青少年特发性脊柱侧凸患者脊柱前后柱骨骺软骨的组织形态学对比研究

目的：探讨青少年特发性脊柱侧凸（adolescentid iopathic scoliosis，AIS）患者脊柱前后柱软骨组织学和软骨细胞的增殖与凋亡有无差异及其对脊柱侧凸发生、进展的影响。方法：26例11～16岁AIS患者随机分为2组．A组12例行前路松解术或前路矫形内固定术；B组14例行后路矫形内固定术。A组取胸弯上端椎、顶椎和下端椎椎体生长板，B组取下关节突软骨．进行组织学观察及免疫组织化学测定其软骨细胞的细胞增殖核抗原（proliferation cell nuclear antigen，PCNA）指数和聚腺苷二磷酸-核糖聚合酶（poly ADP-ribose polymerase，PARP）指数。采用组织学分级作为生长潜能的指标，PCNA指数和PARP指数分别代表细胞增殖指数和凋亡指数作为软骨内成骨活跃度的指标。结果：A组AIS患者前柱椎体生长板组织学分级、增殖-肥大层软骨细胞的增殖指数（PCNA）和凋亡指数（PARP）均明显高于B组AIS患者后柱下关节突软骨．且有统计学差异（P〈0．05）。结论：相同年龄段AIS患者脊柱前、后柱生长潜能和软骨内成骨活跃程度存在差异．可能导致前柱生长过快、后柱生长缓慢，从而可能对脊柱侧凸的发生和进展发挥重要作用。     

青少年特发性脊柱侧凸患者身高增长速率高峰的预测

青少年特发性脊柱侧凸(AIs)的病因学说很多,目前尚无明确定论.由于多数患者在青春发育期发病且随着生长发育而不断进展,生长发育和特发性脊柱侧凸(IS)的关系早已受到学者的关注.Porter [1]认为IS可能是由于神经骨生长发育失衡引起.Guo等 [2-3]研究发现IS患者存在脊柱前柱相对过度生长,并认为这可能是导致侧凸的原因.朱锋等 [4]通过对AIS患者脊柱前后柱次发性生长骨骺的增殖和凋亡研究发现,AIS患者青春期脊柱前柱软骨细胞生长活性明显高于后柱,提示AIS患者脊柱前柱生长过快.     

青少年特发性脊柱侧凸患者下关节突软骨的组织形态学研究

目的：观察青少年特发性脊柱侧凸（adolescent idiopathic scoliosis，AIS）患者上、下端椎及顶椎凸、凹侧下关节突软骨组织学分级和软骨细胞的增殖与凋亡，探讨其软骨内成骨性生长在侧凸进展中的作用。方法：16例AIS患者，平均年龄13．5岁。取上、下端椎和顶椎凸、凹侧下关节突进行组织学观察及免疫组织化学测定其软骨细胞的增殖指数（proliferation cell nuclear antigen，PCNA）和凋亡指数（Poly ADP-ribose pdymerase，PARP）。采用PCN/PARP比值及组织学分级作为软骨内成骨活跃程度的指标，并对其进行比较。结果：AIS患者上、下端椎和顶椎凸、凹侧下关节突软骨组织学分级、软骨细胞的增殖指数（PCNA）、凋亡指数（PARP）和PCNA／PARP比值的比较均没有统计学差异（P〉0．05）。结论：AIS患者上、下端椎和顶椎凸、凹侧下关节突软骨内成骨活跃程度没有差异，关节突软骨内成骨性生长发育可能对脊柱侧凸进展没有明显的作用。     

