多孔钽钉植入治疗早期股骨头缺血性骨坏死

目的:总结多孔钽钉植入治疗成人早期股骨头缺血性骨坏死(avascular necrosis of the femoral head,ANFH)的手术方法及临床疗效.方法:2008年3月-2009年2月,采用多孔钽钉植入治疗10例(共11髋)ANFH患者.男7例,女3例;年龄18-36岁,平均28岁.致病原因:创伤性2例,激素性2例,酒精性1例,特发性6例.单侧9例,双侧1例.左侧5髋,右侧6髋.根据1995年Steinberg分型:Ⅰ期3例3髋,Ⅱ期7例8髋.Harris评分为(52.3±1.2)分.病程11-26个月,平均15个月.术前术后影像学对比.结果:手术时间平均25min,平均出血量50ml.术后患者切1:2均Ⅰ期愈合,无感染等并发症发生.10例均获随访,随访时间7-14个月,平均11个月.患者术前疼痛及功能受限症状均明显缓解.术后Harris评分为(82.9±1.4)分,与术前比较差异有统计学意义(P<0.05);影像学显示术后坏死程度没有进展或改善.结论:多孔钽钉植入是治疗早期ANFH理想的微创手术疗法,特别是骨坏死处于Ⅰ期和Ⅱ期的年轻病人,既解除疼痛又可最大限度减少并发症,至少延缓甚至避免了关节置换,但远期疗效尚待大样本特别是多中心水平的长期随访观察.     

Experimental anatomical basis for a new method of revascularizing the femoral head for the treatment of avascular necrosis

Two series of experiments were performed in rabbits of both sex at the age of 2-6 months. In I series (42 rabbits) the modelling of Perthes' diseases was performed by a lesion produced in the proximal diaepiphysial femoral growth zone. Character and course of pathological processes in the femoral head and neck were studied. They were mainly correspond to 5 clinical roentgenological stages of Perthes' disease. In II series (52 rabbits) with the model of Perthes' disease the suggested operation on revascularization of the femoral head by means of a periosteal muscular graft on a feeding peduncle was applied. Histological, angiological, roentgenological investigations and the method on indication of radioactive phosphorus (P32) demonstrated good vascularizational and reparative properties of the transplant applied. In 50 patients with Perthes' disease the result of a conservative treatment were studied. In 25 patients the operation on revascularization of the femoral head by means of a periosteal muscular transplant on a feeding peduncle was applied according to the technique suggested. The analysis of the treatment results demonstrated that restoration of the femoral bone configuration and that of functioning of the coxofemoral joint occurred sooner, further progressive course of the disease was stopped, duration of treatment was shorter as compared to the conservative methods. The operation suggested could be applied together with other operative methods for treatment of Perthes' disease.     

股骨头缺血坏死介入治疗的临床应用研究

目的:探讨介入治疗股骨头缺血坏死的临床应用价值。方法:采用Seldinger技术对28例患者行超选择股骨头供血动脉插管,动脉造影、溶通治疗。结果:28例患者治疗后髋部疼痛及关节功能障碍均有不同程度的减轻及改善,有效率96.4%;治疗后病变区血管分支增多、增粗;影像随访显示股骨头骨质不同程度修复。结论:介入治疗具有创伤小、并发症低、血管再通率高、临床症状改善明显的优势,能有效的改善股骨头的局部血液循环和髋关节的疼痛、活动功能,应大力推广。     

成骨细胞移植和成骨生长肽对股骨头坏死修复作用的实验研究

目的：研究成骨细胞移植和成骨生长肽（OGP）对激素性股骨头坏死的影响。方法：25只健康成年日本大耳白兔,随机分为正常组（5只）,实验组（10只）和对照组（10只）。实验组和对照组注射醋酸泼尼松龙致使激素性股骨头坏死后,前者成骨细胞移植于动物股骨头并且OGP注射4、8周,后者注射等量生理盐水。测定血清碱性磷酸酶（ALP）、骨钙素（BGP）,测试股骨头力学性质,通过光镜和扫描电镜观察股骨头的形态结构。结果：实验组血清ALP、BGP明显高于对照组（P〈0．05）。实验组股骨头的最大压缩载荷及载荷／位移较对照组高（P〉0.05）。光镜、扫描电镜观察到实验组股骨头中骨小梁形态及胶原纤维排列有序性明显好于对照组。结论：成骨细胞移植和OGP注射对股骨头坏死具有一定的修复作用。     

