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1.
J Biomech ; 171: 112159, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38852480

ABSTRACT

Degenerative disc disease (DDD), regardless of its phenotype and clinical grade, is widely associated with low back pain (LBP), which remains the single leading cause of disability worldwide. This work provides a quantitative methodology for comparatively investigating artificial IVD degeneration via two popular approaches: enzymatic denaturation and fatigue loading. An in-vitro animal study was used to study the time-dependent responses of forty fresh juvenile porcine thoracic IVDs in conjunction with inverse and forward finite element (FE) simulations. The IVDs were dissected from 6-month-old-juvenile pigs and equally assigned to 5 groups (intact, denatured, low-level, medium-level, high-level fatigue loading). Upon preloading, a sinusoid cyclic load (Peak-to-peak/0.1-to-0.8 MPa) was applied (0.01-10 Hz), and dynamic-mechanical-analyses (DMA) was performed. The DMA outcomes were integrated with a robust meta-model analysis to quantify the poroelastic IVD characteristics, while specimen-specific FE models were developed to study the detailed responses. The results demonstrated that enzymatic denaturation had a more significantly pronounced effect on the resistive strength and shock attenuation capabilities of the intervertebral discs. This can be attributed to the simultaneous disruption of the collagen fibers and water-proteoglycan bonds induced by trypsin digestion. Fatigue loading, on the other hand, primarily influenced the disc's resistance to deformation in a frequency-dependent pattern, where alterations were most noticeable at low loading frequencies. This study confirms the intricate interplay between the biochemical changes induced by enzymatic processes and the mechanical behavior stemming from fatigue loading, suggesting the need for a comprehensive approach to closely mimic the interrelated multifaceted processes of human disc degeneration.


Subject(s)
Finite Element Analysis , Intervertebral Disc Degeneration , Intervertebral Disc , Animals , Intervertebral Disc Degeneration/physiopathology , Intervertebral Disc/physiopathology , Swine , Stress, Mechanical , Weight-Bearing/physiology , Protein Denaturation , Biomechanical Phenomena , Models, Biological
2.
Turk Neurosurg ; 34(4): 640-646, 2024.
Article in English | MEDLINE | ID: mdl-38874242

ABSTRACT

AIM: To explore the relationship between the retroperitoneal vasculature and anterior surface of the lower spine, and to establish values for aiding in prediction of the pertinence of anterior approach at the L4-L5 and L5-S1 intervertebral discs. MATERIAL AND METHODS: The study included 13 fresh human cadavers. After exploration of the abdominal cavity and removal of the visceral organs, the vasculature, and anterior spinal surface were revealed beneath the lower extension of the perirenal fascia. Morphometric measurements of the great vessels and the intervertebral discs were obtained. All measurements were analyzed and presented as mean and standard deviation. Differences in the values between sexes were assessed. RESULTS: The anterior height of the L4-L5 and L5-S1 intervertebral disc was 6.8 ± 0.81 mm and 6.7 ± 0.99 mm, respectively. The widths of the aorta, inferior vena cava, right and left common iliac arteries, and right, and left common iliac veins were 16.4 ± 3.58, 20.6 ± 3.36, 11.5 ± 2.32, 11.5 ± 2.43, 14.7 ± 3.13, and 15.5 ± 3.27 mm, respectively. The mean aortic bifurcation angle was 45.5°. The aortic bifurcation was located above the lower endplate of the L4 vertebrae in 53.8% of the cadavers. The area of the interarterial and interiliac trigones was 14.6 ± 5.33 cm < sup > 2 < /sup > and 7.1 ± 4.35 cm2, respectively. No statistically significant differences were noted between the sexes. CONCLUSION: An elaborate radiological examination of the vasculature should be performed prior to surgery to avoid unwanted vascular complications during the anterior approach. Knowing the area of the interarterial and interiliac triangles and the aortic bifurcation location could be aid in assessing the safe working zone.


