Development of a Clinically Relevant Animal Model for the Talar Osteonecrosis in Sheep

There are a lot of reports and reviews about osteonecrosis of the talus (ONT), yet reports about the animal model of ONT to evaluate proper therapeutic approaches are rarely heard. In our study, a novel animal model was established. Pure ethanol was injected into the cancellous bone of sheep''s talus. Macroscopic observation, X-ray, CT and histology were performed at two, four, 12 and 24 weeks postoperatively. It was revealed that the trabeculae of talar head began to change their structure after two weeks postoperatively compared to the normal talus. The ONT was obvious at the end of the fourth week, and their outstanding feature was the damage of trabeculae bone and formation of cavities. CT scans and pathological changes of the subjects all showed characteristics of the early stage of osteonecrosis, also the sections of the specimens confirmed necrosis of tali. By 12 weeks, the phenomenon of necrosis still existed but fibrous tissue proliferated prominently and bone reconstruction appeared in certain area. Most specimens (3/4) got late stage necrosis which presented as synarthrosis in X-ray and mass proliferation of fibrous tissue in histology at the end of 24 weeks. The novel animal model of ONT was successful, and it is inclined to deteriorate without any intervention. The study provides us a new way to evaluate various treatments on ONT in laboratory, which may eventually pave way to clinical applications.     

家兔激素性股骨头坏死的血液流变学改变及意义

目的：血液流变学改变在家兔激素性股骨头坏死发病机制中的作用。方法：雄性家兔30只,随机分为激素组（短期注射地塞米松）及对照组（注射生理盐水）,观察血清总胆固醇（TC）、甘油三脂（TG）血流流变学参数、免股骨头骨陷窝空虚率的阶段性变化。结果：实验15、30d,激素组的TG、TC、全血粘度,血浆粘度显著高于对照组,实验60d,激素组血清TC、血浆粘度仍然显著高于对照组。激素组合35、70d双侧股骨头骨陷窝空虚率均显著高于对照组,结论：地塞米松冲击应用可造成家兔血液流变特性恶性化,可能是激素性股骨头坏死的重要原因。     

体外冲击波疗法结合同种异体骨钉治疗成人股骨头缺血性坏死

目的探讨体外冲击波疗法（ESWT）结合同种异体骨钉治疗成人股骨头缺血性坏死的疗效。方法2003年7月～2007年1月,采用体外冲击波或结合同种异体皮质骨钉植入术治疗54例（84髋）股骨头缺血性坏死患者并随访观察。男41例,女13例;年龄20～61岁,平均30岁。按Ficat分期,Ⅱ期55髋,Ⅲ期29髋。其中40髋（Ⅱ期27髋,Ⅲ期13髋）,采用ESWT结合同种异体骨钉治疗,治疗后6、12、24个月复查双髋X线、MRI及髋关节Harris评分（HHS）。44髋（Ⅱ期28髋,Ⅲ期16髋）患者采用单纯ESWT治疗。对两组治疗结果进行统计学分析。结果随访24～29个月,平均25．7个月。二者治疗后Harris评分分别为83．71±18．76和57．20±12．82,二者比较差异有统计学意义妒〈0．01）：影像学X光片评估：ESWT结合同种异体骨钉术后随访股骨头塌陷12髋,塌陷率为30％,单纯ESWT治疗随访股骨头塌陷25髋,塌陷率为56．8％。结论体外冲击波疗法结合同种异体骨钉是治疗中期ONFH的方法之一,它不但具有冲击波疗法促进骨愈合作用,而且复合骨钉移植可起到骨传导及骨支撑作用,近期可以减少股骨头塌陷发生。     

伤科接骨片对激素性股骨头缺血性坏死血液流变性的实验研究

目的 :探讨伤科接骨片对激素性股骨头缺血性坏死血液流变性的影响。方法 :45只健康成年三黄鸡随机分为三组 :对照组、模型组和伤科接骨片组 ,模型组和伤科接骨片组采用胸肌注射地塞米松磷酸钠建立激素性股骨头缺血性坏死模型。对照组同一时间经胸肌注射等量生理盐水。 12周后取材 ,测定血液流变学指标和股骨头内PO2值。结果 :模型组股骨头内PO2值明显下降 ,全血粘度、血浆粘度、红细胞聚集指数明显升高 ,而红细胞变形指数明显下降 ,与对照组比较有显著性差异 (P <0 .0 5或P <0 .0 1) ,应用伤科接骨片后各项指标明显改善 ,与模型组比较有显著性差异 (P <0 .0 5或P <0 .0 1)。结论 :伤科接骨片能够改善股骨头微循环和血液流变特性 ,对激素诱导的股骨头缺血性坏死有较好的防治作用。     

ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.     

Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells

PurposeTo explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs) to treat osteonecrosis of the femoral head (ONFH).ResultsAfter mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheral mononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually.ConclusionWe confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are related to the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression.     

微循环障碍与激素性股骨头坏死相关性实验研究

目的 研究激素性股骨头坏死的发病原因。方法 用糖皮质激素诱导出股骨头缺血坏死的兔子模型,对比检测实验组和对照组的微循环状况以及与微循环有关的毛细血管内血液的流速,血液粘滞度,成份改变和病理组织学改变,弄清发病的主要相关因素。结果 实验组毛细血管中红细胞聚集,血液流速明显缓慢;血脂、血浆蛋白含量增高;股骨头内毛细血管数量减少,血管襻迂曲变长。结论 激素性股骨头缺血坏死的发病与微循环障碍有明显的关系。     

Clinical Results of Auto-Iliac Cancellous Bone Grafts Combined with Implantation of Autologous Bone Marrow Cells for Osteonecrosis of the Femoral Head: A Minimum 5-Year Follow-Up

Purpose

There are no reports about bone graft and cell therapy for the osteonecrosis of femoral head (ONFH). We prospectively evaluated the clinical results of auto-iliac cancellous bone grafts combined with implantation of autologous bone marrow cells for ONFH.

Materials and Methods

Sixty-one hips in 52 patients with ONFH treated with bone graft and cell therapy were enrolled, and the average follow-up of the patients was 68 (60-88) months. Necrotic lesions were classified according to their size by the Steinberg method and location of necrosis.

Results

At the last follow-up, the percentage of excellent or good results was 80% (12/15 hips) in the small lesion group, 65% (17/26 hips) in the medium size group, and 28% (6/20 hips) in the large size group. The procedures were a clinical success in 4 of 5 hips (80%) of stage I, 23 of 35 hips (65.7%) of stage II, 7 of 18 hips (38.9%) of stage III, and 1 of 3 hips (33.3%) of stage IV grade, according to the Association Research Circulation Osseous grading system. Among the 20 cases with large sized necrotic lesions, 17 cases were laterally located and this group showed the worst outcomes, with 13 hips (76.5%) having bad or failed clinical results.

Conclusion

The results of the present study suggested that patients who have a large sized lesion or medium sized laterally located lesion would not be good candidates for the head preserving procedure. However, for medium sized lesions, this procedure generated clinical results comparable to those of other head preserving procedures.     

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,松质骨的微观结构特征与力学性能大致呈Y型分布,Y形区域内松质骨的力学性能高于其他区域,该分布特点与股骨头内的主压应力束的位置相吻合。结论 位于股骨头Y形区域内的坏死灶对股骨头内应力分布的影响程度会更大,更有可能导致病情恶化。临床诊断中应充分考虑坏死灶和Y形区域的位置关系。     

股骨头颈骨外营养血管的应用解剖学研究

本文采用显微解剖剥离方法对25例(50侧)胎儿股骨头颈骨外营养血管的分布、变异及应用解剖学进行了研究。以期为临床应用提供更加详细的解剖学资料。     

血清岩藻糖苷酶在股骨头坏死保髋患者预后判断中的临床价值

目的 探究血清岩藻糖苷酶对股骨头坏死保髋患者预后的预测价值。方法 对2009年1月~2016年12月在我院骨伤科行保髋手术的210例患者（共311髋）进行股骨头坏死相关血清学指标分析,包括血清岩藻糖苷酶、γ谷氨酰转移酶、甘油三酯、高密度脂蛋白、低密度脂蛋白、总胆固醇、碱性磷酸酶,分别于术前及术后5~7 d测定以上各指标,此后对各患者进行为期1.5~8年随访,根据随访结果分组,组间对比各指标并进行统计分析。结果 术后血清岩藻糖苷酶水平较之术前显著下降[（13.257±5.29）U/L vs（19.796±6.30）U/L]（P＜0.01）,且保髋成功患者较保髋失败患者下降程度更加明显[（11.361±4.29）U/L vs（14.216±4.77）U/L]（P＜0.05）;[Δ（9.164±4.31）U/L vs Δ（5.895±3.98）U/L ]（P＜0.01）。术后γ谷氨酰转移酶、甘油三酯,高密度脂蛋白,低密度脂蛋白,总胆固醇及碱性磷酸酶水平与术前相比差异无统计学意义（P＞0.05）。结论 股骨头坏死行保髋手术患者术后血清岩藻糖苷酶水平显著下降,且下降后水平与预后呈负相关。     

Association of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in Koreans

Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 − 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH ( P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population.     

