Vascular deprivation-induced necrosis of the femoral head of the rat. An experimental model of avascular osteonecrosis in the skeletally immature individual or Legg-Perthes disease

The blood supply of rats' femoral heads was severed by cutting the ligamentum teres and stripping the periostium. Histologically, necrosis of the marrow was apparent on the 2nd postoperative day, necrosis of the bone on the 5th postoperative day and fibrous ingrowth on the 7th postoperative day. During the following 5 weeks, progressive resorption of the intertrabecular necrotic debris and necrotic bony trabeculae and subchondral bone plate and, concurrently, appositional and intramembranous new bone formation resulted in remodeling of the femoral heads. In 2 of 7 femoral heads, replacement of the necrotic bone by viable bone was complete at the 42-day postoperative interval. Also, the articular cartilage of the deformed and flattened femoral heads was undergoing degenerative changes. Reduplicating the pathogenically inferred clinical settings of blood supply deprivation, it is proposed that this model, in a small laboratory animal, satisfies the requirements sought for preclinical studies of treatment modalities of avascular osteonecrosis in man.     

Postosteonecrotic osteoarthritis-like disorder of the femoral head of rats

The femoral heads of 15 rats were studied histologically 3 months after the induction of ischaemic necrosis by incising the cervical periosteum and cutting the ligamentum teres. The epiphyses consisted of immature disorganized subchondral and trabecular bone. The inter-trabecular spaces contained fibrous or haematopoietic tissue. Residual necrotic bone was rare. There was marked osteoblastic and osteoclastic activity. The articular aspect of the heads showed a spectrum of changes, ranging from cartilaginous degeneration with fibrillation and loss of glycosaminoglycans to an eburnated and polished bony surface. In seven rats, transphyseal bridges connected the epiphyseal and metaphyseal bony trabeculae to each other. It is suggested that the postnecrotic reparative processes, including the resorption of the necrotic debris and its replacement by newly formed, weak bone, led to an osteoarthritis-like disorder. This healing pattern of the necrotic femoral head was reminiscent of the progressive remodelling that occurs in rings in femoral capital osteonecrosis of adult human patients and in Perthes's disease of children.     

Computer-assisted image analysis of the rat postosteonecrotic remodeled femoral head.

Osteonecrosis of rat femoral heads was induced by stripping the periosteum of the neck and cutting the ligamentum teres. The epiphyseal marrow and bone were necrotic on the 5th postoperative day. Specimens obtained 18 and 36 days postoperatively showed fibrous and hematopoietic-fatty tissue in the intertrabecular spaces, osteoclastic bone resorption, osteogenesis, and degeneration of the joint cartilage. Morphometrically, the means of the height-to-length ratios of the control, 6-day, 18-day, and 36-day femoral heads were 0.26, 0.28, 0.48, and 0.29, respectively. The shape factor of the femoral heads of the control rats was higher than 0.81 in 80% of the cases, while those of rats killed on the 6th, 18th, and 36th postoperative day were higher than 0.81 in 65, 60, and 50% of cases, respectively. Statistically, the means of the height-to-length ratios and the values of the shape factors of the femoral heads of the rats killed 18 days postoperatively differed significantly from those of the other three groups of rats. The quantitatively gauged data of the remodeled epiphyses negate the authors' subjective impression concerning early flattening of the femoral heads after surgically produced osteonecrosis.     

股骨头坏死术前术后DSA评价

目的：通过对股骨头坏死病例术前术后行DSA检查,了解其术前股骨头血供情况,评价术后疗效。方法：对55例股骨头坏死病例行DSA检查。手术前病例25例,其中FicatⅡ期10例、Ⅲ-Ⅳ期15例,均伴髋关节异常。手术后30例,其中大转子转移股骨头成形术15例,带血管蒂髂骨骨瓣移植髓腔减压术15例。所有患者均选择旋股内外血管造影。结果：术前25例患者中20例旋股内动脉终末支中断、消失,3例股骨头染色良好,2例支持带动脉正常;25例均未见髋部静脉显影。术后30例髋部动脉造影示全部病例随手术方式不同出现髋部动脉发生解剖性变化,股骨头圆韧带动脉均未见显示。结论：股骨头坏死术前DSA造影可准确判断病侧股骨头动脉供血情况,对确定手术方式具有指导意义。手术后DSA造影对判断疗效具有重要价值。     