青少年特发性脊柱侧凸患者终板软骨的组织形态学研究

目的:观察青少年特发性脊柱侧凸(adolescent idiopathic scoliosis;AIS)患者终板软骨的组织学形态;探讨其与AIS发生、发展的关系.方法:20例AIS患者;前路手术时分别获取20份顶椎及18份下端椎终板软骨;每份均包含凸侧与凹侧.切片行HE染色;光镜下观察终板软骨组织形态;采用病理图像分析系统测量终板软骨肥大区的厚度、细胞巢面积、巢内细胞数及增殖区细胞数(个/视野).参照Enileking法设定曲度因子(factor of curve;FC);将顶椎标本分为FC≤6组(11例)和FC＞6组(9例).比较上述指标在不同部位、不同FC分组下的差异.结果:顶椎凸侧的上述指标均显著高于凹侧(P＜0.05);下端椎仅凸侧肥大区细胞巢平均面积显著大于凹侧(P＜0.05);顶椎与下端椎间同侧比较;仅下端椎凹侧肥大区的细胞数显著大于顶椎(P＜0.05).FC＞6组的顶椎凸侧和凹侧终板软骨肥大区的巢内细胞数显著小于FC≤6组(P＜0.05);FC＞6组的凸侧增殖区细胞数也显著小于FC≤6组(P＜0.05).结论:AIS患者终板软骨的组织学变化特征更倾向于与脊柱不同部位、不同状态下机械应力差异有关的继发性改变;但组织学变化与机械应力变化之间不完全平行;AIS的发生、发展可能伴有生物力学以外的因素.     

青少年特发性脊柱侧凸患者凸凹侧椎体生长板组织形态学研究

[目的]探讨AIS患者椎体生长板凸、凹侧组织学及软骨细胞增殖与凋亡差异在AIS发生、发展中目的作用.[方法]本研究中取AIS患者椎体生长板,应用HE染色评估生长板凸、凹侧目的组织学分级差异,应用免疫组织化学方法及TUNEL方法评估生长板凸、凹侧软骨细胞增殖与凋亡指数,并对其进行比较.[结果]光镜下椎体生长板凸侧可见正常分层结构,生长板凹侧分层结构排列混乱.顶椎椎体牛长凸、凹侧组织学分级差异有统计学意义(＜0.05).终椎凹侧生长板和顶椎凹侧生长板组织学分级有明显差异且有统计学意义(P＜0.05).顶椎生长板凸侧软骨细胞增殖指数和凋亡指数明显高于凹侧,其差异有统计学意义(P＜0.05).在上终椎椎体牛长板凸、凹侧软骨细胞PCNA增殖指数有明显差异且有统计学意义(P＜0.05).上、下终椎椎体生长板和顶椎椎体生长板凹侧软骨细胞增殖和凋亡指数有差异且统计学意义(P＜0.05).在上、下终椎和顶椎椎体生长板凸侧软骨细胞TUNEL凋亡指数有差异且有统计学意义(P＜0.05).[结论]AIS患者上、下终椎和顶椎椎体生长板凸、凹侧组织学分级目的差异和软骨细胞目的增殖与凋亡指数差异可能表明椎体生长板凸、凹侧存在生长动力学差异,这可能影响侧凸[目的]进展.     

青少年特发性脊柱侧凸软骨Sox9表达及意义

[目的]检测Sox9及软骨特异性标记物Ⅱ型胶原及Aggrecan在青少年特发性脊柱侧凸(adolescent idiopathic scoliosis, AIS)患者关节突软骨细胞中的表达,探讨其与AIS发生、发展的关系。[方法]收集我院行后路脊柱侧凸矫形术的15例AIS患者的关节突软骨标本,设为AIS组;取同年龄段无脊柱侧凸行脊柱融合术的10例患者正常软骨标本,设为对照组。分别分离软骨细胞体外培养,分别采用RT-PCR,免疫组化,免疫荧光染色和Westen-blotting等方法检测AIS组及对照组软骨Sox9及Ⅱ型胶原及Aggrecan的表达情况,进行两组间比较和AIS组凸侧与凹侧间比较。[结果] AIS组患者软骨细胞内的Sox9及软骨特异性标记物CollagenⅡ及Aggrecan的表达明显高于非AIS组患者。相比于凹侧,AIS患者顶椎凸侧原代软骨细胞中Sox9及软骨特异性标记物CollagenⅡ及Aggrecan表达明显升高。[结论] Sox9在AIS患者体内及原代软骨细胞中的表达异常是AIS患者体内软骨发育异常及脊柱不平衡生长的重要原因,可能是AIS发生、发展的原因之一。     

