胸椎黄韧带骨化与腰椎黄韧带退变的病理及基本代谢元素的比较研究

目的：探讨胸椎黄韧带骨化的病因。方法：对１４例胸椎黄韧带骨化（包括５例氟骨症）及１４例腰椎管狭窄症患者手术切除的黄韧带标本作病理研究；对患者血清及黄韧带采用雾化原子吸收法等方法测定钙、磷、镁、锌、铜、锰、钼、氟含量，取急性外伤性截瘫患者为对照。结果：（１）骨化黄韧带初期的病理改变与黄韧带退变性质类似；（２）除氟元素外，７种基本代谢元素在骨化与退变患者血清及黄韧带中含量均呈基本一致的变化规律；（３）非氟骨症骨化患者黄韧带中氟含量显著增高（Ｐ＜０．０１）。结论：本文证实胸椎黄韧带骨化发生于黄韧带退变的基础之上，但退变不直接导致骨化，元素氟是诱导退变黄韧带进一步骨化的重要诱因。     

过量氟化物导致大鼠腰椎黄韧带退变与骨化

[目的]研究氟化物在黄韧带骨化中可能的作用机理。[方法]36只雄性SD大鼠，实验组饮用含NaF（质量分数为1014）蒸馏水，分别于3个月及6个月时，检测骨密度，血清、骨组织标本中Ca、P^3＋、Mg、Zn、Cu、Fe、F^-含量和血清碱性磷酸酶（ALP）活性；行大鼠腰段标本X线检查后组织病理观察。[结果]3个月实验组10只大鼠中6只出现氟斑牙：6个月实验组均出现氟斑牙，且大鼠中轴骨骨密度显著增加（P〈0．05）。X线检查，6个月实验组中有4只可见黄韧带嵴状骨化影。病理观察，3个月实验组大鼠黄韧带呈退行性改变；6个月实验组部分黄韧带骨化，骨化类型以膜内骨化为主。[结论]过量氟化物可造成SD大鼠腰椎黄韧带的退变、骨化，在黄韧带的骨化中可能起重要作用。     

胸椎黄韧带骨化患者黄韧带细胞的体外培养及初步鉴定

目的探讨胸椎黄韧带骨化的发病机理。方法2004年3月-2004年12月对8例行后路减压的下胸椎黄韧带骨化患者（男性5例，女性3例，平均年龄55岁）进行术中取材，采用组织块培养法，体外培养下胸椎黄韧带骨化患者非骨化区域的黄韧带细胞，并进行细胞化学，免疫细胞化学等方面研究；同时对7例急性外伤性下胸椎压缩骨折行胸椎后路减压术的患者（男性5例，女性2例，平均年龄28岁）进行术中取材，体外培养青壮年患者的下胸椎黄韧带细胞作为正常对照。结果体外成功地培养出黄韧带细胞15株，其中骨化患者黄韧带细胞8株（OLF1～OLF8），正常黄韧带细胞7株（NLF1～NLF7），黄韧带细胞可以在体外增殖和传代，通常正常黄韧带生长较慢，而骨化患者的黄韧带细胞则生长较快，并且可形成典型的钙结节样结构；80％以上的细胞呈碱性磷酸酶（ALP）强阳性反应；细胞内的ALP活性及其合成的骨钙素（BGP）含量均较正常对照组明显升高；细胞浆有BMP-2与TGF—betal的阳性表达，表明体外培养的下胸椎黄韧带骨化患者非骨化区域的黄韧带细胞呈现典型的成骨细胞表型特征：而正常黄韧带细胞主要为成纤维细胞表型。结论胸椎黄韧带骨化患者的非骨化区域中存在大量具备典型的成骨细胞表型特征的细胞，可能被骨形成蛋白等骨生长因子所调控。     