3D打印导航模板辅助髓芯减压植骨治疗ARCOⅡ期非创伤性股骨头坏死

文题释义：3D打印导航模板：即3D打印技术与计算机虚拟导航相结合的技术,依据CT或者MRI成像的三维模型,结合快速成型的3D打印技术将虚拟三维导航模板打印成实体用于设计手术方案或引导术中操作。髓芯减压植骨：股骨头坏死非塌陷期常用的保髋术式之一,通过钻孔降低股骨头内的高压,改善静脉回流,促进毛细血管再生,同时通过减压通道对股骨头内坏死区域植入人工骨或自体骨,分散股骨头局部应力集中,避免股骨头进一步塌陷。 背景：髓芯减压植骨是治疗ARCOⅡ期非创伤性股骨头坏死的主要术式,但是存在定位不准确,坏死骨清除不彻底或过多的风险。 目的：观察3D打印导航模板辅助髓芯减压植骨治疗ARCOⅡ期非创伤性股骨头坏死的精确性和安全性。方法：收集2017年1至11月西安交通大学附属红会医院收治的80例(96髋)ARCOⅡ期非创伤性股骨头坏死患者,将其随机分为2组,3D组40例(48髋)行3D打印导航模板辅助髓芯减压植骨;对照组40例(48髋)行传统髓芯减压植骨,即未使用导航模板。2组患者对治疗方案均知情同意,且得到医院伦理委员会批准。分别记录2组手术时间、术中透视次数、术中失血量,观察术后第3,6,12,24个月X射线片复查结果,评估股骨头存活率、髋关节Harris评分、疼痛目测类比评分等指标,进行疗效对比。结果与结论：①3D组与对照组比较,手术时间由(132.57±14.86) min缩短至(82.63±10.31) min,术中透视次数由(16.80±2.15)次降低至(4.93±1.36)次,失血量由(143.23±17.98)mL降低至(75.64±16.23)mL,3D组在手术时间、透视次数、失血量方面均优于对照组(P < 0.05);②术后24个月影像学随访结果显示,3D组仅2例股骨头发生塌陷,但髋关节功能尚可,未行人工髋关节置换,股骨头存活率为96%;对照组中有9例股骨头发生塌陷,其中4例因髋关节活动受限行人工全髋置换,股骨头存活率为81%;3D组股骨头存活率高于对照组(P=0.024);③与对照组比较,3D组在Harris评分、目测类比评分方面均有所改善(P < 0.05);④提示将3D 打印导航模板应用于髓芯减压植骨治疗ARCOⅡ期非创伤性股骨头坏死,可减少手术时间、术中透视次数及出血量,提高术中定位的精确性和安全性。 ORCID: 0000-0001-8758-1626(陈冬冬) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

Runx2,Osterix及MMP-13在大鼠激素性股骨头无菌性坏死组织中的表达及意义

目的探讨Runx2,Osterix及MMP-13蛋白及基因在大鼠激素性股骨头无菌性坏死组织中的表达。方法40只成年Wistar大鼠随机分为模型组(30只)和对照组(10只)。模型组大鼠接受地塞米松20 mg/kg肌肉注射,1次/周,注射后,在跑步机上对动物进行训练。模型组根据训练时间分为3组(各10只):A组8周;B组10周;C组12周。采用PCR和Western blot方法检测大鼠股骨头组织中基因及蛋白变化。结果模型组大鼠脂肪细胞最大直径、空骨陷窝率高于对照组,且随着训练时间的增加,脂肪细胞最大直径、空骨陷窝率逐渐增加,差异具有统计学意义(P<0.00);模型组骨小梁面积低于对照组,且随着训练时间的增加,骨小梁面积逐渐降低,差异具有统计学意义(P<0.00)。模型组大鼠Runx2,Osterix蛋白与基因表达量低于对照组,且随着时间的延长,表达量逐渐降低,差异具有统计学意义(P<0.05)。模型组大鼠MMP-13蛋白与基因表达量高于对照组,且随着时间的延长,表达量逐渐增加,差异具有统计学意义(P<0.05)。结论激素性股骨头坏死组织中Runx2,Osterix在mRNA和蛋白表达水平均低于正常股骨头组织,MMP-13高于正常股骨头组织。     