Microarray analysis of long-noncoding RNAs and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head

This study performed the first microarray analysis of long-noncoding RNA (lncRNA) and mRNA expression profiles in human steroid-induced avascular necrosis of the femoral head (SAVNFH). Expression levels of lncRNAs and mRNAs in three human SAVNFH samples and three human femoral head fracture samples (controls) were detected using third-generation lncRNA microarrays (KangChen Biotech, Shanghai, China). The fold change, false discovery rate, and P value were utilized to filter genes with significant differential expression in the SAVNFH samples compared with the control samples. In total, there were 1179 upregulated and 3214 downregulated lncRNAs (P2. zerofold, P < 0.05). Meanwhile, 1092 upregulated and 565 downregulated mRNAs were found in the SAVNFH samples compared with the control samples. Then, quantitative real-time polymerase chain reaction was used to confirm the previous microarray results using 8 and 20 selected dysregulated lncRNAs and mRNAs, respectively, and the results generally confirmed the microarray findings. Finally, we used Gene Ontology (GO) and pathway analysis to investigate the functions of the altered mRNAs and their associated GO terms and biological pathways. The Immune system process term (GO:0002376) was the most significantly upregulated GO term, and the Regulation of blood coagulation term (GO:0030193) was the most significantly downregulated GO term in the biological process category for the SAVNFH samples. “Hematopoietic cell lineage - Homo sapiens (human) (Pathway ID: hsa04640)” and “Complement and coagulation cascades - Homo sapiens (human) (Pathway ID: hsa04610)” were the most significantly up- and downregulated pathways in the SAVNFH samples compared with the controls. In conclusion, the differential expression of lncRNAs and mRNAs may be correlated with the pathogenesis of SAVNFH, and these significantly dysregulated lncRNAs and mRNAs may function through networks or participate in several specific biological processes. Further research is needed to understand their exact functions and mechanisms in SAVNFH.     

超选择性股动脉内骨髓单个核细胞移植治疗股骨头坏死187例

目的 研究自体骨髓单个核细胞移植对股骨头坏死患者缺血状态的改善程度和治疗效果.方法 选取2004 年7 月至2010 年11 月期间187 例252 髋股骨头坏死患者,应用自体骨髓单个核细胞移植治疗,分别采集 187 例患者骨髓200 -360 ml,采用 Ficoll 密度梯度离心法分离单个核细胞,单个核细胞总数为（2.4 ~ 7.8）× 108 个,流式细胞仪检测 CD34＋ 细胞和 CD133＋ 细胞在所分离出的干细胞悬液中的含量分别为2.47﹪± 0.58﹪和1.29﹪± 0.35﹪,然后将单个核细胞用生理盐水制备成细胞悬液 20 - 30 ml,使用数字减影血管造影技术（DSA）行超选择性股骨头供血动脉内干细胞移植术.按世界骨循环研究学会（ARCO）对骨坏死分期,设自身前后对照观察疗效.移植术后第 3、6、12、24、36 和48 个月,根据髋关节 Harris 评分评价疗效,移植术后6 个月通过复查患者股骨头供血动脉 DSA,观察其新生血管形成情况,以后每隔 6 个月采用影像学方法观察股骨头形态学变化.结果 （1）临床疗效：对接受自体骨髓单个核细胞移植治疗的187 例患者随访 3 ~ 48（24.2 ± 4.5）个月,其中髋关节疼痛缓解者 158 例（占患者总数的 84.5﹪）,髋关节功能改善者 146 例（占患者总数的 78.1﹪）,行走间距延长者 149 例（占患者总数的 79.7﹪）;（2）影像学检查：干细胞移植术后 6 个月187 例患者中54 例行股骨头供血动脉 DSA 检查,48 例显示供血动脉较移植术前明显增多、增粗,血流速度增快,12 ~ 24个月后 72 例患者股骨头区骨质病变获得改善.结论 超选择性动脉内骨髓单个核细胞移植方法简便、安全有效,对因缺血导致坏死的股骨头无再次损伤,能够有效治疗缺血性股骨头坏死.     