Subject(s)
Cadaver , Intervertebral Disc , Lumbar Vertebrae , Humans , Lumbar Vertebrae/anatomy & histology , Lumbar Vertebrae/surgery , Male , Female , Intervertebral Disc/anatomy & histology , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/surgery , Middle Aged , Aged , Iliac Vein/anatomy & histology , Iliac Artery/anatomy & histology , Iliac Artery/diagnostic imaging , Vena Cava, Inferior/anatomy & histology , Vena Cava, Inferior/surgery , Retroperitoneal Space/anatomy & histology , Adult
3.
Sci Adv ; 10(23): eadj3194, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848366

ABSTRACT

Persistent inflammation has been associated with severe disc degeneration (DD). This study investigated the effect of prolonged nuclear factor κB (NF-κB) activation in DD. Using an inducible mouse model, we genetically targeted cells expressing aggrecan, a primary component of the disc extra cellular matrix, for activation of the canonical NF-κB pathway. Prolonged NF-κB activation led to severe structural degeneration accompanied by increases in gene expression of inflammatory molecules (Il1b, Cox2, Il6, and Nos2), chemokines (Mcp1 and Mif), and catabolic enzymes (Mmp3, Mmp9, and Adamts4). Increased recruitment of proinflammatory (F4/80+,CD38+) and inflammatory resolving (F4/80+,CD206+) macrophages was observed within caudal discs. We found that the secretome of inflamed caudal disc cells increased macrophage migration and inflammatory activation. Lumbar discs did not exhibit phenotypic changes, suggestive of regional spinal differences in response to inflammatory genetic overactivation. Results suggest prolonged NF-κB activation can induce severe DD through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and activation of macrophage cell populations.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Macrophages , NF-kappa B , Animals , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , NF-kappa B/metabolism , Macrophages/metabolism , Mice , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Disease Models, Animal , Inflammation/metabolism , Inflammation/pathology , Cytokines/metabolism , Signal Transduction
4.
Cells ; 13(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38891119

ABSTRACT

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.


Subject(s)
Alginates , Disease Models, Animal , Intervertebral Disc Degeneration , Intervertebral Disc , Animals , Dogs , Alginates/chemistry , Alginates/pharmacology , Intervertebral Disc/surgery , Intervertebral Disc/pathology , Intervertebral Disc/drug effects , Rabbits , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Degeneration/therapy , Proof of Concept Study , Gels , Bone Marrow Cells/cytology , Mesenchymal Stem Cells/cytology , Magnetic Resonance Imaging , Male , Bone Marrow Transplantation/methods
5.
Sci Rep ; 14(1): 13181, 2024 06 08.
Article in English | MEDLINE | ID: mdl-38849364

ABSTRACT

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.


Subject(s)
Finite Element Analysis , Range of Motion, Articular , Scoliosis , Spinal Fusion , Humans , Scoliosis/surgery , Scoliosis/physiopathology , Adult , Male , Biomechanical Phenomena , Spinal Fusion/methods , Pedicle Screws , Tomography, X-Ray Computed , Stress, Mechanical , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Intervertebral Disc/diagnostic imaging , Thoracic Vertebrae/surgery , Thoracic Vertebrae/physiopathology
6.
Cell Rep ; 43(6): 114342, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38865240

ABSTRACT

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-CreERt2 mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-CreERt2 IVD cells indicate enrichment for TGF-ß signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-ß/BMP mediator Smad4 results in loss of Tagln+ cells and abnormal NP morphologies. We propose Tagln+ PeriNP cells are potential progenitors crucial for NP homeostasis.


Subject(s)
Intervertebral Disc Degeneration , Nucleus Pulposus , Stem Cells , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/genetics , Animals , Humans , Mice , Stem Cells/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Transforming Growth Factor beta/metabolism
7.
Med Eng Phys ; 129: 104189, 2024 07.
Article in English | MEDLINE | ID: mdl-38906572

ABSTRACT

Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.


