Clinical characteristics of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament

Endo, Tsutomu; Takahata, Masahiko; Koike, Yoshinao; Iwasaki, Norimasa

doi:10.1007/s00774-019-01026-8

Cited by 31 publications

(45 citation statements)

References 11 publications

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“…18 In comparison with thoracic OLF combined with OPLL, the proportion of severe obesity in multilevel thoracic OLF was significantly lower; however, we succeeded in characterizing that OLF with a high severity of ossification also contains a high proportion of obesity. An association between obesity and OPLL has been established, 15,16,21,22 but the association between obesity and OLF has not been reported. Such a high prevalence of severe obesity in patients with thoracic OLF has not been recognized may be because most patients with thoracic OLF have co-existing cervical or thoracic OPLL and these patients have not been classified as either OPLL or OLF.…”

Section: Discussionmentioning

confidence: 99%

Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity

Endo

Koike

Hisada

et al. 2021

Global Spine Journal

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Study Design: Retrospective cross-sectional study. Objectives: There is insufficient data on the clinical features of ossification of the ligamentum flavum (OLF) of the thoracic spine and the risk of progression of ossified lesions. The link between obesity and ossification of the posterior longitudinal ligament (OPLL), which frequently coexists with OLF, has been demonstrated. However, the link between obesity and OLF has not been recognized. We aimed to determine the prevalence of obesity in thoracic OLF and whether the severity of OLF is associated with the degree of obesity. Methods: A total of 204 symptomatic Japanese subjects with thoracic OLF and 136 subjects without spinal ligament ossification as controls were included. OLF subjects were divided into 3 groups: 1) localized OLF (OLF <2-intervertebral regions); 2) multilevel OLF (OLF ≥3-intervertebral regions); and 3) OLF + OPLL. The severity of OLF was quantified using the OLF index using computed tomography imaging of the entire spine. Results: The proportion of severely obese subjects (BMI ≥ 30 kg/m2) was significantly higher both in the multilevel OLF group (25.5%) and the OLF + OPLL group (44.3%) than in the localized OLF group (3.6%) and the control group (1.4%) ( P < 0.01). BMI, age, and coexistence of cervical OPLL and lumbar OLF were associated with thoracic OLF index in the multiple regression analysis. Conclusions: Our findings demonstrated that obesity is a distinct feature of multilevel OLF in the thoracic spine and that the severity of OLF is associated with the degree of obesity.

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Section: Discussionmentioning

confidence: 99%

Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity

Endo

Koike

Hisada

et al. 2021

Global Spine Journal

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“…As a multifactorial disease, obesity has been considered as an important risk factor associated with the pathogenesis of OLF. 10,17 However, obesity-mediated genetic mechanism underlying the progression of OLF has not been fully understood. In this study, GSE106253 was selected as expression pro ling by high-throughput sequencing dataset in our analysis.…”

Section: Discussionmentioning

confidence: 99%

Deciphering Expression Profiling and Functional Signatures of Individualized Obesity-Associated Genes in Ossification of Ligamentum Flavum Through RNA-Sequence Data Mining

Zhang

Yuan

Chen

et al. 2021

Preprint

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Background: Obese individuals predispose to ossification of ligamentum flavum (OLF), whereas the underlying connections between obesity phenotype and OLF pathomechanism are not fully understood, especially during early life. This study aimed to explore obesity-associated genes and their functional signatures in OLF. Methods: Gene microarray expression data related to OLF were downloaded from the GSE106253 dataset in the Gene Expression Omnibus (GEO) database. The potential obesity-related differentially expressed genes (ORDEGs) in OLF were screened. Then, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for these genes. Furthermore, protein-protein interactions (PPI) were used to identify hub ORDEGs, and Metascape was used to further verify the key signaling pathways and immune-related function signatures of hub ORDEGs. Finally, correlation analysis of hub ORDEGs and identified OLF-related infiltrating immune cells (OIICs) was constructed to understand the possible mechanical link among obesity, immune response and OLF. Results: OLF-related differentially expressed genes and 2051 obesity-related genes from four databases were intersected to obtain 99 ORDEGs, including 54 upregulated and 55 downregulated genes. GO and KEGG analysis revealed that these genes were mainly involved in metabolism, inflammation and immune-related biological functions and pathways. A PPI network was established to determine 14 hub genes (AKT1, CCL2, CCL5, CXCL2, ICAM1, IL10, MYC, PTGS2, SAA1, SOCS1, SOCS3, STAT3, TNFRSF1B and VEGFA). The co-expression network demonstrated that this module was associated with cellular response to biotic stimulus, regulation of inflammatory response, regulation of tyrosine phosphorylation of STAT protein. Furthermore, Metascape functional annotations showed that hub genes were mainly involved in receptor signaling pathway via JAK-STAT, response to TNF and regulation of defense response, and their representative enriched pathways were TNF, adipocytokine and JAK-STAT signaling pathways. Subgroup analysis indicated that T cell activation might be potential immune function processes involved, and correlation analysis revealed that cDCs, memory B-cells and preadipocytes were highly correlated infiltrating immune cells. Conclusions: Our study deciphered individualized obesity-associated gene signature for the first time, which may facilitate exploring the underlying cellular and molecular pathogenesis and novel therapeutic targets of obesity-related early-onset OLF.

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“…[9][10][11] Recent epidemiological studies have reported that obesity is a common aggravating factor in patients with diffuse types of OPLL and OLF, in which the entire spinal ligament tends to ossify. [10][11][12][13][14][15] This suggests that lifestyle-related diseases and visceral obesity may be involved in the development and progression of these conditions. [11][12][13] Dyslipidemia is caused by malnutrition, obesity, sarcopenic obesity, and genetic predisposition and is closely related to metabolic disturbances.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13][14][15] This suggests that lifestyle-related diseases and visceral obesity may be involved in the development and progression of these conditions. [11][12][13] Dyslipidemia is caused by malnutrition, obesity, sarcopenic obesity, and genetic predisposition and is closely related to metabolic disturbances. [16][17][18] If dyslipidemia is left untreated, atherosclerosis will develop.…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22] In recent years, the association of OPLL/OLF with obesity, malnutrition, genetic factors, and metabolic dysfunction-associated fatty liver disease (MAFLD) has become clear. [10][11][12][13][14][15][23][24][25][26] This suggests that metabolic disturbances related to spinal ligament ossi cation could affect systemic bone metabolism and trigger ectopic ossi cation. Despite the common features of dyslipidemia and spinal ligament ossi cation, no study has investigated their relationship in detail.…”

Section: Introductionmentioning

confidence: 99%

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Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments

Endo

Takahata

Fujita

et al. 2022

Preprint

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Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL(+), n = 215; DL(−), n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6–2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(−) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF.

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Clinical characteristics of patients with thoracic myelopathy caused by ossification of the posterior longitudinal ligament

Cited by 31 publications

References 11 publications

Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity

Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity

Deciphering Expression Profiling and Functional Signatures of Individualized Obesity-Associated Genes in Ossification of Ligamentum Flavum Through RNA-Sequence Data Mining

Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments

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