颈椎黄韧带退变和脊髓型颈椎病的相关性研究

目的：探讨颈椎黄韧带退变和脊髓型颈椎病的相关性。方法：收集10例脊髓型颈椎病和19例颈椎外伤患者的黄韧带标本，对其进行厚度测量及组织学检查；用Woessner法及盐析法测定黄韧带中Ⅰ型与Ⅱ型胶原含量的比值；对黄韧带厚度与Ⅰ、Ⅱ型胶原含量的比值进行相关性研究。结果：颈椎黄韧带退变后弹力纤维含量下降，排列紊乱，胶原纤维含量增加，颈椎病组黄韧带厚度和Ⅰ/Ⅱ型胶原含量的比值与对照组比较有显著性差异（P〈0.05）；颈椎不稳节段的黄韧带胶原含量较其它节段显著增加。结论：颈椎不稳与黄韧带退变密切相关，黄韧带中Ⅱ型胶原过度增加可能是脊髓型颈椎病发生的重要因素之一。     

胸椎黄韧带骨化症骨桥形成的特点及其意义

目的　探讨胸椎黄韧带骨化症患者椎体骨桥形成的特点及其意义。方法　分析手术治疗的 5 0例胸椎黄韧带骨化症中骨桥形成 2 8例 (占 5 4 % )的临床表现及影像学资料。结果　①骨桥与黄韧带骨化位置的关系 :骨桥与骨化黄韧带紧邻者 15例 ;其中 ,4例在某些节段可见黄韧带骨化与骨桥发生于同一间隙 ,间隔一个椎间隙的 10例、间隔 2个椎间隙的 1例、间隔 3个椎间隙的 2例。②骨桥形成的节段 :形成于一个椎间隙的 14例、2个椎间隙的 7例、3个椎间隙的 5例、5个和 7个椎间隙的各 1例。③骨桥形成的特点是在椎间形成高密度的连续骨化影。这种表现主要发生在与黄韧带骨化节段相邻的部位。结论　骨桥形成在胸椎黄韧带骨化症中出现是退变的一种表现形式 ;进一步说明胸椎黄韧带骨化是脊柱退变的一部分     

胸椎黄韧带骨化的临床病因分析

目的 通过对142例胸椎黄韧带骨化症（TOLF）患者临床资料及影像学特点的回顾性研究,从临床的角度探讨该病的不同病因.方法 1989年7月至2005年11月,收治胸椎黄韧带骨化症142例,手术治疗121例.从临床病因学的角度分为三大类型：（1）原发性TOLF（组1,90例）,不合并与黄韧带骨化相关的疾病,且Ca、P、AKP均正常;（2）全身骨化疾病性TOLF（组2,30例）,其中强直性脊柱炎6例,弥漫性特发性骨肥厚症（DISH）3例,氟骨症10例,后纵韧带骨化症（OPLL）11例;（3）脊柱局部病变性TOLF（组3,22例）,其中陈旧性脊柱骨折5例,脊柱结核4例,椎体后缘骨内软骨结节13例.分析各组临床及影像特点,并测量胸椎、胸腰段后凸角,椎体楔变角.按Epstein标准评定手术效果.结果 （1）组1病变类型以连续型居多（67/90,74%）,以局灶型最少（4/90,5%）;组2中,以连续型居多（21/30,70%）,无局灶型病例,发病节数最多（平均每例6.2节）;组3以局灶型多见（18/22,82%）.（2）组1下胸椎及胸腰段最多见（225/486,47%）;组2中病变多累及整个胸椎,12例颈椎、腰椎同时发生OLF;组3骨化部位与原发疾病部位相近.（3）组1 81%（73/90）胸椎曲度无异常,组2 87%（26/30）有异常,组3 82%（18/22）无异常.结论 TOLF由不同病因引起,本研究发现与全身骨化性因素、脊柱的载荷改变、退变等因素有关;应根据病因进行临床分类.     