青少年特发性脊柱侧凸椎体软骨终板核心蛋白、转化生长因子β1及碱性成纤维细胞生长因子的表达

青少年特发性脊柱侧凸(adolescent idiopathic scoliosis，AIS)的发病原因不明，临床上AIS患者侧凸椎体存在着不同程度的椎体楔形变，人体发育过程中椎体的生长需通过软骨终板的软骨内骨化来完成，对于软骨终板在侧凸中的变化迄今文献报道较少。研究表明，细胞因子同细胞的生长发育、再生及创伤的愈合有关。本研究选择北京协和医院骨科收治的年龄10岁以上并排除先天性、神经肌肉性等原因所导致的脊柱侧凸及成人脊柱侧凸患者，对前路手术切除的软骨终板研究细胞因子和蛋白多糖核心蛋白的变化。     

镍钛记忆合金加压钉对山羊胸椎骨骺生长的影响观察

目的目前对脊柱侧凸伴发的脊柱前凸研究较少。通过观察镍钛记忆合金加压钉(Staple钉)所致的脊柱前凸骨骺组织学变化,探讨Staple钉对胸椎前凸生长的影响。方法 2～3月龄雌性山羊18只,体重8～12kg,随机分为长钉组、短钉组、空白对照组,每组6只。长钉组和短钉组分别于山羊T6～11节段植入Staple长钉(7mm齿深)、Staple短钉(4mm齿深),空白对照组不进行干预。术前及术后3个月行X线片观察Cobb角变化,然后处死山羊取脊柱顶椎生长板和下关节突组织进行HE染色观察骨骺软骨细胞,并行免疫组织化学聚腺苷酸二磷酸核糖聚合酶-p85片段和细胞核增殖抗原双重染色法对软骨细胞进行计数,并计算各组软骨细胞增殖活跃度。结果术后3个月,长钉组和短钉组Cobb角均显著高于术前,且显著高于空白对照组,差异均有统计学意义(P<0.05);长钉组及短钉组间比较差异无统计学意义(P>0.05)。HE染色和免疫组织化学双重染色显示:与空白对照组相比,长钉组和短钉组生长板及下关节突软骨骨骺的增殖层和肥大层的软骨细胞数均明显减少,软骨细胞柱状排列更不规则,细胞外基质所占体积比增高;长钉组的这种趋势较短钉组更为明显。长钉组和短钉组HE染色组织学分级与空白对照组比较差异均有统计学意义(P<0.05),长钉组与短钉组间差异无统计学意义(P>0.05)。长钉组和短钉组椎体生长板及下关节突软骨增殖活跃度与空白对照组比较差异均有统计学意义(P<0.01),长钉组和短钉组间比较差异无统计学意义(P>0.05)。结论 Staple钉通过影响山羊胸椎的远端生长板及其下关节突的骨骺软骨细胞增殖活跃度,从而影响骨生长,导致脊柱后凸增加。     

青少年特发性脊柱侧凸软骨终板蛋白质组学研究

目的 通过对青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)患者侧凸顶椎椎间盘软骨终板进行蛋白质组学鉴定,尝试寻找诱发或加重椎间盘不均衡发育的分子因素.方法 经一期前路脊柱侧凸矫形术获取6例AIS患者主弯顶椎椎间盘的软骨终板组织,提取蛋白组织,用Brad-ford法对所获取蛋白质样品进行浓度测定;通过SDS-聚丙烯酰胺凝胶蛋白电泳(sodium dodecyl sulfate-polyacrylamide gel electrophoresis,SDS-PAGE)对蛋白质总量和分子量范围进行初步鉴定;最后用鸟枪法蛋白质组鉴定技术比较凸、凹侧所含蛋白成分的异同,分析蛋白的种类和功能.结果 Bradford法测量软骨组织中获得的平均蛋白质浓度为3.02 mg/ml;SDS-PAGE显示顶椎凸侧终板软骨内所含蛋白质的种类明显多于凹侧;从凸侧软骨终板中鉴定出103种蛋白质,凹侧软骨终板内鉴定出55种蛋白质,其中凸侧特有蛋白58种,凹侧特有蛋白10种.结论 对AIS患者侧凸顶椎软骨终板蛋白质进行分类研究后表明侧凸顶椎软骨终板凸、凹两侧的特有蛋白与脊柱侧凸顶椎椎间盘的不对称发育存在一定的联系.     

