Characteristics of ossification of the spinal ligament; incidence of ossification of the ligamentum flavum in patients with cervical ossification of the posterior longitudinal ligament – Analysis of the whole spine using multidetector CT

doi:10.1016/j.jos.2016.04.009

Journal of Orthopaedic Science

Volume 21, Issue 4, July 2016, Pages 439-445

https://doi.org/10.1016/j.jos.2016.04.009 Get rights and content

Abstract

Background

Ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) are characterized by replacement of ligamentous tissue by ectopic new bone formation. Although the background of both diseases might be similar, there are some differences between two diseases. Some patients have both OPLL and OLF. However, the incidence of both OPLL and OLF is still unclear and the precise lesions have not been investigated, yet. This study was conducted to evaluate OLF of the whole spine in patients with cervical OPLL and to analyze the relationship of the ossified lesions between OLF and OPLL.

Methods

One hundred seventy eight patients who were diagnosed as cervical OPLL by plain radiographs were included. CT images of the whole spine were taken. Ossified lesions were checked at each level of vertebral body and intervertebral disc. The ossification index of OPLL (OPLL OS index) was determined by the sum of the levels of vertebral bodies and intervertebral discs where OPLL existed. The same index was applied for detecting the level of OLF (OLF OS index). Age, gender and OPLL characteristics were compared between the OLF(+) group, OLF was seen at any levels of the spinal canal, and the OLF(−) group, OLF was not seen.

Results

The most frequent level of OPLL was at C5 vertebral level and OLF was predominant at upper and lower thoracic levels. Seventeen patients (9.6%) had OPLL and OLF at the same spinal level. The averaged OPLL OS index of the total spine in these patients was 8.7 ± 6.1, ranged from 1 to 36. The averaged OLF OS index of the total spine was 3.1 ± 2.2 (ranged from 1 to 13) in the patients who had OLF at any levels of the whole spine. One hundred fifteen patients (64.6%) with cervical OPLL had OLF at any levels of the whole spine. No relationship was found between the OPLL OS index and the OLF OS index. There was no significant difference among the data between the OLF(+) group and the OLF(−) group.

Conclusions

This study demonstrated 64.6% of the patients with cervical OPLL had OLF, mainly in the thoracic spine. However, there was no relationship regarding the severity of the ossified lesions between OPLL and OLF. CT analysis of the whole spine should be carried out for the early detection of OPLL and OLF in patients with cervical OPLL.

Introduction

Ossified lesions in the spinal canal have a risk of spinal cord and nerve roots compression. Diseases, such as ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF), are in the category of ossified lesions in the spinal canal. OPLL and OLF are characterized by replacement of ligamentous tissue by ectopic new bone formation [1], [2], [3]. Although the background of both diseases might be similar, there are some differences between two diseases. OPLL mainly affects the cervical spine, and often results in cervical myelopathy [4]. In contrast, OLF is predominantly observed at the upper or lower third of the thoracic spine and may cause thoracic myelopathy due to narrowing of the spinal canal [5], [6]. The etiology of OPLL and OLF is still unknown. Some studies have found that genetic background is strongly related to OPLL [7]. Several candidate genes for cervical OPLL were identified to date [8], [9], [10]. But, no significant candidate genes were found for OLF. In the clinical practice, we sometimes encounter the cases who have OPLL in the cervical spine and OLF in the thoracic spine [11], [12], [13], [14]. Some cases have spinal cord compression by both OPLL and OLF at the same spinal level, especially in the thoracic spine. These cases were very difficult to treat. However, the precise lesions of OPLL and OLF are still unclear. Recently, we performed the study to evaluate the coexisting OPLL in patients with cervical OPLL using multi-detector CT of the whole spine [15]. The study demonstrated that more than half of the patients with cervical OPLL had coexistent OPLL in the thoracic and/or lumbar spine. Our study regarding OPLL lesions of the whole spine by CT can also be used for the detection of OLF in the spinal canal. This information should be very beneficial to consider the therapeutic strategy in patients with ossified lesions in the spinal canal. The purpose of this study was to evaluate OLF of the whole spine in patients with cervical OPLL and to analyze the relationship of the ossified lesions between OLF and OPLL.

