ArticleLiterature Review

Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs

August 2010
Medical Hypotheses 75(2):169-71

DOI:10.1016/j.mehy.2010.02.012

Source
PubMed

Authors:

The intravertebral vacuum phenomenon (VP) is usually associated with degenerative disc disease, which could be related to the low back pain. Various theories related to the pathogenesis of VP have been proposed, but these theories have not been critically examined and remain hypothetical. In this article, we review the possible role of endplate degeneration in the pathogenesis of VP, and discuss several pathways possibly linked to them. Due to the endplate calcification and activated cytokines, the transport pathway of the nutrition for the intervertebral disc was blocked, resulting in the metabolic unbalance and decrease of the synthesis of matrix structural proteins. It could promote the matrix decomposition, causing the decrease of the quantity of matrix and the changes of stress distribution in intervertebral disc. As a result, the structure of intervertebral discs became increasingly unstable. While compression happened, the intravertebral cleft could occur and be gradually filled with gas, which may cause low back pain and aggravate the intervertebral discs degeneration. As outlined above, we hypothesize that endplate degeneration might be the origination of the vacuum phenomenon.

Intradiscal vacuum phenomenon and spinal degeneration: a cross-sectional analysis of 219 subjects

Article

Oct 2021
CURR MED RES OPIN

Introduction: Intradiscal vacuum phenomenon (IVP) is the collection of gas within the intervertebral discs. It has been reported with various spinal disorders. The exact role of IVP in spinal degeneration leading to low back pain (LBP) is unclear. We aimed to obtain the prevalence of IVP in patients with LBP. Our second aim was to understand whether IVP was associated with intervertebral disc degeneration (IVDD), Modic changes, and subchondral sclerosis (SS). Methods: A total of 12.450 consecutive patients with chronic LBP were evaluated in terms of having abdominal computed tomography (CT) scan concomitant with lumbar spine magnetic resonance imaging (MRI) using radiological database of three spine centers. We excluded the patients with a history of malignancy, metabolic disease, spinal infection, traumatic or osteoporotic spine fracture, and spine surgery. All lumbar levels were evaluated in terms of IVDD and Modic changes on MRI, while they were evaluated in terms of IVP and SS on CT scans. Results: We included 219 patients. Severe IVDD, Modic changes, IVP, and SS were seen in 53.9% (n: 118), 38.8% (n: 85), 26.5% (n: 58), and 16% (n: 35) of the patients, respectively. Intradiscal vacuum phenomenon was closely associated with severe IVDD (OR: 8.204), Modic changes (OR: 3.547) and SS (OR: 4.231). Discussion: Intradiscal vacuum phenomenon was closely associated with severe IVDD, Modic changes, and SS. Further prospective clinical and laboratory studies are necessary to better delineate the pathogenesis of IVP.

SYMPTOMATIC INTRADISCAL VACUUM PHENOMENON

Article

Full-text available

Dec 2019

Objective: Intradiscal vacuum phenomenon (IVP) is a common finding in the study of degenerative disc disease. Discogenic low back pain can be manifested in different ways, including irradiation to the lower limbs. This study aims to acknowledge the complementary studies used to diagnose IVP, determine their sensitivity, and assess the correlation between clinical and imaging findings. Methods: This is a descriptive, observational and prospective study involving clinical and imaging evaluation of 100 patients with IVP, using dynamic and plain radiographs, computed tomography and magnetic resonance imaging. The factors of analysis include sex, age, reason for consultation, visual analogue scale, irradiation and topography of the pain, the existence of sciatica and claudication, smoking status, and body mass index. Results: The overall average age of the patients was 64.6 years, who particularly evidence degenerative pathology. IVP was observed in 99 CT, 85 dynamic radiographs, 80 plain radiographs and 65 nuclear magnetic resonance images (MRI). Conclusion: The most useful studies for diagnosing the vacuum disc phenomenon are plain and dynamic radiographs, tomography, and magnetic resonance. The CT is the most sensitive imaging study for IVP detection, followed by dynamic radiographs obtained during extension. A correlation was observed between older age, overweight, and IVP. Level of evidence IV; Case-series.

Correlation between sagittal morphology of lower lumbar end plate and degenerative changes in patients with lumbar disc herniation

Article

Sep 2024
J Craniovertebr Junction Spine

Objective As an important anatomic factor in the process of lumbar disc herniation (LDH), the correlation between end plate sagittal morphology and intervertebral disc degeneration (IDD) is unclear. Moreover, research on imaging data of lumbar end plate in patients with LDH is still insufficient. Our study aimed to observe the morphological change of the lower lumbar end plate (L3-S1) in patients with LDH on magnetic resonance imaging (MRI) and analyze its correlation with the degree of IDD. Materials and Methods A total of 116 patients were included in the study. Based on their MRI, we divided end plates into three types (concave, flat, and irregular), assigned intervertebral discs with Grade I–V given 1–5 points successively according to the Pfirrmann system, and determined whether there was Modic change of each end plate. The correlation between the morphology of the end plate and the degree of IDD was analyzed. Results There was an excellent interobserver agreement for each item we analyzed (interclass correlation coefficient >0.75). Concave end plate appeared most frequently (187, 53.7%) and was mainly distributed in L3/4 and L4/5, whereas irregular end plate was the least common type (54, 15.5%) and mainly concentrated in L5/S1. The IDD degree of the corresponding disc increased gradually from concave (3.27 ± 0.81) to irregular end plates (4.25 ± 0.79) (P < 0.05). Irregular end plates were more likely to have Modic changes than concave and flat end plates (P < 0.05). Conclusion The sagittal morphology of the lower lumbar end plate is related to modic changes and degree of IDD (based on the Pfirrmann grading system) in patients with LDH, and the concave end plate mostly reflects a lower degree of lumbar disc degeneration, which has substantial clinical significance.

Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy

Article

Full-text available

Jan 2021
STEM CELLS

Degeneration of the cartilage endplate (CEP) induces intervertebral disc degeneration (IVDD). Nucleus pulposus cell (NPC) apoptosis is also an important exacerbating factor in IVDD, but the cascade mechanism in IVDD is not clear. We investigated the apoptosis of NPCs and IVDD when stimulated by normal cartilage endplate stem cell (CESC)-derived exosomes (N-Exos) and degenerated CESC-derived exosomes (D-Exos) in vitro and in vivo. Tert-butyl hydroperoxide (TBHP) was used to induce inflammation of CESCs. The bioinformatics differences between N-Exos and D-Exos were analyzed using mass spectrometry, heat map, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. NPC apoptosis was examined using TUNEL staining. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, Western blotting, and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in rats with IVDD. TBHP effectively induced inflammation and the degeneration of CEP in rat. N-Exos were more conducive to autophagy activation than D-Exos. The apoptotic rate of NPCs decreased obviously after treatment with N-Exos compared to D-Exos. N-Exos inhibited NPCs apoptosis and attenuated IVDD in rat via activation of the AKT and autophagy pathways. These results are the first findings to confirm that CEP delayed the progression of IVDD via exosomes. The therapeutic effects of N-Exos on NPC apoptosis inhibition and the slowing of IVDD progression were more effective than D-Exos due to activation of the PI3K/AKT/autophagy pathway, which explained the increase in the incidence of IVDD after inflammation of the CEP.

Correlation between Sagittal Morphology of Lower Lumbar Endplate and Degenerative Changes in Patients with Lumbar Disc Herniation

Preprint

Full-text available

Aug 2020

Background: As an important anatomic factor in the process of Lumbar disc herniation (LDH), the correlation between endplate sagittal morphology and intervertebral disc degeneration (IDD) is unclear. and research on imaging data of lumbar endplate in patients with LDH is still insufficient. Our study aimed to observe the morphological change of the lower lumbar endplate (L3-S1) in patients with LDH on magnetic resonance imaging (MRI), and analyze its correlation with the degree of IDD. Methods/Design: All 116 patients were included. Based on their MRI, we divided endplates into three types (concave, flat and irregular), assigned intervertebral discs with Grade I-V given 1-5 points successively according to Pfirrmann system, and determined whether there was Modic change of each endplate. The correlation between the morphology of endplate and the degree of IDD was analyzed. Results: There were excellent inter-observer agreement for each item we analyzed (ICC > 0.75). Concave endplate appeared most frequently (187, 53.7%) and mainly distributed in L3/4 and L4/5, while irregular endplate was the least common type (54, 15.5%) and mainly concentrated in L5/S1. The IDD degree of corresponding disc increased gradually from concave (3.27 ± 0.81) to irregular endplates (4.25 ± 0.79) (P < 0.05). Irregular endplates were more likely to have Modic changes than concave and flat endplates (P < 0.05). Conclusion: The sagittal morphology of lower lumbar endplate is related to Modic changes and degree of IDD (based on Pfirrmann grading system) in patients with LDH, and the concave endplate mostly reflects a lower degree of lumbar disc degeneration, which has substantial clinical significance.

Exosomes from normal cartilage endplate stem cells ameliorate intervertebral disc degeneration more effectively than exosomes from degenerated cartilage endplate stem cell by activating the AKT/autophagy pathway

Preprint

Full-text available

Jun 2020

Background Nucleus pulposus cells (NPCs) apoptosis is an important factor in exacerbating intervertebral disc degeneration (IVDD) that can be effectively suppressed by exosomes. The aim of this study was to reaearch whether normal cartilage endplate stem cells (CESCs) derived exosomes (N-Exos) were more conducive to activation of autophagy and inhibition of NPCs apoptosis and IVDD than degenerated CESCs derived exosomes (D-Exos) or not. Methods Rat CESCs were isolated and identified, and the exosomes produced by normal CESCs and degenerated CESCs were extracted. The bioinformatics differences between normal CESCs derived exosomes (N-Exos) and degenerated CESCs derived exosome (D-Exos) were analyzed by mass spectrometry, heat map and KEGG enrichment analysis biology. The effects of N-Exos and D-Exos on the inhibition of NPCs apoptosis were examined by TUNEL staining, flow cytometry and western blotting. The involvement of the AKT and autophagy signaling pathways was investigated using the signaling inhibitor LY294002. Magnetic resonance imaging, western blotting and immunofluorescence staining were used to evaluate the therapeutic effects of N-Exos in vivo. Results CESCs in the cartilage endplate (CEP) could secrete a large amount of exosomes. N-Exos were more conducive to activation of autophagy than D-Exos. The apoptotic rate of NPCs was decreased obviously after treatment with N-Exos than after D-Exos treatment. N-Exos inhibited NPCs apoptosis or attenuated IVDD in a rat tail model by activating the AKT and autophagy signaling pathways. Conclusions It was the first to confirm that CEP could delay the progression of IVDD through exosomes secreted by normal CESCs. The therapeutic effects of N-Exos on inhibiting NPCs apoptosis and slowing IVDD progression was more effective than D-Exos by activating the PI3K/AKT/autophagy pathway, which explained the reason that the incidence of IVDD was increased after inflammation of the CEP.

Death by hanging: a retrospective case-control investigation of the intervertebral disc vacuum phenomenon on PMCT

Article

Full-text available

Dec 2018
Forensic Sci Med Pathol

During hanging gravitational forces affect the spine. Intervertebral vacuum phenomenon (VP) implies that gas accumulations in the discs are caused by degeneration of the spine and trauma. It was hypothesized that VP detected on postmortem computed tomography (PMCT) has a higher incidence in hanging deaths, which can be correlated to age, degenerative spinal changes and type of hanging (complete-incomplete). Secondly, it was investigated whether the presence of Simon’s bleedings is related to hanging type and VP on PMCT. A retrospective hanging case-control study of 72 cases was conducted. PMCT data were evaluated by two observers for the presence of VP and its localization within the thoracic and lumbar discs, and for any degenerative changes of the spine. Autopsy protocols were assessed for the presence of Simon’s bleedings during autopsy. VP did not statistically differ among hanging and control cases but it was statistically correlated to complete hanging, increasing age and degenerative spinal changes. Centrally located VP within the discs was correlated to hanging, especially complete hanging, and younger ages, contrary to control cases that showed gas at the disc periphery. Simon’s bleedings were correlated with complete hanging and centrally located VP. Centrally located VP within the discs increases the probability for complete hanging, while increasing age and degenerative changes reduce this probability. Intervertebral VP is multifactorial radiological entity. The presence of centrally located VP can indicate that hanging could be considered as an alternative mechanism of death and that great forces and loads may have affected the spine perimortem, especially with decreasing age and when Simon’s bleedings are present.

The pathogenesis and targeted therapies of intervertebral disc degeneration induced by cartilage endplate inflammation

Article

Full-text available

Dec 2024

Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, where degeneration and death of nucleus pulposus cells within the intervertebral disc (IVD) can be obviously revealed. This degeneration can result in an imbalance in the extracellular matrix due to the loss of proteoglycans and water content, which can further lead to catabolic and anabolic dysfunction of the IVD. Recently, the dysfunction of cartilage endplate (CEP) during aging has drawn large attention due to its essential functions in contributing nutrient exchange and maintaining IVD homeostasis. Furthermore, the inflammation and disturbed homeostasis of CEP not only accelerate the degradation of nucleus pulposus extracellular matrix, but also exacerbate IVDD by causing nucleus pulposus cell death through other pathological factors. Here in this review, we summarized the possible pathological factors and the underlying mechanisms of the CEP inflammation-induced IVDD, including exosomes degeneration, CEP calcification, ferroptosis, mechanical changes, and cell senescence. Besides, changes of miRNAs, pain-related neural reflex arc and pathways associated with CEP inflammation-induced IVDD are also reviewed. In addition, new strategies specifically designed for CEP inflammation-induced IVDD are also discussed in the last section. We hope this paper can not only offer some new insights for advancing novel strategies for treating IVDD, but also serve as a valuable reference for researchers in this field.

