力学载荷对骨整合影响的动物实验

植入体的骨整合使植入体与骨组织间形成牢固的接合, 可承受功能性生理载荷. 加载时间是决定植入体骨整合进程的关键因素. 然而, 关于初期载荷是否影响骨整合的进程, 或者, 无载荷愈合期是否可以缩短等问题现在还不清楚. 本文通过动物实验, 研究在骨愈合初期, 外部载荷如何影响骨整合的进程. 将钛植入体侧向植入山羊胫骨, 从术后4周开始, 对植入体加不同大小轴向载荷. 加载两周时, 取下连带植入体的胫骨; 设计专门的“拔出”力测试实验, 以检测不同分组(包括加载组和无载荷组)植入体的拔出力、骨-植入体界面的剪切强度. 并采用组织学染色、能量色散谱(energy dispersive spectroscopy, EDS)和扫描电子显微镜(scanning electron microscope, SEM)分析骨-植入体界面特征, 以评价骨整合状态. 结果表明, 术后4周时, 骨-植入体界面没有良好的骨整合, 在无载荷组样本的骨-植入体界面处可发现成纤维样组织, 而轴向10 N加载组样本的骨-植入体界面则发生良好的骨整合. 这表明, 植入手术后一定的载荷可以有利于骨整合的发生. 本研究提示, 术后初期的载荷会影响植入体骨整合的进程, 而适宜的载荷可缩短术后骨整合发生的时间.     

应力叩击仪促进胫骨骨折外固定架术后骨折愈合的临床观察

目的:探讨应力叩击仪促进胫骨骨折外固定架术后骨折愈合的临床价值。方法:选取132例胫骨骨折患者为研究对象,随机抽样法分成研究组和对照组两组,各66例。对照组采用术后常规干预方案,研究组予以术后应力叩击仪叩击治疗方案。比对两组患者的骨不愈合率、骨延迟愈合率、骨折愈合时间、完全负重时间、骨折6个月时Lane-Sandhu X线评分及Johner-wruh评估情况。结果:1研究组骨不愈合率及骨延迟愈合率分别为4.5%和7.6%,均显著低于对照组的19.7%和22.7%(P0.05);2研究组骨折愈合时间及完全负重时间分别为(82.6±9.2)d和(101.5±10.5)d,均显著短于对照组的(105.9±10.3)d和(122.4±10.3)d,(P0.05);对照组骨折6个月时Lane-Sandhu X线评分为(2.2±0.5)分,显著低于研究组的(3.0±0.5)分,(P0.05);3研究组骨折6个月时Johner-wruh优良率为90.1%,显著高于对照组的75.8%(P0.05)。结论:应力叩击仪应用于胫骨骨折患者外固定架手术后的康复治疗中,可有效缩短骨折愈合时间、提高骨折愈合率,对加快骨痂生长速度、促进病情转归有利。     

糖尿病对大鼠骨折愈合影响的实验研究

目的:观察糖尿病大鼠的骨折愈合过程,探讨糖尿病影响大鼠骨折愈合的可能的机制,为临床实践提供理论依据。方法:雄性Wister大鼠140只,随机分成二组,每组70只,A组为糖尿病骨折组;B组为非糖尿病骨折组。建立糖尿病动物模型后,无菌条件下在各组大鼠胫骨中点用手术方法制成骨折模型。术后1周、2周、4周、6周、8周各时间点进行X线检查,观察骨折愈合情况。术后1周、2周、3周、4周、6周、8周分别用ELISA法检测血清中IGF-1含量。分别在1、2、4、6、8周各时间点观察5只大鼠骨痂生长情况并取骨折断端组织行HE染色光镜观察。术后4周、6周、8周每组处死10只大鼠留取双侧胫骨标本,冷冻保存后集中进行生物力学检测。结果:1、大体标本观察结果:各时间点A组骨痂生长减缓延迟。2、X线结果:A组骨折愈合质量在各时间点均明显低于B组。3、生物力学测定结果:4周、6周、8周个时间点A组骨折处骨痂的机械强度均明显低于B组。4、组织学染色显示:术后各时间点1、2、4、6、8周A组与B组相比骨折处局部骨痂成熟延迟并且软骨细胞肥大。5、血清IGF-1含量测定:A组大鼠血清中IGF-1含量低于B组,且高峰延迟1周。结论:1.患有糖尿病后大鼠骨折愈合质量差,比较容易出现愈合延迟甚至不愈合;2.患有糖尿病的大鼠骨折后血清中的IGF-1表达明显低于对照组,且高峰推迟1周。     