Section snippets

Materials and methods

This study included 178 patients who were diagnosed as cervical OPLL by plain radiographs. All of the patients were treated in our university hospital. There were 108 men and 70 women, with an average age of 67.0 years old (range, 36–86 years). Informed consent was obtained from each patient before enrollment in the study, and the study was approved by the institutional review board of our university hospital. Regarding medical history, 79 patients had a history of cervical laminoplasty which

Inter-rater and intra-rater reliability and agreement

Averaged Fleiss' Kappa coefficient of inter-rater agreement of OLF was 0.61 ± 0.11 in three observers. The intra-rater reliability for the existence of OPLL was 94.6% (95% CI 94.4–94.8), 93.5% (95% CI 93.2–93.7) and 94.5% (95% CI 94.2–94.7), respectively.

Incidence of spinal level of OPLL and OLF

OPLL was seen both at vertebral and intervertebral levels (Fig. 1). The most frequent level of OPLL was at C5 vertebral level where 82% of the patients had OPLL. Subsequently, C4 and C6 vertebral level was frequent. At the thoracic and lumbar

Discussion

Our previous study revealed the precise ossified lesion of OPLL at the whole spine using CT images [15]. As for the evaluation for OPLL, the averaged Fleiss Kappa coefficient of inter-rater agreement was 0.83 ± 0.008. The intra-rater reliability for the existence of OPLL was 81.5% (95%confidence interval, 77.7–84.7), 98.1% (95% confidence interval, 96.5–99.0), and 92.7% (95% confidence interval, 90.0–94.7). The current study focused on OLF using the same CT images. Similarly to the previous

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgment

The work reported in this article was supported by grants from the Ministry of Health, Labour and Welfare of Japan: Committee for Study of Ossification of Spinal Ligament and Committee for Research and Development of Therapies for Ossification of Posterior Longitudinal Ligament.

The authors thank Mika Kigawa, for her effort in statistical analysis.

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Cited by (57)