HIF-2α/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration

Article

Full-text available

May 2024

Backgroud Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, the mechanisms responsible for iron ion accumulation in tissues and the mechanism that regulate iron homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as the primary cellular iron gate, playing a pivotal role in controlling intracellular iron levels, however its involvement in IDD pathogenesis and the underlying mechanism remains obscure. Methods Firstly, IDD mice model was established to determine the iron metabolism associated proteins changes during IDD progression. Then CEP chondrocytes were isolated and treated with TBHP or pro-inflammatory cytokines to mimic pathological environment, western blotting, immunofluorescence assay and tissue staining were employed to explore the underlying mechanisms. Lastly, TfR1 siRNA and Feristatin II were employed and the degeneration of IDD was examined using micro-CT and immunohistochemical analysis. Results We found that the IDD pathological environment, characterized by oxidative stress and pro-inflammatory cytokines, could enhance iron influx by upregulating TFR1 expression in a HIF-2α dependent manner. Excessive iron accumulation not only induces chondrocytes ferroptosis and exacerbates oxidative stress, but also triggers the innate immune response mediated by c-GAS/STING, by promoting mitochondrial damage and the release of mtDNA. The inhibition of STING through siRNA or the reduction of mtDNA replication using ethidium bromide alleviated the degeneration of CEP chondrocytes induced by iron overload. Conclusion Our study systemically explored the role of TFR1 mediated iron homeostasis in IDD and its underlying mechanisms, implying that targeting TFR1 to maintain balanced iron homeostasis could offer a promising therapeutic approach for IDD management. The translational potential of this article Our study demonstrated the close link between iron metabolism dysfunction and IDD, indicated that targeting TfR1 may be a novel therapeutic strategy for IDD.

Nrf2 protects against cartilage endplate degeneration through inhibiting NCOA4‑mediated ferritinophagy

Article

Full-text available

Dec 2023

Iron overload and ferroptosis are associated with intervertebral disc degeneration (IDD); however, the mechanism underlying the regulation of iron homeostasis remains to be elucidated. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been reported to regulate cellular iron homeostasis; however, its impact on IDD pathology and the underlying mechanism of action requires further investigation. In the present study, immunohistochemistry analysis of Nrf2 expression in the cartilage endplate (CEP) was conducted and it was demonstrated that Nrf2 expression was increased in the CEP at the early stages of the development of IDD, whereas it was decreased at the late stages of the development of IDD. The results of western blot analysis indicated that the inadequate activation of Nrf2 may aggravate mitochondrial dysfunction and oxidative stress, thus promoting CEP chondrocyte degeneration and calcification. It was also revealed that Nrf2 was involved in TNF-α-induced CEP chondrocyte iron metabolism dysfunction and ferroptosis. Inhibition of Nrf2 expression using Nrf2 small interfering RNA could enhance the process of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and increase ferrous ion content, which may promote CEP chondrocyte ferroptotic cell death and extracellular matrix degradation. Furthermore, a decrease in cellular iron concentration may inhibit CEP chondrocyte ferroptosis, and CEP degeneration and calcification. The present study highlights the role of the Nrf2/NCOA4 axis in chondrocyte ferroptosis and IDD pathogenesis, thus suggesting that activation of Nrf2 may be a promising strategy for IDD treatment.

Cartilage Endplate-Derived Stem Cells for Regeneration of Intervertebral Disc Degeneration: An Analytic Study

Article

Full-text available

Dec 2023

Purpose Intervertebral disc degeneration (IDD) is considered the predominant cause of low back pain (LBP) and accounts for global disability and a substantial socioeconomic burden. Given the unsatisfactory outcomes of current treatment strategies, cartilage endplate-derived stem cells (CESCs) are increasingly used in intervertebral disc regeneration. However, comprehensive analyses on CESCs remain rare. Herein, we examined the biological functions and applications of CESCs in IDD. Methods PubMed, Embase, and Cochrane Library databases were searched to identify studies focused on CESCs. Relevant information from included studies was extracted. Descriptive statistics were performed. Correlation analysis was conducted to determine the relationship among Web of Science (WoS) citations, Dimensions, and Altmetric Attention Score (AAS). Results Twenty-six studies were included in this study. Most studies (n=20) isolated CESCs from humans, followed by rats (n=5) and rabbits (n=1). Twenty studies were performed in vitro, and the remaining six were implemented both in vivo and in vitro. The findings of this study provide insight into the biological properties of CESCs and clarify their potential application for intervertebral disc regeneration. There was a very high correlation between WoS and Dimensions citation count (p<0.001, r=0.988). Conclusion This study, for the first time, elaborates biological features of CESCs and analyzes their potential applications in regenerating intervertebral discs. CESCs may be promising candidates for protecting the intervertebral disc from degeneration and contributing to intervertebral disc regeneration.

Association between the upper instrumented vertebra screw angles and proximal junctional complications in patients with de novo degenerative lumbar scoliosis

Article

Oct 2023

OBJECTIVE The aim of this study was to investigate the impact of upper instrumented vertebra (UIV) screw angles on proximal junctional complications in patients with de novo degenerative lumbar scoliosis (DNDLS). METHODS A total of 120 patients with DNDLS who underwent posterior long-segment instrumentation and fusion were included. Patients were divided into a proximal junctional kyphosis/failure (PJK/PJF) group and a non-PJK/PJF group. Radiographic parameters were measured, including UIV screw angle, UIV slope, UIV screw slope, fixed segmental angle (FSA), and spinopelvic parameters. Clinical and radiographic data were compared between the two groups. Multivariate logistic regression was used to analyze the independent risk factors of PJK/PJF. Receiver operating characteristic (ROC) curve analysis was used to determine the threshold value to predict PJK/PJF. RESULTS Thirty-six patients (30.0%) developed PJK or PJF during follow-up. Patients in the PJK/PJF group had a larger postoperative UIV screw angle, a larger postoperative UIV screw slope, and a larger postoperative PJA. A significant increase was observed in UIV screw angle from immediately postoperative assessment to the final follow-up in two groups (p < 0.001). Multivariate logistic analysis indicated that a larger positive postoperative UIV screw angle was an independent risk factor for PJK/PJF (OR 1.546, 95% CI 1.274–1.877). ROC curve analysis indicated that a UIV screw angle ≥ 1° is more likely to develop PJK/PJF. Compared with group A patients (UIV screw angle < 1°), group B patients (UIV screw angle ≥ 1°) had a higher incidence of PJK, PJF, UIV screw loosening, and worse functional scores at the final follow-up. CONCLUSIONS Avoiding insertion of cranially directed UIV pedicle screws may help prevent the development of PJK and PJF in patients with DNDLS.

Factors Associated with Intradiscal Vacuum Phenomenon after Traumatic Thoracolumbar Fracture

Article

Full-text available

Sep 2023

Introduction Posttraumatic kyphosis of the thoracolumbar spine is a possible cause of deterioration of activities of daily living. Thus, postoperative kyphosis is an important issue in treating traumatic thoracolumbar fractures. The intradiscal vacuum phenomenon (IVP) after a traumatic thoracolumbar fracture is considered an important predictor of severe kyphosis after implant removal. However, the associated factors are not yet clear. Methods The study included data from 94 intervertebral discs on the cephalocaudal side of 47 fractured vertebrae of 45 patients for traumatic thoracolumbar fracture due to high-energy trauma. We assessed the demographics of patients (age, sex, cause of injury, location of injured vertebra, fracture type, cephalocaudal side), imaging finding (kyphosis angle of fractured vertebra at the injury, endplate fracture on computed tomography [CT], intervertebral injury on magnetic resonance image [MRI]), and IVP on CT conducted more than 6 months after surgery. We divided the intervertebral discs into an IVP group and a non-IVP group. To identify factors associated with an IVP, univariate analysis and multivariate logistic regression analysis were conducted. Results IVP was observed in 27 (29%) of 94 intervertebral discs on CTs conducted at an average of 14.0 months postoperatively. In univariate analysis, the IVP group (n = 27) had a significantly more cephalic side of the injured vertebra, endplate fracture on CT, and disc injury on MRI compared with the non-IVP group (n = 67). A multivariate logistic regression analysis was conducted to identify factors associated with IVP. The cephalic side (odds ratio [OR] = 4.183, 95% confidence interval [CI] = 1.269–13.785) and endplate fracture on CT (OR = 9.564, 95% CI = 1.940–47.143) were identified as independent factors associated with IVP. Conclusions IVP was observed in 27 (29%) of 94 intervertebral discs. The cephalic side and endplate fracture on CT were identified as independent factors associated with IVP.

Association between Modic changes and intervertebral vacuum phenomenon severity in patients undergoing percutaneous cement discoplasty

Article

Aug 2023
ACTA RADIOL

Background: Modic changes and intervertebral vacuum phenomenon (IVP) are considered spinal degenerative changes. The correlation between Modic and IVP has not been analyzed in the literature. Purpose: To analyze the correlation between IVP severity, Modic changes, and subchondral sclerosis across the lumbar spine in patients with lumbar degeneration. Material and methods: This is a retrospective study analyzing patients who underwent percutaneous cement discoplasty at a single institution between 2015 and 2020. Preoperative magnetic resonance imaging and computed tomography scans were analyzed to make the measurements. Modic type and grade as well as severity of IVP were preoperatively measured. The association between Modic type, grade, subchondral sclerosis, and the presence of IVP was analyzed. Results: In total, 110 patients (mean age = 77.03 ± 7.1 years) were finally included in the study. Per level correlation analysis showed a significant positive association between IVP and Modic type, IVP and Modic grade, and IVP and subchondral sclerosis. Moreover, subchondral sclerosis was significantly associated with Modic type and grade. Conclusion: Our study showed a significant positive correlation among Modic changes, IVP, and subchondral sclerosis throughout the lumbar spine. Our findings support the theory that endplate degeneration parameters are associated with the presence and severity of IVP.

PTEN inhibitor VO-OHpic protects endplate chondrocytes against apoptosis and calcification via activating Nrf-2 signaling pathway

Article

Full-text available

Mar 2023

Cartilage endplate (CEP) degeneration and calcification is an important contributor to the onset and pathogenesis of intervertebral disc degeneration (IDD). However, the underlying mechanisms of CEP degeneration remain elusive, let alone according treatment strategies to prevent CEP degeneration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that promotes cell apoptosis, and recent studies indicated that PTEN is overexpressed in degenerated intervertebral disc. However, whether direct inhibition of PTEN attenuates CEP degeneration and IDD development remains largely unknown. In the present study, our in vivo experiments demonstrated that VO-OHpic could attenuate IDD progression and CEP calcification. We also found that VO-OHpic inhibited oxidative stress induced chondrocytes apoptosis and degeneration by activating Nrf-2/HO-1 pathway, thus promoted parkin mediated mitophagy process and inhibited chondrocytes ferroptosis, alleviated redox imbalance and eventually improved cell survival. Nrf-2 siRNA transfection significantly reversed the protective effect of VO-OHpic on endplate chondrocytes. In conclusion, our study demonstrated that inhibition of PTEN with VO-OHpic attenuates CEP calcification and IDD progression. Moreover, VO-OHpic protects endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 mediated mitophagy process and ferroptosis inhibition. Our results suggest that VO-OHpic may be a potential effective medicine for IDD prevention and treatment.

Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension

Article

Full-text available

Mar 2023
J Orthop Surg Res

Background This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT). Methods According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin–eosin staining, and senescence-associated β-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified. Results In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration. Conclusions ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

Effect of sagittal screw angle and distance of screw apex to superior endplate on adjacent segment disease after posterolateral lumbar fusion: a retrospective study

Article

Full-text available

Nov 2022
J Orthop Surg Res

Abstract Background Numerous complications of lumbar fusion surgery have been reported, with adjacent segment disease (ASD) being one of the most important. Few studies describe the effect of sagittal, horizontal screw angles and distance of pedicle screw apex to superior endplate on the incidence of ASD in lumbar spine. The purpose of this retrospective study is to evaluate the hypothesis that unsatisfactory pedicle screw insertion positions would increase the likelihood of ASD. Methods Outpatients with lumbar spinal stenosis underwent posterolateral lumbar fusion at L4-S1 with a least 2-year follow-up were studied. ASD at L3–L4 was defined as a condition in which intervertebral disk narrowing, posterior vertebral opening, and vertebral slippage progress at the last follow-up in comparison with the postoperative. Independent t test was performed to compare data between two groups; Spearman analysis was performed to analyze the relationship between two continuous variables. Multivariate binary logistic models were performed to identify the independent risk factors of ASD. The receiver operating characteristic (ROC) curve was performed to measure model discrimination and Hosmer–Lemeshow (H–L) test was used to measure calibration. ROC curve evaluated the discrimination ability of sagittal screw angle and distance in predicting incidence of ASD. Results Patients in ASD group exhibit higher incidence of osteoporosis, higher Visual analogue scale (VAS), Oswestry disability index (ODI), bigger sagittal screw angle, shorter distance of pedicle screw apex to superior endplate than those in non-ASD group (p

Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension

Preprint

Full-text available

Nov 2022

The present study aimed to explore the underlying mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension. According to Pfirrmann grade evaluationclassification, 30 human endplate cartilage tissues were divided into LVF and LDH two groups. We found that the distribution of chondrocytes in LDH group endplate cartilage was disordered and hypertrophy were observed compare with LVF group. Through a series of functional experiments showed that with the deterioration of endplate cartilage, expression of collagenⅡand Sox-9 was decreased, p53 and p21 was increased, expression of YAP1 was decreased and a series of manifestations of senescence occurred in degenerative endplate cartilage. Toluidine blue staining showed that with the increase of loading force the morphology of endplate chondrocytes gradually changed after ICMT stimulation, ICMT 16% group the cell arrangement became sparse. RT-PCR and Western blot showed reductions in the expression of COL-2A, Sox9,YAP1,CTGF in the endplate cartilage after ICMT loading. ICMT not only caused degeneration of endplate chondrocytes, but also reduced cell proliferation and stimulated cell senescence. The degree of endplate cartilage degeneration was correlated with senescence level and YAP1 expression. Through a series of experiments suggested that over-expression of YAP1 alleviated ICMT-induced endplate chondrocyte degeneration and senescence in vitro. MRI examination and Pfirrmann grade evaluation suggested that YAP1 interference therapy could alleviate IDD in rats tail in vivo.

Icariin protects vertebral endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 pathway

Article

Full-text available

Sep 2022

Cartilage endplate (CEP) plays important roles in the onset and progression of intervertebral disc degeneration (IVDD). Icariin (ICA) is the major active ingredient of Herba Epimedii and has various biological activities such as anti-inflammatory and antioxidant, which is used to treat many degenerative diseases. However, the effects and mechanism of ICA on endplate chondrocytes are still unclear. Herein, we studied the effects of ICA on CEP degeneration and elucidated the underlying mechanisms. Endplate chondrocytes were isolated, and TNF-α and TBHP were applied to mimic an IVDD pathological environment. Also, an IVDD mice model was established by transection of bilateral facet joints to investigate the protective effect of ICA in vivo. We found that ICA treatment inhibited the chondrocytes apoptosis and the decrease of extracellular matrix production in a dose-dependent manner. Our in vivo experiments demonstrated that ICA could ameliorate IVDD development and CEP calcification. We also found that the ICA-activated Nrf-2/HO-1 pathway thus promoted the Parkin-mediated mitophagy process and inhibited chondrocytes ferroptosis, thus alleviated redox imbalance and mitochondrial dysfunction and eventually improved cell survival. Knockdown of Nrf-2 using siRNA reversed the protective effect of ICA on endplate chondrocytes apoptosis and degeneration. In conclusion, our study demonstrated that ICA could protect against CEP degeneration and calcification under IVDD pathological conditions, the associated mechanism may be related to Nrf-2/HO-1-mediated mitophagy activation and ferroptosis inhibition. Our results suggest that ICA may be a potential effective medicine for IVDD prevention and treatment.

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

Article

Full-text available

Jun 2022
INT J MOL SCI

Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs' development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes.

Gas within the Intervertebral Disc Does Not Rule Out Spinal Infection-A Case Series of 135 Patients with Spontaneous Spondylodiscitis

Article

Full-text available

Apr 2022

Gas in the intervertebral disc is mainly associated with degenerative disc diseases and experts generally assume that it is unlikely in spinal infection. However, large-scale studies supporting this notion are lacking, which is why our study's aim was to analyze the prevalence of and factors associated with the occurrence of gas in patients with spontaneous spondylodiscitis. Patients presenting with spontaneous spondylodiscitis from 2006 to 2020 were included retrospectively. Exclusion criteria were previous interventions in the same spinal segment and missing imaging data. Clinical data were retrieved from electronic medical reports. Computed tomography (CT) scans were evaluated for the presence of intervertebral gas. Causative pathogens were identified from CT-guided biopsy, open biopsy, intraoperative tissue samples, and/or blood cultures. 135 patients with a mean age of 66.0 ± 13.7 years were included. In 93 patients (68.9%), a causative pathogen was found. Intervertebral gas was found in 31 patients (23.0%) in total and in 19 patients (20.4%) with positive microbiology. Patients with gas presented with significantly higher body temperatures (37.2 ± 1.1 vs. 36.8 ± 0.7 °C, p = 0.044) and CRP levels (134.2 ± 127.1 vs. 89.8 ± 97.3 mg/L, p = 0.040) on admission. As a considerable number of patients with spondylodiscitis showed intervertebral gas formation, the detection of intervertebral gas is not suited to ruling out spondylodiscitis but must be interpreted in the context of other imaging and clinical findings, especially in elderly patients.

Advanced disc degeneration, bi-planar instability and pathways of peri-discal gas suffusion contribute to pathogenesis of intradiscal vacuum phenomenon

Article

Full-text available

Mar 2022
EUR SPINE J

Purpose Intradiscal vacuum phenomenon (IDVP), despite being ubiquitous, is poorly understood. The dynamic passage of peri-discal gases into the degenerated disc is a commonly accepted theory. But the reasons behind its selective appearance in some discs are unevaluated. Methods 721 patients with chronic low back pain ± radiculopathy, were evaluated with AP and flexion–extension lateral radiographs and MRI. IDVP was classified based on its morphology and location. Radiographic parameters including sagittal translation, sagittal angulation, lateral listhesis, eccentric disc collapse, Pfirrmann’s grade, disc height, Modic changes, anterior longitudinal ligament status, and primary spinal disease at the level of IDVP was analyzed. Results IDVP was present in 342 patients, and they had a higher mean age (57.2 ± 12.5 years) than controls (p < 0.001). Eccentric disc space narrowing (26.5% vs 1.3%, p < 0.01), coronal listhesis (7.83% vs 1.1%, p < 0.001), sagittal angular motion difference (11.3 ± 4.6°, p < 0.001), higher mean disc degeneration (4.36 ± 0.69, p < 0.001), ALL disruption (30.3% vs 2.2%, p < 0.001) and Modic changes (88.6% vs 17.5%, p < 0.001) were significantly higher in IDVP discs (vs. non-IDVP). Binary logistic regression analysis indicated sagittal angular motion difference was the most predictive factor. IDVP was classified into three types—dense type (47.5%), linear (29.5%), dot type (23%). Dense type matched radiological correlations of IDVP while dot types behaved like non-IDVP discs. Conclusion Modic disc-endplate contacts, ALL disruption and coronal translation could be pathways for the passage of peri-discal gases into the degenerated disc. In the pathogenesis of IDVP, advanced disc degeneration, the presence of pathways of gas transfer and angular/coronal instability seem to play complementary roles.

Association between non-traumatic vertebral fractures and adjacent discs degeneration: a cross-sectional study and literature review

Preprint

Full-text available

Jul 2020

Background Previous clinical studies reported that thoracolumbar vertebral fractures (VFs) associated with high energy spine trauma cause adjacent intervertebral disc (IVD) degeneration; however, the effect of non-traumatic VFs on the progression of adjacent disc degeneration remains to be determined. The purpose of this study was to examine the association between non-traumatic VFs and degenerative changes of adjacent IVDs. Methods 98 consecutive patients undergoing spinal surgery were included in this study. VFs were semi-quantitatively evaluated by lateral lumbar radiography. 588 vertebral bodies (from T12 to L5) and 486 discs (from T12/L1 to L4/L5) were analyzed. The degree of IVD degeneration was evaluated by magnetic resonance imaging (MRI) and classified into two groups according to Pfirrmann’s classification. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage. Intradiscal vacuum phenomena (VPs) were evaluated by computed tomography. Adjacent IVDs were categorized according to the locations of VFs (superior, inferior, and bilateral). Associations between the presence of VFs and the extent of IVD degeneration or the presence of VPs were statistically analyzed. Results IVDs adjacent to VFs were identified in 115 IVDs (31.1% of total; superior: 11.4%, bilateral: 8.6%, inferior: 11.1%). The presence of VFs was significantly associated with MRI grades of adjacent IVD degeneration (P<0.01) and the prevalence of VPs within adjacent IVDs (P<0.01). From logistic regression analysis, age, disc level, and VFs were independent related factors for disc degeneration (P<0.05). Conclusion This study showed that VFs were an independent related factor for adjacent disc degeneration and occurrence of intradiscal VPs. VFs may affect the micro-environment of adjacent IVDs, leading to disc degeneration and disc rupture.

Association between non-traumatic vertebral fractures and adjacent discs degeneration: a cross-sectional study and literature review

Preprint

Full-text available

Jul 2020

Association between non-traumatic vertebral fractures and adjacent discs degeneration: a cross-sectional study and literature review

Article

Full-text available

Nov 2020
BMC MUSCULOSKEL DIS

Background Previous clinical studies reported that thoracolumbar vertebral fractures (VFs) associated with high energy spine trauma cause adjacent intervertebral disc (IVD) degeneration; however, the effect of non-traumatic VFs on the progression of adjacent disc degeneration remains to be determined. The purpose of this study was to examine the association between non-traumatic VFs and degenerative changes of adjacent IVDs. Methods Ninety-eight consecutive patients undergoing spinal surgery were included in this study. VFs were semi-quantitatively evaluated by lateral lumbar radiography. Five hundred eighty-eight vertebral bodies (from T12 to L5) and 486 discs (from T12/L1 to L4/L5) were analyzed. The degree of IVD degeneration was evaluated by magnetic resonance imaging (MRI) and classified into two groups according to Pfirrmann’s classification. Grades I, II and III were defined as the early stage of IVD degeneration and Grades IV and V as the advanced stage. Intradiscal vacuum phenomena (VPs) were evaluated by computed tomography. Adjacent IVDs were categorized according to the locations of VFs (superior, inferior, and bilateral). Associations between the presence of VFs and the extent of IVD degeneration or the presence of VPs were statistically analyzed. Results IVDs adjacent to VFs were identified in 115 IVDs (31.1% of total; superior: 11.4%, bilateral: 8.6%, inferior: 11.1%). The presence of VFs was significantly associated with MRI grades of adjacent IVD degeneration (P < 0.01) and the prevalence of VPs within adjacent IVDs (P < 0.01). From logistic regression analysis, age, disc level, and VFs were independent related factors for disc degeneration (P < 0.05). Conclusion This study showed that VFs were an independent related factor for adjacent disc degeneration and occurrence of intradiscal VPs. VFs may affect the micro-environment of adjacent IVDs, leading to disc degeneration and disc rupture.

METTL3 promotes IL‐1β–induced degeneration of endplate chondrocytes by driving m6A‐dependent maturation of miR‐126‐5p

Article

Full-text available

Oct 2020
J CELL MOL MED

METTL3 is an important regulatory molecule in the process of RNA biosynthesis. It mainly regulates mRNA translation, alternative splicing and microRNA maturation by mediating m6A‐dependent methylation. Interleukin 1β (IL‐1β) is an important inducer of cartilage degeneration that can induce an inflammatory cascade reaction in chondrocytes and inhibit the normal biological function of cells. However, it is unclear whether IL‐1β is related to METTL3 expression or plays a regulatory role in endplate cartilage degeneration. In this study, we found that the expression level of METTL3 and methylation level of m6A in human endplate cartilage with different degrees of degeneration were significantly different, indicating that the methylation modification of m6A mediated by METTL3 was closely related to the degeneration of human endplate cartilage. Next, through a series of functional experiments, we found that miR‐126‐5p can play a significant role in IL‐1β–induced degeneration of endplate chondrocytes. Moreover, we found that miR‐126‐5p can inhibit the PI3K/Akt signalling pathway by targeting PIK3R2 gene, leading to the disorder of cell vitality and functional metabolism. To further determine whether METTL3 could regulate miR‐126‐5p maturation, we first confirmed that METTL3 can bind the key protein underlying pri‐miRNA processing, DGCR8. Additionally, when METTL3 expression was inhibited, the miR‐126‐5p maturation process was blocked. Therefore, we hypothesized that METTL3 can promote cleavage of pri‐miR‐126‐5p and form mature miR‐126‐5p by combining with DGCR8.

