Association between two polymorphisms of the bone morphogenetic protein-2 gene with genetic susceptibility to ossification of the posterior longitudinal ligament of the cervical spine and its severity

Background Ossification of the posterior longitudinal ligament （OPLL） has a strong genetic background. Previous studies have shown that bone morphogenetic protein-2 （BMP2） and BMP2 mRNA are expressed in ossifying matrix and chondrocytes adjacent to cartilaginous areas of OPLL tissues and mesenchymal cells with fibroblastic features in the immediate vicinity of the cartilaginous areas. It is suggested that BMP2 plays different roles in the different stages of development of OPLL. However, it remains unknown which factors induce ligament cells to produce BMP2. Methods OPLL patients （n=-192） and non-OPLL controls （n=304） were studied. Radiographs of the cervical spine were analyzed for extent of OPLL. We investigated whether single nucleotide polymorphisms of exons 3（-726） T/C and 3（-583） NG in the BMP2 gene are statistically associated with genetic susceptibility to OPLL in Chinese Han subjects. Results There was no statistical difference between the occurrence of exons 3（-726） T/C and 3（-583） NG and the occurrence of OPLL in the cervical spine. However, there was a significant association between occurrence of exon 3（-726） T/C polymorphism and occurrence of OPLL in males of cases and controls in the cervical spine. In addition, no significant association was found between the exons 3（-726） T/C and 3（-583） A/G with number of ossified cervical vertebrae in OPLL patients. Conclusions Exon 3（-583） A/G polymorphism in BMP2 gene is not associated with the occurrence and the extent of OPLL in the cervical spine. Chinese Han male patients with TC and CC genotypes in exon 3（-726） T/C have genetic susceptibility to OPLL but not to more extensive OPLL in the cervical spine.

A Case of Acute Cauda Equina Syndrome for Combined Lumbar Ossification of the Posterior Longitudinal and Yellow Ligament

Acute cauda equina syndrome is known as a symptom of lumbar disc herniation, but to date, there have been no reports of cases caused by lumbar vertebral ligament ossification. We encountered a 61-year-old female patient with acute cauda equina syndrome associated with lumbar vertebral OPLL and OLF. The symptoms were improved by emergency laminectomy. One year after the surgery, the disturbances of gait and urination have been resolved.

Regression of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament:A case report

BACKGROUND Intervertebral disc calcification(IDC)combined with ossification of the posterior longitudinal ligament(OPLL)in cervical discs is rarely reported.This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment.CASE SUMMARY Here,we present a case of a 6-year-old Asian boy with severe neck pain and stiffness.Physical examination showed no neurological or other abnormalities.Digital radiography and computed tomography(CT)revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae.The spinal canal compromise at C2-C3 was approximately 50%on magnetic resonance imaging.The final diagnosis was IDC combined with OPLL.We applied a neck brace for the patient to protect the neck.The patient's neck pain and stiffness recovered significantly within approximately 3 wk.At the 3 mo follow-up,the follow-up CT showed resolution of the ossified intervertebral disc herniation,and a small amount of calcification and slight OPLL remained at the involved segment.CONCLUSION IDC combined with OPLL is a relatively rare condition in children.However,the majority of patients could have a favorable outcome,and the ossified mass in the canal would be spontaneously resolved with conservative therapy.

Enlarged laminectomy for ossification of posterior longitudinal ligament in cervical spine

Objective To introduce surgical strategy of enlarged laminectomy (with partial facet joint dissection to expose nerve root) ,and to discuss its benefit for cervicalossification of posterior longitudinal ligament (OPLL)

The clinical features and treatment strategies of thoracic ossification of posterior longitudinal ligament

Objective To study the clinical features and surgical strategies of thoracic spinal stenosis caused by ossification of posterior longitudinal ligament(OPLL).Methods From January 2004 to March 2009,21 cases of tho-racic spinal stenosis

"Cave-in"technique: 360° circumferential decompression for thoracic spinal stenosis with ossification of posterior longitudinal ligament

Objective To investigate the surgical techniqueand efficiency of the "Cave-in" 360° circumferential decompression for thoracic spinal stenosis(TSS)with ossification of posterior longitudinal ligament(OPLL).Methods From October 2005 to

Analysis of amelioration of neurological function on cervical degeneration disease after treatment with cervical spine locking plate

Objective To discuss the clinical effect of treatment with anterior decompression, bone graft and cervical locking plate fixation for cervical degeneration disease.Method 23 patients with cervical spondylotic myelopathy and cervical ossification of the posterior longitudinal ligament have undergone the treatment of anterior cervical spine locking plate fusion.Neurological signs and symptoms were evaluated before and after surgery, and mean follow up time was 11.3 months.Result In all cases,radiography demonstrated a solid bony fusion.Additional general complications include a large wound hematoma in one and hoarseness in one.All patients’ neurological function were improved.Conclusion The clinical effect of treatment with anterior decompression, bone graft and cervical locking plate fixation for cervical degeneration disease is satisfactory.

