腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变Pfirrmann分级的相关性

目的 探讨腰椎椎间隙高度与上位椎体高度的比值与椎间盘退行性变程度之间的关系,为腰椎椎间盘退行性疾病的诊断和治疗提供客观准确的依据。方法 回顾性分析2019年1月—2019年6月来本院就诊的61例腰椎椎间盘退行性变患者临床资料。在腰椎侧位X线片上测量腰椎椎间隙及相应上位椎体的高度,并计算椎间隙高度与上位椎体高度的比值;在腰椎矢状位MRI上评估腰椎椎间盘退行性变Pfirrmann分级;比较不同Pfirrmann分级椎间盘的椎间隙高度与上位椎体高度比值的差异,并采用Spearman相关分析研究椎间隙高度与上位椎体高度比值与相应节段椎间盘Pfirrmann分级之间的相关性。结果 除L₁/L₂节段,其余各节段椎间隙高度与上位椎体高度比值均随着Pfirrmann分级增加而逐渐减小,差异均有统计学意义（P < 0.05）。相同Pfirrmann分级的不同节段椎间盘之间椎间隙高度与上位椎体高度比值差异无统计学意义（P > 0.05）。Spearman相关分析结果显示,L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段Pfirrmann分级与椎间隙高度与上位椎体高度比值呈负相关（r =-0.568,P < 0.05）。结论 临床上测量L₂/L₃、L₃/L₄、L₄/L₅、L₅/S₁节段椎间隙高度与上位椎体高度比值对腰椎椎间盘退行性疾病的诊断可能具有重要意义。     

Lumbar disc and back muscle degeneration on MRI: correlation to age and body mass.

Lumbar intervertebral discs and paraspinal muscles in 74 healthy volunteers ranging in age from 19 to 74 years were evaluated with MRI, and the occurrence of degeneration was correlated to age and body mass. Muscle size and the amount of fat in the muscles was studied from MRI cross sections. When the back muscles were degenerated, they were small and contained fat deposits. By contrast, the psoas muscles never showed gross fat deposits. Degeneration of both the lumbar discs and muscles increased with age. No correlation was found between muscle degeneration and overweight. Muscle degeneration is as common as disc degeneration in the lumbar area. MRI is an excellent method to assess both muscle and disc degeneration.     

基于MRI的腰椎间盘退变程度评价系统的研究进展

基于MRI的腰椎间盘退变程度评价系统对于研究腰椎间盘退变及指导临床治疗十分必要,是新近研究的热点。本文就定性、定量研究椎间盘退变程度的方法做一综述,试图为判断腰椎间盘退变程度提供一个良好的评价系统,为更好地选择治疗方案提供依据。     

Bone formation in rabbit's leg muscle after autologous transplantation of bone marrow-derived mesenchymal stem cells expressing human bone morphogenic protein-2

Background:

To test whether autologous transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) expressing human bone morphogenic protein-2 (hBMP-2) can produce bone in rabbit leg muscles.

Materials and Methods:

MSCs were isolated from BM of the iliac crest of rabbits and then infected with lentiviral vectors (LVs) bearing hBMP-2 and green fluorescent protein under the control of the cytomegalovirus (immediate early promoter). Differentiation of transduced MSCs to osteoblasts in vitro was evaluated with an alkaline phosphatase activity assay and immuohistochemistry against osteoblast specific markers. MSCs expressing hBMP-2 were placed in an absorbable gelatin sponge, which was then transplanted into the gastrocnemius of rabbits from which MSCs were isolated. Bone formation was examined by X-ray and histological analysis.

Results:

LVs efficiently mediated hBMP-2 gene expression in rabbit BM-MSCs. Ectopic expression of hBMP in these MSCs induced osteoblastic differentiation in vitro. Bone was formed after the MSCs expressing hBMP-2 were transplanted into rabbit muscles.

Conclusion:

Ectopic expression of hBMP-2 in rabbit MSCs induces them to differentiate into osteoblasts in vitro and to form a bone in vivo.     

Bone union rate with recombinant human bone morphogenic protein-2 versus autologous iliac bone in PEEK cages for anterior lumbar interbody fusion

Purpose

Autologous iliac crest bone graft (ICBG) is the gold standard material for spinal fusion. Bone graft substitutes, such as recombinant human bone morphogenic protein 2 (rhBMP-2) have been developed to promote spinal fusion and address morbidity issues related to ICBG harvesting. The objective of this study was to compare bone fusion rates after anterior lumbar interbody fusion (ALIF) between ICBG and rhBMP-2 by examining thin-cut computed tomography (CT) images at the one year follow-up.