Prevalence and distribution of ossification of the ligamenta flava in a 16th–18th century skeletal population sample from Poland
2023, International Journal of Paleopathology
This study aimed to determine the prevalence of the ossification of the ligamenta flava (OLF) among skeletal remains from Poland.
124 skeletons aged 25 years and older were analyzed. The presence and size of OLF were observed macroscopically. OLF was recorded at the cranial and caudal attachment sites of each vertebra. The following factors were analyzed: age at death, sex, and presence of other spondyloarthropathies.
The crude prevalence of OLF in the analyzed series was 68.55 %. OLF was located most frequently in the lower thoracic spine. A statistically significant relationship was observed between the presence of OLF and age at death. OLF coincided with degenerative spondyloarthropathies of the thoracolumbar spine.
The results of this study indicate that OLF was not a rare condition in past populations of European ancestry. Analysis of OLF prevalence in skeletal materials can contribute to reconstruction of the conditions and lifestyles of past people.
This study shed new light on the prevalence of OLF and provides information on the variability of OLF in past European populations. The evaluation of the prevalence of OLF represents an important contribution to the field of paleopathology in understanding disease changes in prehistoric and historic human populations.
The analyzed material came from unknown populations without demographic data. Sex and age at death were assessed using standard anthropological methods.
It is important to understand the influence of sociocultural factors and physical activity patterns on the development of OLF.
Piezo1 involves in intracellular osteogenic transformation signal to promote the ossification of ligamentum flavum
2023, Biochemical and Biophysical Research Communications
Ectopic osteogenesis refers to the occurrence of osteoblasts in soft tissues other than bone tissue and the formation of bone tissue. The ligamentum flavum is an essential connecting structure between adjacent vertebral lamina, which participates in the formation of the vertebral canal's posterior wall and maintains the vertebral body's stability. Ossification of the ligamentum flavum (OLF) is one of the manifestations of systemic ossification of the spinal ligaments and one of the degenerative diseases related to the spine. However, there is a lack of research on the expression and biological function of Piezo1 in ligamentum flavum. Whether Piezo1 participates in the development of OLF is still unclear. The FX-5000C cell or tissue pressure culture and real-time observation and analysis system was applied to stretch ligamentum flavum cells to detect the expression of mechanical stress channel and osteogenic markers after the effect of different stretching durations. The results showed elevated expression of mechanical stress channel Piezo1 and osteogenic markers with the effect of tensile time duration. In conclusion, Piezo1 involves in intracellular osteogenic transformation signal to promote the ossification of ligamentum flavum. An approved explanatory model and further research will be required in the future.
Radiologic risk factors associated with development of myelopathy in patients with ossification of the posterior longitudinal ligament of the cervical spine
2023, Clinical Neurology and Neurosurgery
Retrospective Cohort Study
Myelopathy following ossification of the posterior longitudinal ligament (OPLL) is one of the devastating clinical features in these patients, while we still know little about which factors are associated with development of myelopathy. We evaluated the difference of radiologic measurements between OPLL patients with or without myelopathy and searched for the clinical significance with emphasis on the impact of dynamic motion.
305 patients diagnosed of OPLL were enrolled for retrospective review. They were divided into two groups according to the coexistence of radiographic evidence of myelopathy. Demographic data as well as radiologic measures including the presence of disc degeneration (DD), anterior-posterior diameter (APD) of central canal, canal compromise (CC) ratio, global and segmental range of motion (gROM and sROM), OPLL type (morphologic classification) and K-line were collected.
APD (odds ratio (OR); 0.411), CC ratio (OR; 1.100) and sROM (OR; 1.371) were significantly associated with the presence of myelopathy in the multivariate analysis. While the statistically significant factors were same in OPLLs with CC larger than 50%, presence of DD (OR; 4.509) and sROM (OR; 1.295) were significantly associated with myelopathy but not the CC itself in OPLLs with CC smaller than 50%.
We discovered that the APD, CC ratio and sROM had significant association with development of myelopathy in OPLLs. And the presence of dynamic factors had significant association with myelopathy in OPLLs with smaller CC ratios. This observation and its clinical significance on development of myelopathy might enhance our understanding of OPLL.
Classification, epidemiology, and genetics of degenerative cervical myelopathy
2023, Degenerative Cervical Myelopathy: from Basic Science to Clinical Practice
Degenerative cervical myelopathy (DCM) represents a group of age-related degenerative disorders of the cervical spine that result in a form of chronic spinal cord injury (SCI), presenting with a diverse natural history, and in general, a better prognosis than acute forms of SCI. Classically, this condition was mostly referred to cervical spondylotic myelopathy, but the recognition this term lacked precision and that OPLL and degenerative herniated disk disease, for example, were inconsistently included resulted in the reidentification of the term under DCM in 2015. There has been significant progress in detailing the epidemiological parameters and investigations of genetic factors that can be associated with the spectrum of pathology. This chapter explores this new classification and discusses the epidemiology and genetic factors under this new perspective.
Incidence of ossification of the spinal ligaments in acromegaly patients
2022, Bone Reports
Some previous case reports have implied a relationship between acromegaly and ossification of the spinal ligaments. However, there have been no reports of a case series exploring the incidence of ossification of the spinal ligaments in patients with acromegaly. To this end, computed tomography (CT) of the spine in 10 consecutive patients with acromegaly was examined in this study. Five out of 10 patients had ossification of the spinal ligaments. Among them, two patients had ossification of the posterior longitudinal ligament (OPLL), which was noticeably higher than the prevalence of OPLL in the general adult population (1.9–4.3 %). Body mass index was significantly higher in the group with spinal ligament ossification (p = 0.03), but there were no significant differences in age, sex, serum phosphate, albumin-adjusted calcium, growth hormone (GH), standard deviation of insulin-like growth factor-1 (IGF-1), or the incidence of diabetes mellitus between the groups with or without ossification of the spinal ligaments. The ossification index (OS index) was used to determine the severity of spinal ligament ossification, and there were no significant correlations between the OS index and GH or IGF-1 (p = 0.51 and 0.75, respectively). This study was the first to report a high prevalence of spinal ossification in patients with acromegaly. In conclusion, this study suggested a possible association between acromegaly and ossification of the spinal ligaments, although the number of patients was insufficient to draw a conclusion. Acromegaly patients should be tested to confirm, or rule out, spinal ossification, and further studies to clarify the underlying mechanism of spinal ossification in acromegaly patients are warranted.
Coexistence of flavum ligament ossification with diffuse idiopathic skeletal hyperostosis in the cervical spine: Review of literature and technical note starting from a rare case
2022, Neurochirurgie
Citation Excerpt :
This major finding coexists with calcified cartilage areas and already ossified zones of lamellar or trabecular bone with or without continuity with laminae [6,8,16] (Fig. 5). At other hand, calcification is characterized by foci of calcium hydroxyapatite depositions into already degenerated ligament, with no mature bone forming within the ligament itself [3,6,8,16]. Ossification of ligamentum flavum is an uncommon condition at all spinal level in Caucasians [3,17].
Cervical flavum ligament ossification (C-OLF) is very rare source of myeloradiculopathy. Less than 100 cases have been reported in modern English literature up to 2020. Association between C-OLF and Diffuse Idiopathic Skeletal Hyperostosis (DISH) at cervical level has never been described.
In this article we performed a systematic review about epidemiology, physiopathology, clinical and surgical management of C-OLF. Moreover, we research its possible association with other cervical spine ligament ossification and in particular with anterior longitudinal ligament ossification. We report a case of 73 years-old woman experiencing mild cervical myeloradiculopathy caused by C6-C7 C-OLF compression and coexistence of DISH at cervico-thoracic level. A brief technical note about intraoperative management of C-OLF has also been described.
Our research found 81 previous reported case of C-OLF. The coexistence of Posterior longitudinal ligament ossification has been reported in 21.3% of C-OLF case. Conversely, we reported the first case describing the association between DISH and C-OLF. Posterior surgical decompression is the only useful treatment providing good long-term functional outcome. Instrumentation should be tailored according to pre-operative findings.
C-OLF is a rare source of myeloradiculopathy and it may coexists with DISH probably due to alteration in the cervical mechanical stress and tendency of bone formation in patients harboring coexistent ligament ossifications. According to our result, skip en-bloc microsurgical laminectomy is safe and less invasive method to avoid complication and to provide optimal cervical spinal cord and nerve decompression avoiding CSF-leak.

