Update on the Correlation Between Mitochondrial Dysfunction and Intervertebral Disk Degeneration.

Low back pain (LBP) is a common disorder in orthopedic outpatients, affecting people of all ages, and some patients may develop chronic LBP. As a complex organelle, mitochondria are not only energy workstations but also regulate cell senescence, apoptosis, and homeostasis. Mitochondrial dysfunction promotes disk degeneration by affecting a variety of pathophysiological processes, including oxidative stress, mitophagy, mitochondrial homeostasis, cellular senescence, and cell death. We review the molecular mechanisms underlying the relationship between mitochondrial dysfunction and intervertebral disk degeneration (IDD) to provide a theoretical basis for IDD treatment using pharmacological or tissue-engineering approaches.

The Mechanism and Function of miRNA in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) disease has been considered as the main cause of low back pain (LBP), which is a very common symptom and the leading cause of disability worldwide today. The pathological mechanism of IDD remains quite complicated, and genetic, developmental, biochemical, and biomechanical factors all contribute to the development of the disease. There exists no effective, non-surgical treatment for IDD nowadays, which is largely related to the lack of knowledge of the specific mechanisms of IDD, and the lack of effective specific targets. Recently, non-coding RNA, including miRNA, has been recognized as an important regulator of gene expression. Current studies on the effects of miRNA in IDD have confirmed that a variety of miRNAs play a crucial role in the process of IDD via nucleus pulposus cells (NPC) apoptosis, abnormal proliferation, inflammatory factors, the extracellular matrix (ECM) degradation, and annulus fibrosus (AF) degeneration. In the past 10 years, research on miRNA has been quite active in IDD. This review summarizes the current research progression of miRNA in the IDD and puts forward some prospects and challenges on non-surgical treatment for IDD.

Does discectomy improve low back pain as well as radiating pain in patients with lumbar herniated intervertebral disc (HIVD)?

ABSTRACT: Most postoperative patients with herniated lumbar disc complained of lower leg radiating pain (LRP), referred buttock pain (RBP), and low back pain (LBP). When discectomy is performed, improvement in LRP is observed due to spinal nerve irritation. However, long-term LBP due to degenerative changes in the disc may occur postoperatively. In addition, limited research has been reported on the short-term (within 1 year) improvement in LBP after discectomy. This study aimed to evaluate the effectiveness of discectomy in reducing LBP within 1 year postoperatively.Among the 183 patients who underwent discectomy performed by a single surgeon from January 2010 to December 2016, 106 who met the inclusion and exclusion criteria were enrolled. In the 106 patients who underwent lumbar discectomy, 3 types of spine-related pain were pre-operatively assessed and 3, 6, and 12 months postoperatively. Functional outcomes were evaluated, and quality of life was assessed 12 months postoperatively by using the Short-Form 36 questionnaire, which was subdivided into mental and physical components.LBP showed both statistical and clinical improvement within the first 3 months postoperatively, but the improvement was not observed until 12 months postoperatively. RBP and LRP showed both statistical and clinical improvement within the first 3 months and further consistently showed statistical improvement. LBP improved clinically only until 3 months postoperatively regardless of the type of herniation.LBP showed improvement within the first 3 months postoperatively and plateaued afterward, and RBP and radiculopathy showed consistent improvement until 12 months postoperatively. This may explain why patients from 12-month follow-up showed improvement in RBP and radiculopathy but not LBP.

The Effects of Elgucare on Degenerated Intervertebral Disc-Induced Low Back Pain and Disc Regeneration: A Clinical Trial.

INTRODUCTION: Chronic low back pain (LBP) has a wide range of causes. However, most cases are induced by degeneration of the lumbar intervertebral discs (IVDs), and the aching caused by local compression of the affected region has considerable impacts on quality of life. This clinical trial investigated the use of Elgucare, a Chinese herbal formula, as a food supplement to reduce the pain of patients with LBP induced by degeneration of the lumbar IVDs. METHODS: The study assessed patient subjective quality of life, functional limitations caused by LBP, and variations in pain. The assessment was done through the visual analogue scale (VAS) and effects on lumbar IVD thickness, water content, and bone mineral density (BMD). These parameters were evaluated before and after the administration of Elgucare or a placebo, one of which was taken by each participant for a 12-month period. RESULTS: Elgucare reduced the patients' mean VAS pain score by 2.25 points and improved their mean LBP-hampered mobility as assessed by the Roland-Morris Questionnaire by 5.17 points. The results of another questionnaire indicated that Elgucare slowed the LBP-induced deterioration of patients' quality of life, while objective assessment indices obtained through X-ray and magnetic resonance imaging showed that the height and water retention of their IVDs were increased. However, the BMD results showed no improvements. CONCLUSIONS: Elgucare can increase the water retention and height of IVDs and reduce LBP, thereby enhancing quality of life. Therefore, Elgucare can potentially be used as a clinical supplement.