Autosomal dominant avascular necrosis of femoral head in two Taiwanese pedigrees and linkage to chromosome 12q13

Avascular necrosis of the femoral head (ANFH) is a debilitating disease that commonly leads to destruction of the hip joint in adults. The etiology of ANFH is unknown, but previous studies have indicated that heritable thrombophilia (increased tendency to form thrombi) and hypofibrinolysis (reduced ability to lyse thrombi), alcohol intake, and steroid use are risk factors for ANFH. We recently identified two families with ANFH showing autosomal dominant inheritance. By applying linkage analysis to a four-generation pedigree, we excluded linkage between the family and three genes related to thrombophilia and hypofibrinolysis: protein C, protein S, and plasminogen activator inhibitor. Furthermore, by a genomewide scan, a significant two-point LOD score of 3.45 (recombination fraction [theta] = 0) was obtained between the family with ANFH and marker D12S85 on chromosome 12. High-resolution mapping was conducted in a second family with ANFH and replicated the linkage to D12S368 (pedigree I: LOD score 2.47, theta = 0.05; pedigree II: LOD score 2.81, theta = 0.10). When an age-dependent-penetrance model was applied, the combined multipoint LOD score was 6.43 between D12S1663 and D12S85. Thus, we mapped the candidate gene for autosomal dominant ANFH to a 15-cM region between D12S1663 and D12S1632 on chromosome 12q13.     

The influence of the biomechanical parameters of the hip on the outcome of treatment of hips subject to avascular necrosis of the femoral head

We were interested in whether or not the biomechanical status of the hip influences the course of avascular necrosis of the femoral head. To investigate this, we used a computer aided system based on a three dimensional mathematical model for determining the stress distribution in the hip joint from standard anteroposterior rentgenographs (X-ray images) of both hips and pelvis. Based on the results of our study, we suggest that the biomechanical parameters of the hip play an important role in the outcome of treatment of hips affected by avascular necrosis of the femoral head.     

Avascular necrosis of the femoral head in childhood systemic lupus erythematosus

Four of 10 children with SLE kept under observation over the past nine years have developed avascular necrosis (AN) of the femoral head. The symptoms of AN are insidious and unpredictable and predate the radiologic diagnosis by weeks to months. In a comparison of these children with SLE, with and without AN, with a group of patients with nephrosis treated with corticosteroids and a group with glomerulonephritis treated with azathioprine, AN was related to the duration of daily steroid therapy rather than the total duration of steroid treatment; this was not true for azathioprine. The occurrence of AN in our patients while they were on alternate-day steroid therapy, or coincident with a relapse, suggests that its development is determined by underlying disease.     

Bone morphogenetic proteins (BMPs) expression in the femoral heads of patients with avascular necrosis

Avascular necrosis (AVN) is a disorder of the bone repair process which usually results in femoral head (FH) destruction. Bone morphogenetic proteins (BMPs) are the key proteins regulating bone remodelling and healing. BMPs gene expression levels were analyzed in the normal and necrotic sites of osteonecrotic FHs. Quantitative RT-PCR for BMP-2, -4, -6, -7 genes was performed in bone tissue samples from 47 osteonecrotic FHs. Protein levels of BMP-2, -4, -6 were estimated by Western Blot. Statistical analysis was performed using the Wilcoxon signed rank test. BMP-2 and BMP-6 mRNA levels were higher in the normal than the necrotic site (normal/necrotic: 16.8/6.8 and 1.75/1.64, respectively). On the contrary, BMP-4 mRNA levels were higher in the necrotic (0.75) than the normal (0.62), while BMP-7 mRNA levels were extremely low. At the protein level, BMP-2 continued to have a higher expression in the normal region (normal/necrotic: 0.67/0.64). BMP-4 and -6 were detected at higher levels in the necrotic site (normal/necrotic: 0.51/0.61 for BMP-4, 0.51/0.56 for BMP-6), while BMP-7 was not detectable. Different BMP levels between the normal and necrotic site, as well as discrepancies between the gene and protein expression pattern suggest a different regulation mechanism for BMPs between the two regions of FHs. The understanding of the expression pattern and the correlation of BMPs could lead to a more successful use in the prevention and treatment of AVN.     

Self-healing and injectable hybrid hydrogel for bone regeneration of femoral head necrosis and defect

Background

HA modified by bisphosphonate (BP) (HA-BP) was synthesized by chemical reaction and possessed promising properties such as self-healing, injection ability, and strong adhesion. The main aim of this study was to confirm its role in promoting osteogenic differentiation in vitro and bone regeneration in vivo.