Methods

Fifty one patients (62 levels) who underwent single- or two-level ALIF via the video-assisted minimally invasive anterior approach in our institution were assessed. Radiolucent cages were inserted in all cases. Each cage has a middle beam delimiting two chambers. Grafting was performed as follows: one chamber was filled with autologous ICBG, and the other chamber was filled with 6 mg of rhBMP-2. Thin-cut CT-scan multiplanar reconstruction analyses were performed to assess the rate and quality of bone fusion at one year of follow-up.

Results

Fusion was observed in 55 levels (88.7 %), with significant differences in fusion rates with rhBMP-2 and ICBG (71 % vs. 88.7 %) (P=0.001). Osteogenesis in the rhBMP-2 chamber had a centripetal pattern in all cases, leaving a central void in 97.7 % of cases representing 38.3 % of the surface of its chamber (range 0–80.3 %). In ICBG chambers, graft resorption was present in 44.4 %, representing 9.8 % of the chamber surface (range 0–52.2 %).

Conclusion

RhBMP-2 was inferior to ICBG in terms of rate and quality of bone fusion in one- or two-level ALIF.     

Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis.

BACKGROUND CONTEXT: Disc degeneration includes dysfunction and loss of disc cells leading to a decrease in extracellular matrix (ECM) components. Apoptosis has been identified in degenerated discs. Bone morphogenetic protein-7 (BMP-7) has been reported to stimulate ECM synthesis in the intervertebral disc (IVD), but its effect on disc cell viability is unknown. PURPOSE: To investigate whether BMP-7 can protect disc cells from programmed cell death while enhancing ECM production. STUDY DESIGN: An in vitro study to examine the effect of BMP-7 on apoptosis of IVD cells. METHODS: Human nucleus pulposus (NP) cells were cultured in monolayer, and human recombinant pure BMP-7 (rhBMP-7) was added to the medium when the cells were in the second passage. Thereafter, apoptosis was induced by either tumor necrosis factor-alpha (TNF-alpha) or hydrogen peroxide (H(2)O(2)). Cellular apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and caspase-3 activity. ECM synthesis was assessed by immunofluorescence for collagen-2 and aggrecan. To study the possibility of bone induction by rhBMP-7 in disc cells, alkaline phosphatase activity and Alizarin red-S staining were evaluated. RESULTS: Apoptosis was induced by both TNF-alpha and H(2)O(2). Addition of rhBMP-7 resulted in inhibition of the apoptotic effects caused by both inducers. Further, BMP-7 decreased caspase-3 activity. In the presence of BMP-7, ECM production was maintained by the cells despite being in an apoptotic environment. No osteoblastic induction of the disc cells was seen. CONCLUSIONS: BMP-7 was demonstrated to prevent apoptosis of human disc cells in vitro. One of the antiapoptotic effects of BMP-7 on NP cells might be a result of its inactivation of caspase-3. Collagen production was maintained by addition of rhBMP-7 in an apoptotic environment.     

颈椎间盘退变MRI分级标准的研究进展

颈椎前、后路手术对于解除颈脊髓或神经根压迫的效果明确,但术后生物力学的改变可能会导致邻近椎间盘退变的速度加快,尤以颈椎前路手术最为明显;而已存在退变且初次手术未处理的椎间盘可能会在随访期间导致再次手术[1].因此,术前明确椎间盘退变程度与颈椎术后再手术风险的相关性对于初次手术方式和范围的确定具有重要意义.MRI对于颈椎间盘内髓核、纤维环退变最为敏感,但目前临床多用于评价颈脊髓、神经根的压迫范围和程度.尽管已有作者参照Pfirrmann建立的腰椎间盘退变分级系统开展了颈椎间盘退变分级的研究,但是关于各系统的可信性和临床效力并不明确.现就目前各类颈椎间盘MRI退变分级系统综述如下.     