Dorsal Epidural Gas after Lumbar Microdiskectomy Treated with CT-guided Needle Aspiration

Article

Full-text available

Aug 2020

To present a case of unusual dorsal epidural gas (EG) accumulation after a simple lumbar microdiskectomy (MD), treated with computed tomography (CT)-guided needle aspiration. A 78-year-old woman underwent simple lumbar MD at the L3-4 level. One week after the operation, the patient complained of severe back pain radiating to the right thigh. Follow-up magnetic resonance imaging (MRI) and CT revealed huge EG formation at the dorsal L3-4 epidural space. Conservative treatment did not resolve the patient's pain. We performed CT-guided needle aspiration after 1 week of conservative treatment. The patient's pain fully resolved after aspiration, but it recurred 1 week later. Follow-up MRI and CT revealed re-accumulation of the dorsal EG at the L3-4 level. CT-guided needle aspiration was repeated, again leading to full pain resolution. Follow-up CT 6 months after the second aspiration showed no recurrent dorsal EG. The patient has been symptom-free for 1 year since the second aspiration. CT-guided needle aspiration is a safe and effective alternative to re-operation in the context of dorsal EG formation after MD.

CT Classification of Vacuum Phenomenon Morphology and its Utility in Predicting Lumbar Vertebral Instability

Preprint

Full-text available

Aug 2020

Background: Lumbar vacuum phenomenon (VP) within the intervertebral disc has been classified based on CT imaging. We compared same-patient sagittal CT images and dynamic flexion-extension x-rays to determine if there is a difference in the amount of vertebral instability present between three VP morphologies on CT. Methods: Anterior subluxation measurements on x-ray were compared with same-segment VP on CT images from the same patient when both findings were present. VP were classified as spot, island, or linear. It was determined if there was a difference in the amount of anterior subluxation between the three morphologies. Secondary analysis looked at whether there was a difference in anterior subluxation between the three groups if patients had undergone a prior lumbar fusion surgery or not. Results: There was no difference in anterior subluxation between the three groups on dynamic flexion-extension x-rays. There was also no difference between the three groups on flexion-extension x-rays when patients were separated based on if they had received or not received a previous lumbar fusion surgery. Conclusion: IVD VP morphology is not a useful indicator in determining vertebral instability pre-operatively according to CT scan. Further fine-tuning of an IVD VP CT classification is needed to help radiologists and spine surgeons know when IVD VP presence is important.

Association Between Non-traumatic Vertebral Fractures and Adjacent Discs Degeneration: A Cross-sectional Study and Literature Review

Preprint

Full-text available

Jul 2020

Background Previous clinical studies reported that thoracolumbar vertebral fractures (VFs) associated with high energy spine trauma cause adjacent intervertebral disc (IVD) degeneration; however, there has been no study that evaluates the effect of non-traumatic VFs on the progression of adjacent disc degeneration. The purpose of this study was to examine the association between non-traumatic VFs and degenerative changes of adjacent IVDs. Methods 98 consecutive patients undergoing spinal surgery were included in this study. VFs were semi-quantitatively evaluated by lateral lumbar radiography. The degree of IVD degeneration was evaluated by MRI and classified into two groups (early and advanced). Intradiscal vacuum phenomena (VPs) were evaluated by computed tomography. Adjacent IVDs were categorized according to the locations of VFs (superior, inferior, and bilateral). Associations between the presence of VFs and the extent of IVD degeneration or the presence of VPs were statistically analyzed. Results IVDs adjacent to VFs were identified in 115 IVDs (31.1% of total; superior: 11.4%, bilateral: 8.6%, inferior: 11.1%). The presence of VFs was significantly associated with MRI grades of adjacent IVD degeneration (P < 0.01) and the prevalence of VPs within adjacent IVDs (P < 0.01). From logistic regression analysis, age, disc level, and VFs were independent related factors for disc degeneration (P < 0.05). Conclusion This study showed that VFs were an independent related factor for adjacent disc degeneration and occurrence of intradiscal VPs. VFs may affect the micro-environment of adjacent IVDs, leading to disc degeneration and disc rupture.

Glucose regulates tissue-specific chondro-osteogenic differentiation of human cartilage endplate stem cells via O-GlcNAcylation of Sox9 and Runx2

Article

Full-text available

Nov 2019

Background: The degenerative disc disease (DDD) is a major cause of low back pain. The physiological low-glucose microenvironment of the cartilage endplate (CEP) is disrupted in DDD. Glucose influences protein O-GlcNAcylation via the hexosamine biosynthetic pathway (HBP), which is the key to stem cell fate. Thiamet-G is an inhibitor of O-GlcNAcase for accumulating O-GlcNAcylated proteins while 6-diazo-5-oxo-L-norleucine (DON) inhibits HBP. Mechanisms of DDD are incompletely understood but include CEP degeneration and calcification. We aimed to identify the molecular mechanisms of glucose in CEP calcification in DDD. Methods: We assessed normal and degenerated CEP tissues from patients, and the effects of chondrogenesis and osteogenesis of the CEP were determined by western blot and immunohistochemical staining. Cartilage endplate stem cells (CESCs) were induced with low-, normal-, and high-glucose medium for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. CESCs were induced with low-glucose and high-glucose medium with or without Thiamet-G or DON for 21 days, and chondrogenic and osteogenic differentiations were measured by Q-PCR, western blot, and immunohistochemical staining. Sox9 and Runx2 O-GlcNAcylation were measured by immunofluorescence. The effects of O-GlcNAcylation on the downstream genes of Sox9 and Runx2 were determined by Q-PCR and western blot. Results: Degenerated CEPs from DDD patients lost chondrogenesis, acquired osteogenesis, and had higher protein O-GlcNAcylation level compared to normal CEPs from LVF patients. CESC chondrogenic differentiation gradually decreased while osteogenic differentiation gradually increased from low- to high-glucose differentiation medium. Furthermore, Thiamet-G promoted CESC osteogenic differentiation and inhibited chondrogenic differentiation in low-glucose differentiation medium; however, DON acted opposite role in high-glucose differentiation medium. Interestingly, we found that Sox9 and Runx2 were O-GlcNAcylated in differentiated CESCs. Finally, O-GlcNAcylation of Sox9 and Runx2 decreased chondrogenesis and increased osteogenesis in CESCs. Conclusions: Our findings demonstrate the effect of glucose concentration on regulating the chondrogenic and osteogenic differentiation potential of CESCs and provide insight into the mechanism of how glucose concentration regulates Sox9 and Runx2 O-GlcNAcylation to affect the differentiation of CESCs, which may represent a target for CEP degeneration therapy.

The influence of artificial nucleus pulposus replacement on stress distribution in the cartilaginous endplate in a 3-dimensional finite element model of the lumbar intervertebral disc

Article

Full-text available

Dec 2017

Objective: This study aimed to investigate the effects involved with the artificial nucleus pulposus (NP) replacement on stress distribution of the cartilaginous endplate (CEP) in a 3-dimensional lumbar intervertebral disc (IVD) model using a finite element (FE) analysis. Methods: A healthy male volunteer was recruited for the purposes of the study and a spiral computed tomography scan was subsequently conducted to obtain the data information in relation to the L4/5 motion segment. An FE model of the L4/5 motion segment constructed, on the basis of which degenerative IVD, IVD with NP removal, and IVD with NP replacement were in turn built. The stress distribution of the CEP and bulging of IVD were estimated using various motion states, including axial loading, forward flexion, backward extension, left axial rotation, and right axial rotation. Results: Under different motion states, the vertebral stress was higher in the degenerative IVD, the IVD with NP removal, and the IVD with NP replacement, in comparison to that of the normal IVD. Furthermore, a higher vertebral stress was detected in the degenerative IVD than the IVD with NP removal and the IVD with NP replacement. An even distribution of vertebral stress was observed in the IVD model with an artificial NP replacement, while the vertebral stress and bulging displacement were lower than after NP removal. Our findings provided confirmation that stress of the CEP was consistent with the vertebral stress. Conclusion: This study provided evidence suggesting that NP replacement, vertebral stress, and bulging displacement are lower than that of degenerative IVD and IVD with NP removal under different motion states.

General regulatory effects of hypoxia on human cartilage endplate‑derived stem cells: A genome‑wide analysis of differential gene expression and alternative splicing events

Article

Full-text available

Jun 2017

Intervertebral disc (IVD) degeneration of is considered to be initiated by the degeneration of the cartilage endplate (CEP). CEP‑derived stem cells (CESCs) with the capacity for osteochondrogenic differentiation may be responsible for CEP cartilage restoration. As CEP is avascular and hypoxic, and hypoxia can greatly influence biological activities of stem cells, physiological hypoxia may serve important roles in regulating the physiological functions of CESCs. The aim of the present study was to investigate the mechanisms of hypoxia‑regulated CESCs fate by using the Human Transcriptome Array 2.0 system to identify differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) in CESCs cultured under hypoxic and normoxic conditions. The high‑throughput analysis of both DEGs and ASGs were notably enriched in the immune response signal, which so far has not been investigated in IVD cells, due to their avascular nature and low immunogenicity. The present results provided a referential study direction of the mechanisms of hypoxia‑regulated CESC fate at the level of gene expression and alternative splicing, which may aid in our understanding of the processes of CEP degeneration.

A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells

Article

Full-text available

Jun 2017

It has been hypothesized that intervertebral disc degeneration is initiated by degeneration of the cartilage endplate (CEP), which is characterized by cartilage ossification. CEP‑derived stem cells (CESCs), with the potential for chondro‑osteogenic differentiation, may be responsible for the balance between chondrification and ossification in the CEP. The CEP remains in an avascular and hypoxic microenvironment; the present study observed that hypoxia was able to markedly inhibit the osteogenic differentiation of CESCs. This tissue‑specific CESC differentiation in response to a hypoxic microenvironment was physiologically important for the prevention of ossification in the CEP. In order to study the hypoxia‑regulated mechanisms underlying osteogenic differentiation of CESCs, a Human Transcriptome Array 2.0 was used to detect differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) during the osteogenic differentiation of CESCs under hypoxia, compared with those induced under normoxia. High‑throughput analysis of DEGs and ASGs demonstrated that genes in the complement pathway were enriched, which may be a potential mechanism underlying hypoxia inhibition of CESCs osteogenesis. The results of the present study may provide a basis for future mechanistic studies regarding gene expression levels and alternative splicing events during the hypoxia‑regulated inhibition of osteogenesis, which may be helpful in identifying targets for CEP degeneration therapy.

Document S2. Article plus Supplemental Information

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Aug 2016

Which vacuum phenomenon is more predictive for future junctional disorders?: Intradiscal or Intrafacet?

Article

Sep 2024
J CLIN NEUROSCI

Recent spine studies focused on identifying whether intradiscal vacuum phenomenon (VP) was associated with spinal instability. However, none of them reported a direct association between VP and spinal instability following fusion for degenerative lumbar spine disorders (DSDs), namely junctional disorders. In the present study, we aimed to evaluate whether the VP was predictive for junctional disorders in patients who underwent short-segment lumbar decompression and fusion for DSDs at a tertiary spine center. We retrospectively reviewed prospectively collected database of patients who underwent short-segment decompression and fusion for DSDs. Pre-operative sagittal and axial computed tomography (CT) scans were evaluated in terms of intradiscal and intrafacet VP at all lumbar levels, respectively. Each VP was scored as 1 point. Then, the total VP scores was calculated as the sum of intradiscal VP score and intrafacet VP score. Then, we analyzed the possible predictivity of VP for junctional disorders at final follow-ups of the patients operated for short-segment lumbar decompression and fusion. Patients with junctional disorders had significantly higher total and intrafacet VP scores compared to those without junctional disorders. Total VP score had an OR of 1.217 (p= 0.014) and intrafacet VP score had an OR of 1.465 (p=0.008). The ROC analysis depicted that the cut-offs value for total and intrafacet VP scores to predict junctional disorders following short-segment lumbar decompression and fusion were 1.5 points and 0.5 point, respectively. Vacuum phenomenon could be associated with junctional disorders in patients who underwent short-segment lumbar decompression and fusion for DSD. Intrafacet VP was more important than intradiscal VP in predicting junctional disorders. Proper surgical planning including the evaluation of both intrafacet and intradiscal VP at all lumbar levels is crucial to decrease the likelihood of junctional disorders.

Evolution of Lumbar Degenerative Spondylolisthesis with Key Radiographic Features

Article

Jan 2024
SPINE J

Severe Intervertebral Vacuum Phenomenon is Associated With Higher Preoperative Low Back Pain, ODI, and Indication for Fusion in Patients With Degenerative Lumbar Spondylolisthesis

Article

Aug 2023

Study design: Retrospective study of prospective collected data. Objective: To analyze the association between intervertebral vacuum phenomenon (IVP) and clinical parameters in patients with degenerative spondylolisthesis. Summary of background data: IVP is a sign of advanced disc degeneration. The correlation between IVP severity and low back pain in patients with degenerative spondylolisthesis has not been previously analyzed. Methods: We retrospectively analyzed patients with degenerative spondylolisthesis who underwent surgery. Vacuum phenomenon was measured on computed tomography scan and classified into mild, moderate, and severe. A lumbar vacuum severity (LVS) scale was developed based on vacuum severity. The associations between IVP at L4/5 and the LVS scale, preoperative and postoperative low back pain, as well as the Oswestry Disability Index was assessed. The association of IVP at L4/5 and the LVS scale and surgical decision-making, defined as decompression alone or decompression and fusion, was assessed through univariable logistic regression analysis. Results: A total of 167 patients (52.7% female) were included in the study. The median age was 69 years (interquartile range 62-72). Overall, 100 (59.9%) patients underwent decompression and fusion and 67 (40.1%) underwent decompression alone. The univariable regression demonstrated a significantly increased odds ratio (OR) for back pain in patients with more severe IVP at L4/5 [OR=1.69 (95% CI 1.12-2.60), P=0.01]. The univariable regressions demonstrated a significantly increased OR for increased disability with more severe L4/L5 IVP [OR=1.90 (95% CI 1.04-3.76), P=0.04] and with an increased LVS scale [OR=1.17 (95% CI 1.02-1.35), P=0.02]. IVP severity of the L4/L5 were associated with higher indication for fusion surgery. Conclusion: Our study showed that in patients with degenerative spondylolisthesis undergoing surgery, the severity of vacuum phenomenon at L4/L5 was associated with greater preoperative back pain and worse Oswestry Disability Index. Patients with severe IVP were more likely to undergo fusion.

Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway

Article

Apr 2023

Background: Cartilage endplate (CEP) degeneration is an important initiating factor leading to intervertebral disc degeneration (IVDD). Astaxanthin (Ast) is a natural lipid-soluble and red-orange carotenoid which possesses various biological activities, including antioxidant, anti-inflammatory, and anti-aging effects in multiple organisms. However, the effects and mechanism of Ast on endplate chondrocytes remain largely unknown. The objective of the current study was to investigate the effects and of Ast on CEP degeneration and its underlying molecular mechanisms. Methods: Tert-butyl hydroperoxide (TBHP) was used to mimic the IVDD pathological environment. We investigated the effects of Ast on the Nrf2 signaling pathway and damage-associated events. The IVDD model was constructed by surgical resection of L4 posterior elements to explore the role of Ast in vivo. Results: We found that the activation of the Nrf-2/HO-1 signaling pathway was enhanced by Ast, thus promoted mitophagy process, inhibited oxidative stress and CEP chondrocytes ferroptosis, eventually ameliorated extracellular matrix (ECM) degradation, CEP calcification and endplate chondrocytes apoptosis. Knockdown of Nrf-2 using siRNA inhibited Ast induced mitophagy process and its protective effect. Moreover, Ast inhibited oxidative stimulation-induced NF-κB activity and could ameliorate the inflammation response. The results also were confirmed by experiments in vivo, Ast alleviated IVDD development and CEP calcification. Conclusions: Ast could protect vertebral cartilage endplate against oxidative stress and degeneration via activating Nrf-2/HO-1 pathway. Our results imply that Ast may serve as a potential therapeutic agent for IVDD progression and treatment.

Effect of Preoperative Severity and Location of Lumbar Intervertebral Disc Vacuum Phenomenon on Surgical Outcomes After Single-Level Transforaminal Lumbar Interbody Fusion

Article

Mar 2023

Objective: This study aimed to examine whether preoperative severity and location of lumbar intervertebral disc vacuum phenomenon (VP) influence surgical outcomes after single-level transforaminal lumbar interbody fusion (TLIF). Methods: We included 106 patients (age: 67.4 ± 10.4 years; 51 male/55 female) with lumbar degenerative diseases, who were treated with single-level TLIF. Severity of VP (SVP) score was measured preoperatively. SVP score at fused disc was used as SVP (FS) score, and at non-fused discs was used as SVP (non-FS) score. Surgical outcomes were assessed using Oswestry disability index (ODI) and visual analogue scale (VAS; low back pain (LBP), lower-extremity pain, numbness, LBP in motion, in standing, and in sitting). The patients were divided into Severe VP (FS or non-FS) and Mild VP (FS or non-FS) groups, and surgical outcomes were compared between the two groups. Correlations between each SVP score and surgical outcomes were analyzed. Results: There were no differences in surgical outcomes between the Severe VP (FS) and Mild VP (FS) groups. Postoperative ODI, VAS for LBP, lower-extremity pain, numbness, and LBP in standing were significantly worse in the Severe VP (non-FS) group than in the Mild VP (non-FS) group. SVP (non-FS) scores significantly correlated with postoperative ODI, VAS for LBP, lower extremity pain, numbness, and LBP in standing; however, SVP (FS) scores did not correlate with any surgical outcomes. Conclusion: Preoperative severity of VP at fused disc is not associated with surgical outcomes, however, severity of VP at non-fused discs is correlated with clinical outcomes.

Intervertebral vacuum phenomenon - prevalence and severity CT-scan analysis in patients older than 50 years: a retrospective cohort study

Article

Full-text available

Dec 2022
ACTA RADIOL

Background: Chronic low back pain secondary to degenerative changes in the spine is a common cause of disability, and disc degeneration is one of the most frequent imaging findings. Intervertebral vacuum phenomenon (IVP) is usually observed in advanced degeneration. Recently, this phenomenon has gained interest due to a relatively new surgical technique called percutaneous discoplasty, aimed at treating low back pain secondary to degenerative disc disease in elderly patients. Purpose: To analyze the prevalence and related factors of the vacuum phenomenon in adult patients. Material and methods: A retrospective cohort study was performed of patients who underwent abdominal computed tomography (CT) for non-spine-related reasons. Age, body mass index, smoking, and CT-based characteristics as presence of IVP, subchondral sclerosis, and facet joint degeneration at the lumbar spine from L1 to the sacrum were included in order to determine the prevalence of the vacuum phenomenon in this population and establish a relationship between this condition and patient demographics and other signs of spine degeneration, such as sclerosis and facet joint disease. Results: A total of 238 patients were included in the study (114 men, 124 women; mean age = 75.6 ± 12.3 years. In total, 91 (38%) patients had at least one level of IVP; 59 (25%) patients exhibited subchondral sclerosis, and 235 (98%) facet joint degeneration. Among risk factors, age, smoking, and subchondral sclerosis were significantly associated with the presence of vacuum. Conclusion: IVP was present in 38% of participants. Risk factors associated with vacuum were age, smoking, and subchondral sclerosis.

Iron overload promotes intervertebral disc degeneration via inducing oxidative stress and ferroptosis in endplate chondrocytes

Article

Aug 2022
FREE RADICAL BIO MED

Iron overload is a common phenomenon in the elderly population. Many clinical studies have indicated an association between iron overload and the incidence and pathological progression of intervertebral disc degeneration (IVDD). However, the role and underlying mechanism by which iron participates in the progression of IVDD has not yet been reported. In the present study, we aimed to elucidate the connection between iron overload and IVDD, and explore the underlying mechanisms of disease. Firstly, a clinical epidemiology study was conducted and revealed that iron overload is an independent risk factor for human IVDD. To elucidate the role of iron overload in IVDD, an iron overload mouse model was established, and we observed that iron overload promoted IVDD and cartilage endplate degeneration in a dose dependent manner. Endplate chondrocytes were further isolated and treated with FAC to mimic iron overload in vitro. Excess iron significantly promoted mineralization of endplate chondrocytes in addition to their degeneration via oxidative stress. Moreover, a high dose of excess iron promoted chondrocytes ferroptosis. An iron chelator (DFO), an antioxidant (NAC) and a ferroptosis inhibitor (Fer-1) demonstrated effective inhibition of endplate chondrocyte degeneration induced by iron overload, and our in vivo studies further demonstrated that DFO, NAC and Fer-1 could rescue high dose iron-induced IVDD and cartilage endplate calcification. In conclusion, our results indicate that iron overload is strongly associated with the onset and development of IVDD via oxidative stress and ferroptosis. Inhibiting oxidative stress or ferroptosis could therefore be promising therapeutic strategies for IVDD induced by iron overload.

miR-637 Inhibits Osteogenic Differentiation of Human Intervertebral Disc Cartilage Endplate Stem Cells by Targeting WNT5A

Article

Mar 2022

Background: Degenerative disk disease (DDD) remains the leading incentive of severe lumbago. DDD is mainly caused by degeneration of cartilage endplate (CEP). Cartilage endplate stem cells (CESCs) are essential in chondrogenesis and osteogenesis of CEP. This study investigated the mechanism of miR-637 inhibiting osteogenic differentiation of human CESC by regulating WNT5A. Methods: The degenerative CEP (N = 10) and non-degenerative CEP (N = 6) were obtained from patients undergoing disk fusion surgery. CESCs were examined for surface stem cell markers, alkaline phosphatase (ALP) levels, osteogenic differentiation, osteogenic genes (Runx2, COL1), and chondrogenic gene (COL2). The miR-637 expression in CESCs was detected. The targeting relationship of miR-637 and WNT5A was confirmed. After miR-637 overexpression/WNT5A down-regulation, the action of miR-637/WNT5A on osteogenic differentiation of CESCs was evaluated. After simultaneous overexpression of miR-637/WNT5A, the effect of miR-637 on osteogenic differentiation of CESCs was assessed. Results: miR-637 was down-expressed in degenerative CESCs (D-CESCs), and miR-637 overexpression inhibited the osteogenic differentiation of D-CESCs, while inhibition of miR-637 promoted the osteogenic differentiation ability of D-CESCs. miR-637 targeted WNT5A and down-regulation of WNT5A inhibited the osteogenic differentiation of D-CESCs. Up-regulated WNT5A partially annulled the inhibitory action of miR-637 overexpression on osteogenic differentiation of D-CESCs. Conclusion: miR-637 inhibited osteogenic differentiation of D-CESCs via targeting WNT5A.

Vacuum Phenomenon in the Lumbar Spine: A Useful Tool for Neuroradiologists and Spine Surgeons?

Article

Jan 2021

The vacuum phenomenon in the lumbar spine is a common finding on radiographs and CT imaging. Its presence has been known for more than a century and has been increasing in spine literature during the past 20 years. Although once thought of as an incidental finding, further research may yield important findings about the vacuum phenomenon, which may allow radiologists to understand its meaning more clearly when it is encountered.Learning Objective: The goal of this article is to present the reader with a better understanding of the vacuum phenomenon as it pertains to the lumbar spine and with its history in radiology and surgery literature, its presence in recent literature, and how it may impact spine radiology and surgery moving forward.

Transforaminal endoscopic decompression and uninstrumented allograft lumbar interbody fusion: A feasibility study in patients with end-stage vacuum degenerative disc disease

Article

Jun 2020
CLIN NEUROL NEUROSUR

OBJECTIVE The authors investigated the feasibility of a transforaminal endoscopic decompression and un-instrumented lumbar interbody fusion procedures with cancellous bone allograft in patients painful with end-stage degenerative vacuum disc disease. PATIENTS & METHODS :Twenty-nine patients who underwent endoscopic transforaminal foraminal and lateral recess decompression and direct intraoperative endoscopic visualization of a painful, hollow collapsed, rigid intervertebral disc space were grafted with cancellous allograft chips. In addition to the radiographic assessment of fusion, patients were followed for a minimum of 2 years postoperatively, and clinical outcomes were evaluated with VAS, ODI, and modified MacNab criteria. RESULTS At the final follow, mean VAS and ODI scores reduced from 7.34 ± 1.63 and 50.03 ± 10.64 preoperatively to 1.62 ± 1.741 and 6.69 ± 4.294 postoperatively (p < 0.0001). Excellent and Good clinical outcomes, according to Macnab criteria, were obtained in 34.5% and 62.1% of patients, respectively. Only one patient had minimal improvement from "Poor" preoperatively to "Fair" postoperatively. This female patient was treated for lumbar disc herniation L5/S1 and had an incomplete fusion at the final follow up. Computed tomography assessment of interbody fusion at the last follow-up showed successful fusion in 91.4% of patients. CONCLUSIONS Un-instrumented interbody fusion by packing a hollow interspace with cancellous bone allograft chips can be considered as an adjunct to endoscopic foraminal and lateral recess decompression in select patients with validated painful, collapsed, and rigid motion segments. It can be safely done in an outpatient setting at a low burden to patients.

Comprehensive review on intravertebral intraspinal, intrajoint, and intradiscal vacuum phenomenon: From anatomy and physiology to pathology

Article

May 2020

The term “vacuum phenomenon” (VP), is characterized by gas-like density areas due to a rapid increase in the joint space volume (“acute VP”) or represent a chronic gas collection. It can occur within a collapsed vertebral body, the spinal canal, joints but mainly the intervertebral disc. Studies support that VP is originated by a dynamic process involving the balance between tissues’ liquid and gaseous components, influenced by the duration and the depth of mechanical and metabolic alterations, by the nature of neighboring tissues and the variability in both pressure and permeability of disc or vertebral or joint structures. Prevalence of VP in the general population is about 2%, reaching 20% in the elderly with disc degeneration. Although it’s often a random finding in asymptomatic patients, VP is an eventually painful expression of disc degeneration, or disc or vertebral fracture, or bone lesions. In sporadic cases, intradiscal gas can be expelled (all-in-one or gradually), resulting in a gaseous cyst, causing pain and neurological symptoms. Considering that spontaneous resolution and recurrence after surgery are both possible, most of the authors recommend conservative treatment in patients with intradiscal and intravertebral VP; occasionally percutaneous CT(computed tomography) -guided aspiration or vertebral stabilization.

circRNA_0058097 promotes tension‐induced degeneration of endplate chondrocytes by regulating HDAC4 expression through sponge adsorption of miR‐365a‐5p

Article

Jun 2019

Excessive mechanical tension can lead to the degeneration of endplate chondrocytes. The presence of tension‐sensitive circRNA_0058097 molecules has been detected in human endplate chondrocytes, where it was found to be a potential competing endogenous RNA. Indeed, inhibiting the expression of circRNA_0058097 effectively enhanced the stress resistance of endplate chondrocytes, suggesting that it may be an important trigger point for the degeneration of endplate cartilage. Through a series of experiments, we reveal that circRNA_0058097 can upregulate the expression of downstream target gene histone deacetylase 4 by sponge adsorption of miR‐365a‐5p, which promoted morphological changes of endplate chondrocytes, and increased extracellular matrix degradation and degeneration of endplate cartilage. Therefore, circRNA_0058097 may provide a new way to prevent and treat endplate cartilage degeneration. Excessive intermittent cyclic mechanical tension can induce the degeneration of endplate chondrocytes. Tension‐sensitive circRNA_0058097 can upregulate the expression of downstream target gene histone deacetylase 4 by sponge adsorption of miR‐365a‐5p, which promoted morphological changes of endplate chondrocytes, and increased extracellular matrix degradation and degeneration of endplate cartilage.

