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Posterior longitudinal ligament ossification of cervical spine is a rare condition among caucasians. A 42 years old japanese patient with progressive walking difficulty was diagnosed with this pathology by CT scan and MRI and treated surgically by an anterior approach with arthrodesis. Pathophysiology, racial prevalence, clinical picture, radiological characteristics and surgical approaches options are revised.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To clarify this mechanism, we investigated the effects of in vitro cyclic stretch (120% peak to peak, at 0.5 Hz) on cultured spinal ligament cells derived from OPLL (OPLL cells) and non-OPLL (non-OPLL cells) patients. The mRNA expressions of Cbfa1 (an osteoblast-specific transcription factor), type I collagen, alkaline phosphatase (ALP), osteocalcin and integrin beta1 (a mechanotransducer) were increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells. The effects of cyclic stretch on the spinal ligament tissues derived from OPLL and non-OPLL patients were also analyzed by immunohistochemistry using an antibody against Cbfa1. The expression of Cbfa1 was increased by cyclic stretch at the center of the spinal ligament tissues of OPLL patients, whereas no change was observed in the tissues of non-OPLL patients. Furthermore, U0126, a specific inhibitor of MAPK kinase (MEK), suppressed the stretch-induced mRNA expressions of Cbfa1, ALP and type I collagen in OPLL cells. These results suggest that in OPLL cells, mechanical stress is converted by integrin beta1 into intracellular signaling and that Cbfa1 is activated through the MAP kinase pathway. Therefore, we propose that mechanical stress plays a key role in the progression of OPLL through an increase in Cbfa1 expression.
Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.
Ossification of the posterior longitudinal ligament lessens the sagittal diameter of the cervical canal and compresses the spinal cord anteriorly, and may produce severe disabling myelopathy. The anterior floating method is one of the anterior decompression and reconstructions used in the treatment of cervical myelopathy caused by ossification of the posterior longitudinal ligament. This procedure consists of subtotal resection of vertebral bodies and discs, with slight thinning and release of the ossified ligament using air instrumentation. This is followed by reconstruction of the cervical spine using autogenous strut bone graft accompanied by postoperative application of a halo vest. This method is indicated for patients who present with moderate or severe myelopathies, and especially in those where the canal narrowing ratio exceeds 60%. This radical procedure causes decompression of the spinal cord and restores its function by enlarging the neural canal with anterior migration of the ossified ligament. The procedure minimizes the extent of surgical invasions and avoids damage to the neural tissue, because it does not require the removal of the ossification of the posterior longitudinal ligament. It also stops postoperative regrowth of the ossification. The operative results with long term followup indicate a 71% average recovery rate based on the criteria established by the Japan Orthopedic Association.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To elucidate this mechanism, we investigated the effects of in vitro sinusoidal cyclic stretch (120% peak to peak, at 1 Hz) on cultured spinal ligament cells derived from OPLL and non-OPLL patients. The mRNA expressions of alkaline phosphatase (ALP), osteopontin, bone morphogenetic protein (BMP)-2, BMP-4, and BMP receptors as well as ALP activity in cell layers and production of BMPs into the conditioned medium were significantly increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells. A stretch-activated Ca(2+) channel blocker, Gd(3+), the voltage-dependent L-type Ca(2+) channel blockers diltiazem and nifedipine, and Ca(2+)-free medium suppressed stretch-induced ALP activity, which suggests a role of Ca(2+) influx in the signal transduction of mechanical stress to the osteogenic response of OPLL cells. Our study provides first evidences that mechanical stress plays a key role in the progression of OPLL through the induction of osteogenic differentiation in spinal ligament cells and the promotion of the autocrine/paracrine mechanism of BMPs in this lesion.
Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL.
Ossification of the posterior longitudinal ligament in the cervical spine may be a cause of cervical myelopathy. This ossification has often been encountered in Japan, but only sporadically among the Caucasian races. It is therefore probable that racial factors are relevant to the pathology. During the past four years, due to the routine use of computerised axial tomography (CAT) in the pre-operative study of cervical myelopathy, we were able to show that in 13 cases stenosis of the vertebral canal was due to ossification of the posterior longitudinal ligament. This was visible in the standard radiographs in only two out of these 13 cases. The clinical data, diagnostic criteria and results of treatment are reported. This is the largest series yet reported outside Japan.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments, and mechanical stress has been suggested to play an important role in the progression of OPLL. To identify the genes that participate in OPLL, the differential display reverse transcription-polymerase chain reaction (RT-PCR) method was used. A 283-base pair cDNA fragment corresponding to prostaglandin I2 (PGI2) synthase was highly expressed in OPLL cells compared with non-OPLL cells. To examine the effect of mechanical stress on the expression of PGI2 synthase, cells were subjected to uniaxial cyclic stretch (0.5 Hz, 20% stretch), and PGI2 synthase mRNA expression was assessed by quantitative RT-PCR. Cyclic stretch induced an increase in PGI2 synthase in OPLL cells in a time-dependent manner, whereas no change was observed in non-OPLL cells. Cyclic stretch for 9 h also induced a 2.86x increase in PGI2 production. Beraprost (a stable PGI2 analog) and dibutyryl cAMP (a membrane-permeable cAMP analog) increased the mRNA expression of alkaline phosphatase (ALP) as a marker for osteogenic differentiation up to 240 and 200%, respectively, in OPLL cells, whereas no change was observed in non-OPLL cells. The increases in ALP mRNA induced by beraprost and cyclic stretch were both inhibited by SQ22536, a potent adenylate cyclase inhibitor. These data suggest that the increase in PGI2 synthase induced by mechanical stress plays a key role in the progression of OPLL, at least in part through the induction of osteogenic differentiation in spinal ligament cells via the PGI2/cAMP system.