骨水泥凝固前有无血液环境对骨水泥与骨界面稳定性的影响

目的:研究在有血和无血环境下粘合骨水泥和骨,比较两种粘合骨水泥的方式对骨与骨水泥界面稳定性影响的区别。方法:选取新鲜猪肱骨头20块,随机分成两组:实验组在有血的环境下用骨水泥将股骨头与金属粘合;对照组在无血的环境下用骨水泥将肱骨头和金属粘合,再将两组实验材料分别做拉伸试验,至骨与骨水泥界面断裂,最后再沿垂直于截骨面的方向做骨切片,在扫描电镜下观察并测量出每个实验对象中骨水泥的最大浸润深度。比较两组实验过程中拉力的最大载荷和断裂时的拉力以及骨水泥最大浸润深度。结果:实验组10个实验对象拉力最大载荷平均为738.50±262.15 N,断裂时的拉力平均为656.50±242.88N,骨水泥最大浸润深度平均为1.22±0.19 MM;对照组10个实验对象实验过程中拉力最大载平均为739.60±306.98 N,断裂时的拉力平均为658.80±264.56 N,骨水泥最大浸润深度平均为1.22±0.21 MM。20个实验对象在实验过程中均无意外断裂的情况发生,均在骨与骨水泥界面发生断裂。两组实验的拉力最大载荷与断裂拉力以及骨水泥最大浸润深度,均无统计学差异(P0.05)。结论:血液环境不能增加骨与骨水泥界面的不稳定因素。因此,与应用止血带相比,在TKA手术中不用止血带可能不会对骨与骨水泥界面稳定性和假体的寿命产生影响。     

利用共振频率分析牙种植体骨愈合期稳定性变化 与早期边缘骨吸收的关系

目的:利用共振频率测量仪(Osstell)连续监测骨愈合期种植体稳定性变化与早期边缘骨吸收的关系。方法:本研究于2010-2011年期间根据纳入及排除标准连续纳入32名成年男性患者作为实验对象共植入45枚Strauman种植体,每名患者选择一颗(4.8mm×10mm)种植体,共计32颗种植体,种植区位于下颌后牙(骨质均为Ⅱ或Ⅲ类骨)。利用共振频率分析仪(Osstell)测量种植体的稳定性,测量时间点为植入时以及术后第1,2,3,4,6,8,12周。另外,影像学分析测量32颗种植体12周时的边缘骨吸收;结果:本实验中所有种植体在12周均实现骨结合,并成功完成种植修复。通过重复性方差分析,见表1,在种植体植入时,初期稳定系数(ISQ)均值为(79.03±6.756)。术后一周,种植体稳定系数(ISQ)均值均呈下降趋势,至术后第2周时达到最低点,与植入时稳定性有统计学差异(P<0.05)。从术后第3周开始种植体稳定系数(ISQ)均值逐渐上升。其中,稳定系数(ISQ)均值在第6周时与第12周无统计学差异,已达到延期稳定期。32颗种植体在第12周的边缘骨吸收均值为(0.86±0.068mm),而在第12周的种植体的稳定系数均值与种植体植入时的稳定系数均值无统计学差异。结论:本实验通过共振频率测量仪(OsstellTM)连续监测,目前的结果认为种植体愈合期边缘骨吸收对种植体愈合期稳定性变化没有影响。     