Numerical studies on alternative therapies for femoral head necrosis: A finite element approach and clinical experience

Numerical investigations with regard to the subtrochanteric fracture risk induced by three alternative methods for the treatment of femoral head necrosis are outlined in this presentation. The traditional core decompression technique will be compared with minimal invasive multiple low diameter drillings and the implantation of an innovative tantalum implant. With emphasis to the newly introduced computational strategies and modeling approaches, the modeling of critical loading conditions as well as mesh convergence is outlined in detail. In addition to the immediate postoperative fracture risk, the long-term stability of the different approaches for treating femoral head necrosis is predicted by performing well-established bone remodeling simulation techniques. The computed results are augmented for results obtained from clinical experience.     

STAT1-caspase 3 pathway in the apoptotic process associated with steroid-induced necrosis of the femoral head

Osteocyte apoptosis is the main manifestation of steroid-induced avascular necrosis of the femoral head (SANFH). STAT1 and caspase 3 participate in the process of apoptosis and STAT1 upregulates the expression of caspase 3. We examined the relationship between the STAT1-caspase 3 pathway and apoptosis in SANFH. All specimens were divided into four groups: the negative control group, Ficat I–II group, Ficat III group, and Ficat IV–V group, and examined histologically, with a TUNEL assay, immunohistochemically, with a caspase 3 activity assay, with ELISAs of STAT1 and phospo-STAT1 (p-STAT1), with a western blotting analysis of p-STAT1 and with real-time RT-PCR. The proportion of empty lacunae increased significantly with the development of SANFH. The proportion of TUNEL-positive cells and immunohistochemical analysis of caspase 3 also increased significantly, although the Ficat I–II group did not differ significantly from the negative control group. Immunohistochemical analysis of STAT1 and p-STAT1, caspase 3 activity all showed significant differences among the groups. An ELISA and a western blotting analysis of p-STAT1 showed significant differences among the groups. An ELISA of STAT1, real-time RT-PCR analysis of caspase 3 and STAT1 all showed significant differences among the groups except between the Ficat I–II and negative control groups. The correlation analysis showed strong positive relationships between the proportion of empty lacunae and the proportion of TUNEL-positive cells between caspase 3 activity and the proportion of TUNEL-positive cells and between the levels of p-STAT1 protein and caspase 3 mRNA. The apoptotic process in SANFH develops with the upregulated expression of caspase 3 via the expression and activation of STAT1. The STATI-caspase 3 pathway plays a critical role in the development of SANFH.     

Stratophenetic analysis of avascular necrosis in turtles: Affirmation of the decompression syndrome hypothesis

• 1.1. The decompression syndrome hypothesis, as an explanation of the etiology of avascular necrosis, is further substantiated through analysis of its occurrence in turtles.
• 2.2. No examples were identified in terrestrial or aquatic forms diving to depths insufficient for development of decompression syndrome.
• 3.3. The “population” frequency of avascular necrosis has substantially diminished over geologic time.
• 4.4. A frequent occurrence in Cretaceous marine turtles, it is only rarely observed in specimens younger than Miocene age.
• 5.5. Evolution of physiologic and/or behavioral protective mechanisms appears to be responsible for reduced susceptibility to the underlying decompression syndrome.

     

Maintaining transparency: a review of the developmental physiology and pathophysiology of two avascular tissues

The lens and cornea are transparent and usually avascular. Controlling nutrient supply while maintaining transparency is a physiological challenge for both tissues. During sleep and with contact lens wear the endothelial layer of the cornea may become hypoxic, compromising its ability to maintain corneal transparency. The mechanism responsible for establishing the avascular nature of the corneal stroma is unknown. In several pathological conditions, the stroma can be invaded by abnormal, leaky vessels, leading to opacification. Several molecules that are likely to help maintain the avascular nature of the corneal stroma have been identified, although their relative contributions remain to be demonstrated. The mammalian lens is surrounded by capillaries early in life. After the fetal vasculature regresses, the lens resides in a hypoxic environment. Hypoxia is likely to be required to maintain lens transparency. The vitreous body may help to maintain the low oxygen level around the lens. The hypothesis is presented that many aspects of the aging of the lens, including increased hardening, loss of accommodation (presbyopia), and opacification of the lens nucleus, are caused by exposure to oxygen. Testing this hypothesis may lead to prevention for nuclear cataract and insight into the mechanisms of lens aging. Although they are both transparent, corneal pathology is associated with an insufficient supply of oxygen, while lens pathology may involve excessive exposure to oxygen.