The Impact of Degenerative Disc Disease on Regional Volumetric Bone Mineral Density (vBMD) measured by Quantitative Computed Tomography

Article

May 2019
SPINE J

Background context: It has been reported that degenerative disc disease (DDD) is associated with higher spinal bone mineral density (BMD) based on previous studies that used dual X-ray absorptiometry (DXA). However, DDD is often associated with proliferative bone changes and can lead to an overestimation of BMD measured with DXA. Trabecular volumetric BMD (vBMD) in the vertebral body measured with quantitative computed tomography (QCT) is less affected by those changes and can be a favorable alternative to DXA for patients with degenerative spinal changes. Purpose: The purpose of this study is to investigate the effect of DDD on regional trabecular vBMDs in the vertebral body measured by QCT. Study design/setting: Cross-sectional observational study at a single academic institution. Patients sample: Consecutive patients undergoing posterior lumbar spinal fusion between 2014 and 2017 who had a routine preoperative CT scan and magnetic resonance imaging (MRI) within a 90-day interval. Outcome measures: Regional trabecular vBMDs in the vertebral body by QCT. Methods: QCT measurements were conducted in L1-S1 vertebral trabecular bone. Any apparent sclerotic lesions that might affect vBMD values were excluded from the region of interest. The vBMDs of each level were defined as the average vBMD of the upper and lower vertebrae. To evaluate DDD, Pfirrmann grade, Modic grade, total end plate score, and vacuum phenomenon were documented. Univariate regression analysis and multivariate analyses with a linear mixed model adjusted with individual variability of segmental vBMDs were conducted with vBMD as the response variable. Results: Of 143 patients and 715 disc levels, 125 patients and 596 discs met our inclusion criteria. Mean vBMD (±standard deviation [SD]) of all levels was 119.0±39.6 mg/cm3. After adjusting for all covariates, Pfirrmann grade was not an independent contributor to vBMD, but the presence of any Modic change (type 1, β=6.8, p≤.001; type 2, β=6.7, p<.001; type 3, β=43.6, p<.001), high TEPS (score 10-12, β=14.2, p<.001), or vacuum phenomenon (β=9.0, p<.001) was shown to be independent contributors to vBMD. Conclusions: Our results showed that the presence of certain end plate lesions (Modic changes and high TEPS) on MRI was significantly associated with increased regional QCT-vBMDs in the vertebral body, but no significant association was observed with disc nucleus pathology, unless it was associated with a vacuum phenomenon. When end plate lesions with Modic changes and high TEPS are present at the measuring level, care must be taken to interpret vBMD values, which might be overestimations even if the trabecular area appears normal.

Rapamycin Induced Autophagy Inhibits Inflammation‐Mediated Endplate Degeneration by Enhancing Nrf2/Keap1 Signaling of Cartilage Endplate Stem Cells

Article

Mar 2019

Cartilage endplate (CEP) calcification inhibits the transport of metabolites and nutrients in the intervertebral disc and is an important initiating factor of intervertebral disc degeneration. However, the mechanisms governing CEP degeneration have not been thoroughly elucidated. In this study, we established a mouse CEP degeneration model and showed that autophagy insufficiency caused the degeneration of CEP. We found that the inflammatory cytokine tumor necrosis factor-α (TNF-α) increased the level of intracellular reactive oxygen species (ROS) and caused cell senescence and osteogenic differentiation of cartilage endplate stem cells (CESCs), whereas rapamycin-induced autophagy protected CESCs from TNF-α-induced oxidative stress and cell senescence. Furthermore, rapamycin-induced autophagy helped CESCs maintain the chondrogenic properties and inhibited extracellular matrix protease expression and osteogenic differentiation. Further study revealed that autophagy activated by rapamycin or inhibited by chloroquine influenced the expression and nuclear translocation of Nrf2, thereby controlling the expression of antioxidant proteins and the scavenging of ROS. Taken together, the results indicate that rapamycin-induced autophagy enhances Nrf2/Keap1 signaling and promotes the expression of antioxidant proteins, thereby eliminating ROS, alleviating cell senescence, reducing the osteogenic differentiation of CESCs, and ultimately protecting CEPs from chronic inflammation-induced degeneration. Stem Cells 2019.

Effects of Concomitant Decompression Adjacent to a Posterior Lumbar Interbody Fusion Segment on Clinical and Radiologic Outcomes: Comparative Analysis 5 Years After Surgery

Article

Full-text available

Oct 2018

Study design: Retrospective cohort study. Objective: To examine the effects of concomitant decompression adjacent to the posterior lumbar interbody fusion (PLIF) segment on the clinical and radiological outcomes 5 years after surgery. Methods: Forty-five consecutive patients who had undergone L3/4 decompression with L4/5 PLIF for multilevel stenosis with degenerative spondylolisthesis (DS), and were followed for 5 years, were enrolled (group D). As a control group, 45 age-, sex- and preoperative disc height at L3/4-matched patients who had undergone L4/5 PLIF alone for L4/5DS were randomly selected (group A). Disc height, vertebral slippage, range of motion, posterior opening angle, segmental lordotic angle, presence of the intradiscal vacuum phenomenon (IVP) at the L3/4 level were measured on radiographs. Japanese Orthopaedic Association (JOA) score and the requirement for additional L3/4 surgery were evaluated. Results: In terms of pre-/postoperative radiographic changes between the groups, significant differences were detected regarding disc height narrowing of ≥3 mm (group D 31%, group A 9%) and IVP (group D 33%, group A 11%). There were no significant differences in other radiological parameters. The recovery rate of the JOA score (group D 58%, group A 61%) and reoperation rate (group D 2.2%, group A 6.7%) were not significantly different between the groups. Conclusion: Concomitant decompression adjacent to the PLIF segment accelerated adjacent disc degeneration compared to PLIF alone, but it did not predispose to the development of instability 5 years after surgery. Moreover, the JOA score and reoperation rate were not significantly different between groups D and A.

Effects of intradiscal vacuum phenomenon on surgical outcome of lateral interbody fusion for degenerative lumbar disease

Article

Dec 2016
J NEUROSURG-SPINE

OBJECTIVE The authors investigated whether the presence of intradiscal vacuum phenomenon (IVP) results in greater correction of disc height and restoration of segmental lordosis (SL). METHODS A retrospective chart review was performed on every patient at the University of South Florida's Department of Neurosurgery treated with lateral lumbar interbody fusion between 2011 and 2015. From these charts, preoperative plain radiographs and CT images were reviewed for the presence of IVP. Preoperative and postoperative posterior disc height (PDH), anterior disc height (ADH), and SL were measured at disc levels with IVP and compared with those at disc levels without IVP using the t-test. Linear regression was used to evaluate the factors that predict changes in PDH, ADH, and SL. RESULTS One hundred forty patients with 247 disc levels between L-1 and L-5 were treated with lateral lumbar interbody fusion. Among all disc levels treated, the mean PDH increased from 3.69 to 6.66 mm (p = 0.011), the mean ADH increased from 5.45 to 11.53 mm (p < 0.001), and the mean SL increased from 9.59° to 14.55° (p < 0.001). Significantly increased PDH was associated with the presence of IVP, addition of pedicle screws, and lack of cage subsidence; significantly increased ADH was associated with the presence of IVP, anterior longitudinal ligament (ALL) release, addition of pedicle screws, and lack of subsidence; and significantly increased SL was associated with the presence of IVP and ALL release. CONCLUSIONS IVP in patients with degenerative spinal disease remains grossly underreported. The data from the present study suggest that the presence of IVP results in increased restoration of disc height and SL.

Vertebral Pseudarthrosis in the Osteoporotic Spine

Article

Full-text available

Nov 1998

Radiologic and operative findings of intravertebral cleft in the osteoporotic spine were investigated and the pathomechanism discussed. To clarify the pathologic features of the intravertebral cleft. Intravertebral "vacuum" cleft is one of the common radiographic findings in the osteoporotic spine. It is thought that the cleft is a rare lesion of an ununited fracture, or pseudarthrosis. Evidential findings of the disease, however, have never been reported. Simple bone grafting was performed in five cases (average age, 76.8 years) of thoracolumbar intravertebral cleft in osteoporotic spine in patients who had been suffering from prolonged pain of the back or leg. Preoperative radiologic evaluation using flexion-extension radiograph and magnetic resonance imaging was performed in all patients. At operation, the cleft and the components of the structure were macroscopically and microscopically observed. The fluid content in the cleft was biochemically analyzed. In all patients, preoperative flexion-extension radiographs showed intravertebral instability at the location of the clefts that indicated gas density in three cases and water density in two cases. Magnetic resonance imaging showed that, for the most part, the cleft was low intensity on the T1-weighted image and high intensity on the T2-weighted scans, regardless of the radiographic findings. At operation, abnormal movement was observed at the cleft of the affected body, which was covered with hypertrophic membrane. The serous fluid within the cleft was aspirated before the excision of soft tissue. The thick membrane was excised and showed that the cleft was lined by smooth fibrocartilaginous tissue and the great degree of motion between the fracture ends that is consistent with the pathologic appearance of pseudarthrosis. The unstable cleft in the affected vertebral body of the osteoporotic spine with magnetic resonance findings of low intensity on the T1-weighted scans and high intensity on the T2-weighted scans suggests that the cleft is a false joint lined by fibrocartilaginous tissue with notable movement consistent with pseudarthrosis.

The spectrum of vacuum phenomenon and gas in spine

Article

Full-text available

Jan 2004
J Belg Radiol

Bruno Coulier

Although true physical-chemical experimental proofs are lacking in the literature, numerous clinical reports have shown that many radiological manifestations of the so-called vacuum phenomenon (VP) only represent snapshots of a complex dynamic hydropneumatical continuum extending from true vacuum to gas and/or fluid and vice versa. In the great majority of cases, VP remains an incidental accessory or anecdotal finding but, nevertheless, it occasionally represents a useful clinical or radiological sign of critical importance for the understanding, clinical diagnosis, prognosis, and therapeutic implications of several spinal diseases. VP and gas collections have been described in segments of the spine including the disc space, Schmorl nodes and vertebral structures, the epidural and intradural spaces, synovial cysts, and facet joints. In this article the author discusses and illustrates many aspects of VP and gas in the spine through selected examples collected over an 18-month period of time.

The intravertebral vacuum phenomen as specific sign of osteonecrosis in vertebral compression fractures: Results from a radiological and histological study

Article

Full-text available

Oct 2007

This study investigated the prevalence of the intravertebral vacuum phenomenon (IVP) and osteonecroses in vertebral compression fractures (VCFs). We therefore performed an histological analysis of biopsies obtained from VCFs prior to balloon kyphoplasty. Computed tomography (CT) scans were reviewed regarding the presence of an IVP (i.e. cleft sign, Kümmell disease). We reviewed the data of 266 consecutive patients treated by balloon kyphoplasty in 501 procedures from 2002 to 2004. From 180 patients (68%) we obtained adequate bone tissue for histological evaluation. Biopsy specimens were analysed regarding the presence of osteoporosis, infection, malignancy and osteonecrosis. CT scans of all 180 patients were reviewed for presence of an IVP. Histological examination revealed 135 (75%) osteoporoses, 20 (11%) neoplasms, 12 (7%) trauma cases and 13 (7%) osteonecroses. An IVP was present in 12 (7%) patients. There was a significant association of osteonecrosis and IVP (P < 0.0001). Eleven of 12 patients with a vacuum phenomenon showed an osteonecrosis on histology, whereas 11 of 13 patients with osteonecrosis showed an IVP on CT. The IVP is a specific sign of osteonecrosis in vertebral compression fractures (sensitivity 85%, specificity 99%, positive predictive value 91%). Our findings strongly support the thesis that an IVP indicates local bone ischemia associated with a non-healing vertebral collapse and pseudarthrosis.