续断对兔骨折愈合过程中相关基因表达和血钙、磷含量的影响

本研究通过检测中药材续断对家兔骨折模型愈合过程中与成骨密切相关基因的表达,以及血清中钙、磷含量变化,探讨其对骨折愈合的促进机制。构建家兔骨折缺损模型,术后按组分别给予续断和蒸馏水灌胃,并分别检测骨保护素(OPG)、骨保护素配体(OPGL)、局部转化生长因子β1(TGF-β1)和骨形态发生蛋白-2(BMP-2)的基因表达以及血清中Ca、P、碱性磷酸酶(ALP)含量。结果表明,续断治疗组中血钙、血磷和ALP的含量在灌胃第2周,第3周和第4周后均有明显升高,且在第三周时达到最大值。同时,OPG、TGF-β1、BMP-2三个基因在用续断治疗的不同时期呈现不同程度的表达上调,OPGL则在治疗早期表达下调。推测续断对骨折的治疗可能是通过调控OPG、OPGL、TGF-β1、BMP-2等基因在骨愈合不同阶段的表达量和血清中Ca、P、ALP的含量来促进骨骼生长。     

一种新型椎体后凸成型术重建胸腰椎骨折椎体的基础研究

目的:评估一种一种新型椎体后凸成型术的临床操作可行性及力学测试。方法:将16个新鲜椎体标本(T12-L3)随机分为2组,模拟临床手术操作进行椎体强化,一组采用新型椎体后凸成型术,另一组采用传统注射式椎体成型术,并对强化后的椎体进行力学测试,观察骨水泥的渗漏率、强化后伤椎的强度和刚度。结果:新型椎体后凸成型术组没有出现骨水泥渗漏,传统注射式椎体成型术组有2例出现骨水泥渗漏。新型椎体后凸成型术组术后伤椎的强度和刚度分别为(3457.4±653.7)N和(787.5±283.6)N/mm,传统注射式椎体成型术后伤椎的强度和刚度分别为(2584.2±414.3)N和(524.4±157.4)N/mm,新型椎体后凸成型术术后伤椎强度和刚度的恢复明显优于传统注射式椎体成型术。结论:采用新型囊袋状的扩张器行椎体后凸成型术可以明显降低骨水泥的渗漏率,可以明显恢复伤椎的强度和刚度,新型囊袋状式椎体后凸成型术是治疗胸腰椎骨折一种有效方法。     

种植体稳定系数测定与种植体负重时机选择

目的:通过测量ITI和Osstem-SS种植系统的稳定系数(ISQ),评价这两种种植体的骨结合情况,为临床确定其上部结构修复时机提供依据。方法:93例牙列缺损患者共植入179颗种植体,根据患者种植区骨量情况分为两组,其中A组为种植区骨量良好,不需骨增量手术病例(62例);B组为种植区骨量不足,需进行骨增量手术病例(31例)。A组共植入125颗种植体,其中ITI种植系统64颗,OSSTEM-SS种植系统61颗;B组共植入54颗种植体,其中ITI种植系统28颗,OSSTEM-SS种植系统26颗。术后即刻及第4、6、8、12、16、24周分别测量各时期种植体稳定系数(ISQ),并同期进行临床和影像学检查。结果:A组中ITI种植系统术后8周ISQ值平均(74.17±1.85),进行负重;OSSTEM-SS种植系统术后12周ISQ值平均(72.00±2.59),进行负重。B组中ITI种植系统术后16周ISQ值平均(65.09±3.42),进行负重;OSSTEM-SS种植系统术后24周ISQ值平均(62.09±6.16),进行负重。负重后临床随访3-24个月所有病例均成功,咀嚼功能良好,患者满意。结论:种植体稳定系数(ISQ)能反应种植体骨结合情况,可以协助医生选择种植后合适的冠修复时机。     

CGRP和NPY 在大鼠股骨闭合骨折愈合不同阶段的变化及意义

目的:探讨交感神经分泌的神经肽Y(NPY)和感觉神经分泌的钙基因相关肽(CGRP)在体内骨折愈合的不同阶段的变化及意义。方法:选择6-8月龄的雄性大鼠,建立大鼠的股骨闭合骨折模型,术后2、4、8、12周取材。进行扫描电镜,免疫组织荧光染色和血清Elisa检测。结果:1骨折愈合不同时期感觉神经肽类物质CGRP和交感神经肽类物质NPY都有表达,且其含量有先增加后减少的趋势,并在骨折后8周含量达到最高。2骨折愈合不同阶段的大鼠血清感觉神经肽类物质CGRP和交感神经肽类物质NPY均呈上升趋势,差异有统计学意义(P0.05),且NPY的含量比CGRP的含量高。骨折后2-4周,CGRP含量增加较快;骨折后4-8周NPY含量增加较快。结论:骨折愈合的不同阶段,感觉神经肽类物质CGRP和交感神经肽类物质NPY含量先升后降,对不同阶段的骨形成及骨吸收产生影响。     

