Effect of bone mesenchymal stem cells transplantation on the micro-environment of early osteonecrosis of the femoral head

Autologous implantation of bone mesenchymal stem cells (BMSCs) has achieved promising clinical efficacy for the treatment of early-stage osteonecrosis of the femoral head (ONFH). However, the underlying mechanisms are not completely elucidated. Here, we investigated the effect of BMSCs on the early ONFH in vitro and in vivo. In co-cultured system, primary BMSCs enhanced the activity and inhibited the apoptosis of primary OB. The concentrations of VEGF and BMP-2 in the co-cultured medium were significantly higher than those without co-culture. Importantly, BMSCs implantation increased OB, capillaries and VEGF and BMP-2 expressions of the necrotic areas of femoral head in the ONFH rabbits. In conclusion, our results indicated that BMSCs treated the early ONFH possibly through increasing OB and capillaries, as well as VEGF and BMP-2 expression in the femoral head. These results provided possible mechanisms for the treatment of early-stage ONFH with BMSCs transplantation.     

骨内注射无水乙醇建立兔股骨头坏死模型

背景：目前还难以建立合适的早期股骨头坏死的动物模型。 目的：建立一个简单、标准和可靠的股骨头坏死动物模型用于实验研究。 方法：X射线透视下将新西兰兔右侧股骨头中心钻孔并注入无水乙醇,左侧不做处理做对照。经过2,4和6周麻醉下处死动物获取股骨头。 结果与结论：大体及X射线观察显示,造模侧股骨头第2周关节软骨颜色变暗、骨质密度不均匀;第6周,关节面有轻微凹陷,骨质低密度影较前进一步增大。MRI显示,造模侧股骨头第2周,T1加权股骨头负重区显示线样或不规则低信号,T2加权呈高信号;第6周,股骨头变性,软骨下骨折,关节面塌陷,新月体形成。对照侧第2,4,6周股骨头结果均常。组织病理学观察显示,造模侧股骨头第2周后,骨细胞核固缩、变性坏死。结果证实,2周后兔股骨头均发生了部分坏死,股骨头坏死的完整的外观形态,大体循环和关节软骨与人类早期股骨头坏死是相似的,提示实验建立了良好的股骨头坏死动物模型。     

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.     

股骨头坏死修复材料研究进展

股骨头坏死(ONFH)好发于青壮年。病变进展会显著影响患者的生活质量以及工作能力。因此在ONFH早期进行治疗以防止股骨头塌陷,保护关节功能并延迟关节置换的时间显得极为重要。而ONFH的保头治疗的重点都在于如何有效重建股骨头内支撑结构,延缓股骨头坏死的病情进展,尽可能的保留髋关节功能。用于重建股骨头的修复材料是股骨头早期手术治疗的重点,直接关系到股骨头的存活及髋关节功能的保留程度。本文就各种用于重建股骨头内支撑的修复材料的研究进展做一综述。     

股骨头坏死动物模型评价方法的优缺点及展望

背景:股骨头坏死发病机制仍需要进一步研究,因此需要建立一个能够高度模拟人类股骨头坏死的动物模型,而如何正确评价股骨头坏死动物模型,是建立股骨头坏死动物模型的前提条件。目的:归纳总结近几年国内外对股骨头坏死动物模型的评价方法,综述各评价方法的优缺点,并探索新的评价方法,为动物模型的建立提供参考。方法:以“股骨头坏死,动物模型,评价方法”为检索词检索CNKI中国知网、万方、维普数据库,以“osteonecrosis of femoral head,femoral head necrosis,animal model,evaluation methods”为检索词检索PubMed、Web of Science及Medline数据库,检索2010年1月至2020年9月发表关于股骨头坏死动物模型评价方法的文献。结果与结论:①根据纳入标准通过阅读文献进行初步筛选,共获得51篇文章进行综述,其中中文文献33篇,英文文献18篇;②近年来,随着影像技术的发展和新技术的引入,股骨头坏死动物模型评估方法的选择增多,而选择合理的评价方式能减少建立动物模型过程中的工作量,并为后续研究提供参考,因此需要继续完善和改进。     

Weight bearing does not contribute to the development of osteonecrosis of the femoral head