Linkage of three polymorphisms on chromosome 20p12 to ossification of the posterior longitudinal ligament of spine and its severity in Han Chinese patients

Background Ossification of the posterior longitudinal ligament （OPLL） is characterized by the replacement of ligamentous tissue with new ectopic bone formation, and has a strong genetic background. Because of the abnormal bone metabolic features and the strong genetic component, osteoporosis is a related disorder with OPLL. Three polymorphisms on chromosome 20p12 were identified associated with the risk of osteoporosis and osteoporotic fracture.The rs996544 （C/T） ＂TT＂ and rs965291 （G/A） ＂AA＂ genotypes conferred higher risks for vertebral and hip fractures. The osteoporosis haplotype is defined by two polymorphisms, rs1116867 （A） and D35548 （T）. However, it remains unknown whether these three polymorphisms predispose to an increased frequency and severity of OPLL in Han Chinese patients.Methods A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. Three single nucleotide polymorphisms （SNPs）, rs996544 （C/T）, rs965291 （G/A） and rs1116867 （A/G）, were analyzed by direct sequencing.Associations between these SNPs with the occurrence and extent of OPLL were statistically evaluated.Results There was no significant association between the rs996544 （C/T） polymorphism and the prevalence of OPLL.The rs1116867 （A/G） polymorphism ＂AG＂ genotype was associated with the occurrence of OPLL. The rs1116867 （A/G） polymorphism ＂G＂ allele was associated with the occurrence of OPLL, but not with the extent of OPLL. The rs965291 （G/A） polymorphism in female patients was statistically different between cases and controls （P 〈0.05）. The rs965291 （G/A） polymorphism ＂A＂ allele was associated with the occurrence of OPLL in female patients. For the rs965291 （G/A）polymorphism, patients with the ＂A＂ allele （genotype, ＂AG＂ or ＂AA＂） showed a significantly greater number of ossified cervical vertebrae than those without the ＂A＂ allele （genotype, ＂GG＂, P 〈0.05）, particularly in female patients.Conclusions The rs1116867 （A/G） and rs965291 （G/A） polymorphisms on chromosome 20p12 are associated with the occurrence and the extent of OPLL, at least in Han Chinese subjects. Our data should advance our understanding of the molecular etiology of OPLL and may guide approaches to prevent the onset of OPLL.

A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene （109T〉G） affects the Smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine

Background Although various systemic and local factors such as abnormal carbohydrate or calcium metabolism, aging, and hormonal disturbances have been suggested as causes of ossification of the posterior longitudinal ligament （OPLL）, the etiology of OPLL is not fully understood. The purpose of this study was to investigate whether bone morphogenetic protein （BMP）-2 is a candidate gene to modify the susceptibility of OPLL and the mechanism of signal transduction in ossification. Methods A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. The complete coding sequence of the human BMP-2 gene was analyzed using polymerase chain reaction （PCR） and direct sequencing. All single nucleotide polymorphisms （SNPs） were detected and genotyped. BMP-2 expression vectors containing positive polymorphisms were constructed and transfected into the C3H10T1/2 cells. The expression of BMP-2 and the Smad signal pathway in positive cell clones were detected by Western blotting. The alkaline phosphatase （ALP） activity was determined using quantitative detection kits. Results The frequencies for the 109T〉G and 570A〉T polymorphisms were different between the case and control groups. The ＂TG＂ genotype in 109T〉G polymorphism is associated with the occurrence of OPLL, the frequency of the ＂G＂ allele is significantly higher in patients with OPLL than in control subjects （P 〈0.001）. The ＂AT＂ genotype in 570A〉T polymorphism is associated with the occurrence of OPLL, the frequency of the ＂T＂ allele is significantly higher in patients with OPLL than in control subjects （P=0.005）. Western blotting analysis revealed that the expression of P-Smadl/5/8 protein transfected by wild-type or mutant expression vectors were significantly higher than control groups （P 〈0.05）, but there was no statistical difference in each experimental group （P 〉0.05）. The expression of Smad4 protein transfected by wild-type or mutant expression vectors was significantly higher than control groups （P 〈0.05）. The expression of Smad4 protein transfected by pcDNA3.1-BMP2 （109G） and pcDNA3.1-BMP2 （109G, 570T） was significantly higher than the other experimental groups （P 〈0.05）. The increase in ALP activity has been detected in pcDNA3.1-BMP2 （109G） and pcDNA3.1-BMP2 （109G, 570T） transfected cells up to 4 weeks after stable transfection. Activity of ALP was （30.56±0.46） nmol.min^-1.mg^-1 protein and （29.62±0.68） nmol.min^-1.mg^-1 protein, respectively. This was statistically different compared with the other experimental groups （P 〈0.05）. Conclusions BMP-2 is the predisposing gene of OPLL. The ＂TG＂ genotype in the 109T〉G and the ＂AT＂ genotype in the 570A〉T polymorphisms are associated with the occurrence of OPLL. The 109T〉G polymorphism in exon-2 of the BMP-2 gene is positively associated with the level of Smad4 protein expression and the activity of ALP. The Smad mediated sicjnaling pathway plays an important role durincl the Datholoqical process of OPLL induced by SNPs of BMP-2 aene.