9 例盖氏骨折术后骨不连合并下尺桡关节炎的疗效分析

目的:探讨手术治疗盖氐骨折术后骨不连合并下尺桡关节炎的方法和临床疗效。方法:对2010年1月至2015年6月收治的9例盖氐骨折术后骨不连合并下尺桡关节炎患者的临床资料进行回顾性分析,评价其骨不连愈合率、前臂旋转活动度,采用DASH问卷评估上肢功能,记录术中及术后并发症的发生情况。结果:9例患者随访13-78个月,平均45.4个月所有骨不连在24周都获得愈合,愈合时间12-24周;术后前臂旋转功能平均115.56±26.74°,显著高于术前(P0.01);而DASH评分从术前48.56±8.71分降至20.11±8.08分(P0.05);根据Anderson前臂功能评分标准,优2例,良5例,中2例,优良率为77.8%所有患者均对手术效果十分满意。结论:尺骨头切除术联合桡骨切开植骨内固定术操作简单有效,可显著改善盖氐骨折术后骨不连合并下尺桡关节炎患者的上肢功能。     

The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and fracture healing in rat tibias

Local and systemic release of transforming growth factor beta 1 (TGF-beta1) is known to increase during the process of fracture healing and this cytokine stimulates bone healing. The majority of the non steroidal anti inflammatory drugs (NSAIDs) inhibit fracture healing. Granulocyte colony stimulating factor (G-CSF) is a hematopoietic growth factor that stimulates bone marrow. In this study, the effects of the NSAID naproxen sodium, G-CSF, and both of them in combination on the TGF-beta1 serum level in rats with tibia fractures were measured and fracture healing was evaluated by histopathologic and radiologic examination. The TGF-beta1 serum levels obtained on day one (24 h after fracture but before administration of naproxen or G-CSF) were found to be similar in all of the five groups (p > 0.05). At the end of the first week, TGF-beta1 levels were significantly lower in naproxen-treated rats than those of the other groups excluding control (p = 0.002). Similar changes in TGF-beta1 levels were found at the end of the second and fourth weeks. TGF-beta1 levels were significantly higher in G-CSF-treated rats at the end of the first, second and fourth weeks (p < 0.05). Fracture healing scores measured with histopathological and radiological methods were higher in G-CSF-treated rats than in naproxen-treated ones. When both naproxen and G-CSF were given, the scores resumed to normal. The results point to the negative effect of naproxen sodium on fracture healing is due to its decreasing effect on the level of TGF-beta1, which may be a new possible mechanism. Moreover, this negative effect can be inhibited by the use of G-CSF.     

Biological Characteristics and Effect of Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) Grafting with Blood Plasma on Bone Regeneration in Rats

We evaluated the biological characteristics/effect of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) grafting with blood plasma on bone regeneration in rat tibia nonunion. SD rats (142) were randomly divided into four groups: fracture group (positive control); nonunion group (negative control); hUC-MSCs grafting with blood plasma group; and hUC-MSCs grafting with saline group. Rats were administered tetracycline (30 mg/kg) and calcein blue (5 mg/kg) 8 days before killing. The animals were killed under deep anesthesia at 4 and 8 weeks post fracture for radiological evaluation and histological/immunohistological studies. The hUC-MSCs grafting with blood plasma group was similar to fracture group: the fracture line blurred in 4 weeks and disappeared in 8 weeks postoperatively. Histological/immunohistological studies showed that hUC-MSCs were of low immunogenicity which merged in rat bone tissue, differentiated into osteogenic lineages, and completed the healing of nonunion. After stem cell transplantation, regardless of whether plasma or saline was used, new multi-center bone formation was observed; fracture site density was better in stem cell grafting with blood plasma group. We, therefore, concluded that the biological characteristics of hUC-MSCs-treated nonunion were different from the standard fracture healing process, and the proliferative and localization capacity of hUC-MSCs might benefit from the use of blood plasma.     

