椎体终板与椎间盘退变

椎间盘退变是导致下腰痛的常见原因,与之密切相关的椎体终板退变也逐渐受到重视.MRI的T1和T2加权像上,退变的椎体终板表现为终板与终板下骨相对于正常终板的信号改变,且与对应的椎间盘退变有较高的相关性.经椎体终板的弥散是椎间盘获得营养的主要途径,同时椎体终板又是脊柱运动单位中最容易受损伤的部位,轴向负荷可导致软骨终板、骨性终板及终板下骨小梁弯曲变形,软骨终板与骨性终板分离.这一系列的终板损伤和软骨终板钙化和骨化会妨碍椎间盘营养供应,导致椎间盘组织学退变.新近研究进一步表明椎体终板与椎间盘退变不仅在组织学上密切相关,而且在力学上也密不可分,椎板形状如曲率也与椎间盘退变和突出存在一定的关联.     

Association and histological characteristics of endplate injury and intervertebral disc degeneration in a rat model

IntroductionThe purpose of this study was to construct a rat caudal vertebral body fracture model and to analyze the association and histological characteristics of vertebral body fracture with endplate injury and adjacent intervertebral disc degeneration.Materials and methodsThis study included 144 clean-grade male Sprague-Dawley rats, which were randomly divided into a control, middle vertebral body injury (MI), and endplate injury (EI) groups. A vertebral body fracture with or without endplate injury was developed by either drilling a hole in the middle of a rat caudal vertebral body to create a fracture with an intact endplate or drilling a hole in the vertebral body near the intervertebral disc to create a vertebral body fracture with endplate injury. The histological differences in the adjacent intervertebral discs of vertebral body fractures with or without endplate injury were detected using imaging, non-specific histological staining, immunohistochemistry and TUNEL assay.ResultsImaging results revealed that the EI group showed a significant decrease in intervertebral space height and intervertebral disc T2 signal over time. Non-specific histological staining revealed that in the EI group, the intervertebral disc was degenerative. Immunohistochemistry indicated that Aggrecan and Collagen-II were decreased and inflammatory factors were increased in the EI group. The TUNEL detection found that apoptosis was significantly increased in the EI group as compared with the MI and control groups.ConclusionIn rat caudal vertebral body fractures, a fracture with endplate injury is more likely to induce or accelerate degeneration of adjacent intervertebral discs.     

Effect of endplate reduction on endplate healing morphology and intervertebral disc degeneration in patients with thoracolumbar vertebral fracture

Objective

To determine the effect of endplate reduction on the final healing morphology and degenerative changes in intervertebral discs.

Methods

Forty-eight patients with single-level thoracolumbar fractures with endplate injury were included. All patients underwent posterior reduction and pedicle screw fixation, and postoperative imaging was used to determine whether endplate reduction was successful. The healing morphology of the endplate was divided into three types: increased endplate curvature, irregular healing and traumatic Schmorl node. MRI was performed at baseline and at the last follow-up evaluation to observe changes in disc degeneration (disc height and nucleus pulposus signal) and Modic changes.

Results

The reduction rate in the central area was significantly lower than that in the peripheral area (P = 0.017). In patients with successful reduction, 90.9% (20/22) of the endplates healed with increased curvature. In patients with an unsuccessful endplate reduction, 63.4% (26/41) of the endplates healed irregularly, and 34.1% (14/41) of the endplates formed traumatic Schmorl nodes. Endplate reduction was closely related to the final healing morphology of the endplate (P < 0.001), which had a significant protective effect on the degeneration of the intervertebral disc. At the last follow-up evaluation, there was no statistically significant correlation between different endplate healing morphologies and new Modic changes.

Conclusions

The reduction rate in the central area is significantly lower than that in the peripheral area. Although all of the intervertebral discs corresponding to fractured endplates had degenerated to different degrees, successful endplate fracture reduction can obviously delay the degeneration of intervertebral discs.