股骨头坏死中松质骨微观力学特性的演变规律

目的采用结合显微CT和显微有限元分析方法,即基于显微CT图像建立三维有限元模型并进行数值模拟仿真分析,无创研究不同分期的坏死股骨头松质骨的微结构和微观力学性能,以期了解在股骨头坏死的发展过程中,松质骨微结构和微观力学特性的变化规律,为临床预测股骨头坏死提供理论基础。方法采集10例股骨头坏死患者的股骨头标本的显微CT图像,按照国际骨循环研究学会分期标准分为Ⅱ期样本3例,Ⅲ期3例,Ⅳ期4例。将图像中骨组织进行阈值分割,分区域建立坏死区、侧向区、硬化区和远端区的松质骨块三维有限元模型(边长8 mm),并根据CT值赋予非均匀材料属性。利用ImageJ软件中的BoneJ插件通过识别显微CT组图像,计算测量各区域松质骨的微结构参数,包括骨体积分数、骨小梁厚度、骨小梁间隙、结构模型指数。对松质骨块施加表观应变为1%的压缩载荷,计算骨组织应力和松质骨表观刚度等参数,对比分析各分期、各分区结果。结果在松质骨微结构方面,Ⅳ期较Ⅱ期的股骨头内部硬化区和坏死区的变化最为明显,硬化区的骨体积分数不断上升,骨小梁间隙下降,结构模型指数减小,而坏死区域与之相反;在骨组织微观受力方面,Ⅱ期到Ⅲ期坏死区域的应力并没有明显变化,而硬化区域随着分期增加应力不断上升,侧向区的应力不断下降。表观刚度变化与应力变化一致。结论随着股骨头坏死程度的加剧,硬化区的松质骨微结构和力学性能变化最大,应作为临床早期诊断中重点关注的区域。此外,微结构参数并不能准确体现松质骨的力学行为,而股骨头塌陷最终取决于其力学特性,因此结合有限元分析方法可更加全面了解股骨头坏死的微观力学演变规律。     

介入导向溶栓治疗股骨头缺血坏死──附12例报告

目的：探索股骨头缺血坏死的介入治疗方法。方法：采用Seldinger穿刺超选择插管至旋股外、内动脉，灌入溶栓药物，治疗12例14个股骨头缺血坏死。洁果：介入治疗后，髋关节疼痛明显缓解或消失，活动自如，骨质逐步修复。结论：股骨头缺血坏死是由微循环障碍引起，介入导向溶栓对治疗股骨头缺血坏死有明显的疗效。     

Runx2，Osterix 及MMP-13在大鼠激素性股骨头无菌性坏死组织中的表达及意义

目的　探讨Runx2,Osterix及MMP-13蛋白及基因在大鼠激素性股骨头无菌性坏死组织中的表达。 方法　40只成年Wistar大鼠随机分为模型组（30只）和对照组（10只）。模型组大鼠接受地塞米松20 mg/kg肌肉注射,1次/周,注射后,在跑步机上对动物进行训练。模型组根据训练时间分为3组（各10只）：A组8周;B组10周;C组12周。采用PCR和Western blot方法检测大鼠股骨头组织中基因及蛋白变化。 结果　模型组大鼠脂肪细胞最大直径、空骨陷窝率高于对照组,且随着训练时间的增加,脂肪细胞最大直径、空骨陷窝率逐渐增加,差异具有统计学意义（P<0.00）;模型组骨小梁面积低于对照组,且随着训练时间的增加,骨小梁面积逐渐降低,差异具有统计学意义（P<0.00）。模型组大鼠Runx2,Osterix蛋白与基因表达量低于对照组,且随着时间的延长,表达量逐渐降低,差异具有统计学意义（P<0.05）。模型组大鼠MMP-13蛋白与基因表达量高于对照组,且随着时间的延长,表达量逐渐增加,差异具有统计学意义（P<0.05）。 结论　激素性股骨头坏死组织中Runx2,Osterix在mRNA和蛋白表达水平均低于正常股骨头组织,MMP-13高于正常股骨头组织。     