Three-dimensional load measurements in an external fixator

On the basis of a six-degree-of-freedom adjustable fracture reduction hexapod external fixator, a system which can be used for measuring axial and shear forces as well as torsion and bending moments in the fixator in vivo was developed. In a pilot study on 9 patients (7 fresh fractures and 2 osteotomies of the tibia), the load in the fixator during the healing process was measured after 2, 4, 8 and 12 weeks and at fixator removal. The measured values enabled both the type of fracture to be determined as well as the monitoring of the healing process. In well-reduced type A3 fractures small axial (direction of the bone axis) forces were found in the fixator. A2, B2 and C3 fractures showed distinct axial forces, which decreased during the healing process, according to an increasing load transfer over the bone. Bending moments in the fixator showed good correspondence with the clinical healing process, except in the case of a C3 fracture. A combination of bending moment and axial force proved to be particularly suitable to assess fracture healing. In transverse fractures, the well-known resorption phenomenon of bone in the fracture gap at approximately 4 weeks was detected by the system. Compared with other external fixator load measurements in vivo, the hexapod offers the advantage of being able to measure all forces and moments in the fixator separately and with a relatively simple mechanical arrangement. In our opinion, it will be possible to control fracture healing using this system, thereby minimizing radiation exposure from radiographs. Furthermore, the measurement system is a step towards the development of external fixator systems that enable automatic adjustments of the callus mechanical situation ("automatic dynamization") and inform the patients about the optimal weight bearing of their extremity ("intelligent fixator").     

复合负压吸引的外固定钢板治疗四肢开放性骨折的应用价值

目的:探讨复合负压吸引的外固定钢板治疗四肢开放性骨折的应用价值。方法:选择2014年1月到2017年1月到我院诊治的胫腓骨中下段开放性骨折患者共68例为研究对象,根据随机信封抽签原则分为观察组与对照组,每组34例。对照组给予负压封闭引流(vacuum sealing drainage,VSD)的常规外固定钢板治疗,观察组给予复合负压吸引的外固定钢板治疗,记录和比较围手术期严重并发症的发生情况、手术时间、骨折愈合时间、临床疗效和创口愈合情况。结果:两组患者都完成手术,围手术期并无严重并发症发生。观察组的手术时间与骨折愈合时间分别为38.24±8.16 min和8.83±1.01周,均明显少于对照组(49.50±9.87min和12.23±0.91周)(P0.05)。术后3个月,观察组和对照组的疗效优良率分别是97.1%、82.4%,观察组明显高于对照组(P0.05);观察组的创口甲级愈合28例,乙级愈合6例,丙级愈合0例;对照组甲级愈合21例,乙级愈合8例,丙级愈合5例,观察组创口愈合情况明细优于对照组(P0.05)。结论:复合负压吸引的外固定钢板治疗四肢开放性骨折能明显缩短手术时间,促进骨折愈合,提高创口愈合质量,提高临床疗效。     

髓腔内固定联合低强度脉冲超声对兔股骨中段骨折愈合作用研究

摘要 目的：针对髓腔内固定联合低强度脉冲超声对兔股骨中段骨折愈合作用进行研究。方法：选择成年兔股骨中段骨折40只,作为本次的研究对象,将其平均分为对照组和观察组。所有兔子,在手术前禁水、禁食,对其右后肢进行备皮,称重、麻醉,对照组实施髓腔内固定治疗,观察组实施髓腔内固定联合低强度脉冲超声治疗。治疗后1、2、3、4周对兔子的骨折部位进行影像学检查确定兔子的骨折线模糊情况,并在各周采集样品进行组织学检查。治疗4周后对骨折愈合情况进行检查。结果：观察组愈合程度I级、II级、II级比例均低于对照组相应比例,差异具有统计学意义（P＜0.05）,观察组IV级、V级比例分别为35.0 %、55.0 %,均高于对照组的5.0 %、5.0 %,差异具有统计学意义（P＜0.05）;观察组兔子的在1 w、2 w、3 w、4 w骨折线模糊程度评分高于对照组相应时间评分,差异具有统计学意义（P＜0.05）。结论：在兔股骨中断骨折治疗中,实施髓腔内固定联合低强度脉冲超声,可以提高骨折的愈合速度,加速骨折修复,整体治疗效果显著,可以在临床上进行推广实施。     