     

一氧化氮诱导腰椎软骨终板退变的实验研究

目的探讨一氧化氮（nitricoxide，NO）诱导腰椎软骨终板退变的机制。方法取长枫杂种猪腰椎间盘软骨终板细胞，于含20％胎牛血清的DMEM中培养，建立体外软骨终板细胞培养模型，以光镜及苏木精-伊红染色观察其生物学表现，Ⅱ型胶原免疫细胞化学染色对软骨终板细胞进行鉴定，以外源性NO-硝普钠（sodium nitroprusside，SNP）2mmol／l处理软骨终板细胞、^35S掺入法和^3H-脯氨酸掺入法检测蛋白多糖及胶原的合成，放射性免疫测定法测炎性细胞因子IL-1β、IL-6、TNF-α的生成，碘化丙啶荧光染色及DNA片段电泳观察软骨终板细胞凋亡。结果原代细胞生物学性状最接近体内细胞，多次传代后细胞呈现衰老现象，经免疫细胞化学染色证实此细胞具有Ⅱ型胶原表达。施加SNP后，软骨终板细胞蛋白多糖及胶原合成明显减少（P〈0．01），炎性细胞因子含量明显升高（P〈0．01），细胞凋亡率显著增高（P〈0．01）。结论NO抑制软骨终板细胞蛋白多糖及胶原合成，促进炎性细胞因子及细胞凋亡增加，从而促进软骨终板退变。     

Vertebral endplate change as a feature of intervertebral disc degeneration: a heritability study

Purpose

To study the prevalence of vertebral endplate or Modic change (MC), the progression of MC over a 10-year follow-up and the heritability of MC prevalence in a classical twin study.

Methods

The study population was recruited from TwinsUK register between 1996 and 2000. MC was evaluated from T2-weighted lumbar magnetic resonance imaging (MRI) at baseline and follow-up. Heritability was estimated using variance components analysis. Baseline MRI with appropriate data was available for 831 twins and follow-up for 436 twins. In total, both baseline and follow-up imaging were available for 347 twins.

Results

Mean age of the study population was 54.1 years (range 45.7–62.5) and females comprised 96 %. The prevalence of MC at baseline was 32.1 % and at follow-up 48.4 %. The incidence of MC during the 10-year follow-up was 21.6 % and was highest at L4–5 and L5–S1. MC regressed totally in 3.5 % of twins. Twins with prevalent MC at baseline demonstrated a higher incidence of MC at upper lumbar levels during follow-up compared to twins without baseline MC (p = 0.009). Probandwise concordance rates were higher in monozygotic (0.56) than dizygotic twin pairs (0.39) suggestive of familial influence. Heritability of MC prevalence was estimated at 30 (16–43) %.

Conclusions

The results suggest that MC is generally progressive in middle age and furthermore is heritable. Since MC is associated with disc degeneration, which is also heritable, further work on potential shared mechanisms is needed.     

巨大腰椎间盘突出症伴终板早期退变的非融合治疗

[目的]回顾性研究非融合技术(Wallis)治疗伴有Modie Ⅰ型改变的巨大腰椎间盘突出症的临床疗效及影像学结果,观察腰背痛缓解程度及终板变化情况.[方法]2008年1月～2008年8月,共治疗26例腰椎间盘突出症伴Modie Ⅰ型改变的患者,均为L4,5间隙.男10例,女16例;平均年龄38岁.所有病例均行椎间盛突出髓核摘除+Wallis动态固定术.患者术前、术后3个月及末次随访时摄腰椎正侧位及动力位X线片,分别测量椎间盘前、后缘高度,椎间孔高度,观察术前及末次随访手术节段MRI T2加权像终板变化,同时进行Oswestry功能障碍评分(ODI)、疼痛视觉模拟评分(VAS).术后平均随访24.2(20～29)个月.[结果]术后3个月及未次随访的ODI及VAS评分均较术前有明显下降(P<0.001),术后3个月时椎问盘后缘高度及椎间孔高度较术前明显增加(P<0.05),椎间盘前缘高度较术前略有增加(P>0.05),但末次随访时高度呈卜降趋势.获得随访的20例MRI表现仅有2例手术节段终板退变为Modic Ⅱ型.[结论]棘突间撑开装置Wallis作为一种颅防及治疗腰椎早期退变疾病的非融合技术,能有效缓解腰腿痛,一定程度上延缓病变节段椎间盘的退变,同时能较好的维持手术节段的椎间盘及椎间孔高度,远期疗效尚需长期的随访研究.     