Pyogenic granuloma-like reaction in the necrotic, vessels-deprived femoral head of the rat

Osteonecrosis of the femoral head was produced in rats by cutting the ligamentum teres and incising the cervical periosteum. As of the second postoperative week, fibrous tissue pervaded the necrotic epiphyses, macrophages and osteoclasts removed the debris, osteoblasts deposited lamellar-fibred and woven-fibred intramembranous bone, and remodeling began. In 16% of the rats killed during the 2nd postoperative week, the epiphyses contained big fragments of necrotic bone enclosed by densely packed, capillary-sized vessels. Ingrowth of this hypervascularized, pyogenic granuloma-like tissue is presumably due to the presence of excessive growth factors, reflecting an exaggerated pathophysiological reaction within the framework of organization of the necrotic epiphyses.     

Repairing Defect and Preventing Collapse of Canine Femoral Head Using Titanium Implant Enhanced by Autogenous Bone Graft and rhBMP-2

There is a direct relationship between mechanical stress and the progressive collapse of the necrotic region in osteonecrosis of the femoral head. The titanium implant combined with autogenous bone graft and recombinant human bone morphogenetic protein (rhBMP)-2 to repair the defect and prevent collapse of the femoral head was investigated. The femoral head defects were made by the trapdoor procedure and then the defects were filled, respectively, with the titanium implant combined with autogenous bone graft and rhBMP-2, with autogenous bone graft and rhBMP-2, and with autogenous bone graft alone. Roentgenographic and histological examinations were performed at various times postoperatively. The defects were repaired completely and the titanium implant was integrated with the surrounding bone tissues. The defects healed faster than did without rhBMP-2. No trapdoor cartilage collapsed and joint space narrowed. The titanium implant combined with autogenous bone graft and rhBMP-2 can enhance the repairing procedure and prevent the collapse of the femoral head.     

股骨头缺血性坏死多层螺旋CT三维构筑及介入治疗的临床意义

目的:探讨采用多层螺旋CT对股骨头缺血性坏死进行三维立体构筑的技术方法及介入治疗的临床价值.方法:使用Siemens Somatom Definition 64层螺旋CT对31例股骨头缺血性坏死患者共36髋进行薄层扫描,利用Inspace软件和NeuroDSA软件进行影像重组和三维立体构筑,并在X、Y和Z轴上旋转,观察股骨头的解剖形态.对I期坏死患者采用单纯经股骨头供血动脉灌注扩张血管及溶栓药物进行介入治疗;对II期及股骨头外形完整的III期患者首先采用介入治疗,然后经环钻剜出坏死骨植入混合自体骨髓间充质干细胞的自体松质骨.结果:容积重组图像显示早期缺血坏死的股骨头解剖形态基本正常,股骨头表面可见凹凸不平.股骨头坏死区的体积I期(8髋)为(1218.97±449.93)mm3,II期(22髋)为(3671.19±1316.83)mm3,股骨头完整的III期(6髋)为(7874.18±2381.22)mm3.根据HHS评分,疗效优23髋(63.89%),良10髋(27.78%),可3髋(8.33%),差0髋.结论:多层螺旋CT三维重组技术能够立体构筑股骨头的解剖形态,并在不同层面上对坏死区的大小进行测量,对股骨头缺血性坏死患者治疗方法的选择具有重要的临床指导意义.     

Cortical Imaging on a Head Template: A Simulation Study Using a Resistor Mesh Model (RMM)

The T1 head template model used in Statistical Parametric Mapping Version 2000 (SPM2), was segmented into five layers (scalp, skull, CSF, grey and white matter) and implemented in 2 mm voxels. We designed a resistor mesh model (RMM), based on the finite volume method (FVM) to simulate the electrical properties of this head model along the three axes for each voxel. Then, we introduced four dipoles of high eccentricity (about 0.8) in this RMM, separately and simultaneously, to compute the potentials for two sets of conductivities. We used the direct cortical imaging technique (CIT) to recover the simulated dipoles, using 60 or 107 electrodes and with or without addition of Gaussian white noise (GWN). The use of realistic conductivities gave better CIT results than standard conductivities, lowering the blurring effect on scalp potentials and displaying more accurate position areas when CIT was applied to single dipoles. Simultaneous dipoles were less accurately localized, but good qualitative and stable quantitative results were obtained up to 5% noise level for 107 electrodes and up to 10% noise level for 60 electrodes, showing that a compromise must be found to optimize both the number of electrodes and the noise level. With the RMM defined in 2 mm voxels, the standard 128-electrode cap and 5% noise appears to be the upper limit providing reliable source positions when direct CIT is used. The admittance matrix defining the RMM is easy to modify so as to adapt to different conductivities. The next step will be the adaptation of individual real head T2 images to the RMM template and the introduction of anisotropy using diffusion imaging (DI).     