Osteoblast-targeted disruption of glucocorticoid signalling does not delay intramembranous bone healing

Objective

Glucocorticoids at pharmacological doses have been shown to interfere with fracture repair. The role of endogenous glucocorticoids in fracture healing is not well understood. We examined whether endogenous glucocorticoids affect bone healing in an in vivo model of cortical defect repair.

Methods

Experiments were performed using a well characterised mouse model in which intracellular glucocorticoid signalling was disrupted in osteoblasts through transgenic overexpression of 11β-hydroxysteroid-dehydrogenase type 2 (11β-HSD2) under the control of a collagen type I promoter (Col2.3-11β-HSD2). Unicortical bone defects (∅0.8 mm) were created in the tibiae of 7-week-old male transgenic mice and their wild-type littermates. Repair was assessed via histomorphometry, immunohistochemistry and microcomputed tomography (micro-CT) analysis at 1-3 weeks after defect creation.

Results

At week 1, micro-CT images of the defect demonstrated formation of mineralized intramembranous bone which increased in volume and density by week 2. At week 3, healing of the defect was nearly complete in all animals. Analysis by histomorphometry and micro-CT revealed that repair of the bony defect was similar in Col2.3-11β-HSD2 transgenic animals and their wild-type littermates at all time-points.

Conclusion

Disrupting endogenous glucocorticoid signalling in mature osteoblasts did not affect intramembranous fracture healing in a tibia defect repair model. It remains to be shown whether glucocorticoid signalling has a role in endochondral fracture healing.     

Virtual structural analysis of tibial fracture healing from low-dose clinical CT scans

Quantitative assessment of bone fracture healing remains a significant challenge in orthopaedic trauma research. Accordingly, we developed a new technique for assessing bone healing using virtual mechano-structural analysis of computed tomography (CT) scans. CT scans from 19 fractured human tibiae at 12 weeks after surgery were segmented and prepared for finite element analysis (FEA). Boundary conditions were applied to the models to simulate a torsion test that is commonly used to access the structural integrity of long bones in animal models of fracture healing. The output of each model was the virtual torsional rigidity (VTR) of the healing zone, normalized to the torsional rigidity of each patient’s virtually reconstructed tibia. This provided a structural measure to track the percentage of healing each patient had undergone. Callus morphometric measurements were also collected from the CT scans. Results showed that at 12 weeks post-op, more than 75% of patients achieved a normalized VTR (torsional rigidity relative to uninjured bone) of 85% or above. The predicted intact torsional rigidities compared well with published cadaveric data. Across all patients, callus volume and density were weakly and non-significantly correlated with normalized VTR and time to clinical union. Conversely, normalized VTR was significantly correlated with time to union (R² = 0.383, p = 0.005). This suggests that fracture scoring methods based on the visual appearance of callus may not accurately predict mechanical integrity. The image-based structural analysis presented here may be a useful technique for assessment of bone healing in orthopaedic trauma research.     

Biomechanical Characteristics of Osteoporotic Fracture Healing in Ovariectomized Rats: A Systematic Review