Classification and management of the tandem ossification of the posterior longitudinal ligament and flaval ligament

Objective To provide appropriate guidelines for treatment of tandem ossification of the posterior longitudinal ligament （OPLL） and flaval ligament （OFL）. Data sources Published articles about OPLL and OFL were selected using Medline and Embase electronic databases. Study selection An English literature search from January 1980 to December 2006 was conducted. Because many reported cases were incorporated in OFL studies, the key words for search were OFL or OFL and OPLL. The first step revealed 93 studies of which 13 reports of tandem OPLL and OFL （tandem ossification） were selected. Results All studies were case series or case report and advocated that the primary therapy for tandem ossification should be operative. The clinical outcomes of surgery were evaluated in most reports, predominantly using the JOA scores. Gender is the only factor which has prognostic value. A higher proportion of women was found in the failure group A two- stage classification of tandem ossification was developed to relate diagnosis to outcome. Conclusions All patients with suspected ossification of the spinal ligaments should undergo routine MRI screening of the whole spine. The correlation of the classification with surgical treatments needs further studies to validate its usefulness. Chin Med J 2009; 122（2）：219-224

Clinical results and intramedullary signal changes of posterior decompression with transforaminal interbody fusion for thoracic myelopathy caused by combined ossification of the posterior longitudinal ligament and ligamentum flavum

Background Surgical treatment of thoracic myelopathy caused by ossification of the posterior longitudinal ligament （OPLL） and ossification of the ligamentum flavum （OLF） is technically demanding, and the results tend to be unfavorable. Various operative approaches and treatment strategies have been attempted, and posterior decompression with transforaminal thoracic interbody fusion （PTTIF） may be the optimal method with which the anterior-posterior compression was removed in one step. It is comparatively less traumatic with fewer serious complications.

T allele at site 6007 of bone morphogenetic protein-4 gene increases genetic susceptibility to ossification of the posterior longitudinal ligament in male Chinese Han population

Background Several candidate genes of ossification of the posterior longitudinal ligament （OPLL） susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 （BMP4） is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C〉T（rs17563） of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated. Methods A case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism （SNP） of -5826G〉A（rs1957860） 5＇ of the transcription start site and 6007C〉T（rs17563） in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed. Results A significant statistical difference in genotype of 6007C〉T polymorphism between male OPLL patients and male controls was evident, and the frequency of ＂TT＂ genotype in male OPLL patients was significantly higher than in male controls （P=0.039）. The frequency of the ＂T＂ allele was also significantly higher in male OPLL subjects than in male controls （P=0.014, OR=1.57）. A significant difference was also observed between the 6007C〉T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G〉A polymorphism and OPLL occurrence. Conclusions The T allele in the 6007C〉T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C〉T genotypes have a genetic susceptibility to OPLL and more extensive OPLL in the cervical spine.