Subject(s)
Cell Survival , Compressive Strength , Finite Element Analysis , Glucose , Intervertebral Disc , Tensile Strength , Glucose/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/cytology , Models, Biological , Biomechanical Phenomena , Stress, Mechanical
8.
Front Biosci (Landmark Ed) ; 29(6): 224, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38940022

ABSTRACT

BACKGROUND: The objective of this research was to identify differentially expressed genes (DEGs) related to ferroptosis in the annulus fibrosus (AF) during intervertebral disc degeneration (IDD). METHODS: We analyzed gene data from degenerated and normal AF obtained from the GSE70362 and GSE147383 datasets. An analysis to determine the functional significance of the DEGs was conducted, followed by the creation of a network illustrating the interactions between proteins. We further analyzed the immune infiltration of the DEGs and determined the hub DEGs using LASSO regression analysis. Finally, we identified the hub ferroptosis-related DEGs (FRDEGs) and verified their expression levels using Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, Immunohistochemical Staining (IHC), and Immunofluorescence (IF). RESULTS: By analyzing the GSE70362 and GSE147383 datasets, we identified 118 DEGs. In degenerative AF groups, we observed a significant increase in immune infiltration of resting memory CD4+ T cells. LASSO regression analysis revealed 9 hub DEGs. The construction of a Receiver Operating Characteristic (ROC) curve yielded an Area Under the Curve (AUC) value of 0.762. Furthermore, we found that MGST1 is a hub gene related to ferroptosis. Our examination of immune infiltration indicated that MGST1 primarily influences macrophage M0 in different immune cell expression groups. Finally, our observations revealed a marked upregulation of MGST1 expression in the degenerated annulus fibrosus tissue. CONCLUSION: Our findings indicate an upsurge in MGST1 levels within degenerative AF, potentially playing a crucial role in the exacerbation of IDD. These findings provide a foundation for further exploration of the pathological mechanisms underlying IDD and offer potential drug targets for intervention.


Subject(s)
Annulus Fibrosus , Computational Biology , Ferroptosis , Glutathione Transferase , Intervertebral Disc Degeneration , Humans , Annulus Fibrosus/metabolism , Annulus Fibrosus/pathology , Computational Biology/methods , Databases, Genetic , Ferroptosis/genetics , Gene Expression Profiling/methods , Gene Regulatory Networks , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Protein Interaction Maps/genetics , Glutathione Transferase/genetics , Glutathione Transferase/metabolism
9.
Med Eng Phys ; 127: 104158, 2024 05.
Article in English | MEDLINE | ID: mdl-38692761

ABSTRACT

BACKGROUND: The intervertebral disc exhibits not only strain rate dependence (viscoelasticity), but also significant asymmetry under tensile and compressive loads, which is of great significance for understanding the mechanism of lumbar disc injury under physiological loads. OBJECTIVE: In this study, the strain rate sensitive and tension-compression asymmetry of the intervertebral disc were analyzed by experiments and constitutive equation. METHOD: The Sheep intervertebral disc samples were divided into three groups, in order to test the strain rate sensitive mechanical behavior, and the internal displacement as well as pressure distribution. RESULTS: The tensile stiffness is one order of magnitude smaller than the compression stiffness, and the logarithm of the elastic modulus is approximately linear with the logarithm of the strain rate, showing obvious tension-compression asymmetry and rate-related characteristics. In addition, the sensitivity to the strain rate is the same under these two loading conditions. The stress-strain curves of unloading and loading usually do not coincide, and form a Mullins effect hysteresis loop. The radial displacement distribution is opposite between the anterior and posterior region, which is consistent with the stress distribution. By introducing the damage factor into ZWT constitutive equation, the rate-dependent viscoelastic and weakening behavior of the intervertebral disc can be well described.