Ossification of the posterior longitudinal ligament (OPLL) is an intractable disease developing into severe myelopathy and often accompanied by ossification of several other spinal ligaments and articular ligaments. Therefore, it is highly probable that predisposition to systemic ossification underlies the onset of this disease. Terayama et al(1981) reported that the nuchal skin of OPLL patients tended to be tougher than that of healthy individuals. Decorin is a component of the extracellular matrix which antagonistically regulates the action of Transforming growth factor-beta (TGF-beta). Imamura et al(1995) demonstrated immunohistochemically that decorin increased in the epidermis of the nuchal skin of OPLL patients. This suggests an abnormal expression of the extracellular matrix in the skin of OPLL patients. In the present study, in situ hybridization with non-radioactive synthetic oligodeoxynucleotide probes revealed an enhanced expression of decorin mRNA in the epidermal keratinocytes of OPLL patients. The increased expression of decorin mRNA in the epidermis of OPLL patients may be interpreted as reflecting abnormalities of the matrix associated with ossification of the ligaments. Studies on the role of decorin in ossification will contribute to clarification of the pathophysiology and pathogenesis of OPLL.
Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine associated with diffuse idiopathic skeletal hyperostosis is described in a 70-year-old Caucasian man presenting with a rapidly progressive myelopathy. The acute nature of his myelopathic symptoms and cervical canal stenosis necessitated posterior decompressive surgery. Four other patients with OPLL are presented to illustrate the spectrum of imaging findings. The computed tomographic features of OPLL are distinctive.A 2-5 mm thick linear ossified strip along the posterior vertebral margin usually at mid cervical (C3 to C5) level characterises the condition. Magnetic resonance (MR) imaging is valuable in excluding possible cord damage and associated disc lesions prior to surgery. A calcified central sequestrated disc is the only condition that may be mistaken for the segmental and retrodiscal forms of OPLL In a clinical setting of compressive myelopathy, it is pertinent to distinguish between these two conditions since a sequestrated disc has a more favourable surgical prognosis. The merits and relevance of anterior and posterior surgery together with their possible complications are outlined.
Ossification of the posterior longitudinal ligament, despite its rare occurrence in Caucasians, is one further cause of cervical myelopathy and radiculopathy that should be included in the differential diagnosis. A recent case is reported.
Ossification of the posterior longitudinal ligament is a human genetic disease in which pathological ectopic ossification of the spinal ligaments develops. This leads to myelopathy or radiculopathy due to compression of the spinal cord. In this study, we investigated the histological features of orthotopic ossification of the spinal ligaments of senile Zucker fatty rats. A remarkably high incidence of orthotopic ossification was observed mainly in the thoracic spinal ligaments as compared with controls. The histopathological findings were similar to those for ossification of the human posterior longitudinal ligament. Bone morphogenetic proteins and activins, which exert their effects by way of specific type-I and type-II serine/threonine kinase receptors, play important roles in the formation of bone and cartilage. In the spinal ligaments of Zucker fatty rats, bone morphogenetic protein receptors and activin receptors were immunohistochemically detected around the ossified foci in a manner similar to that previously shown for the ossified tissue from patients who had ossification of the posterior longitudinal ligament. Thus, bone morphogenetic proteins and activin receptors might play important roles in orthotopic ossification of the spinal ligaments of Zucker fatty rats as well as in ossification of the posterior longitudinal ligament of humans. In addition, bone morphogenetic protein-receptor-IA was expressed in the nonossified ligament, suggesting that the spinal ligaments, of the rats may have a predisposition to orthotopic ossification. In the controls, no expression of bone morphogenetic protein receptors or of activin receptors was observed. In conclusion, there is a great degree of similarity between orthotopic ossification of the spinal ligaments of Zucker fatty rats and ossification of the posterior longitudinal ligament of humans. Thus, the rats provide a useful animal model for the study of ossification of the human posterior longitudinal ligament.
Ossification of the posterior longitudinal ligament in the cervical region is generally regarded as a rare disease, though a Japanese series of 185 cases has been reported. The main symptoms arise from a myelopathy, the degree of which varies from moderate to severe, due to stenosis of the spinal canal. In order to clarify the relationship between the severity of symptoms and the cross-sectional area of ossification, axial transverse tomography of the cervical spine has been carried out on twenty-six patients at intervals of 5 millimetres over the full extent of the ossification. In this way the cross-sectional areas of the ossified tissue and of the spinal canal were calculated. The former varied from a minimum of 0.8 to a maximum of 1.8 square centimetres. In cases of severe myelopathy the ossification was mainly at the fourth and fifth cervical levels and the stenosis ration exceeded 30 per cent.