Optimization of puncture injury to rat caudal disc for mimicking early degeneration of intervertebral disc

The caudal discs of rats have been proposed as a puncture model in which intervertebral disc (IVD) degeneration can be induced and novel therapies can be tested. For biological repair, treatments for ongoing IVD degeneration are ideally administered during the earlier stages. The purpose of this study was to elucidate the optimal puncture needle size for creating a model that mimicked the earlier stages of IVD degeneration. According to the disc height index, histologic score, and MRI grading, a puncture needle sized 21G or larger induced rapid degenerative processes in rat caudal discs during the initial 2–4 weeks. The degenerative changes were severe and continued deteriorating after 4 weeks. Conversely, puncture injury induced by needles sized 25G or smaller also produced degenerative changes in rat caudal discs during initial 2–4 weeks; however, the changes were less severe. Furthermore, the degenerative process became stabilized and showed no further deterioration or spontaneous recovery after 4 weeks. In the discs punctured by 25G needles, the expression of collagen I was increased at 2–4 weeks with a gradually fibrotic transformation thereafter. The expressions of collagen II and SOX9 were enhanced initially but returned to pre‐injury levels at 4–8 weeks. The above‐mentioned findings were more compatible with earlier degeneration in discs punctured by needles sized 25G or smaller than by needles sized 21G or larger, and the appropriate timing for intradiscal administration of proposed therapeutic agents would be 4 weeks or longer after puncture. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:202–211, 2018.     

Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model

Purpose

Previous studies have shown that blocking the endplate nutritional pathway with bone cement did not result in obvious intervertebral disc degeneration (IDD) in mature animal models. However, there are very few comparable studies in immature animal models. As vertebroplasty currently is beginning to be applied in young, even biologically immature patients, it is important to investigate the effect of cement blocking at the endplate in an immature animal model.

Methods

Two lumbar intervertebral discs in eight immature pigs were either blocked by cement in both endplate pathways or stabbed with a scalpel in the annulus fibrosus (AF) as a positive control, and with a third disc remaining intact as a normal control. Magnetic resonance imaging (MRI) and histology study were performed.

Results

After three months, the cement-blocked discs exhibited severe IDD, with the percentage of disc-height index (DHI), nucleus pulposus (NP) area, and NP T2 value significantly lower than the normal control. These IDD changes were histologically confirmed. Post-contrast MRI showed diseased nutritional diffusion patterns in the cement-blocked discs. Moreover, the degenerative changes of the cement-blocked discs exceeded those of the injured AF positive controls.

Conclusions

The endplate nutritional pathway was interfered with and diseased after three months of bone cement intervention in an immature porcine model. Severe interference in the endplate nutritional pathway in an immature porcine model caused IDD. These findings also draw attention to the fact that interference in endplate nutritional pathways in immature or young patients may affect the vitality of adjacent discs.     

去势小鼠椎体骨质疏松和终板重塑导致椎间盘退变

目的通过去势小鼠模型探讨椎体骨质疏松(osteoporosis,OP)是否影响椎间盘退变(intervertebral disc degeneration,IVDD),并初步阐明OP相关性IVDD的发病机制。方法 30只8周龄健康雌性C57BL/6 J小鼠(16.8±0.6) g,随机分为正常对照组(CT组,n=15)和去势组(OVX组,n=15)。适应性饲养3 d后分别行假手术和双侧卵巢摘除,记录体重等一般资料。术后12周处死小鼠,取下L4/5脊柱节段。Micro-CT检测小鼠L5椎体骨量、微结构、终板孔隙率以及L4/5椎间盘体积变化;番红O-固绿染色观察椎间盘病理改变;免疫组织化学法检测椎间盘Col2的表达,免疫荧光检测椎间盘血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达。结果 OVX组小鼠与CT组相比,腹腔内可见大量脂肪堆积,卵巢明显萎缩,伴随体重明显增加及子宫重量明显减轻(~*P0.05)。Micro-CT结果显示,OVX小鼠可见明显的椎体骨质疏松,与CT组相比骨结构参数骨体积分数、骨小梁数量、骨小梁连接密度明显降低,而骨小梁变异系数及模型指数明显升高(~*P0.05);终板出现明显的骨化重塑和孔隙率增加,同时伴有椎间盘体积的明显降低(~*P0.05)。番红O-固绿染色显示OVX小鼠L4/5椎间盘出现明显退变,可见终板明显骨化和增厚,髓核细胞外基质的降解和结构紊乱。椎间盘免疫组化显示OVX小鼠椎间盘中Col2表达明显降低,在终板骨化区和纤维环中尤其明显,免疫荧光显示在椎间盘终板中VEGF表达明显增加。结论 OVX小鼠椎体OP和终板骨化重塑可促使椎间盘发生退变,终板孔隙的增加及血管新生并不能为椎间盘修复提供更多营养,反而是导致IVDD的重要因素。     