褪黑素信号通路对青少年特发性脊柱侧凸软骨细胞增殖的影响

【摘要】 目的：检测褪黑素对青少年特发性脊柱侧凸（adolescent idiopathic scoliosis,AIS）患者软骨细胞增殖的影响,并探讨其与AIS病因学的关系。方法：选取2009年1月～2010年12月在我院手术治疗的15例AIS患者（AIS组）和6例非脊柱侧凸患者（对照组）的软骨组织（髂软骨或棘突软骨）行软骨细胞培养。取P2代细胞分别用浓度为0M、10-11M、10-9M、10-7M、10-5M褪黑素连续刺激3d。加入Brdu 12h后用ELLSA法标记,显色后在酶标仪450nm波长下检测光密度（optical density,OD）值以评估软骨细胞的增殖情况。结果：不同浓度（10-11M、10-9M、10-7M、10-5M）褪黑素刺激以后,对照组软骨细胞的OD值分别增加了（5.7±6.7）%、（32.1±11.1）%、（57.5±11.9）%、（103.2±16.2）%（P<0.05）。AIS组软骨细胞的OD值相分别增加了（-0.3±22.3）%、（5.8±29.9）%、（12.7±36.1）%、（10.2±44.0）%（P>0.05）。结论：褪黑素可以有效促进正常软骨细胞增殖,但是却无法有效促进AIS患者软骨细胞的增殖,说明AIS患者中褪黑素信号通路调节软骨内成骨的过程可能存在异常。     

Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis

Asymmetrical growth of the vertebrae has been implicated as one possible etiologic factor in the pathogenesis of adolescent idiopathic scoliosis. The longitudinal vertebral growth derives from the endochondral ossification of the vertebral growth plate. In the present study, the growth plates from the convex and concave side of the vertebrae were characterized by the method of histology and immunohistochemistry to evaluate the growth activity, cell proliferation, and apoptosis. Normal zoned architectures were observed in the convex side of the growth plate and disorganized architectures in the concave side. The histological grades were significantly different between the convex and the concave side of the growth plate in the apex vertebrae (P < 0.05). The histological difference was also found significant statistically between end vertebrae and apex vertebrae in the concave side of vertebral growth plates (P < 0.05). The proliferative potential indexes and apoptosis indexes of chondrocytes in the proliferative and hypertrophic zone in the convex side were significantly higher than that in the concave side in the apex vertebral growth plate (P < 0.05). There was a significant difference of the proliferative potential index (proliferating cell nuclear antigen, PCNA index) between convex side and concave side at the upper end vertebra (P < 0.05). The difference of the proliferative potential index and apoptosis index were found significant statistically in the concave side of the vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). The same result was also found for the apoptosis index (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labeling assay, TUNEL index) in the convex side of vertebral growth plate between end vertebrae and apex vertebrae (P < 0.05). Some correlation were found between radiographic measurements and proliferation and apoptosis indexes. The difference in histological grades and cellular activity between the convex and concave side indicated that the bilateral growth plate of the vertebrae in AIS patients have different growth kinetics which may affect the curve progression.     

Cobb angle versus spinous process angle in adolescent idiopathic scoliosis. The relationship of the anterior and posterior deformities

The standard clinical measurement for adolescent idiopathic scoliosis is the Cobb angle, measured from the end-plates of the end vertebral bodies in a standing radiograph. This measurement of anterior column structures describes the anterior spinal deformity. The posterior spinal deformity can be described by the "spinous process angle," measured from a curve joining the tips of the spinous processes. A computer model, and a radiographic study of Cobb angle, spinous process angle and vertebral rotation show that adolescent idiopathic scoliosis results in larger angulations of the anterior elements than posterior elements. This helps to explain some of the inherent limitations of posterior instrumentation, including Cotrel-Dubousset instrumentation, and of noninvasive posterior surface measurement systems.     