Circumferential decompression via the posterior approach for the surgical treatment of multilevel thoracic ossification of the posterior longitudinal ligaments： a single institution comparative study

Background The treatment strategies for multilevel thoracic ossification of the posterior longitudinal ligaments （T-OPLL） were rarely reported. The aim of this study was to investigate the clinical outcomes and complications of circumferential decompression for multilevel T-OPLL and compare two different methods in the management of the OPLL （resection or floating）. Methods Data of sequentially treated patients who received surgical treatment for thoracic spinal stenosis caused by multilevel T-OPLL from January 2005 to February 2012 were retrospectively reviewed. Based on the surgical approaches applied, the patients were divided into two groups. Group A consisted the patients who received posterior decompression and group B consisted the patients who received circumferential decompression via the posterior approach. Group B was further divided into two subgroups： subgroup 1 （the resection group） where the OPLL was completely resected and subgroup 2 （the floating group） where the OPLL was floated. Results A total of 49 patients were included in the study. Fourteen patients with single posterior decompression were included in group A and 35 patients who received circumferential decompression were included in group B. In group B, 29 patients had complete resection of the ossified posterior longitudinal ligaments, while the other six underwent a flotation procedure. The follow-up data were available in 39 patients. Mean JOA scores improved from 5.4 ± 1.8 to 7.5 ± 2.8 in group A and from 3.7 ± 1.8 to 7.9 ± 2.4 in group B. The main complications included cerebrospinal fluid （CSF） leakage and postoperative neurelogic deterioration （ND）. Twenty-three of the 25 cases with postoperative CSF leakage achieved a complete recovery at the last follow-up and 12 of the 15 cases with ND achieved some neurological improvement at the last follow-up. Conclusions Circumferential decompression via the posterior approach is an effective surgical method for thoracic spinal stenosis caused by multilevel OPLL of the thoracic spine. Patients who receive complete resection of the ossified posterior longitudinal ligaments may have better recovery rate than the ＂floating＂ group.

Removal versus preservation of the posterior longitudinal ligament in Bryan cervical disc arthroplasty

Background Bryan cervical disc arthroplasty can be used to restore and maintain the mobility and function of the involved cervical spinal segments. The efficiency of posterior longitudinal ligament （PLL） resection in anterior cervical decompression and fusion has been demonstrated. However, no clinical reports have compared PLL removal with preservation in Bryan cervical disc arthroplasty. This study aimed to assess the role of removal of PLL in Bryan cervical disc arthroplasty at an 18-month follow-up.

自噬相关基因Beclin1和LC3在颈椎后纵韧带骨化组织中的表达及其与成骨因子的相关性分析

目的:探讨自噬相关基因Beclin1和LC3在颈椎后纵韧带骨化组织中的表达水平及其与成骨因子的相关性。方法:收集2020年10月~2021年5月经手术切除的颈椎后纵韧带骨化(ossification of posterior longitudinal ligament,OPLL)患者的18例后纵韧带组织标本(OPLL组)和15例非骨化的颈椎后纵韧带组织标本(非OPLL组)。苏木精-伊红(hematoxylin-eosin,HE)染色观察颈椎后纵韧带组织形态学改变;Von Kossa染色观察颈椎后纵韧带钙盐沉积情况;通过免疫组织化学染色及实时定量聚合酶链反应(RT-qPCR)技术分别测定两组标本中Beclin1、微管相关蛋白轻链(microtubule associated protein light chain 3,LC3)和Runt-相关转录因子-2(runt-related transcription factor 2,RUNX2),骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)及Osterix的mRNA及蛋白的表达水平;采用Pearson相关性分析行Beclin1、LC3与RUNX2、BMP2及Osterix的关系研究。结果:与非OPLL组相比,OPLL组细胞形态较大且形状不规则,细胞核较明显;Von Kossa染色可见非OPLL组无明显钙盐沉积,而OPLL组可见棕黑色钙盐并聚积成片状或团状;Beclin1、LC3、RUNX2、BMP2及Osterix的蛋白及mRNA在OPLL组中的表达水平显著高于非OPLL组(P<0.05);Beclin1 mRNA表达水平与BMP2、RUNX2和Osterix具有显著相关性(P<0.05,r>0.5),而LC3与成骨因子不具备相关性。结论:自噬相关基因Beclin1和LC3在颈椎OPLL组织中显著高表达,Beclin1与后纵韧带成骨密切相关。

OPLL后路单开门椎管扩大成形术后C_(5)神经根麻痹的风险

目的 探讨颈椎后纵韧带骨化症(OPLL)椎管占位严重程度与后路单开门椎管扩大成形术后C_(5)神经根麻痹的关系。方法 纳入2019年12月~2021年12月该院收治的88例OPLL患者,采用单开门椎管扩大成形术治疗,术后根据是否发生C_(5)神经根麻痹分组,比较两组术前椎管占位率以及性别、年龄、手术节段等临床资料,并采用多因素分析椎管占位率、C_(5)椎间孔宽度等与C_(5)神经根麻痹的关系。结果 88例OPLL患者术后19例发生C_(5)神经根麻痹;麻痹组与非麻痹组椎管占位率、C_(5)椎间孔宽度、术后脊髓漂移距离、手术节段数、年龄差异具有统计学意义(P<0.05);组间性别、OPLL类型差异无统计学意义(P>0.05);多因素分析显示,椎管占位率、C_(5)椎间孔宽度、脊髓漂移距离是术后C_(5)神经根麻痹的危险因素(P<0.05)。结论 OPLL单开门椎管扩大成形术后C_(5)神经根麻痹发生率较高,椎管占位率、C_(5)椎间孔宽度、脊髓漂移距离是危险因素之一。