Subject(s)
Compressive Strength , Intervertebral Disc , Stress, Mechanical , Animals , Intervertebral Disc/physiology , Sheep , Biomechanical Phenomena , Tensile Strength , Weight-Bearing , Elasticity
10.
Ageing Res Rev ; 98: 102323, 2024 07.
Article in English | MEDLINE | ID: mdl-38734147

ABSTRACT

Oxidative stress is one of the main driving mechanisms of intervertebral disc degeneration(IDD). Oxidative stress has been associated with inflammation in the intervertebral disc, cellular senescence, autophagy, and epigenetics of intervertebral disc cells. It and the above pathological mechanisms are closely linked through the common hub reactive oxygen species(ROS), and promote each other in the process of disc degeneration and promote the development of the disease. This reveals the important role of oxidative stress in the process of IDD, and the importance and great potential of IDD therapy targeting oxidative stress. The efficacy of traditional therapy is unstable or cannot be maintained. In recent years, due to the rise of materials science, many bioactive functional materials have been applied in the treatment of IDD, and through the combination with traditional drugs, satisfactory efficacy has been achieved. At present, the research review of antioxidant bioactive materials in the treatment of IDD is not complete. Based on the existing studies, the mechanism of oxidative stress in IDD and the common antioxidant therapy were summarized in this paper, and the strategies based on emerging bioactive materials were reviewed.


Subject(s)
Antioxidants , Intervertebral Disc Degeneration , Oxidative Stress , Oxidative Stress/physiology , Oxidative Stress/drug effects , Humans , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/therapy , Intervertebral Disc Degeneration/drug therapy , Antioxidants/therapeutic use , Antioxidants/pharmacology , Animals , Reactive Oxygen Species/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/drug effects
11.
Matrix Biol ; 131: 46-61, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38806135

ABSTRACT

Syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan, is known to regulate matrix catabolism by nucleus pulposus cells in an inflammatory milieu. However, the role of SDC4 in the aging spine has never been explored. Here we analyzed the spinal phenotype of Sdc4 global knockout (KO) mice as a function of age. Micro-computed tomography showed that Sdc4 deletion severely reduced vertebral trabecular and cortical bone mass, and biomechanical properties of vertebrae were significantly altered in Sdc4 KO mice. These changes in vertebral bone were likely due to elevated osteoclastic activity. The histological assessment showed subtle phenotypic changes in the intervertebral disc. Imaging-Fourier transform-infrared analyses showed a reduced relative ratio of mature collagen crosslinks in young adult nucleus pulposus (NP) and annulus fibrosus (AF) of KO compared to wildtype discs. Additionally, relative chondroitin sulfate levels increased in the NP compartment of the KO mice. Transcriptomic analysis of NP tissue using CompBio, an AI-based tool showed biological themes associated with prominent dysregulation of heparan sulfate GAG degradation, mitochondria metabolism, autophagy, endoplasmic reticulum (ER)-associated misfolded protein processes and ER to Golgi protein processing. Overall, this study highlights the important role of SDC4 in fine-tuning vertebral bone homeostasis and extracellular matrix homeostasis in the mouse intervertebral disc.


Subject(s)
Aging , Bone Diseases, Metabolic , Homeostasis , Mice, Knockout , Syndecan-4 , Animals , Mice , Syndecan-4/metabolism , Syndecan-4/genetics , Aging/metabolism , Aging/genetics , Bone Diseases, Metabolic/genetics , Bone Diseases, Metabolic/metabolism , Bone Diseases, Metabolic/pathology , X-Ray Microtomography , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Extracellular Matrix/metabolism , Extracellular Matrix/genetics , Spine/metabolism , Spine/pathology , Spine/diagnostic imaging , Annulus Fibrosus/metabolism , Annulus Fibrosus/pathology , Osteoclasts/metabolism
12.
Eur Spine J ; 33(6): 2439-2450, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705903