Anterior surgery for adolescent idiopathic scoliosis

Anterior open scoliosis surgery using the dual rod system is a safe and rather effective procedure for the correction of scoliosis (50–60 %). Thoracic hypokyphosis and rib hump correction with open anterior rather than posterior instrumentation appear to be the better approaches, although the latter is somewhat controversial with current posterior vertebral column derotation devices. In patients with Risser grade 0, hyperkyphosis and adding-on may occur with anterior thoracic spine instrumentation. Anterior thoracoscopic instrumentation provides a similar correction (65 %) with good cosmetic outcomes, but it is associated with a rather high risk of instrumentation (pull-out, pseudoarthrosis) and pulmonary complications. Approximately 80 % of patients with adolescent idiopathic scoliosis (AIS) curves of >70° have restrictive lung disease or smaller than normal lung volumes. AIS patients undergoing anterior thoracotomy or anteroposterior surgery will demonstrate a significant decrease in percentage of predicted lung volumes during follow-up. The thoracoabdominal approach and thoracoscopic approach without thoracoplasty do not produce similar changes in detrimental lung volume. In patients with severe AIS (>90°), posterior-only surgery with TPS provides similar radiographic correction of the deformity (44 %) with better pulmonary function outcomes than anteroposterior surgery. Vascular spinal cord malfunction after segmental vessel ligation during anterior scoliosis surgery has been reported. Based on the current literature, the main indication for open anterior scoliosis instrumentation is Lenke 5C thoracolumbar or lumbar AIS curve with anterior instrumentation typically between T11 and L3.     

Relative anterior spinal overgrowth in adolescent idiopathic scoliosis. Results of disproportionate endochondral-membranous bone growth

We undertook a comparative study of magnetic resonance imaging (MRI) vertebral morphometry of thoracic vertebrae of girls with adolescent idiopathic thoracic scoliosis (AIS) and age and gender-matched normal subjects, in order to investigate abnormal differential growth of the anterior and posterior elements of the thoracic vertebrae in patients with scoliosis. Previous studies have suggested that disproportionate growth of the anterior and posterior columns may contribute to the development of AIS. Whole spine MRI was undertaken on 83 girls with AIS between the age of 12 and 14 years, and Cobb's angles of between 20 degrees and 90 degrees, and 22 age-matched controls. Multiple measurements of each thoracic vertebra were obtained from the best sagittal and axial MRI cuts. Compared with the controls, the scoliotic spines had longer vertebral bodies between T1 and T12 in the anterior column and shorter pedicles with a larger interpedicular distance in the posterior column. The differential growth between the anterior and the posterior elements of each thoracic vertebra in the patients with AIS was significantly different from that in the controls (p < 0.01). There was also a significant positive correlation between the scoliosis severity score and the ratio of differential growth between the anterior and posterior columns for each thoracic vertebra (p < 0.01). Compared with age-matched controls, the longitudinal growth of the vertebral bodies in patients with AIS is disproportionate and faster and mainly occurs by endochondral ossification. In contrast, the circumferential growth by membranous ossification is slower in both the vertebral bodies and pedicles.     

Does image guidance decrease pedicle screw-related complications in surgical treatment of adolescent idiopathic scoliosis: a systematic review update and meta-analysis

European Spine Journal - Surgical treatment of severe adolescent idiopathic scoliosis (AIS) with posterior spinal instrumentation and fusion with pedicle screws is common, requiring careful screw...     

Comparison of four correction techniques for posterior spinal fusion in adolescent idiopathic scoliosis

European Spine Journal - When performing posterior spinal fusion for adolescent idiopathic scoliosis (AIS), it is of major importance to address both coronal and sagittal deformities. Although...     