氟化钠对人黄韧带细胞碱性磷酸酶活性及骨钙素合成的影响

目的 探讨氟化钠(NaF)对体外培养条件下人黄韧带细胞碱性磷酸酶(alkaline phosphatase,ALP)活性及骨钙素(bone gla protein,BGP)合成的影响.方法 依据手术标本来源不同,分为正常黄韧带细胞(NLF)组(取自急性外伤性胸腰椎骨折截瘫患者,7例)、退变黄韧带细胞(DLF)组(取自退变性腰椎管狭窄症患者,9例)及骨化黄韧带细胞(OLF)组(取自胸椎黄韧带骨化患者,8例).采用组织块贴壁法进行体外细胞培养,共获得24组传代细胞.取第五代细胞加入不同浓度的NaF,观察细胞形态变化,并测定NaF对各组人黄韧带细胞的ALP活性和BGP合成的影响.结果 不同来源的人黄韧带细胞均可在体外增殖并传代,DLF与OLF组人黄韧带细胞呈多形性表现,并可形成钙结节.体外培养条件下,高浓度(1.0mmol/L)NaF可导致人黄韧带细胞发生中毒反应;低浓度(0.01～0.125 mmol/L)NaF可促进DLF组黄韧带细胞增殖、钙结节形成,ALP活性上调,BGP合成明显增加,而对OLF与NLF组人黄韧带细胞则无明显效应.结论 体外培养条件下,低浓度(0.01～0.125 mmol/L)NaF可促进人退变黄韧带细胞的ALP活性增高及BGP合成增加,提示低浓度NaF可能促进人退变黄韧带细胞向成骨方向分化.     

胸椎黄韧带骨化症的手术治疗

目的探讨胸椎黄韧带骨化症的手术治疗效果。方法同顾性分析8例胸椎黄韧带骨化症患者的临床表现、影像学特征和手术治疗效果。结果全部病例经术后随访7个月～8年,手术优良率为75％（6／8）：结论手术治疗胸椎黄韧带骨化症疗效满意。     

胸椎黄韧带骨化症的诊断与治疗

本文报告１１例胸椎黄韧带骨化症的临床资料，其中５例是氟骨症患者，临床表现及影象学检查均较为严重，且手术治疗效果差，胸椎黄韧带骨化症常表现为较典型的胸椎管狭窄症状，早期症状主要表现为下肢麻木、无力，好发部位为Ｔ９～Ｔ１２，ＣＴ及ＭＲＩ是理想有效的检查手段，治疗目前以后路全椎板切除减压为主。本文就黄韧带骨化的病因进行了探讨     

项韧带骨化相关因素及其组织学变化

目的：探讨脊髓型颈椎病患者项韧带骨化的相关因素及其组织学改变特点.方法：将45例脊髓型颈椎病患者根据项韧带有无骨化分为两组,观察并统计两组患者的年龄、性别组成、颈椎椎间退变和颈椎稳定性情况,对各指标与项韧带骨化的关系进行相关性分析,同时观察项韧带骨化的组织学改变.结果：统计分析表明,项韧带骨化和颈椎椎间退行性改变及颈椎不稳定之间具有相关性（P＜0.05）;同时还与患者年龄、性别组成有相关性（P＜0.05）.项韧带骨化的组织学改变以软骨内化骨为主.结论：项韧带骨化与颈椎退行性改变及颈椎椎间关节不稳定具有相关性,组织学改变以软骨内化骨为主.     

Thoracic ossification of ligamentum flavum caused by skeletal fluorosis

Thoracic ossification of ligamentum flavum (OLF) caused by skeletal fluorosis is rare. Only six patients had been reported in the English literature. This study reports findings from the first clinical series of this disease. This was a retrospective study of patients with thoracic OLF due to skeletal fluorosis who underwent surgical management at the authors' hospital between 1993 and 2003. Diagnosis of skeletal fluorosis was made based on the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis was present. Neurological status was evaluated preoperatively, at the third day postoperatively, and at the end point of follow-up using the Japanese Orthopaedic Association (JOA) scoring system of motor function of the lower extremities. A total of 23 cases were enrolled, 16 (69.6%) males and 7 (30.4%) females, age ranging from 42 to 72 years (mean 54.8 years). All patients came from a high-fluoride area, and 22 (95.7%) had dental fluorosis. Medical imaging showed OLF together with ossification of many ligaments and interosseous membranes, including interosseous membranes of the forearm (18/23 patients 78.3%), leg (14/23 patients 60.9%), and ribs (11/23 patients 47.8%). OLF was classified into five types based on MRI findings: localized (4/23 patients 17.4%), continued (12/23 patients 52.2%), skip (3/23 patients 13.0%), combining with anterior pressure (2/23 patients 8.7%), and combining with cervical and/or lumbar stenosis (2/23 patients, 8.7%). Urinalysis showed a markedly high urinary fluoride level in 14 of 23 patients (60.9%). Patients were followed up for an average duration of 4 years, 5 months. Paired t-test showed that the JOA score was slightly but nonsignificantly increased relative to preoperative measurement 3 days after surgery (P = 0.0829) and significantly increased at the end of follow-up (P = 0.0001). In conclusion, Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. Comparing with other OLF series, a larger number of spinal segments were involved. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptom, imaging study findings, and urinalysis. En bloc laminectomy decompression was an effective method.     