ABSTRACT

PURPOSE: To describe the physiology of spinal growth in patients with adolescent idiopathic scoliosis (AIS). METHODS: Narrative review of the literature with a focus on mechanisms of growth. RESULTS: In his landmark publication On Growth and Form, D'Arcy Thompson wrote that the anatomy of an organism reflects the forces it is subjected to. This means that mechanical forces underlie the shape of tissues, organs and organisms, whether healthy or diseased. AIS is called idiopathic because the underlying cause of the deformation is unknown, although many factors are  associated. Eventually, however, any deformity is due to mechanical forces. It has long been shown that the typical curvature and rotation of the scoliotic spine could result from vertebrae and intervertebral discs growing faster than the ligaments attached to them. This raises the question why in AIS the ligaments do not keep up with the speed of spinal growth. The spine of an AIS patient deviates from healthy spines in various ways. Growth is later but faster, resulting in higher vertebrae and intervertebral discs. Vertebral bone density is lower, which suggests  less spinal compression. This also preserves the notochordal cells and the swelling pressure in the nucleus pulposus. Less spinal compression is due to limited muscular activity, and low muscle mass indeed underlies the lower body mass index (BMI) in AIS patients. Thus, AIS spines grow faster because there is less spinal compression that counteracts the force of growth (Hueter-Volkmann Law). Ligaments consist of collagen fibres that grow by tension, fibrillar sliding and the remodelling of cross-links. Growth and remodelling are enhanced by dynamic loading and by hormones like estrogen. However, they are opposed by static loading. CONCLUSION: Increased spinal elongation and reduced ligamental growth result in differential strain and a vicious circle of scoliotic deformation. Recognising the physical and biological cues that contribute to differential growth  allows earlier diagnosis of AIS and prevention in children at risk.


Subject(s)
Scoliosis , Spine , Humans , Scoliosis/physiopathology , Adolescent , Biomechanical Phenomena/physiology , Intervertebral Disc/physiopathology
13.
Eur Spine J ; 33(6): 2405-2419, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38730057

ABSTRACT

PURPOSE: In vivo studies of continuous lumbar sagittal plane motion have found passive intervertebral motion to be more uneven in patients with chronic nonspecific low back pain (CNSLBP) than healthy controls, but the mechanisms are unclear. This study aimed to compare patients with CNSLBP with a matched group of pain-free controls for intervertebral restraint during passive recumbent bending. METHODS: Seventeen patients with CNSLBP and minimal disc degeneration who had quantitative fluoroscopy investigations were matched to 17 healthy controls from a database acquired using the same imaging protocol. The entire database (n = 136) was examined for clustering of peaking times, magnitudes and ROM of the first derivatives of the intervertebral angle/motion curves (PTFD, PMFD and ROM) during flexion and return that might introduce confounding. The groups were then compared for differences in these variables. RESULTS: There were significant segmental ROM differences among clusters in the database when PMFD and ROM were used as clustering variables, indicating heterogeneity. However, in the patient-control study, it was PTFD (velocity) that differentiated the groups. At L5-S1, this was at 10.82% of the motion path compared with 25.06% in the controls (p = 0.0002). For L4-5, PTFD was at 23.42% of the motion path in patients and 16.33% in controls (p = 0.0694) suggesting a reduced initial bending moment there. There were no significant differences for PMFD or ROM. CONCLUSION: Peaking time of passive intervertebral velocity occurs early at L5-S1 in patients with CNSLBP; however, these findings should be treated with caution pending their replication. Future studies should explore relationships with altered disc pressures and biochemistry. Usefulness for monitoring regenerative disc therapies should be considered.


Subject(s)
Low Back Pain , Range of Motion, Articular , Humans , Low Back Pain/therapy , Low Back Pain/physiopathology , Male , Female , Adult , Retrospective Studies , Middle Aged , Range of Motion, Articular/physiology , Lumbar Vertebrae/diagnostic imaging , Intervertebral Disc/physiopathology , Intervertebral Disc/diagnostic imaging , Chronic Pain/therapy , Chronic Pain/physiopathology , Case-Control Studies , Cohort Studies
14.
Med Sci Monit ; 30: e944335, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38783538