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.     

全髋置换术治疗成人髋臼发育不良伴股骨头坏死

目的：探讨全髋置换术治疗成人髋臼发育不良伴股骨头缺血坏死的手术方法。方法：15例成人髋臼发育不良伴股骨头坏死病例，采用自体骨植骨造盖、重建髋臼等方法以达和谐臼容关系、平衡负重力线，恢复股骨头前倾角和颈干角纠正股骨头颈畸形。结果：15例均获随访，随访时间9个月至3年4个月，平均2．6年。术后髋关节功能Harris评分平均81．6分。术后下肢短缩0～2．5cm，平均0．8cm。术后X线显示臼容关系良好，植骨块融合。术后2例两侧肢体不等长仍大于2cm，行走时轻微跛行。结论：成人髋臼发育不良伴股骨头坏死全髋置换术，可以采用自体股骨头松质骨植骨造盖、重建髋臼等方法以达到和谐臼容关系、恢复负重力线，改善病人步态等目的，是一种行之有效的治疗方法。     

Comparison of bone marrow mesenchymal stem cells and core decompression in treatment of osteonecrosis of the femoral head: a meta-analysis

The study aims to compare the clinical efficacy of core decompression (CD) and bone marrow mesenchymal stem cells (BMMSC) on the patients with osteonecrosis of the femoral head (ONFH). A detailed literature search of PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google scholar for all relevant papers published was performed. Pooled odds ratio (OR) or weighted mean differences (WMD) and 95% confidence interval (CI) were used to evaluate the clinical efficacy of CD and BMMSC with the clinical outcome on the patients with ONFH. A total of 219 hips in 4 studies were indentified in this current meta-analysis. The OR of 2 separate studies consisting of 115 hips (CD group 63 hips; BMMSC group 52 hips) of patients were pooled and suggested BMMSC group had significantly less number of progressed vascularized bone grafting events than CD group (OR = 0.11; 95% CI: 0.03~0.43; P < 0.01). In addition, WMD of other 2 separate studies consisting of 104 hips (CD group 52 hips; BMMSC group 52 hips) in patients were pooled, and significant differences (P < 0.01) in Harris Hip Score (HHS) were observed between these two treatment groups at the end of follow-up study, BMMSC group had significantly better clinical outcome than CD group (WMD = 8.69; 95% CI: 3.76~13.62; P < 0.01). BMMSC may perform a better therapeutic effect than CD on the patients with osteonecrosis of the femoral head.     

中西医结合三联疗法对股骨头缺血性坏死患者足甲襞微循环的影响

目的:观察中西医结合三联疗法对股骨头缺血性坏死(ANFH)患者足甲襞微循环的影响。方法:60例患者随机分为三组,每组20例。三联治疗组:运用腰交感神经毁损术(LS)、针刀和中药3法同时治疗;针药治疗组:运用针刀加中药同时治疗;中药治疗组:只运用中药治疗。比较三组的临床疗效,并比较治疗前、治疗1周末和治疗结束后患者足甲襞微循环变化。结果:三联治疗组疗效明显优于其它两组(P<0.05或P<0.01)。甲襞微循环比较:三组治疗前各项指标均显著高于正常对照组(P<0.01);治疗1周末三联治疗组微循环较治疗前有明显改善(P<0.05或P<0.01),且三联治疗组各项积分均明显优于其它两组(P<0.05或P<0.01);治疗结束后各组与治疗前相比均有显著性改善(P<0.05或P<0.01),针药治疗组改善幅度明显优于中药治疗组,而三联治疗组改善幅度又明显优于针药治疗组(P<0.05或P<0.01),并接近正常。结论:LS、针刀和中药联合治疗能快速而又持久地改善ANFH的微循环状况,取得更好的临床疗效,且明显优于针刀和中药的单独或联合作用。