腰椎间盘突出症患者突出椎间盘及相邻椎间盘退变程度的MRI分析

目的:分析腰椎间盘突出症患者突出椎间盘及相邻椎间盘的术前MRI表现,评估其退变程度。方法:回顾性分析2014年6月~2015年12月在宁夏医科大学总医院脊柱骨科已行手术治疗的的单节段腰椎间盘突出症患者100例,其中男56例,女44例,年龄23~79岁(51.68±5.60岁),将所有患者以10年为一年龄段进行分组。突出椎间盘发生在L4/5节段50个,其相邻椎间盘100个;L5/S1节段50个,其相邻椎间盘50个。观察术前腰椎MRI,椎间盘采用Pfirrmann分级标准进行评估;软骨终板形态以Pappou分级标准进行评估。年龄段间的比较采用单因素方差分析,相邻椎间盘与退变椎间盘间的相关性采用Pearson相关分析,相邻椎间盘间的比较采用t检验。结果:各年龄段L4/5、L5/S1突出椎间盘的Pfirrmann分级均在Ⅲ级以上、Pappou分级均在Ⅱ级以上,各年龄段间椎间盘退变结果有统计学差异(P0.05);而各年龄段间软骨终板退变结果无统计学差异(P0.05)。各年龄段间突出椎间盘发生在L4/5、L5/S1的上位相邻椎间盘Pfirrmann分级有统计学差异(P0.05),下位相邻椎间盘Pfirrmann分级各年龄段无统计学差异(P0.05),相邻椎间盘软骨终板退变结果各年龄段间无统计学差异(P0.05)。相邻的L3/4椎间盘Pfirrmann分级与突出的L4/5椎间盘Pfirrmann分级有相关性(r=0.696,P=0.000),相邻L5/S1椎间盘Pfirrmann分级与突出L4/5椎间盘Pfirrmann分级间无相关性(r=0.214,P=0.136);相邻的L3/4、L5/S1椎间盘软骨终板形态Pappou分级与突出的L4/5椎间盘软骨终板形态Pappou分级均有相关性(r=0.467,P=0.001;r=0.380,P=0.007)。相邻L4/5椎间盘的Pfirrmann分级与突出L5/S1椎间盘的Pfirrmann分级有相关性(r=0.549,P=0.000);相邻L4/5椎间盘软骨终板形态Pappou分级与突出L5/S1椎间盘的软骨终板形态Pappou分级有相关性(r=0.684,P=0.001)。L4/5椎间盘突出的相邻L3/4椎间盘Pfirrmann分级和软骨终板形态Pappou分级评分分别为3.26±0.87分、1.54±0.50分,均高于相邻L5/S1椎间盘的2.96±0.59分、1.23±0.49分(P0.05)。结论:腰椎间盘突出症患者突出节段的相邻椎间盘及软骨终板的退变与年龄及突出椎间盘退变程度关系密切,且相邻上位椎间盘较下位椎间盘退变更明显。     

Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system

Summary  

The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher.     

Bone marrow and recombinant human bone morphogenetic protein-2 in osseous repair

Bone marrow stem cells and recombinant human bone morphogenetic protein-2 each has the capacity to repair osseous defects. Recombinant human bone morphogenetic proteins require the presence of progenitor cells to function. It is hypothesized that a composite graft of recombinant human bone morphogenetic protein-2 and marrow would be synergistic and could result in superior grafting to autogenous bone graft. Syngeneic Lewis rats with a 5-mm critical sized femoral defect were grafted with recombinant human bone morphogenetic protein-2 and marrow, recombinant human bone morphogenetic protein-2, marrow, syngeneic cancellous bone graft, or carrier alone (control). Serial radiographs (3, 6, 9, 12 weeks) and torque testing (12 weeks) were performed. Bone formation and union were determined. The recombinant human bone morphogenetic protein-2 and marrow composite grafts achieved 100% union at 6 weeks. Recombinant human bone morphogenetic protein alone achieved 80% union by week 12. Both groups yielded a higher union rate and superior mechanical properties than did either syngeneic bone graft (38%) or marrow (47%) alone. The superior performance of recombinant human bone morphogenetic protein-2 combined with bone marrow in comparison with each component alone strongly supports a biologic synergism. This experimentation shows the clinical importance of establishing operative site proximity for the osteoinductive factors and responding progenitor cells.     

Calcification in human intervertebral disc degeneration and scoliosis

Calcification is a pathological process that may lead to impairment of nutrient supply and disc metabolism in degenerative and scoliotic intervertebral discs (IVDs). The purpose of this study was to assess the calcification potential of IVDs in degenerative disc disease (DDD) and adolescent idiopathic scoliosis (AIS). For this purpose, 34 IVDs from 16 adult patients with DDD and 25 IVDs from 9 adolescent patients with AIS were obtained at surgery. The concave and convex parts of the scoliotic discs were analyzed separately. Von Kossa staining was performed to visualize calcium deposits, while type X collagen (COL X) expression associated with endochondral ossification was measured by immunohistochemistry. Alkaline phosphatase activity and calcium and inorganic phosphate concentrations were used as indicators of calcification potential. Results showed the presence of calcium deposits and COL X in degenerative and scoliotic IVDs, but not in control discs, and the level of the indicators of calcification potential was consistently higher in degenerative and scoliotic discs than in control discs. The results suggest that disc degeneration in adults is associated with ongoing mineral deposition and that mineralization in AIS discs might reflect a premature degenerative process. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1888–1895, 2011     

BMP-2对人退变椎间盘髓核细胞影响的实验研究

[目的]探讨BMP -2对人退变髓核细胞合成细胞外基质的影响.[方法]分离、培养人退变椎间盘髓核细胞,取第2代髓核细胞,随机将退变推间盘髓核细胞分为2组.A组:加入100 ng/ml BMP -2,B组:加入200 ng/mlBMP -2,C组:对照组,不加干扰因素.通过对试验组和对照组髓核细胞采用光镜、电镜等形态学方法进行大体形态和超微结构观察,细胞Ⅱ型胶原和糖胺多糖的mRNA表达.ELISA检测细胞培养上清中人Ⅱ型胶原含量,DMMB比色法检测细胞培养上清中糖胺多糖含量.[结果]髓核细胞中Ⅱ型胶原、糖胺多糖表达水平实验组均高于对照组.[结论] BMP-2蛋白可促进退变腰椎间盘细胞分泌蛋白多糖和Ⅱ型胶原,增加细胞活性,恢复椎间盘的功能和活性,因此运用BMP-2椎间盘内注射有望成为椎间盘退变疾病生物治疗的方法之一.     