ABSTRACT

BACKGROUND Either a reduction in antioxidant levels or an accumulation of reactive oxygen species can heighten susceptibility to oxidative damage in disc cells. To date, no research has investigated the levels of lipid peroxidation products (thiobarbituric acid reactive substances [TBARs]), reduced glutathione (GSH), and glutathione peroxidase (GPx) in excised human lumbar disc tissues affected by degenerative disease. Therefore, this study aimed to evaluate lipid peroxidation products in excised disc tissues from patients with degenerative disc disease. MATERIAL AND METHODS Forty-two patients were enrolled. Patients were divided into lumbar disc degeneration (LDD) and nonlumbar disc degeneration (nonLDD) groups according to Pfirrmann classification. Intervertebral discs were obtained from all patients during the operation and were homogenized for analysis. TBARs levels were measured using fluorometry. GSH levels and GPx activity were quantified spectrophotometrically using a kinetic method. RESULTS TBARs levels in excised discs from LDD patients (5.18±4.14) were significantly higher than those from nonLDD patients (2.56±1.23, P=0.008). The levels of TBARs tended to increase with the severity of degeneration according to the Pfirrmann classification. However, these 2 groups showed no significant differences in reduced glutathione levels or glutathione peroxidase activity (P>0.05). Patients with LDD exhibited a worse health-related quality of life, reflected in lower utility and EQ-VAS scores and higher Oswestry disability index scores. CONCLUSIONS There was a notable increase in lipid peroxidation products in the excised intervertebral discs of patients with LDD. This finding suggests that oxidative stress may contribute to the development of disc degeneration.


Subject(s)
Glutathione Peroxidase , Glutathione , Intervertebral Disc Degeneration , Intervertebral Disc , Lipid Peroxidation , Lumbar Vertebrae , Oxidative Stress , Thiobarbituric Acid Reactive Substances , Female , Humans , Male , Middle Aged , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/metabolism , Lipid Peroxidation/physiology , Lumbar Vertebrae/metabolism , Oxidative Stress/physiology , Thiobarbituric Acid Reactive Substances/metabolism , Aged
15.
BMJ Open ; 14(5): e082244, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38719329

ABSTRACT

INTRODUCTION: Bacterial infection and Modic changes (MCs) as causes of low back pain (LBP) are debated. Results diverged between two randomised controlled trials examining the effect of amoxicillin with and without clavulanic acid versus placebo on patients with chronic LBP (cLBP) and MCs. Previous biopsy studies have been criticised with regard to methods, few patients and controls, and insufficient measures to minimise perioperative contamination. In this study, we minimise contamination risk, include a control group and optimise statistical power. The main aim is to compare bacterial growth between patients with and without MCs. METHODS AND ANALYSIS: This multicentre, case-control study examines disc and vertebral body biopsies of patients with cLBP. Cases have MCs at the level of tissue sampling, controls do not. Previously operated patients are included as a subgroup. Tissue is sampled before antibiotic prophylaxis with separate instruments. We will apply microbiological methods and histology on biopsies, and predefine criteria for significant bacterial growth, possible contamination and no growth. Microbiologists, surgeons and pathologist are blinded to allocation of case or control. Primary analysis assesses significant growth in MC1 versus controls and MC2 versus controls separately. Bacterial disc growth in previously operated patients, patients with large MCs and growth from the vertebral body in the fusion group are all considered exploratory analyses. ETHICS AND DISSEMINATION: The Regional Committees for Medical and Health Research Ethics in Norway (REC South East, reference number 2015/697) has approved the study. Study participation requires written informed consent. The study is registered at ClinicalTrials.gov (NCT03406624). Results will be disseminated in peer-reviewed journals, scientific conferences and patient fora. TRIAL REGISTRATION NUMBER: NCT03406624.


Subject(s)
Low Back Pain , Humans , Low Back Pain/microbiology , Case-Control Studies , Biopsy , Intervertebral Disc/microbiology , Intervertebral Disc/pathology , Lumbar Vertebrae/microbiology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/microbiology , Multicenter Studies as Topic , Antibiotic Prophylaxis
16.
Clin Biomech (Bristol, Avon) ; 116: 106266, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38821035