Biomechanical tests are widely used in animal studies on osteoporotic fracture healing. However, the biomechanical recovery process is still unknown, leading to difficulty in choosing time points for biomechanical tests and in correctly assessing osteoporotic fracture healing. To determine the biomechanical recovery process during osteoporotic fracture healing, studies on osteoporotic femur fracture healing with biomechanical tests in ovariectomized rat (OVX) models were collected from PUBMED, EMBASE, and Chinese databases. Quadratic curves of fracture healing time and maximum load were fitted with data from the analyzed studies. In the fitted curve for normal fractures, the predicted maximum load was 145.56 N, and the fracture healing time was 88.0 d. In the fitted curve for osteoporotic fractures, the predicted maximum load was 122.30 N, and the fracture healing time was 95.2 d. The maximum load of fractured femurs in OVX rats was also lower than that in sham rats at day 84 post-fracture (D84 PF). The fracture healing time was prolonged and maximum load at D84 PF decreased in OVX rats with closed fractures. The maximum load of Wister rats was higher than that of Sprague-Dawley (SD) rats, but the fracture healing time of SD and Wister rats was similar. Osteoporotic fracture healing was delayed in rats that were < = 12 weeks old when ovariectomized, and at D84 PF, the maximum load of rats < = 12 weeks old at ovariectomy was lower than that of rats >12 weeks old at ovariectomy. There was no significant difference in maximum load at D84 PF between rats with an osteoporosis modeling time <12 weeks and > = 12 weeks. In conclusion, fracture healing was delayed and biomechanical property decreased by osteoporosis. Time points around D95.2 PF should be considered for biomechanical tests of osteoporotic femur fracture healing in OVX rat models. Osteoporotic fracture healing in OVX rats was affected by the fracture type but not by the strain of the rat.     

Silencing long non‐coding RNA MEG3 accelerates tibia fraction healing by regulating the Wnt/β‐catenin signalling pathway

As fracture healing is related to gene expression, fracture healing is prospected to be implicated in long non‐coding RNAs (lncRNAs). This study focuses on the effects of epigenetic silencing of long non‐coding RNA maternally expressed gene 3 (lncRNA MEG3) on fracture healing by regulating the Wnt/β‐catenin signalling pathway. Genes expressed in fracture were screened using bioinformatics and the subcellular location of MEG3 was determined using FISH. Next, we successfully established tibia fracture (TF) models of C57BL/6J and Col2a1‐ICAT mice and the effect of silencing lncRNA MEG3 on fracture healing was detected after TF mice were treated with phosphate buffer saline (PBS), MEG3 siRNA and scramble siRNA. X‐ray imaging, Safranin‐O/fast green and haematoxylin‐eosin (HE) staining and histomorphometrical and biomechanical analysis were adopted to observe and to detect the fracture healing conditions. Additionally, the positive expression of collagen II and osteocalcin was examined using immunohistochemistry. At last, in the in vitro experiment, the relationship of MEG3 and the Wnt/β‐catenin signalling pathway in fraction healing was investigated. MEG3 was located in the cell nucleus. In addition, it was found that MEG3 and the Wnt/β‐catenin signalling pathway were associated with fraction healing. Moreover, silencing MEG3 was proved to elevate callus area and maximum bending load and to furthermore enhance the recanalization of bone marrow cavity. Finally, MEG3 knockdown elevated levels of Col10a1, Runx2, Osterix, Osteocalcin, Wnt10b and β‐catenin/β‐catenin whereas it reduced p‐GSK‐3β/GSK‐3β levels. Taken together, our data supported that epigenetic silencing of lncRNA MEG3 could promote the tibia fracture healing by activating the Wnt/β‐catenin signalling pathway.     

Changes of substance P during fracture healing in ovariectomized mice

Neuropeptides may play an important role in the healing process of osteoporotic fractures. The objective of this study was to determine the role of substance P during osteoporotic fracture healing.One hundred ninety-two mice were randomized into ovariectomy (OVX) and control (CON) group (n = 96, respectively). Femoral shaft fracture was created 3 weeks after OVX. Bone mineral density (BMD), micro-CT (µCT) analysis of fracture callus formation and mineralization, µCT analysis of fracture site neovascularization and biomechanical property as well as substance P levels were evaluated 1, 2, 4, and 8 weeks after fracture and compared with CON group.Following OVX-induced bone loss, fracture healing in OVX mice was significantly poorer than that in CON mice, with a significant decrease of substance P at the fracture site at all time points and with the level at early stage (1 and 2 weeks) higher than later stage (4 and 8 weeks). Impaired angiogenesis was also noted in OVX mice. No significant change of substance P level in serum was found between different groups or time points.In conclusion, fracture healing is inferior in OVX-induced bone loss and associated with a significant decrease of substance P. Substance P may play an important role during osteoporotic fracture healing.