The effects of enoxaparin on the reparative processes in experimental osteonecrosis of the femoral head of the rat

The blood supply of one femoral head of 6-month-old rats was severed by incising the periosteum of the neck and cutting the ligamentum teres. The rats were killed on the 30th postoperative day and the femoral bones were obtained for semiquantification of the reparative processes in the necrotic heads. Fourteen rats were treated with enoxaparin and 14 untreated animals served as controls. Statistically, the amounts of necrotic bone in the epiphysis were less, the extent of remodeling of the femoral heads was milder, and the articular cartilage degeneration was slighter in the enoxaparin-treated than untreated rats. There was no significant difference in the quantities of newly formed bone in femoral heads of treated and untreated rats. These findings are in agreement with the known effects of unfractionated and low-molecular-weight heparins which enhance osteoclastic bone resorption and angiogenesis and decrease osteoblastic bone formation. The former activities, operative in minimizing the structural distortion of the femoral head, oppose the crucial event in the pathogenesis of post-osteonecrotic osteoarthritis.     

记忆合金网球支架治疗成人股骨头缺血性坏死的生物力学研究

目的：对比研究单纯髓芯减压、髓芯减压＋松质骨移植、髓芯减压＋松质骨移植＋记忆合金网球植入治疗成人股骨头缺血性坏死的生物力学行为。方法：取新鲜人股骨头0根，模拟髓芯减压松质骨移植治疗股骨头缺血性坏死的方法做成髓芯减压后的状态，用MTS生物力学实验机测得每例标本在单纯减压、减压值及植骨＋网球三种状态下的力学刚度，对其结果进行统计学分析。结果：单纯髓芯减压组和髓芯减压＋松质骨移植组统计学无明显差异，髓芯减压＋松质骨移植＋记忆合金网球植入优于前两种状态。结论：镍钛记忆合金网球植入增加了股骨头负重区软骨下骨的机械支撑，降低局部应力有利于股骨头坏死的修复与重建。     

激素诱发兔股骨头坏死的组织学及超微结构观察

目的　探讨激素诱发兔股骨头坏死的机理。方法　采用马血清和大剂量肾上腺糖皮质激素 (氟美松 )诱发成年兔股骨头坏死 ,应用光镜、电镜观察组织学及超微结构变化。结果　①骨髓腔内造血组织显著减少 ,脂肪组织明显增多 ;②在股骨干骺端及软骨下区发现骨小梁萎缩 ,骨细胞核固缩 ,空骨陷窝数目增多 ;③电镜发现骨细胞内有脂滴 ,骨髓腔毛细血管狭窄 ,血管内皮细胞受损。结论　肾上腺糖皮质激素可诱发兔股骨头坏死 ,激素引起脂肪在骨髓腔内堆积 ,骨髓腔内压升高而导致股骨头缺血诱发骨细胞坏死。     

Localization of vascular endothelial growth factor during the early reparative phase of the rats' vessels deprivation-induced osteonecrosis of the femoral heads

The expedited revascularization of the rats' avascular, necrotic femoral heads suggests the operation of angiogenic factor(s). The blood circulation of the epiphysis was interrupted by cutting the cervical periosteum and the ligamentum teres of rats' femoral heads. Three days postoperatively, the marrow was necrotic. Seven days postoperatively, the subchondral bony plate and trabecular bone were necrotic as well. The joint capsule was distended by myriad, so-called synovial fibroblasts, all of which were virtually immunoreactive with an antibody to vascular endothelial growth factor. The expression of this factor in the synovial membrane of non-operated rats was limited to preexisting blood vessels. Revascularization of necrotic, avascular femoral heads makes up the essential step in the chain of events terminating in the repair processes, that is, resorption of the necrotic debris and its substitution by newly formed bony and hematopoietic-fatty tissues. Synthesis and release of excessive amounts of vascular endothelial growth factor by these fibroblasts explain the lively angiogenesis in the necrotic intertrabecular spaces of the femoral heads.     

Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head

In this study, we investigated the feasibility and safety of intravenous transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) for femoral head repair, and observed the migration and distribution of MSCs in hosts. MSCs were labeled with green fluorescent protein (GFP) in vitro and injected into nude mice via vena caudalis, and the distribution of MSCs was dynamically monitored at 0, 6, 24, 48, 72 and 96 h after transplantation. Two weeks after the establishment of a rabbit model of femoral head necrosis, GFP labeled MSCs were injected into these rabbits via ear vein, immunological rejection and graft versus host disease were observed and necrotic and normal femoral heads, bone marrows, lungs, and livers were harvested at 2, 4 and 6 w after transplantation. The sections of these tissues were observed under fluorescent microscope. More than 70 % MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including brain, lungs, heart, kidneys, intestine and bilateral hip joints of nude mice. In rabbits, at 6 w after intravenous transplantation, GFP labeled MSCs were noted in the lungs, liver, bone marrow and normal and necrotic femoral heads of rabbits, and the number of MSCs in bone marrow was higher than that in the, femoral head, liver and lungs. Furthermore, the number of MSCs peaked at 6 w after transplantation. Moreover, no immunological rejection and graft versus host disease were found after transplantation in rabbits. Our results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous transplantation of allogeneic MSCs.     

计算机软件测定股骨头坏死的体积及其意义

目的评估计算机软件测定股骨头坏死体积比的准确性。方法 20个比格犬(40髋)通过液氮冷冻法制成双侧股骨头坏死模型,对股骨头坏死区域体积比通过二种不同的方法来计算:①通过液体测量法测定股骨头体积和坏死股骨头体积,二者相除即为体积比;②将坏死模型的MRI图像以Dicom导入Minics,重建坏死区与股骨头的三维图像,通过逆向工程软件Geomagic处理后,导入Ansys软件划分单元,计算所有坏死单元的体积与整个股骨头单元体积比。结果计算机软件计算的体积比结果为(26.4±10.2)%,实体测定的体积比为(25.8±10.6)%,通过SPPS11.0分析,无统计学差异。结论计算机软件能准确评估股骨头坏死区域体积比,是一个可以提倡的新方法。     

Periosteal donor site regeneration in rats

Periosteal regeneration was investigated in two periosteal donor sites of the femur. The periosteum was taken from the femur epiphyses and diaphyses of 32 rats. The animals were sacrificed 1, 2, 3, 4 and 8 weeks after periosteal stripping. Intense cell proliferation occurred in the first week. After two weeks, a thick tissue layer formed by osteoblasts and undifferentiated cells was seen at the two donor sites. Eight weeks after, the periosteum had the same aspect as that from the right femur, which was used as control. Histomorphometric analysis showed that periosteal regeneration was significantly different between epiphyses and diaphyses. Periosteal regeneration at donor site located in epiphyses presented greater proliferation and better osteogenic activity than that observed in diaphyses.     

股骨头坏死松质骨生物力学特征的空间分布规律

目的 探究股骨头坏死松质骨微观结构参数和力学性能的空间分布规律,为临床诊断中科学评估病灶对病情的影响提供理论依据.方法 结合影像学测量和数值模拟方法,定量分析不同区域松质骨的微观结构参数和力学性能,分别从冠状面、矢状面和水平面投影方向上探究松质骨生物力学特征的空间分布特点.结果 在股骨头冠状面和矢状面投影方向上,松质骨...     