Is anterior release effective to increase flexibility in idiopathic thoracic scoliosis? Assessment by traction films

With the advent of thoracoscopy, anterior release procedures in adolescent idiopathic scoliosis (AIS) have come into more frequent use, however, the indication criteria for an anterior release in thoracic AIS are still controversial in the literature. To date, few studies have assessed the influence on spinal flexibility and no study has so far been able to show a beneficial effect on the correction rate as compared to a single posterior procedure. The objective of this study was to evaluate the influence of thoracic disc excision on coronal spinal flexibility. Six patients (5 females, 1 male) with AIS and a mean age of 15.6 years (range 13–20 years) underwent an open anterior thoracic release prior to posterior instrumentation. Cotrel dynamic traction along with radiographs of the whole spine including traction films were conducted pre- and postoperatively and were evaluated retrospectively. The mean preoperative thoracic curve was 89.7° ± 15.4° (range 65°–110°). The flexibility rate in Cotrel traction was 22.8 ± 8.1%. After performance of the anterior release the thoracic curve showed a mean increase of coronal correction by 5.5° ± 5.0° as assessed by traction radiographs. The flexibility index changed by 6.2 ± 5.6%. After posterior instrumentation the thoracic curve was corrected to a mean of 36.5° ± 10.1° (correction rate 59.6%). Disc excision in idiopathic thoracic scoliosis only slightly increased spinal flexibility as assessed by traction films. In our view a posterior release with osteotomy of the concave ribs (concave thoracoplasty, CTP) is more effective in increasing spinal flexibility. According to our clinical experience, an anterior release prior to posterior instrumentation in AIS should only be considered in hyperkyphosis, coronal imbalance or massive curves.     

The changes of relative position of the thoracic aorta after anterior or posterior instrumentation of type I Lenke curve in adolescent idiopathic thoracic scoliosis

The risk of impingement of the aorta associated with thoracic vertebral screw or pedicle screw instrumentation in the treatment of thoracic scoliosis has been an important concern. To understand this phenomenon more systematically, the relative position of the aorta with reference to the thoracic vertebrae in right thoracic adolescent idiopathic scoliosis (AIS) following anterior and posterior spinal instrumentation was analyzed in detail quantitatively; 34 patients underwent anterior (n = 14) or posterior (n = 20) spinal instrumentation were recruited in the present study. The relative position of the thoracic aorta, vertebral rotation, apical vertebral translation and thoracic kyphosis were measured from pre- and post-operative CT images from T5 to T12. The aorta was found to shift antero-medially in the anterior instrumentation group but not in the posterior spinal instrumentation group. It is likely that the disc removal, soft tissue release and spontaneous vertebral derotation of the scoliosis could account for the antero-medial shifting of the aorta. By the shifting, the space for contralateral screw penetration was reduced.     

The development of adolescent idiopathic scoliosis

There are many conflicting actiological theories for adolescent idiopathic scoliosis. We present a simple new model of scoliosis and a mechanism by which it is initiated and progresses. This mechanism provides a final common pathway for the multiple aetiological factors. A simple model of the spine, incorporating its fundamental mechanical features, was constructed. The model consisted of interconnected anterior compression and posterior tension columns. It allowed normal spinal movements, with flexion limited by the posterior column and rotation centred around the anterior column. It also allowed deformities to develop. The ends of the model were fixed in the position of the vertebrae they represented. Overgrowth of the anterior column relative to the posterior column caused the model to take up the shape of an idiopathic scoliosis. The greater the overgrowth, the more marked the deformity. Normally anterior and posterior column growth are coupled. During the growth spurt the thoracic kyphosis flattens indicating that anterior growth temporarily exceeds posterior growth. If this overgrowth is marked a scoliosis will develop, as demonstrated by the model. Once this occurs the coupling is lost, anterior growth further outstrips posterior growth and the deformity progresses. Not all scolioses worsen, as the tendency to progress is balanced by neuromuscular factors and remodelling. Factors that increase the growth rate, induce asymmetry or decrease the inherent stability of the spine all encourage the development and progression of a scoliosis. This explains the complex biomechanics of scoliosis and provides a final common pathway by which the multiple aetiological factors can induce idiopathic scoliosis. It has important implications for the understanding and treatment of this condition.