手术对照组（Sham），骨质疏松对照组（C1），注射PMMA组（C2），注射CSC组（C3），注射CSC/bBMP组（C4），通过模拟椎体成形术，分别在每只兔子L2、L4、L6椎体注射材料，每组均于术后24小时，6周、12周各处死4只。①采用病理组织学切片的方法观察和评价松质骨骨小梁的二维结构改变。②采用micro-CT进行分析和评价松质骨骨小梁的三维结构改变。③采用生物力学强度试验分析和评估实验动物松质骨骨小梁的骨强度变化。通过“骨二维平面结构-三维立体结构-生物力学强度”的综合手段，评价硫酸钙和硫酸钙复合bBMP材料对提高骨质疏松椎体强度的作用。
四研究结果
第一部分：Sham、OVX-A及OVX-B各组的腰椎BMD测量值在术前分别为：（266.7±38.58）mg/cm~2、（270.1±25.38）mg/cm~2和（272.8±27.08）mg/cm~2手术2个月后，Sham组、OVX-A组和OVX-B组的BMD分别为（281.8±39.22）mg/cm~2、（248.9±26.14）mg/cm~2和（199.9±30.76）mg/cm~2。OVX-B组的BMD较术前平均下降为26.72％。组织学切片观察发现，去势2个月后，OVX-B组椎体及股骨松质骨骨小梁明显稀疏、变细，局部存在骨小梁骨折及骨缺损;而Sham和OVX-A对照组松质骨具有良好的类圆形或椭圆形的完整骨小梁拱形结构。显微CT结果表明：OVX-B组的骨小梁结构改变与Sham组及OVX-A组相比较有显著差异，表现为骨小梁连续性显著下降，骨小梁柱明显变细，而OVX-A组与Sham组相比骨小梁三维结构无显著变化。生物力学实验结果显示，OVX-B组椎体的抗压缩强度（6.8±2.02MPa）较Sham组（14.5±3.74MPa）和OVX-A组（12.8±3.12MPa）均有显著性降低，而OVX-A组与Sham组无显著性差异。
第二部分：在组织病理学切片二维平面观察中，术后6周和12周，CSC组和CSC/bBMP组骨小梁结构形态的改善明显优于C1对照组。骨小梁的微骨折及缺损处显示新生的骨修复和连接，骨小梁柱体变粗，形态比较规则，连续性显著好于对照组。12周时骨小梁结构已经接近Sham对照组。Micro-CT三维重建显示，6周时, CSC组和CSC/bBMP组骨小梁组的骨小梁三维结构参数明显优于C1对照组(P<0.05)，骨密度值也明显优于C1对照组(P<0.05)；12周时，已与Sham对照组无显著性差别。生物力学实验结果表明，在6周时，CSC组椎体的最大抗压缩强度有增加，但与C1对照组相比无显著性差异，而CSC/bBMP组椎体抗压缩强度在6周时显著高于C1对照组；在12周时，CSC组和CSC/bBMP组椎体最大抗压缩强度均较C1对照组有显著性差异(P<0.05)，与Sham组及PMMA组相比，未见显著性差异(P>0.05)。
五结论
1.通过去势+甲强龙肌注的方法，可以在2个月内快速建立兔的骨质疏松模型。
2.兔骨质疏松模型建成后，二维及三维图像显示椎体松质骨内骨小梁稀疏、变细、断裂，可见明确的骨小梁微骨折及骨缺损，骨的三维结构受到严重损坏，从而伴随相应力学强度的降低。是一种理想实用的骨质疏松动物模型。
3.CSC以及CSC为载体复合bBMP的椎体内注射材料，均具有强大的成骨诱导能力，通过快速地改善骨质疏松椎体内骨小梁的三维结构来提高椎体的结构强度，是具有良好应用价值的骨质疏松椎体内充填材料。
Background
The compression fracture in spine is the most complication of osteoporosis.The primary measures are the medical therapies and braces. The surgicalmeasures include internal fixation, vertebroplasty and kyphoplasty.Vertebroplasty is a minimally invasive surgery in spine developed in recent years.It has got good clinical effects in the therapy of benign or malignant lesions andosteoporosis compression fractures in spine. It has become prevalent inminimally invasive surgery of spine for rapidly relieving the back-pain andcorrecting the deformity. Now, the most commonly used cement ispolymethylmethacrylate (PMMA) in vertebroplasty. Unfortunately, PMMA hasseveral potential disadvantages. PMMA is not bioabsorbable and remainspermanently in the body. Its unreacted monomer is toxic, and its highpolymerization temperature has resulted in temperature readings as much as1220C. The high compressive strength and stiffness of PMMA causes a biomechanical mismatch between treated and untreated vertebral levels whichmay increase the risk of adjacent-level fractures. It has been required that theinjecting materials can carry medicine for special treatments in clinic. So PMMAcan not satisfy these demands. How to explore a biological injecting material，which can not only support the vertebrae but also carry medicine for specialtreatments, is the object of this experiment.