Ossification of the posterior longitudinal ligament (OPLL) is a well-documented cause of cervical spine stenosis and myelopathy among Japanese patients. Reports of OPLL in North Americans are rare. Choices of diagnostic method and treatment for this entity remain controversial. The authors report the results of management of 20 patients in the United States with symptomatic OPLL of the cervical spine. These represented 10% to 20% of patients operated on over the last 3 years for myelopathy secondary to structural spinal compression. Most of these OPLL patients were Caucasian (60%), male (male:female 4:1), and middle-aged (median age 47.5 years). Six had previously undergone laminectomy or discectomy. Cervical roentgenograms and standard myelography occasionally suggested the diagnosis. Axial computerized tomography (CT) metrizamide myelography with small interslice intervals proved invaluable for diagnosis and operative planning. Magnetic resonance imaging was not necessary for diagnosis. Retrovertebral calcification extended over one to five bodies (mean 2.75). The mass ranged in size from 5 to 16 mm in anteroposterior diameter and reduced the residual canal diameter to a mean (+/- standard deviation) caliber of 9.42 +/- 2.41 mm (mean narrowing ratio 0.44 +/- 0.12). Anterior cervical decompression by medial corpectomy and discectomy with fusion uniformly reduced preoperative myelopathy. Complications were limited to transient neurological deterioration in two patients, recurrent laryngeal nerve palsy in one, and halo device pin site infections in two. At a mean postoperative interval of 15 months, improvement was seen in each category of deficit: extremity weakness, hypesthesia, hypertonia, and urinary dysfunction. All fusions produced solid unions. It is concluded that OPLL of the cervical spine is an unexpectedly prevalent cause of myelopathy among patients treated in the United States. Thin-section axial CT metrizamide myelography with small interslice intervals is essential for the investigation of patients who may have OPLL. Anterior decompression and stabilization by medial corpectomy, discectomy, removal of the calcified mass, and fusion is a safe and effective method of treatment.
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Two elderly white women with a long history of hypothyroidism and myelopathy showed ossification in posterior longitudinal ligament at their cervical spine. Case histories are presented and the reported association of PLLO with other conditions discussed.
STUDY DESIGN: To determine the osteogenicity of posterior longitudinal ligament ossification, the posterior longitudinal ligament obtained during anterior cervical surgery from patients with the disorder was analyzed with in vitro cultures. OBJECTIVES: To determine the osteogenicity of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: The osteogenicity of posterior longitudinal ligament ossification in North America requires better documentation. METHODS: The posterior longitudinal ligament obtained during anterior cervical corpectomy with fusion from seven patients, three with ossification of the posterior longitudinal ligament documented by magnetic resonance imaging and computed tomography and four with spondylosis, was blindly submitted for in vitro culture. Explants of the posterior longitudinal ligament were placed in Dulbecco modified Eagle medium with 10% fetal calf serum, antibiotics, 4 mmol/L x L-proline, and 50 mg/L ascorbic acid. After reaching confluency, cells were trypsinized, and first-passage cells were used for all osteocalcin measurements to establish their osteoblastic phenotype. Periosteal cells, previously shown to synthesize osteocalcin, were used as a positive control. The cells were incubated with 1,25(OH)2 vitamin D3 at 10E-8 M for 72 hours in serum-free medium. The supernatants were collected and frozen, after which the quantity of osteocalcin induced by exposure to 1,25(OH)2 vitamin D3 was determined using enzyme-linked immunoassay. Control replicate cultures were measured without incubation using vitamin D3. RESULTS: Ossification of the posterior longitudinal ligament cell lines responded positively with osteocalcin synthesis in the 0.1 to 0.4 ng/M range. The cell line of the patient with spondylosis alone did not respond to vitamin D3 priming. CONCLUSIONS: Posterior longitudinal ligament cells from the three North American white patients with ossification of the posterior longitudinal ligament, when cultured in vitro, synthesized osteocalcin on vitamin D3 priming, confirming their osteoblastic phenotype, whereas posterior longitudinal ligament cells from four white patients with isolated spondylosis did not.
An earlier review of the lateral chest radiographs of 8,610 Hiroshima and Nagasaki Adult Health Study subjects revealed 48 persons with posterior longitudinal ligament ossification (PLLO) in the thoracic region. Seven additional PLLO cases detected outside that observation period brought the total to 55. Among them, 15 patients with neurological signs and/or the greatest degree of thoracic PLLO were selected for computed tomography (CT) of the spine in the present study. Computed tomography proved extremely valuable in identifying the location, shape, and severity of PLLO. In two cases, CT differentiated some lesions previously regarded to be PLLO as actually due to hypertrophic margins of vertebral bodies. Possible explanations are included for the development of the laminated or tandem type PLLO, and PLLO that is located laterally rather than in midline.