椎间盘软骨终板退变的研究进展

椎间盘的退变与多种因素相关,其中软骨终板作为椎间盘的组成部分,通过其渗透作用为椎间盘提供大部分营养,在维持椎间盘正常功能方面发挥重要作用。软骨终板退变作为椎间盘退变的始动因素近来受到广泛关注。软骨终板退变的具体机制尚不明确,但现有研究表明其退变与年龄、异常应力、局部炎症因子、软骨细胞凋亡、软骨基质退变等因素相关,深入研究各因素在终板退变过程中的具体作用机制将为治疗椎间盘退变性疾病提供新的方法,现对软骨终板退变的主要因素做如下综述。     

创伤性终板骨折及椎间盘退变对胸腰椎骨折预后的影响

目的探讨创伤性终板骨折及椎间盘退变对胸腰椎骨折预后的影响。方法对98例胸腰椎骨折患者进行手术治疗,依据术前X线片、CT扫描+三维重建诊断分为观察组(有终板骨折,48例)和对照组(无终板骨折,50例)。统计两组末次随访的ODI及VAS评分。结果创伤性终板骨折患者末次随访时的ODI及VAS评分明显高于对照组(P0.05),两组椎间盘退变率比较差异亦有统计学意义(P0.05)。结论创伤性终板骨折会引起椎间盘退变并影响脊柱骨折手术的预后。     

阻断双侧终板营养途径构建山羊椎间盘退变模型

目的通过建立山羊腰椎双侧终板营养途径阻断的动物模型,观察椎间盘退变(IDD)的情况,研究椎间盘营养途径与IDD的相关性。方法选取8只24月龄雌性关中山羊,每只山羊L2~3、L3~4作为实验椎间盘,麻醉后在平行于终板2 mm的椎体骨质处造成骨缺损,并使用骨水泥填塞,阻断椎体和终板之间的营养通路,L1~2、L4~5作为对照椎间盘。分别于术后4、12、24、48周行X线、MRI检查,各时间点随机处死2只山羊,采集椎间盘标本,计算骨水泥有效阻断面积、椎间高度指数(DHI)和Pfirrmann分级,并行HE、Masson三色、蛋白多糖、番红O染色组织学检查。结果术后骨水泥有效阻断面积达49.6%~69.6%(60.7%±5.3%)。术后48周时实验椎间盘DHI百分比为60.5%~81.7%(72.7%±5.6%),椎间高度丢失较对照差异有统计学意义(P<0.01);术后48周时实验椎间盘Pfirrmann分级为3~5(4.0±0.7)分,较对照差异有统计学意义(P<0.01)。组织学检查证实,实验椎间盘术后12周即发生退变,并随时间(24、48周)逐步加重。结论骨水泥填塞阻断双侧终板营养途径可以构建山羊IDD的动物模型,阻断终板营养途径可以导致IDD发生。     

Determinants of evolution of endplate and disc degeneration in the lumbar spine: a multifactorial perspective

Purpose

Evolution and progression of disc and endplate bone marrow degeneration of the lumbar spine are thought to be multifactorial, yet, their influence and interactions are not understood. The aim of this study was to find association of potential predictors of evolution of degeneration of the lumbar spine.

Methods

Patients (n = 90) who underwent two lumbar magnetic resonance imaging (MRI) exams with an interval of at least 4 years and without any spinal surgery were included into the longitudinal cohort study with nested case–control analysis. Disc degeneration (DD) was scored according to the Pfirrmann classification and endplate bone marrow changes (EC) according to Modic in 450 levels on both MRIs. Potential variables for degeneration such as age, gender, BMI, scoliosis and sagittal parameters were compared between patients with and without evolution or progression of degenerative changes in their lumbar spine. A multivariate analysis aimed to identify the most important variables for progression of disc and endplate degeneration, respectively.

Results

While neither age, gender, BMI, sacral slope or the presence of scoliosis could be identified as progression factor for DD, a higher lordosis was observed in subjects with no progression (49° ± 11° vs 43° ± 12°; p = 0.017). Progression or evolution of EC was only associated with a slightly higher degree of scoliosis (10° ± 10° vs 6° ± 9°; p = 0.04) and not to any of the other variables.

Conclusion

While a coronal deformity of the lumbar spine seems associated with evolution or progression of EC, a higher lumbar lordosis is protective for radiographic progression of DD. This implies that scoliotic deformity and lesser lumbar lordosis are associated with higher overall degeneration of the lumbar spine.