ABSTRACT

BACKGROUND: Most ball-in-socket artificial lumbar disc implanted in the spine result in increased hypermobility of the operative level and overloading of the facet joint. METHODS: A finite element model was established and validated for the lumbar spine (L1-L5). The structure of the Mobidisc prosthesis was modified, resulting in the development of two new intervertebral disc prostheses, Movcore and Mcopro. The prostheses were implanted into the L3/L4 level to simulate total disc replacement, and the biomechanical properties of the lumbar spine model were analyzed after the operation. FINDINGS: Following the implantation of the prostheses, the mobility of operative level, peak stress of lumbar spine models, and peak stress of facet joint increased. The performance of mobility was found to be more similar between Movcore and Mobidisc. The mobility and facet joint peak stress of the Mcopro model decreased progressively with an increase in the Young's modulus of the artificial annulus during flexion, extension, and lateral bending. Among all the models, the Mcopro50 model had the mobility closest to the intact model. It showed a 3% decrease in flexion, equal range of motion in extension, a 9% increase in left lateral bending, a 7% increase in right lateral bending, and a 3% decrease in axial rotation. INTERPRETATION: The feasibility of the new intervertebral disc prostheses, Movcore and Mcopro, has been established. The Mcopro prosthesis, which features an artificial annular structure, offers significant advantages in terms of reduced mobility of the operative level and peak stress of facet joint.


Subject(s)
Finite Element Analysis , Intervertebral Disc , Lumbar Vertebrae , Range of Motion, Articular , Humans , Lumbar Vertebrae/surgery , Lumbar Vertebrae/physiopathology , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Biomechanical Phenomena , Prosthesis Design , Total Disc Replacement/methods , Stress, Mechanical , Prostheses and Implants , Computer Simulation , Models, Biological , Zygapophyseal Joint/surgery , Zygapophyseal Joint/physiopathology
17.
J Biomech ; 169: 112131, 2024 May.
Article in English | MEDLINE | ID: mdl-38739987

ABSTRACT

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10-16 m4/Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration.


Subject(s)
Intervertebral Disc , Lumbar Vertebrae , Humans , Lumbar Vertebrae/physiology , Intervertebral Disc/physiology , Middle Aged , Male , Female , Porosity , Adult , Aged , Glycosaminoglycans/metabolism , Biomechanical Phenomena , Cartilage/physiology , Stress, Mechanical
18.
Clin Biomech (Bristol, Avon) ; 116: 106270, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38776646

ABSTRACT

BACKGROUND: A novel interspinous fixation system based on anatomical parameters and incorporating transfacetopedicular screws, was developed to treat degenerative disc diseases. The biomechanical characteristics of the novel system were evaluated using finite element analysis in comparison to other classical interspinous spacers. METHODS: The L1-S1 lumbar spine finite element models were surgically implanted with the novel system, Coflex and DIAM devices at the L4/L5 segment to assess the range of motion, the pression distribution of intervertebral disc, the peak stresses on the spinous process and implant during various motions. FINDINGS: Range of motions of the L4/L5 surgical segment were reduced by 29.13%, 61.27%, 77.35%, 33.33%, and the peak stresses of intervertebral disc were decreased by 36.82%, 67.31%, 73.00%, 69.57% for the novel system in flexion, extension, lateral bending, and axial rotation when compared with the Coflex, and they were declined by 34.53%, 57.86%, 75.81%, 25.21%; 36.22%, 67.31%, 75.01%, 71.40% compared with DIAM. The maximum stresses of the spinous process were 29.93 MPa, 24.66 MPa, 14.45 MPa, 24.37 MPa in the novel system, and those of Coflex and DIAM were 165.3 MPa, 109 MPa, 84.79 MPa, 47.66 MPa and 52.59 MPa, 48.78 MPa, 50.27 MPa, 44.16 MPa during the same condition. INTERPRETATION: Compared to other interspinous spacer devices, the novel interspinous fixation system demonstrated excellent stability, effectively distributing load on the intervertebral disc, and reducing the risk of spinous process fractures. The personalized design of the novel interspinous fixation system could be a viable option for treating degenerative disc diseases.