The hip joint is one of the major structures in the human body and the resultant force acting through the hip joint is 300% of body weight. Therefore, weight bearing, as a cause of ischaemia, may contribute to the development of non‐traumatic osteonecrosis of the femoral head (ONFH). However, it remains unclear whether weight bearing is related to the development of non‐traumatic ONFH. Therefore the aim of this study was to clarify the role of weight bearing in the development of non‐traumatic ONFH. Non‐weight‐bearing (NWB) rats were tail suspended to prevent any weight coming to bear on the hindlimbs from day 1 to the time of sacrifice. The weight‐bearing (WB) group rats were also housed individually, although without tail suspension. All rats were injected with lipopolysaccharide and methylprednisolone to promote the development of non‐traumatic ONFH. All animals were sacrificed three weeks after the final methylprednisolone injection. Histopathological analysis was performed. Osteonecrosis of the femoral head was observed not only in the NWB but also in the WB rats; however, no osteonecrosis of the humeral head was observed in either group. We confirmed that non‐traumatic ONFH developed in NWB rats, suggesting that weight bearing does not contribute to the development of non‐traumatic ONFH in rats.     

Can local Erythropoietin administration enhance bone regeneration in osteonecrosis of femoral head?

Osteonecrosis of femoral head (ONFH) is a challenging disease. Regardless of underlying causes, the ultimate result in all cases is disruption of femoral head blood supply. Once the disease starts, it is progressive in 80% of cases. Since the majority of the affected individuals are young, every effort should be focused on preserving the patients own femoral head. These years, the role of angiogenic growth factors has been investigated with promising results in animal models of ONFH. Erythropoietin (EPO) is a well known hormone that has been used in treatment of chronic anemia for many years with few side effects. Considering the angiogenic properties of EPO, we hypothesize that local delivery of recombinant human EPO during core decompression will enhance bone regeneration in ONFH. In this way we also can avoid systemic side effects of EPO.     

三足负重犬股骨头坏死模型的生物力学相关性研究

目的研究股骨头坏死病程各阶段的生物力学改变,探讨其生物力学发生作用的机制。方法取杂种犬24只,固定一侧前肢建立三足负重犬模型。随机取三足负重犬一侧后肢为实验侧,在股骨头内注射无水酒精,致股骨头坏死;对侧为对照侧,在股骨头内注入等量生理盐水。造模后1、3、6及12周处死动物,每组6只,分别对两组股骨头行大体观察以及放射学、组织学、生物力学检测。结果术后3周股骨头坏死侧点压硬度及中部松质骨弹性模量相对对照侧分别下降29%和32.9%,此时仅MRI可见股骨头出现低密度坏死区,组织学主要表现为骨坏死。术后6、12周股骨头坏死侧点压硬度相对对照侧分别下降了45.5%和48.7%,中部松质骨弹性模量相对对照侧分别下降了34.1%和32.4%。6周时坏死侧X线可见股骨头内密度不均,组织学表现为坏死和修复反应并存,坏死区向软骨下骨区进展。12周时坏死侧X线可见股骨头负重区下出现局部骨密度减低区,组织学出现关节软骨面塌陷和关节间隙狭窄。结论生物力学是股骨头病程进展的重要影响因素;病程进展中,特别是修复期力学性能的显著下降可能是后期塌陷的最直接原因。治疗股骨头坏死不仅应促进骨修复,更应提供病变区一个有利、稳定的生物力学环境。     

保髋治疗股骨头缺血性坏死生存质量的评价标准

背景：目前评价保髋治疗的疗效标准较多,没有统一标准,因此保髋治疗的疗效缺乏一定的可比性。 目的：通过回顾及分析现有的用于保髋治疗疗效的各种评价标准,试图研制一款特异性的用于评价保髋治疗疗效的生存质量量表。 方法：应用计算机检索Pubmed数据库(2000/2010-08),以“Osteonecrosis Femoral Head、quality of life”或“Osteonecrosis Femoral Head、curative effect”为检索词;应用计算机检索CNKI数据库(1994-01/2009-12),以“股骨头坏死、疗效”或“股骨头坏死、生存质量”为检索词。选择与股骨头坏死保髋治疗疗效或生存质量相关,同一领域文献则选择近期发表或发表在权威杂志文章。根据纳入标准共31篇文章进行综述。 结果与结论：现有的评价保髋治疗的疗效标准过分的侧重髋关节的疼痛、功能、关节活动等方面,局限于髋关节或下肢的局部改变情况,对患者整体的生存质量反应不够,而以SF-36为代表的生存质量量表评价标准却缺乏一定的特异性,都未能更全面更具特异性的用于评价保髋治疗的疗效。因此,研制一款特异性的用于评价股骨头坏死保髋治疗疗效的生存质量量表成一种必要。     

Can bisphenol A diglycidyl ether (BADGE) administration prevent steroid-induced femoral head osteonecrosis in the early stage?