MAPK /ERK signaling pathway: A potential target for the treatment of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.

Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance of the anabolic and catabolic processes in the intervertebral disc, leading to an alteration in the composition of the extracellular matrix (ECM), loss of nucleus pulposus (NP) cells, excessive oxidative stress and inflammation. Degeneration of the IVD occurs naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression. IVDD, often referred to as degenerative disc disease (DDD), poses an increasingly substantial financial burden due to the aging population and increasing incidence of obesity in the United States. Current treatments for IVDD include pharmacological and surgical interventions, but these lack the ability to stop the progression of disease and restore the functionality of the IVD. Biological therapies have been evaluated but show varying degrees of efficacy in reversing disc degeneration long-term. Stem cell-based therapies have shown promising results in the regeneration of the IVD, but face both biological and ethical limitations. Exosomes play an important role in intercellular communication, and stem cell-derived exosomes have been shown to maintain the therapeutic benefit of their origin cells without the associated risks. This review highlights the current state of research on the use of stem-cell derived exosomes in the treatment of IVDD.

DNMT3B decreases extracellular matrix degradation and alleviates intervertebral disc degeneration through TRPA1 methylation to inhibit the COX2/YAP axis.

Intervertebral disc degeneration (IVDD) is a main cause of low back pain that is associated with extracellular matrix (ECM) degradation and inflammation. This study aims to investigate the role of DNMT3B and its regulatory mechanisms in IVDD. IVDD rat models were constructed followed by transfections with oe-DNMT3B or oe-YAP in order to explore the role of DNMT3B in the development of IVDD. After that transfection, nucleus pulposus (NP) cells were isolated and transfected with oe-DNMT3B, oe-TRPA1, si-YAP, oe-YAP or oe-COX2 in order to investigate the functions of DNMT3B in NP cells. DNMT3B was poorly expressed in IVDD tissues and NP cells whereas TRPA1, COX2, and YAP were highly expressed. The proliferation or apoptosis of NP cells was detected through CCK-8 assay or flow cytometry, respectively. Overexpression of DNMT3B promoted the proliferation of NP cells, inhibited their apoptosis, as well as increasing the expression of collagen II and aggrecan and decreasing expression of MMP3 and MMP9. Besides, DNMT3B suppressed inflammation and alleviated IVDD. Mechanistically, DNMT3B modified the TRPA1 promoter by methylation to inhibit the expression of COX2. Overexpression of COX2 promoted the apoptosis of NP cells and decreased the expression of YAP, which was reversed by upregulating DNMT3B. DNMT3B may promote the proliferation of NP cells and prevent their ECM degradation through the TRPA1/COX2/YAP axis, thereby alleviating IVDD in rats.

The biomechanical effect on the adjacent L4/L5 segment of S1 superior facet arthroplasty: a finite element analysis for the male spine.

BACKGROUND: The superior facet arthroplasty is important for intervertebral foramen microscopy. To our knowledge, there is no study about the postoperative biomechanics of adjacent L4/L5 segments after different methods of S1 superior facet arthroplasty. To evaluate the effect of S1 superior facet arthroplasty on lumbar range of motion and disc stress of adjacent segment (L4/L5) under the intervertebral foraminoplasty. METHODS: Eight finite element models (FEMs) of lumbosacral vertebrae (L4/S) had been established and validated. The S1 superior facet arthroplasty was simulated with different methods. Then, the models were imported into Nastran software after optimization; 500 N preload was imposed on the L4 superior endplate, and 10 N⋅m was given to simulate flexion, extension, lateral flexion and rotation. The range of motion (ROM) and intervertebral disc stress of the L4-L5 spine were recorded. RESULTS: The ROM and disc stress of L4/L5 increased with the increasing of the proportions of S1 superior facet arthroplasty. Compared with the normal model, the ROM of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 2/5 from the apex to the base. The disc stress of L4/L5 significantly increased in most directions of motion when S1 superior facet formed greater than 3/5 from the ventral to the dorsal or 1/5 from the apex to the base. CONCLUSION: In this study, the ROM and disc stress of L4/L5 were affected by the unilateral S1 superior facet arthroplasty. It is suggested that the forming range from the ventral to the dorsal should be less than 3/5 of the S1 upper facet joint. It is not recommended to form from apex to base. LEVEL OF EVIDENCE: Level IV.

The Application of Mesenchymal Stromal Cells and Their Homing Capabilities to Regenerate the Intervertebral Disc.

Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current "gold standard" for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body's physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.

Clinical Efficacy and Safety of "Three-Dimensional Balanced Manipulation" in the Treatment of Cervical Spondylotic Radiculopathy by Finite Element Analysis.