股骨头坏死保髋治疗常用术式的利与弊

文题释义：股骨头坏死：非创伤性股骨头坏死是造成青壮年髋关节功能障碍或功能丧失的常见疾病,其病因主要为糖皮质激素的大量应用和酒精的过多摄入,根据坏死分期和患髋情况可选择不同的治疗方案,目前此疾病尚无令人满意的完全性治疗手段,延迟或避免关节置换成为主流研究方向。 保留髋关节手术：为延迟或避免行全髋关节置换的一类治疗方法。保髋术式类型较多,针对不同坏死类型可选择不同术式,且各有利弊。现多将多种术式联合应用,取长补短,以达到最好疗效。随着生物制剂和细胞疗法的不断发展,保髋手术与其结合正成为新的趋势。 背景：非创伤性股骨头坏死的保留髋关节治疗方法众多,临床治疗中多以各类坏死分期作为术式选择的决定性因素。以往的相关文献对各类术式有效性的分析较多,但对于失败原因或风险评估介绍较少。 目的：探讨除了坏死分期之外,对于术式本身是否有其他内、外源因素也同时影响了保髋成功率。 方法：由第一作者检索2010至2019年PubMed、Web of Science、Medline、知网、万方数据库中相关文献,检索词为“osteonecrosis of femoral head,core decompression,non-vascularized bone grafting,vascularized free bone grafting,porous tantalum rod implantation,osteotomy,biological agents,cytotherapy,保留髋关节手术,保髋术,髓芯减压术,不带血管的骨移植术,带血管的骨移植术,多孔钽棒置入术,截骨术,生物制剂,细胞疗法”。共检索到214篇文献,查阅全文,依据纳入与排除标准,最终纳入70篇文献进行分析总结。 结果与结论：①各保髋术式均有利弊,须评估利弊风险;②髓芯减压虽操作简单,却不宜单独使用;非血管化骨移植在死骨清理时应适当保留外侧柱,以应对力学减弱;带血管的骨移植转为全髋关节置换术中失血较多、骨折风险较高;钽棒置入易造成应力集中,临床应用较少;③截骨术作为一种创伤较大的保髋手术除了考虑坏死分期外,对患者年龄、体质量指数、坏死范围等均应做详细术前规划;④无论哪种术式,都应长远考虑转为全髋关节置换的手术风险;⑤各术式联合应用,结合生物制剂或能取得更好的疗效。 ORCID: 0000-0001-6117-6147(顾长源) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

有限元分析髓芯减压并同种异体植骨治疗股骨头缺血性坏死的生物力学改变

目的:分析髓芯减压并同种异体植骨治疗早期股骨头缺血性坏死的临床应用。方法:选取收治的1例早期股骨头缺血坏死男性患者,入院后术前对患侧股骨头行多层螺旋CT扫描,然后将CT扫描的图片资料导入专业的有限元分析软件,建立股骨头缺血坏死的有限元模型,在有限元模型上模拟进行髓芯钻孔减压术,隧道植入骨块到软骨下骨约0~6 mm处,自体松质骨夯实。双足站立位为股骨头的模拟受力体位,髋关节的负荷条件为:外展肌合力M、髂胫束力T以及髋关节接触力J分别为1 060、1 721、1 621 N,选取90°、120°以及150°的坏死角度,分别计算未处理过的股骨头坏死模型的塌陷值、行单纯髓芯减压以及行髓芯减压加植骨时的塌陷值。结果:股骨头的正常骨质杨氏模量高于坏死骨的杨氏模量,正常骨质的横向变形系数低于坏死骨。行股骨头髓芯钻孔减压术后,股骨头的塌陷值显著增加,而减压隧道植入同种异体骨后,其塌陷值显著减低,但高于正常的股骨头。同时,由于股骨头坏死角度的增加,其塌陷值也明显增加。结论:髓芯钻孔减压并同种异体植骨术能有效增进坏死区的骨质修复,加强减压通道所致股骨头支撑结构的改变,防止股骨头关节面的塌陷。     

个体股骨头坏死三维有限元模型的建立与应用

同时基于个体股骨头坏死患者的X-ray、CT和MRI图像,采用图像配准和融合技术对包含坏死股骨头的髋关节进行三维重建,获取具有高度几何相似性的三维有限元网格模型。选择1例中年女性股骨头坏死患者,分别获取X-ray、CT和MRI三套图像,采用Mimics 13.1和Pro/E 5.1软件分别基于这三套数据建立相关三维实体模型,经图像投影转换后,确定图像之间的匹配点,进行二维图像配准,配准后对成功融合的图像进行三维有限元网格模型显示。建立了具有良好几何相似性的髋关节三维有限元网格模型,包括正常皮质骨、松质骨、关节软骨和股骨头坏死区、断裂骨小梁等六部份,较真实地反映了包含坏死股骨头的髋关节的形态特征及毗邻关系,为进一步的生物力学分析和手术模拟提供了较理想的研究平台。