Steroid-induced osteonecrosis of the femoral head (ONFH) is associated with increase of intraosseous pressure caused by elevating of adipogenesis and fat cell hypertrophy in the bone marrow, which subsequently decreases the blood flow in the femoral head and finally resulting in bone ischemia. The early femoral head-preserving method has mainly focused on the conventional core decompression procedure. However, it only achieves a slight decrease in intra-medullary pressure with limited clinical outcome. The crucial point in prevention is to achieve a thorough decompression of intra-medullary pressure and improvement of microcirculation of the femoral head. Bisphenol-A-diglycidyl ether (BADGE), an antagonism of PPAR-γ(Peroxisome proliferator-activated receptor gamma), has been shown to successfully reverse bone marrow adipogenesis and fat cell hypertrophy, enhances proliferation of osteoblasts, inhibit osteoclastogenesis. Therefore, we hypothesized that BADGE administration may be an appropriate novel method for the prevention of early stage steroid-induced ONFH.     

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。     

IGF-1在股骨头再造关节软骨化生中的作用

目的观察分析大转子骨瓣表面骨膜及腱膜等纤维结缔组织向关节软骨转化的规律及胰岛素样生长因子-1(IGF-1)在软骨化生过程中的作用。方法制备液氮冷冻双侧股骨头缺血性坏死(Osteonecrosis of femoral head,ONFH)的动物模型。左侧股骨头造模后即缝合关节囊,右侧股骨头根据分组不同采用不同的处理方式:A组(骨瓣治疗组):带血管蒂大转子骨瓣进行股骨头再造;B组(骨瓣加Ad-IGF-1基因治疗治疗组):带血管蒂大转子骨瓣股骨头再造,关节内注入表达IGF-1的腺病毒载体(Ad-IGF-1);两组动物分别于3,6,12,18,24周每批4只处死,对骨瓣进行大体观察,组织病理学观察,免疫组化检测。结果所有动物左侧冷冻区组织坏死,纤维状物覆盖,碎片样组织修复。组织病理切片及免疫组化证实A组右侧骨瓣区自6周出现透明软骨细胞,B组右侧骨瓣区自3周出现透明软骨细胞,B组较A组修复效果好。结果经统计学处理有统计学意义。结论大转子表面的骨膜及腱膜能够向关节软骨化生,IGF-1对大转子表面的骨膜及腱膜向关节软骨化生有促进作用,为ONFH的外科治疗及生长因子的应用提供基础。     

Finite Element Analysis on the Diagnosis and Treatment of Osteonecrosis of Femoral Head

Developing the radiographic images from two to three-dimensional, finite element analysis(FEA) technology can set up the model, predicting diagnosis, treatment design, as well as surgical plan. FEA provides an accurate three-dimensional finite element biomechanical study in osteonecrosis of femoral head(ONFH). The papers in the latest 5 years related to femoral head osteonecrosis and finite element analysis application are concentrated on. We summarize the latest research progress and problems, including the applied research carried out in the femoral head osteonecrosis clinical cases,innovational skills, so as to point out the direction of future research in FEA.     

液氮冷冻兔股骨头坏死模型制备新方法及可靠性评价

目的 建立一种可靠的并可用于治疗和研究新的液氮冷冻法制成的兔股骨头坏死动物模型。方法 采用成年新西兰大白兔21只,无菌条件下手术分离臀肌,切断股骨头圆韧带,显露股骨头。用医用棉签蘸取液氮,对股骨头进行3次冷冻3次复温,制备兔双侧股骨头坏死模型。于术后3、7d及2、4、6、8周进行X线摄片,股骨头大体形态和组织病理学观察。结果 X线摄片结果显示,制模2周时股骨头密度增高;4周时出现密度不均影像;6周时外形出现不规则变化,边缘有透亮区;8周时开始塌陷,关节间隙增大,骺板模糊。股骨头大体形态随时间推移,其受损程度呈加重演变特点。制模3 d的股骨头组织切片可见软骨细胞和骨细胞坏死;2周见骨小梁断裂、排列紊乱;4周见髓腔脂肪细胞坏死,内有新生血管及增生纤维组织;6周时出现匍行附着;而8周可见新骨沉积性生长,骺板处细胞挤压、变形。结论 本实验中建立的液氮冷冻股骨头坏死模型新方法具有创伤性小、贴近人股骨头坏死病理演变规律的优点,为干细胞移植等治疗和研究提供了一种新的模型制备方法。     