Ossification of the ligamentum flavum in a Caucasian man

Abnormal ossification of spinal ligaments is a well-known cause of myelopathy in East Asian populations, with ossification of the ligamentum flavum (OLF) and the posterior longitudinal ligament being the most prevalent. In Caucasian populations, OLF is rare, and there has been only 1 documented case of the disease affecting more than 5 spinal levels. In this report, the authors describe the clinical presentation, imaging characteristics, and management of the second published case of a Caucasian man with OLF affecting almost the entire thoracic spine. The literature is then reviewed with regard to OLF epidemiology, pathogenesis, presentation, and treatment.     

Changes in basic metabolic elements associated with the degeneration and ossification of ligamenta flava

OBJECTIVE: To determine the association between levels of basic metabolic elements and degeneration and ossification of the ligamentum flavum (LF). SUBJECTS: Fourteen consecutive patients with degenerative lumbar stenosis, 11 with ossification of the thoracic ligamenta flava, and 11 control subjects. METHODS: The basic elements of calcium (Ca), phosphorus (P), magnesium (Mg), zinc (Zn), copper (Cu), manganese (Mn), molybdenum (Mo), and fluoride (F) in the specimens were measured using atomic absorption spectrometry, the phosphomolybdic blue method, and a fluoride-selected electrode. RESULTS: Ca content and the ratio of Ca/Mg in the LF specimens increased significantly in the sequence of control, degeneration, and ossification groups. Compared with values for the control group, the Zn, Mn, and Mo contents in the ossification and degeneration groups were significantly lower (P < 0.01); in contrast, Cu content was significantly higher (P < 0.01). As to F, its content in the specimens of the ossification group was much higher than those in the degeneration and control groups (P < 0.01); the F content in the ligamenta flava and sera from patients with fluorosis was also significantly higher than in those from patients without fluorosis (P < 0.01). Compared with the control group, there were no differences in the F content in serum from patients without fluorosis; however, the F content in ligamenta flava specimens from patients without fluorosis was significantly higher (P < 0.01). CONCLUSIONS: There are trends in the contents of basic metabolic elements in the degeneration and ossification of ligamenta flava. These basic metabolic elements may play an important role in this process.     

Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment

The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force.     

腰椎间盘突出症并发小关节囊部黄韧带骨化12例报告

目的：报告１２例腰椎间盘突出症并发小关节囊部黄韧带骨化,旨在提高临床上对于该病的认识以及探讨对其的治疗方法。方法：通过拍摄腰椎Ｘ线片及腰部ＣＴ检查,作出初步诊断。采用手术方法治疗。术中摘除突出的椎间盘,同时彻底切除肥厚骨化的黄韧带,小关节内侧可作部分切除。结果：按照日本Ｎ．Ｎａｋａｎａ和Ｔ．Ｎａｋａｎａ腰背痛手术评定标准,优５例,良６例,可１例。结论：该病病理基础为退行性变。黄韧带劳损导致骨化;充分认识本病对治疗腰腿痛有明显的临床意义;治疗应及早手术为宜。     

Changes in Basic Metabolic Elements Associated With the Degeneration and Ossification of Ligamenta Flava

Abstract

Objective: To determine the association between levels of basic metabolic elements and degeneration and ossification of the ligamentum flavum (LF).

Subjects: Fourteen consecutive patients with degenerative lumbar stenosis, 11 with ossification of the thoracic ligamenta flava, and 11 control subjects.