微RNA在颈椎后纵韧带骨化症中的作用和机制研究进展

颈椎后纵韧带骨化症(OPLL)是附着于椎体后缘的后纵韧带在多因素作用下发生异常增厚和骨化的现象,是常见的颈椎退行性疾病之一,可导致严重的感觉和运动功能障碍^([1])。目前,OPLL的发生机制尚不清楚,其早期诊断和治疗方式仍然有限。有文献^([1])报道,遗传与环境因素共同参与了OPLL的发生。

颈后路椎板减压术在脊髓型颈椎病后纵韧带骨化症中的疗效分析

目的探究颈后路锥板减压术在脊髓型颈椎病后纵韧带骨化症中的治疗效果。方法选择2020年4月—2022年10月于大荔县妇幼保健院接受治疗的96例脊髓型颈椎病后纵韧带骨化症患者作为研究对象,按照随机数表法将其分为研究组(n=48,接受颈后路锥板减压术)与对照组(n=48,接受传统颈椎后路单开门椎管成形术),比较两组患者切口长度、手术时间、透视时间、出血量等手术指标,比较两组患者术前、术后6个月时的JOA评分、Nurick分级、颈椎曲度、椎管占有率差异,统计两组患者术后6个月各类并发症发生率差异。结果研究组患者切口长度、手术时间、透视时间以及出血量均显著低于对照组,差异有统计学意义(P<0.05);术前两组患者JOA评分、Nurick分级、颈椎曲度和椎管占有率比较,差异无统计学意义(P>0.05),术后6个月时研究组患者JOA评分、颈椎曲度高于对照组,Nurick分级、椎管占有率低于对照组,差异有统计学意义(P<0.05),两组患者并发症发生率比较,差异无统计学意义(P>0.05)。结论对脊髓型颈椎病后纵韧带骨化症患者实施颈后路锥板减压术疗效显著,可以有效改善患者颈椎曲度和椎管占有率,相较传统颈椎后路单开门椎管成形术具有术中创伤小、术后康复快的优势,手术安全性较好。

Double Cervical Bird Beak Sign Resulting in Dysphagia

Objective: The authors report a rare case of ossification of the anterior longitudinal ligament in the cervical spine underlying dysphagia. Case Report: We report the case of a 50-year-old male presenting with difficulty swallowing and choking. CT of the cervical spine demonstrated anterior longitudinal ligament hypertrophy with osteophytes worst at C1-C2 and C6-C7, without spinal cord compression. A videofluoroscopic swallow study revealed reduced epiglottic inversion and hyolaryngeal elevation resulting in incomplete clearance from the pharynx, as well as compression of the esophagus. Subsequently, the patient underwent osteophytectomy. There were no intraoperative or postoperative complications. Two weeks after the surgery, videofluoroscopic swallow demonstrated improved function and reduced compression. Four weeks postoperatively, the patient completely regained swallowing function without pain.

颈椎前路椎体骨化物复合体可控前移融合术治疗颈椎后纵韧带骨化症的研究进展

颈椎后纵韧带骨化症是后纵韧带发生病理性异位骨化,缓慢进展的骨化物压迫脊髓、神经根,继而出现一系列神经功能损害的症候群。临床中通过症状体征和影像学检查可明确诊断,其治疗方式的选择依赖于症状的严重性。对于无症状或症状较轻的患者,多采取保守治疗并结合影像学随访;对于出现脊髓或神经病变的患者,则必须采取手术减压治疗。该病的手术入路方式目前主要有前路、后路和前后联合入路3种,不同的手术入路和方式各有其优缺点。颈椎前路椎体骨化物复合体可控前移融合技术是一种治疗颈椎后纵韧带骨化症的新兴术式,经过近几年的推广应用,取得了良好的临床效果。该文结合国内外的临床研究进展,对颈椎前路椎体骨化物复合体可控前移融合技术治疗颈椎后纵韧带骨化症的现状及进展进行综述,为临床工作提供参考。