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Original articleCharacteristics of ossification of the spinal ligament; incidence of ossification of the ligamentum flavum in patients with cervical ossification of the posterior longitudinal ligament – Analysis of the whole spine using multidetector CT

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Inter-rater and intra-rater reliability and agreement

Incidence of spinal level of OPLL and OLF

Discussion

Conflict of interest

Acknowledgment

Spine J

J Clin Neurosci

On an autopsied case of compression myelopathy with a callus formation in the cervical spinal canal

Nihon Geka Hokan

Review of histopathological studies on OPLL of the cervical spine, with insights into the mechanism

Pathology of ossification of the ligamentum flavum

78. Ossification of the posterior longitudinal ligaments. Prevalence, presentation and natural history

Thoracic myelopathy caused by ossification of the ligamentum flavum: clinical features and surgical results in the Japanese population

J Neurosurg Spine

Overview of epidemiology and genetics

A genome-wide sib-pair linkage analysis of ossification of the posterior longitudinal ligament of the spine

J Bone Miner Metab

Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament

PLoS One

A genome-wide association study identifies susceptibility loci for ossification of the posterior longitudinal ligament of the spine

Nat Genet

Original article
Characteristics of ossification of the spinal ligament; incidence of ossification of the ligamentum flavum in patients with cervical ossification of the posterior longitudinal ligament – Analysis of the whole spine using multidetector CT