Is interleukin-1 a good target for therapeutic intervention in intervertebral disc degeneration: Lessons from the osteoarthritic experience

Article

Full-text available

Feb 2007
ARTHRITIS RES THER

IL-1 plays a key role in disc degeneration and could be a valid target for inhibiting this process. IL-1 receptor antagonist (IL-1ra) might be a good candidate to inhibit IL-1 activity. However, many questions need to be addressed before contemplating therapy in humans. IL-1 blockade is also a great challenge in osteoarthritis and results from animal models suggest that IL-1ra may have beneficial effects. The clinical benefit of a local injection of IL-1ra in knee osteoarthritis may be limited by the antagonist's short half-life. Further studies with longer-lasting antagonists are needed to explore this new therapeutic approach.

Intervertebral Disc: Anatomy-Physiology-Pathophysiology-Treatment

Article

Full-text available

Apr 2008
Pain Pract

Phulchand Prithvi Raj

This review article describes anatomy, physiology, pathophysiology and treatment of intervertebral disc. The intervertebral discs lie between the vertebral bodies, linking them together. The components of the disc are nucleus pulposus, annulus fibrosus and cartilagenous end-plates. The blood supply to the disc is only to the cartilagenous end-plates. The nerve supply is basically through the sinovertebral nerve. Biochemically, the important constituents of the disc are collagen fibers, elastin fibers and aggrecan. As the disc ages, degeneration occurs, osmotic pressure is lost in the nucleus, dehydration occurs, and the disc loses its height. During these changes, nociceptive nuclear material tracks and leaks through the outer rim of the annulus. This is the main source of discogenic pain. While this is occurring, the degenerative disc, having lost its height, effects the structures close by, such as ligamentum flavum, facet joints, and the shape of the neural foramina. This is the main cause of spinal stenosis and radicular pain due to the disc degeneration in the aged populations. Diagnosis is done by a strict protocol and treatment options are described in this review. The rationale for new therapies are to substitute the biochemical constituents, or augment nucleus pulposus or regenerate cartilaginous end-plate or finally artificial disc implantation. ▪.

The intravertebral vacuum phenomenon

Article

May 2008

Vertebral vacuum sign is an uncommon finding, which can easily mimic the air within the disc and can be overlooked. We present a case of intravertebral vacuum phenomenon with exquisite multidetector computed tomography and magnetic resonance imaging findings.

'Stress' distributions inside intervertebral discs. The effects of age and degeneration

Article

Nov 1996

We investigated the distribution of compressive 'stress' within cadaver intervertebral discs, using a pressure transducer mounted in a 1.3 mm diameter needle, The needle was pulled along the midsagittal diameter of a lumbar disc with the face of the transducer either vertical or horizontal while the disc was subjected to a constant compressive force, The resulting 'stress profiles' were analysed in order to characterise the distribution of vertical and horizontal compressive stress within each disc, A total of 87 discs from subjects aged between 16 and 87 years was examined, Our results showed that age-related degenerative changes reduced the diameter of the central hydrostatic region of each disc (the 'functional nucleus') by approximately 50%, and the pressure within this region fell by 30%, The width of the functional annulus increased by 80% and the height of compressive 'stress peaks' within it by 160%, The effects of age and degeneration were greater at L4/L5 than at L2/L3, and the posterior annulus was affected more than the anterior, Age and degeneration were themselves closely related, but the stage of degeneration had the greater effect on stress distributions, We suggest that structural changes within the annulus and endplate lead to a transfer of load from the nucleus to the posterior annulus, High 'stress' concentrations within the annulus may cause pain, and lead to further disruption.

Management of Symptomatic Lumbar Degenerative Disk Disease

Article

Mar 2009

Symptomatic lumbar degenerative disk disease, or discogenic back pain, is difficult to treat. Patients often report transverse low back pain that radiates into the sacroiliac joints. Radicular or claudicatory symptoms are generally absent unless there is concomitant nerve compression. Physical examination findings are often unremarkable. Radiographic examination may reveal disk space narrowing, end-plate sclerosis, or vacuum phenomenon in the disk; magnetic resonance imaging is useful for revealing hydration of the disk, annular bulging, or lumbar spine end-plate (Modic) changes in the adjacent vertebral bodies. The use of diskography as a confirmatory study remains controversial. Recent prospective, randomized trials and meta-analyses of the literature have helped expand what is known about degenerative disk disease. In most patients with low back pain, symptoms resolve without surgical intervention; physical therapy and nonsteroidal anti-inflammatory drugs are the cornerstones of nonsurgical treatment. Intradiskal electrothermal treatment has not been shown to be effective, and arthrodesis remains controversial for the treatment of discogenic back pain. Nucleus replacement and motion-sparing technology are too new to have demonstrated long-term data regarding their efficacy.

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury

Article

Mar 1989

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.

Proteoglycan composition of rabbit arterial wall under conditions of experimentally induced atherosclerosis

Article

Feb 1987
Atherosclerosis

The concentration and composition of proteoglycans (PG) of the neointima developed following balloon catheter removal of aortic endothelium in rabbits, were assessed. PG were extracted from the aortic intimal-medial tissues with 4 M guanidinium chloride in the presence of protease inhibitors and purified subsequently by cesium chloride gradient ultracentrifugation and fractionation by high-performance liquid chromatography (HPLC). PG so obtained was analysed for its protein, cholesterol and glycosaminoglycan (GAG) content. For the characterization of the GAG moiety, an exhaustive proteolytic digestion was done. The GAG were then recovered by ethanolic precipitation and their relative distribution was determined after a selective enzymatic digestion using specific enzymes. Results show a significant increase in the amount of PG in the areas of the injured arterial wall covered by regenerated endothelium. In addition, changes in the composition of GAG were also found in the PG isolated from experimental animals when compared to PG isolated from normal aorta. A marked increase in the content of chondroitin sulfates and dermatan sulfate of injured tissue was seen. Hyaluronic acid content also changed in response to de-endothelialization and cholesterol feeding, but only moderately. The content of heparan sulfate remained unaffected in experimental tissues. Furthermore, cholesterol feeding aggravated the injury-induced increment of GAG. These findings are consistent with previously reported morphological observations, and correlate well with reports that arterial injury and cholesterol feeding act synergistically in the evolution of the atherosclerotic lesion and provide further evidence that the interaction of lipid and PG of the arterial wall may be of particular importance to our comprehension of the pathogenesis of atherosclerosis.

Glycosaminoglycan composition and biosynthesis in the endothelium covered neointima of de-endothelialized rabbit aorta

Article

Jul 1985

The biosynthesis and composition of glycosaminoglycans (GAG) in the endothelium-covered neointima, formed in response to de-endothelialization of the rabbit aorta by a balloon catheter, was examined. The [14C]glucosamine incorporation into GAG during an in vitro incubation with intimal-medial tissue was monitored periodically up to 24 hr. The GAG were isolated after an exhaustive proteolytic digestion with pronase and protease followed by ethanolic precipitation at 4 degrees C. Electrophoretic migration on cellulose acetate paper was compared for identification. The distribution of GAG was determined after a selective enzymatic digestion of isolated GAG using specific enzymes. Heparan sulfates were estimated after nitrous acid treatment. The concentration of GAG was measured spectrophotometrically by forming colored complexes with Alcian blue dye. In addition, the specific activity (dpm/microgram GAG) and the rate of GAG synthesis (ng/mg dry defatted tissue/day) were determined. The results indicate that the rate of GAG synthesis by de-endothelialized neointima (DEA) was twice that of intact aorta (control). In the re-endothelialized neointima (REA), the GAG synthetic rate was three times more than in control. However, the release of GAG into medium from REA accounts for only 25% of the GAG synthesized by this tissue type, and the release from DEA accounts for 60% of the synthesized GAG. Similarly, a threefold increase in the GAG concentration in REA compared to control was found. The relative distribution as chondroitin-6-sulfate (C6S), chondroitin-4-sulfate (C4S), dermatan sulfate (DS), heparan sulfate (HS) and hyaluronic acid (HA) was markedly altered in the injured neointima. There was an increase in chondroitin sulfates (CS) and DS concomitant with a decrease in HS. It is concluded that injury to aortic endothelium induces stimulation of GAG synthesis in the arterial wall. Furthermore, the greater release of GAG from DEA, compared to control and REA, suggests that endothelium may function as a "reverse" barrier in the neointima covered by regenerated endothelium.

Kinetics of low density lipoprotein interactions with rabbit aortic wall following balloon catheter deendothelialization

Article

Jul 1984
Arteriosclerosis

The kinetics of the interaction of circulating lipoproteins with the balloon catheter-injured aortic wall of rabbits were investigated. The fate of radioiodinated low density lipoprotein (LDL) was followed up to 48 hours after intravenous injection and compared with radioiodinated albumin injected simultaneously. The accumulation of LDL was calculated from the radioactivity in the aortic tissue divided by the average specific activity, measured from the area below the plasma radioactivity versus the time curve, and expressed as cpm/ml/hr. It was observed that the aortic area of endothelial regeneration (AER), which is relatively impermeable to Evans blue dye and shows very little albumin concentration, accumulated considerably more LDL than control (uninjured) tissues. Furthermore, removal of labeled lipoprotein from the intima during a 24-hour efflux period following the initial 48-hour loading period indicated that there was greater removal from normal and deendothelialized aortic (DEA) tissues than from neointima covered by endothelium. These findings are consistent with previous observations indicating changes in the morphological and chemical composition of AER. There is evidence that greater neointimal lipid accumulation in response to endothelial injury parallels the concentration of glycosaminoglycans (GAG). The relatively increased accumulation of label in AER, while plasma-specific activity is rapidly decreasing, indicates that there may be an ionic interaction of GAG with LDL in the AER.

[Vertebral vacuum phenomena]

Article

Feb 1995

The spinal vacuum phenomenon is a collection of gas within the disk space, the vertebral body, the apophyseal joint or the spinal canal. The intradiscal vacuum phenomenon is frequently observed in degenerative disk disease and crystal-induced diskopathy. This has obvious significance to the radiologist, who, on observing a narrowed disk space or collapsed vertebral body, might otherwise consider infectious or neoplastic spondylitis, a likely possibility. The presence of vacuum phenomenon militates against the diagnosis of infection or tumor.

“Stress” distribution inside inter-vertebral discs. The effects of age and degeneration

Article

Dec 1996

We investigated the distribution of compressive 'stress' within cadaver intervertebral discs, using a pressure transducer mounted in a 1.3 mm diameter needle. The needle was pulled along the midsagittal diameter of a lumbar disc with the face of the transducer either vertical or horizontal while the disc was subjected to a constant compressive force. The resulting 'stress profiles' were analysed in order to characterise the distribution of vertical and horizontal compressive stress within each disc. A total of 87 discs from subjects aged between 16 and 87 years was examined. Our results showed that age-related degenerative changes reduced the diameter of the central hydrostatic region of each disc (the 'functional nucleus') by approximately 50%, and the pressure within this region fell by 30%. The width of the functional annulus increased by 80% and the height of compressive 'stress peaks' within it by 160%. The effects of age and degeneration were greater at L4/L5 than at L2/L3, and the posterior annulus was affected more than the anterior. Age and degeneration were themselves closely related, but the stage of degeneration had the greater effect on stress distributions. We suggest that structural changes within the annulus and endplate lead to a transfer of load from the nucleus to the posterior annulus. High 'stress' concentrations within the annulus may cause pain, and lead to further disruption.

Lumbar Nerve Root Compression Caused by Lumbar Intraspinal Gas

Article

Mar 1997

Three cases of lumbar nerve root compression associated with intradiscal gas formation and its migration are reported. To establish the pathogenic mechanism by which gas is formed in the spinal canal. Few such cases have been reported of patients with clinical symptoms of lumbar radiculopathy resulting from gas in the spinal canal. Surgery with needle aspiration of the gas was performed in all cases. The presence of the gas was detected in the extradural space in one patient and within the nerve sheath in two patients. After surgery, all patients recovered well, and there were no obvious remnant neurologic abnormalities. One year later, all patients were completely free of symptoms. Surgery with needle aspiration of the gas resulted in clinical improvement in all cases, confirming that intraspinal gas is an important cause of lumbar radiculopathy. The composition of the gas in one patient was analyzed by gas chromatography, which revealed an overwhelming preponderance of nitrogen. A relationship between a gas-containing pseudocyst in the spinal canal and a degenerated intervertebral disc was identified, a key finding for understanding the precise nature of this disorder. Intradiscal gas formation and its outward migration as a sequel of intervertebral disc degeneration also has been addressed in this report.