Objective
1. In order to study a rapid osteoporosis animal model which can be used inthe orthopaedic research, the rabbit model is established by ovariectomy (OVX)and injecting solu-medrol. After OVX, it is evaluated by surveying themicro-architectural and biomechanical changes of cancellous and cortical bone.
2. To evaluate the effects of calcium sulfate cement (CSC) and CSCcombined with bovine bone morphogenetic protein (bBMP) on osteoporoticrabbit’s vertebral micro-architecture and biomechanical properties in vivo.
Material and methods
Part1Establishment and evaluation of an osteoporosis rabbit model.
20adult rabbits were divided into three groups randomly, includingsham-operated group (n=8), OVX-A group (n=4) and OVX-B (n=8) group.OVX-B group was started to inject solu-medrol for4consecutive weeks after2weeks late of OVX. Sham group and OVX-A group were control groups. Beforeand2months after the operation, the measure of dual energy x-rayabsorptiometry (DEXA) was done on all the rabbits’ lumbar vertebrae twice.2months after the operation, the rabbits were sacrificed and the femoral condyle andshaft and the spines were harvested. The cortical bone (femoral shaft) andtrabecular bone(spine and femoral condyle) were measured by DEXA andreconstructed by micro-CT. The strength of vertebral bodies was determined by compressive mechanical measurment of vertebra cancellous bone. Themechanical properties of cortical bone (femur shaft) were evaluated bythree-point-bending tests.
Part2the study on the vertebrae augmentaion in osteoporotic rabbitvertebrae with calcium sulfate (CSC)/bBMP composite.
60adult rabbits were were divided into five groups randomly, includingsham-operated group (n=12), C1group (n=12), C2group (n=12), C3group (n=12)and C4group (n=12). C groups were estabilished osteoporotic rabbit modelsaccording to the methods of part1experiments. Sham group and C1group werecontrol groups.0.1-0.2ml PMMA (Group C2), CSC (Group C3) and CSC/bBMP(Group C4) were injected into L2, L4and L6vertebra of every rabbits.4rabbitswere killed respectively from every group in24hours,6weeks and12weeksafter PVP. The changes of trabecular architecture were reviewedhistomorphologically. Micro-architecture changes of vertebrae were measured bymicro-CT after the rabbits were killed. The vetebral specimens’ strength wasevaluated by axial compression tests.
Result
Part1: The lumbar spine BMD of pre-OVX in Sham group, OVX-A andOVX-B group were （266.7±38.58）mg/cm~2、（270.1±25.38）mg/cm~2and（272.8±27.08）mg/cm~2respectively.2months later, the BMD of post-OVX inSham group, OVX-A and OVX-B group were （281.8±39.22） mg/cm~2、（248.9±26.14）mg/cm~2and（199.9±30.76）mg/cm~2respectively. BMD in OVX-Bdecreased by26.72%compared with the pre-OVX BMD. Compared with that insham group and OVX-A group, trabecular bone reduced significantly in OVX-Bgroup, histomorphologically. The microfracture and microdefect of trabecularbone could be seen in OVX-B. The parameters of trabecular bone had significantly difference compared with control groups (p<0.05). In mechanicaltesting, the maximum compression strength of vertebrae decreased significantlyin OVX-B compared with that in the other two groups. In3-point bending test ofcortical bone, no difference was observed between three groups.
Part2: Histomorphologically, compared with that in C1group, theconnectivity in group C3and C4was better respectively at6th week and12thweek. The shape of trabecular bone was also better.The architecture of trabecularbone was same as that in sham group. Microfractures and microdefects were alsoless than that in the C1group. After the injection of CSC or CSC/bBMP, theMicro-CT reconstruction analysis showed that the BMD in group C3and C4were significantly higher than that in group C1respectively at6th week and12thweek(P<0.05). In group C3and C4, the trabecular connectivity, thickness andbone fraction were significantly higher than that in C1group and were as good asthe sham group in12th week. The results of the vertebrae maximum compressionstrength in C4was higher significantly than that in C1group in6th week(P<0.05). It was also higher significantly in both C3and C4than that in C1andhad no significantly difference compared with that in sham group and C2groupin12th week.
Conclusion
1. Osteoporosis rabbit model can be rapidly establisher by ovariectomy andinjecting solu-medrol in2months.
2. In the induced rabbit model, the trabecular bone becomes sparsely andthinning. Microfractures and microdefects occur in trabecular and lead to thedeterioration of bone mechanical properties. It is an ideal osteoporosis model forexperiments.
3. CSC and CSC/bBMP injecting in osteoporosis vertebrae can reinforce the
bone quality significantly by repairing the microfractures and microdefects oftrabecular bone. CSC and CSC/bBMP can be applied in the treatment of vertebralosteoporosis.
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