基因多态性与山东临沂地区激素性股骨头坏死遗传易感性的关联

背景：近年来有研究表明激素性股骨头坏死患者的发病与遗传易感因素有关。 目的：探讨临沂地区人群中候选基因单核苷酸多态性与激素性股骨头坏死的关联。 方法：纳入分析63例激素性股骨头坏死患者和71例使用激素无股骨头坏死的对照组患者的激素总剂量并测定两组ApoB基因C7623T,G12619A,CYP1A2基因G2964A共3个位点的基因多态性,分析它们的基因型与等位基因频率的分布。 结果与结论：两组激素治疗的总剂量比较差异无显著性意义,ApoB C7623T位点TT基因型和T等位基因出现的频率在激素性股骨头坏死组明显高于对照组(P < 0.05)。提示CYP1A2G2964A与ApoB C7623T的基因多态性可能与激素性股骨头坏死的遗传易感性有关。CYP1A2G2964A与ApoB C7623T的基因多态性的协同作用与激素性股骨头坏死相关联。     

Treatment of osteonecrosis of the femoral head with VEGF165 transgenic bone marrow mesenchymal stem cells in mongrel dogs

We evaluated the efficacy of vascular endothelial growth factor 165 (VEGF(165)) transgenic bone marrow mesenchymal stem cells (BMSCs) for the repair of early-stage osteonecrosis of the femoral head (ONFH) in mature mongrel dogs. This animal model was surgically established by femoral neck osteotomy and subsequent repinning. Twenty-seven dogs (54 hips) were divided into 3 equal-sized groups: a pCI-neo-VEGF(165) BMSC group, a pCI-neo BMSC group and a core decompression-alone group. The lipofectamine was used to introduce the VEGF(165) gene into the BMSCs. After core decompression, transgenic and non-transgenic autologous BMSCs were implanted. Therapeutic efficacy, including new bone formation and neovascularization in the femoral head, was examined by computed radiography, single-photon emission computed tomography, histological and histomorphometric analysis and immunofluorescent staining for von Willebrand factor in pathological sections. The femoral osteotomy site healed completely by the 4th week after the osteotomy surgery and regions of histologically evident osteonecrosis were found 12 weeks later. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving implanted VEGF-transgenic BMSCs. The quantity of newly generated capillaries was significantly increased in the pCI-neo-VEGF(165) BMSC group, but there was no significant difference between the pCI-neo BMSC group and the core decompression-alone group. These results demonstrated that VEGF(165) transgenic autologous BMSCs enhanced bone reconstruction and blood vessel regeneration in the ONFH model. Compared with non-transgenic BMSCs, this approach could provide advanced benefits in the treatment of ONFH.     

A Canine Model of Femoral Head Osteonecrosis Induced by an Ethanol Injection Navigated by a Novel Template

There is no consensus on how to establish models of osteonecrosis of the femoral head (ONFH) in large mammals. The aim of this study was to investigate the effectiveness of a novel canine model of ONFH, induced by a navigated injection of absolute ethanol. Using three-dimensional reconstruction and rapid prototyping manufacturing techniques, a new template was designed and processed to navigate the ethanol injection. The femoral heads of 18 adult dogs were injected with ethanol. Macroscopic, X-ray and histological examinations were performed at 3, 6, and 9 weeks after the operation. Further, computed tomography (CT), magnetic resonance imaging (MRI), and radionuclide scans were performed 6 weeks postoperatively. Three weeks after the operation, the femoral heads showed evidence of osteonecrosis including increasing numbers of empty lacunae, decreased hematopoietic cells, and destroyed adipose tissue in the medullary cavity, which increased in severity at the subsequent follow-up evaluations at 6 and 9 weeks. Fractured trabeculae and fibrous tissue were noted 9 weeks postoperatively. Image analysis also revealed evidence of osteonecrosis, such as several osteopenic areas with sclerotic rims on the X-ray, several areas of low bone mineral density with sclerosis on the CT scan, increased uptake of the nuclide species in MRI, and an inhomogeneous long T2 signal on the radioisotopic images. Ethanol injection navigated by our novel template was successful in establishing a canine model of ONFH. This model can be used to test new treatment modalities for human ONFH.