The Intravertebral Vacuum Phenomenon ("Vertebral Osteonecrosis")

Article

Aug 1997

Retrospective cohort. To compare the prevalence of the association between contiguous intervertebral disc and vertebral collapses with or without an intravertebral vacuum phenomenon. The mechanism of occasional gas accumulation within some vertebral collapses is poorly known. The current hypothesis is that this phenomenon is indicative of bone ischemia. In fact, avascular necrosis as the main pathologic event remains speculative, and should not explain per se the presence of gas within a vertebral body. Comparison of the prevalence of intervertebral disc vacuum phenomenon adjacent to the affected vertebral body in 23 cases of intravertebral vacuum phenomenon in 19 patients (intravertebral vacuum phenomenon group) and in 708 osteoporotic collapses without intravertebral vacuum phenomenon in 199 patients (control group). There were no differences in sex and age between the two groups, and all the patients in the intravertebral vacuum phenomenon group had signs of underlying osteoporosis. A vacuum phenomenon in at least one intervertebral disc adjacent to the collapses on radiographs, conventional tomography, computed tomography, or magnetic resonance imaging was found in 19 cases (83%) in the intravertebral vacuum phenomenon group, compared with 13% in the control group (P < 0.0001). Considering plain radiographs only, this association was found in 50% of the intravertebral vacuum phenomenon group and in 9.7% of the control group (P < 0.0001). The intervertebral and intravertebral gaseous collections were connected through a fractured endplate in six cases. The high prevalence of the association of contiguous intervertebral and intravertebral vacuum phenomenon could have implications in the pathogenesis of the intravertebral vacuum phenomenon. We hypothesize that the intravertebral vacuum phenomenon could simply be the result of migration of an intradiscal-gaseous collection through the fractured endplate of some osteoporotic collapses.

Intravertebral Vacuum Phenomenon Following Fractures: CT Study on Frequency and Etiology

Article

Nov 1999

The purpose of this work was to determine the frequency and etiology of the intravertebral vacuum phenomenon (IVP). CT examinations of 96 vertebral fractures were evaluated for IVP. Bone mineral density (BMD) was determined in nonfractured vertebrae. For calibration purposes, densities of a standard phantom measured in 30 patients who underwent quantitative CT examinations in the same time period were used and precision was calculated. Eleven of 96 fractures (11.5%) showed IVP. IVP was present in 4 of 20 fractures at T12 (20%), in 4 of 23 at L1 (17.4%), and 1 IVP was found at L2-4 each. Mean +/- SD age of patients with IVP was 68.3 +/- 10.5 years and without 47.8 +/- 19.4 years (p < 0.001). Mean +/- SD density of nonaffected vertebra was 45.9 +/- 17.0 mg of hydroxyapatite/ml for patients with IVP and 139.5 +/- 62.6 mg/ml for those without IVP (p < 0.0005). An average precision of 1.2% was calculated for the density measurements over the investigated time. Following vertebral fractures, IVP on CT scans is more common than presumed and increases with age. There exists a significant inverse correlation between the BMD and the frequency of IVP.

Change of Barometric Pressure Influences Low Back Pain in Patients with Vacuum Phenomenon Within Lumbar Intervertebral Disc

Article

Sep 2002
J SPINAL DISORD TECH

The present study investigates whether changes in barometric pressure influence low back pain in patients with vacuum phenomenon within lumbar intervertebral discs. Twenty-four patients with low back pain were examined: 12 with vacuum phenomenon within the intervertebral discs (VP [+] group) and 12 without the vacuum phenomenon (VP [-] group). All patients consented to an evaluation of low back pain in a hyperbaric oxygen chamber. In the VP (+) group, low back pain became more severe in one patient when atmospheric pressure was elevated, and in eight patients when atmospheric pressure was decreased. In the VP (-) group, two patients experienced more severe low back pain when atmospheric pressure was decreased. Our study demonstrated that low back pain might be aggravated by atmosphere depression in patients with lumbar disease associated with the vacuum phenomenon.

The Effect of Blocking a Nutritional Pathway to the Intervertebral Disc in the Dog Model

Article

Mar 2004
J SPINAL DISORD TECH

The hypothesis that injecting bone cement adjacent to one or both endplates would bring about degeneration in the intervening disc was tested. In 11 dogs, bone cement was injected just below the superior endplates of L1, L2, and L3 to block the nutritional supply through these endplates to the three intervertebral discs T13-L1, L1-L2, and L2-L3. In one other dog, both the superior and the inferior endplates of the same discs (T13-L1, L1-L2, and L2-L3) were blocked with bone cement. All 12 dogs were euthanized between 31 and 70 weeks after the surgery. The three experimental discs (T13-L1, L1-L2, and L2-L3) and two control discs (T12-T13 and L4-L5) were excised and assessed using enzyme-linked immunosorbent assay (ELISA) and histology. Radiographs of the lumbar spine at the time of death did not show any signs of disc bulging, disc space narrowing, or peripheral osteophyte formation in any of the 12 dogs. The experimental discs as well as the control discs appeared normal in every dog. After the discs were bisected, they were carefully inspected for any visible signs of degeneration. The experimental discs showed no clear signs of disc degeneration and were not distinguishable from the control discs on a gross level. The numerical results from the ELISA showed that in the experimental discs as opposed to the control discs, there were significant increases in proteoglycan content in both the nucleus (P = 0.033) and annulus (P = 0.01) and clear histologic changes in some of the discs. The results show that injecting bone cement adjacent to one or both endplates for up to 70 weeks does not produce degeneration in any visible form in the intervening disc. There were no disc bulging, no apparent annular fissures, and no disc spacing narrowing. There were, however, increases in protoglycan content in both the nucleus and the annulus and clear histologic changes in some of the discs.

Intravertebral vacuum phenomenon in osteoporotic compression fracture: Report of 67 cases with quantitative evaluation of intravertebral instability

Article

Feb 2004
J NEUROSURG

The objectives of this study were to: 1) describe the incidence and clinical features of intravertebral vacuum phenomenon (IVVP) in a relatively large number of cases; 2) quantitatively evaluate intravertebral instability and determine the factors affecting instability; and 3) evaluate the efficacy of percutaneous vertebroplasty in the treatment of this phenomenon. A retrospective review was conducted of the records of 67 patients with IVVP among 652 consecutive cases of osteoporotic compression fracture. Comparisons between the IVVP group and a control group, a stable group, and an unstable group were conducted. Percutaneous vertebroplasty was performed in all patients. There were 67 patients (10.3%) in whom there were 70 vacuum phenomena of the intravertebral space. Intravertebral vacuum phenomena occurred predominantly in the thoracolumbar junction (81%) and in patients with a longer duration of symptoms (10.6 +/- 9.8 months) compared with the control group. Of 59 vertebrae for which flexion-extension radiographs were available, 26 vertebrae were categorized as stable and 33 as unstable. Twenty-one vertebrae (64%) had undergone compression fracture in the unstable group compared with nine (35%) compression fractures in the stable group. There were 28 (85%) fractures of the wedged vertebrae in the unstable group compared with 16 (61%) fractures in wedged vertebrae in the stable group. Percutaneous vertebroplasty was performed with successful clinical outcome. Intravertebral vacuum phenomenon is more common than has been previously appreciated. The results of this study indicate that biomechanics, not ischemic or avascular theory, may play an important role in pathogenesis of this phenomenon. Percutaneous vertebroplasty was found to be a minimally invasive and effective procedure for the treatment of IVVP.

Spontaneous vacuum phenomenon in the lateral compartment of the knee associated with a lateral tibial plateau fracture

Article

Feb 2006
KNEE

A case of spontaneous vacuum phenomenon in the lateral compartment of the knee is presented in an 83-year-old woman who attended the Accident and Emergency department two weeks after a twisting injury to the left knee. At the time of examination she still had a marked effusion in the knee with lateral joint line tenderness. X-rays showed a lateral tibial plateau fracture involving the entire lateral condyle and extending into the opposite compartment beneath the intercondylar eminence. The X-rays also demonstrated the presence of gas in the lateral joint line. This is the first reported case of vacuum phenomenon occurring on the same side as a lateral tibial plateau fracture. It is also demonstrated that the phenomenon may occur in the presence of an effusion.

Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue

Article

Oct 2005
SPINE

This study examines changes in the production of extracellular matrix molecules as well as the induction of tissue degradation in in vitro formed nucleus pulposus (NP) tissues following incubation with tumor necrosis factor (TNF)alpha. To characterize the response of NP cells to TNF-alpha, a proinflammatory cytokine present in herniated NP tissues. TNF-alpha is a proinflammatory cytokine expressed by NP cells of degenerate intervertebral discs. It is implicated in the pain associated with disc herniation, although its role in intervertebral disc degeneration remains poorly understood. In vitro formed NP tissues were treated with TNF-alpha (up to 50 ng/mL) over 48 hours. Tissues were assessed for histologic appearance, proteoglycan and collagen contents, as well as proteoglycan and collagen synthesis. Reverse transcriptase polymerase chain reaction was used to determine the effect of TNF-alpha on NP cell gene expression. Proteoglycan degradation was assessed by immunoblot analysis. At doses of 1-5 ng/mL, TNF-alpha induced multiple cellular responses, including: decreased expression of both aggrecan and type II collagen genes; decreases in the accumulation and overall synthesis of aggrecan and collagen; increased expression of MMP-1, MMP-3, MMP-13, ADAM-TS4, and ADAM-TS5; and induction of ADAM-TS dependent proteoglycan degradation. Within 48 hours, these cellular responses resulted in NP tissue with only 25% of its original proteoglycan content. Because low levels of TNF-alpha, comparable to those present physiologically, induced NP tissue degradation, this suggests that TNF-alpha may contribute to the degenerative changes that occur in disc disease.

Intralamellar relationships within the collagenous architecture of the annulus fibrosus imaged in its fully hydrated state

Article

Nov 2005

The anisotropic, inhomogeneous, multiply collagenous architecture of the annulus reflects the complex pattern of mainly tensile stresses developed in this region of the disc during normal function. Structural and mechanical responses of fully hydrated in-plane sections taken from within single lamellae of the outer annulus of healthy bovine caudal discs have been investigated using a micromechanical technique in combination with simultaneous high-resolution differential interference contrast optical imaging. Responses both along and across (i.e. transverse to) the primary direction of the mono-array of collagen fibres were studied. Stretching along the alignment direction revealed a biomechanical response consistent with the behaviour of an array whose overall strength is governed primarily by the strength of embedding of the fibres in the vertebral endplates, rather than from interfibre cohesion along their length. The mono-aligned array, even when lacerated, is highly resistant to any further tearing across the alignment direction. Although not visible in the relaxed mono-arrays, transverse stretching revealed a highly complex set of interconnecting structures embodying hierarchical relationships not previously revealed. It is suggested that these structures might play an important role in the containment under pressure of the nuclear contents. The dramatic differences in rupture behaviour observed along vs. across the primary fibre direction are consistent with the known clinical consequences arising from varying degrees of annular wall damage, and might also explain various types of disc herniation. The lamellar architecture of the healthy disc revealed by this investigation provides an important reference framework for exploring structural changes associated with disc trauma and degeneration.

Gas-filled parasymphyseal pubic cyst associated with degenerative joint disease

Article

Jul 2007

Parasymphyseal cysts are a rare and poorly understood entity. This case report describes a gas-containing parasymphyseal cystic lesion associated with degenerative change and vacuum phenomenon in the pubic symphysis. The mass was discovered incidentally in a 72-year-old asymptomatic male who underwent a transrectal ultrasound-guided biopsy of the prostate and the nature of the lesion was confirmed on magnetic resonance imaging (MRI) and computed tomography (CT). We hypothesize that the gas within the parasymphyseal cystic mass arose from a vacuum phenomenon in the pubic symphysis, with subsequent extrusion of gas from the joint into the cyst itself. It is important for radiologists to be aware of the existence of this entity to avoid unnecessary surgery for patients.

ALIX catches HIV.

Article

Apr 2007

ESCRT and ESCRT-associated proteins are required during the assembly and release of many RNA viruses, including HIV. Two new papers provide structures for the ESCRT-associated protein ALIX/AIP1 and demonstrate how this protein interacts with HIV Gag. One of these studies provides the clearest evidence to date that ESCRT-III mediates key events in virus release and indicates that there are cellular proteins involved in this process still to be discovered.

Vacuum phenomenon in a dislocated joint

Article

Jan 2008
EMERG MED J

Clinical Symptoms of Patients With Intervertebral Vacuum Phenomenon

Article

Jan 2008
NEUROLOGIST

Intervertebral vacuum phenomenon (IVP) often occurs in lower lumbar intervertebral spaces, however, there are no reports regarding the clinical symptoms of IVP. The purpose of this study was to determine the clinical symptoms of patients with IVP. The subjects enrolled in this study were 105 consecutive patients who visited the spine clinic of our hospital between January and June 2004, and were diagnosed as having lumbar spinal canal stenosis. We interviewed all patients about clinical symptoms patients with lumbar degenerative disease often complain of, and the presence or absence of each symptom was compared between the VP (+) group and VP (-) group. Twenty-nine patients (82.9%) in the VP (+) group and 16 patients (22.9%) in the VP (-) group had more severe lower back pain in the morning (p < 0.0001). As to the actions that exacerbated lower back pain, a significantly higher percentage of patients in the VP (+) group experienced worsening of lower back pain when standing up or rolling over than in the VP (-) group. Twenty-eight patients (80.0%) in the VP (+) group felt they could predict changes in the weather, while only six patients (8.6%) in the VP (-) group felt the same way, showing a statistically significant difference between the two groups (p < 0.0001). The present results suggested that vacuum phenomenon was related to lower back pain in the morning, lower back pain when standing up or rolling over, and lower back pain was influenced by changes in the weather.

The intravertebral vacuum phenomenon (“vertebral osteonecrosis”). Migration of intradiscal gas in a fractured vertebral body?

Jan 1997
1885

Lafforgue

Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs

Abstract

No full-text available

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