Mechanobiology of the intervertebral disc and relevance to disc degeneration

Mechanical loading of the intervertebral disc may contribute to disc degeneration by initiating degeneration or by regulating cell-mediated remodeling events that occur in response to the mechanical stimuli of daily activity. This article is a review of the current knowledge of the role of mechanical stimuli in regulating intervertebral disc cellular responses to loading and the cellular changes that occur with degeneration. Intervertebral disc cells exhibit diverse biologic responses to mechanical stimuli, depending on the loading type, magnitude, duration, and anatomic zone of cell origin. The innermost cells respond to low-to-moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure with increases in anabolic cell responses. Higher magnitudes of loading may give rise to catabolic responses marked by elevated protease gene or protein expression or activity. The key regulators of these mechanobiologic responses for intervertebral disc cells will be the micromechanical stimuli experienced at the cellular level, which are predicted to differ from that measured for the extracellular matrix. Large hydrostatic pressures, but little volume change, are predicted to occur for cells of the nucleus pulposus during compression, while the highly oriented cells of the anulus fibrosus may experience deformations in tension or compression during matrix deformations. In general, the pattern of biologic response to applied loads suggests that the cells of the nucleus pulposus and inner portion of the anulus fibrosus experience comparable micromechanical stimuli in situ and may respond more similarly than cells of the outer portion of the anulus fibrosus. Changes in these features with degeneration are critically understudied, particularly degeneration-associated changes in cell-level mechanical stimuli and the associated mechanobiology. Little is known of the mechanisms that regulate cellular responses to intervertebral mechanobiology, nor is much known with regard to the precise mechanical stimuli experienced by cells during loading. Mechanical factors appear to regulate responses of the intervertebral disc cells through mechanisms involving intracellular Ca(2+) transients and cytoskeletal remodeling that may regulate downstream effects such as gene expression and posttranslational biosynthesis. Future studies should address the broader biologic responses to mechanical stimuli in intervertebral disc mechanobiology, the involved signaling mechanisms, and the apparently important interactions among mechanical factors, genetic factors, cytokines, and inflammatory mediators that may be critical in the regulation of intervertebral disc degeneration.     

MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine

Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2–6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann‐grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1776–1783, 2015.     

Crystal deposits in the human intervertebral disc: implications for disc degeneration.

BACKGROUND CONTEXT: Although crystal deposition in cartilage and synovial fluid has received much attention, crystal formation and the role that crystal deposits play are virtually unexplored in the intervertebral disc. In articular cartilage matrix, crystal deposits are associated with altered extracellular matrix (ECM) and cell phenotypic features, but crystal deposition in the human intervertebral disc has received much less attention. PURPOSE: To determine the incidence of crystal deposits in the annulus and to evaluate associated disc cell and ECM features. STUDY DESIGN/SETTING: Human intervertebral disc annulus tissue was obtained in a prospective study of the presence of crystals in the disc ECM. Human Subjects Institutional Review Board approved experimental studies. PATIENT SAMPLE: Two hundred eight sequential disc specimens were submitted from surgical disc procedures performed on individuals with herniated discs, degenerative disc disease, or recurrent disc herniation. During this same time period, three disc specimens were received from nonsurgical donors and added to the study population. OUTCOME MEASURES: Histologic features with special attention to crystal deposition. METHODS: Specimens were processed undecalcified and examined for the histologic presence of crystal deposits and ECM features around the crystals. RESULTS: The proportion of specimens containing crystals was determined to be 14.7%; crystals displayed varying sizes, morphology, and polarized light birefringence features. Pyrophosphate crystals were most common, but oxalate-like crystals were also present. ECM in crystal regions showed previously recognized alterations. CONCLUSIONS: This study shows that the incidence of crystal deposits in discs is approximately 15% and is thus a relatively common occurrence. These data are important because masses of crystals not only disrupt disc ECM but may also accelerate preexisting degenerative changes via an elevation in matrix metalloproteinases (as previously recognized in cartilage). Because failure of the structural integrity of the disc can result in annular tears and subsequent disc herniation, the mechanisms of crystal formation and the relationship between crystals and disc degeneration merit further investigations.