Subject(s)
Finite Element Analysis , Intervertebral Disc Degeneration , Lumbar Vertebrae , Range of Motion, Articular , Humans , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Degeneration/physiopathology , Lumbar Vertebrae/surgery , Lumbar Vertebrae/physiopathology , Biomechanical Phenomena , Intervertebral Disc/surgery , Intervertebral Disc/physiopathology , Stress, Mechanical , Bone Screws , Computer Simulation , Male , Spinal Fusion/instrumentation , Spinal Fusion/methods
19.
Neurol Med Chir (Tokyo) ; 64(6): 222-229, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38719578

ABSTRACT

The detailed changes in disc properties after intradiscal injection of condoliase remain controversial. At 3 and 9 months after administration, radiographic changes in discs were investigated. A total of 41 patients (men, 25; median age, 46 years) who underwent regular follow-up magnetic resonance imaging at 3 and 9 months after administration without additional invasive therapy were retrospectively investigated. The intensity changes of the nucleus pulposus based on the Pfirrmann disc grading system, midsagittal disc height, and maximum protrusion length of herniation were assessed. In addition, disc height changes were compared between 24 patients aged <50 years (young group) and 17 patients aged ≥50 years (over 50s group). The overall mean disc heights were 9.1, 7.5, and 7.6 mm preoperatively, at 3 months, and at 9 months, respectively, with a significant reduction at 3 months (P < 0.001) and no significant changes thereafter. The mean maximum protrusion length of herniation significantly and gradually decreased. The overall proportions of Pfirrmann disc grades after administration were equivalent between 3 and 9 months. However, the recovery from Pfirrmann disc grades IV to III was confirmed in 8 of 17 cases (47.1%) between 3 and 9 months, whereas 6 of 20 cases (30.0%) showed a decline from III to IV. Patients in the young group with pretreatment disc height >11 mm had the greatest reduction in disc height than the over 50s group. In conclusion, the clinical outcomes in the over 50s group were comparable to those in the young group after injection of condoliase, whereas young patients with higher disc were more susceptible to disc height reduction.


Subject(s)
Intervertebral Disc Displacement , Lumbar Vertebrae , Humans , Intervertebral Disc Displacement/diagnostic imaging , Male , Middle Aged , Female , Adult , Lumbar Vertebrae/diagnostic imaging , Retrospective Studies , Aged , Intervertebral Disc/diagnostic imaging , Hyaluronoglucosaminidase/administration & dosage , Hyaluronoglucosaminidase/therapeutic use , Magnetic Resonance Imaging
20.
J Bodyw Mov Ther ; 38: 384-390, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38763583

ABSTRACT

BACKGROUND: The static sitting position contributes to increased pressure on the lumbar intervertebral disc, which can lead to dehydration and decreased disc height. OBJECTIVE: To systematically investigate the of sitting posture on degeneration of the lumbar intervertebral disc. MATERIALS AND METHODS: One researcher carried out a systematic literature search of articles with no language or time limits. Studies from 2006 to 2018 were found. The searches in all databases were carried out on January 28, 2022, using the following databases: Pubmed, Scopus, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro) databases, and for the grey literature: Google scholar, CAPES Thesis and Dissertation Bank, and Open Grey. The acronym PECOS was used to formulate the question focus of this study: P (population) - male and female subjects; E (exposure) - sitting posture; C (comparison) - other posture or sitting posture in different periods; O (outcomes) - height and degeneration of the lumbar intervertebral disc(s), imaging exam; and S (study) - cross-sectional and case control. RESULTS: The risk of bias was in its moderate totality in its outcome: height and degeneration of the lumbar intervertebral disc(s) - imaging. Of the four selected studies, three found a decrease in the height of the disc(s) in sitting posture. CONCLUSION: The individual data from the manuscripts suggest that the sitting posture causes a reduction in the height of the lumbar intervertebral disc. It was also concluded that there is a need for new primary studies with a more in-depth design and sample size.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Lumbar Vertebrae , Sitting Position , Humans , Lumbar Vertebrae/physiology , Lumbar Vertebrae/physiopathology , Intervertebral Disc/physiology , Biomechanical Phenomena/physiology , Intervertebral Disc Degeneration/physiopathology , Posture/physiology , Male
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