Methods: The basic elements of calcium (Ca), phosphorus (P), magnesium (Mg), zinc (Zn), copper (Cu), manganese (Mn), molybdenum (Mo), and fluoride (F) in the specimens were measured using atomic absorption spectrometry, the phosphomolybdic blue method, and a fluoride-selected electrode.

Results: Ca content and the ratio of Ca/Mg in the LF specimens increased significantly in the sequence of control, degeneration, and ossification groups. Compared with values for the control group, the Zn, Mn, and Mo contents in the ossification and degeneration groups were significantly lower (P < 0.01 ); in contrast, Cu content was significantly higher (P < 0.01 ). As to F, its content in the specimens of the ossification group was much higher than those in the degeneration and control groups (P < 0.01); the F content in the ligamenta flava and sera from patients with fluorosis was also significantly higher than in those from patients without fluorosis (P < 0.01). Compared with the control group, there were no differences in the F content in serum from patients without fluorosis; however, the F content in ligamenta flava specimens from patients without fluorosis was significantly higher (P < 0.01).

Conclusions: There are trends in the contents of basic metabolic elements in the degeneration and ossification of ligamenta flava. These basic metabolic elements may play an important role in this process.     

胸椎黄韧带骨化症的影像诊断

目的:探讨胸椎黄韧带骨化症的诊断及影像学特点。方法:分析90例胸椎黄韧带骨化症患者的CT和/或MRI资料,并根据影像学特征进行分类。按照MRIT2WI轴位脊髓及硬膜囊的受压迫程度分为轻度、中度、重度。9例获CT或/和MRI检查2年以上随访的患者,选择扫描条件、部位一致的骨化节段对比研究其变化情况。结果:MRI扫描的73例患者共发现黄韧带骨化节段421个。骨化节段呈跳跃性分布35例(46.58%)。多节段发生68例(93.15%)。T2WI轴位扫描的365个节段呈现有压迫:轻度193个节段,中度80个节段,重度92个节段。9例2年以上影像随访患者,随访前CT示均匀性骨化的9个节段,随访时骨化块大小密度无变化;随访前不均匀性骨化6个节段,随访时骨化块增大、密度改变。随访前MRI示骨化为无信号9个节段,随访时骨化块的形态、内部信号、对脊髓的压迫程度均无改变;随访前低信号18个节段,随访时15个节段有不同程度的生长,即对脊髓和硬膜囊的压迫程度加重,骨化块形态改变,3个节段只有骨化块信号的改变,脊髓的受压程度无明显变化。结论:胸椎黄韧带骨化多数病例为多节段,分布无明显规律性。骨化程度与对脊髓的压迫程度并不一致。CT和MRI检查可以作为判断胸椎黄韧带骨化是否成熟的手段。     

黄韧带骨化机制与骨质疏松症治疗策略

骨质疏松症是最常见的代谢性骨病,因成骨细胞与破骨细胞功能失衡造成。目前常见的骨质疏松症药物旨在抑制骨吸收。为了更有效地治疗骨质疏松症,刺激新骨形成将是重要策略。成骨细胞特异转录因子Osterix(Osx)是骨形成及成骨细胞分化必需的转录因子,被认为是骨分子开关。全基因组关联分析研究已经证实Osx与骨质疏松表型相关,但仍需进一步研究Osx的作用机制,包括探索Osx上游调节因子。骨质疏松症迫切需要促骨形成新药,Osx是理想的新靶点。而临床上的另外一种疾病为寻找Osx上游因子提供了很好的参考,那就是黄韧带骨化(ossification of the ligamentum flavum,OLF)。黄韧带骨化是脊柱韧带病理性异位骨化性疾病,在骨外组织黄韧带里刺激了新骨的形成,其致病机制尚不明确。本文结合近年来有关黄韧带骨化的一些机制研究进行综述,包括力学因素、遗传因素、内分泌以及微量元素、Notch信号通路、miRNA及炎症因子等。最新发现的一些参与黄韧带骨化的相关因子能够刺激Osx基因的表达,希望通过对黄韧带骨化致病机制的研究,为寻找Osx上游调节因子进而研发促骨形成新药治疗骨质疏松症提供新的思路。