Cervical spondylotic radiculopathy (CSR) is the most commonly encountered cervical spine disorder. Cervical manipulation has been demonstrated as an effective therapy for patients. However, the mechanisms of manipulations have not been elucidated. A total of 120 cervical spondylotic radiculopathy patients were divided into the "three-dimensional balanced manipulation" treatment group (TBM group) and control group randomly. The control group was treated with traditional massage; the TBM treatment group was treated with "three-dimensional balanced manipulation" based on traditional massage. The symptoms and clinical efficacy of the patients were compared before and after treatment for one month. A three-dimensional finite element model was established. The mechanical parameters were imported to simulate TBM, and finite element analysis was performed. The results showed that the total effective rate was significantly higher in the TBM group compared with the control group. The biomechanical analysis showed the vertebral body stress was mainly distributed in the C3/4 spinous processes; the deformation mainly concentrated in the anterior processes of the C3 vertebral body. The intervertebral disc stress in the C3~C7 segment was mainly distributed in the anterior part of the C3/4 intervertebral disc, and the deformation extends to the posterior part of the C3/4 nucleus pulposus. In summary, these data are suggesting that TBM was effective in CSR treatment. The results of the finite element model and biomechanical analysis provide an important foundation for effectively avoiding iatrogenic injuries and improving the effect of TBM in the treatment of CSR patients.

Cell-based strategies for IVD repair: clinical progress and translational obstacles.

Intervertebral disc (IVD) degeneration is a major cause of low back pain, a prevalent and chronic condition that has a striking effect on quality of life. Currently, no approved pharmacological interventions or therapies are available that prevent the progressive destruction of the IVD; however, regenerative strategies are emerging that aim to modify the disease. Progress has been made in defining promising new treatments for disc disease, but considerable challenges remain along the entire translational spectrum, from understanding disease mechanism to useful interpretation of clinical trials, which make it difficult to achieve a unified understanding. These challenges include: an incomplete appreciation of the mechanisms of disc degeneration; a lack of standardized approaches in preclinical testing; in the context of cell therapy, a distinct lack of cohesion regarding the cell types being tested, the tissue source, expansion conditions and dose; the absence of guidelines regarding disease classification and patient stratification for clinical trial inclusion; and an incomplete understanding of the mechanisms underpinning therapeutic responses to cell delivery. This Review discusses current approaches to disc regeneration, with a particular focus on cell-based therapeutic strategies, including ongoing challenges, and attempts to provide a framework to interpret current data and guide future investigational studies.

Biomechanical finite element analysis of vertebral column resection and posterior unilateral vertebral resection and reconstruction osteotomy.

BACKGROUND: Regarding the repair of vertebral compression fractures, there is a lack of adequate biomechanical verification as to whether only half of the vertebral body and the upper and lower intervertebral discs affect spinal biomechanics; there also remains debate as to the appropriate length of fixation. METHODS: A model of old vertebral compression fractures with kyphosis was established based on CT data. Vertebral column resection (VCR) and posterior unilateral vertebral resection and reconstruction (PUVCR) were performed at T12; long- and short-segment fixation methods were applied, and we analyzed biomechanical changes after surgery. RESULTS: Range of motion (ROM) decreased in all fixed models, with lumbar VCR decreasing the most and short posterior unilateral vertebral resection and reconstruction (SPUVCR) decreasing the least; in the long posterior unilateral vertebral resection and reconstruction (LPUVCR) model, the internal fixation system produced the maximum VMS stress of 213.25 mPa in a lateral bending motion and minimum stress of 40.22 mPa in a lateral bending motion in the SVCR. CONCLUSION: There was little difference in thoracolumbar ROM between PUVCR and VCR models, while thoracolumbar ROM was smaller in long-segment fixation than in short-segment fixation. In all models, the VMS was most significant at the screw-rod junction and greatest at the ribcage-vertebral body interface, partly explaining the high probability of internal fixation failure and prosthesis migration in these two positions.

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research.

Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations' processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

Evaluation of nucleus pulposus fluid velocity and pressure alteration induced by cartilage endplate sclerosis using a poro-elastic finite element analysis.

The nucleus pulposus (NP) in the intervertebral disk (IVD) depends on diffusive fluid transport for nutrients through the cartilage endplate (CEP). Disruption in fluid exchange of the NP is considered a cause of IVD degeneration. Furthermore, CEP calcification and sclerosis are hypothesized to restrict fluid flow between the NP and CEP by decreasing permeability and porosity of the CEP matrix. We performed a finite element analysis of an L3-L4 lumbar functional spine unit with poro-elastic constitutive equations. The aim of the study was to predict changes in the solid and fluid parameters of the IVD and CEP under structural changes in CEP. A compressive load of 500 N was applied followed by a 10 Nm moment in extension, flexion, lateral bending, and axial rotation to the L3-L4 model with fully saturated IVD, CEP, and cancellous bone. A healthy case of L3-L4 physiology was then compared to two cases of CEP sclerosis: a calcified cartilage endplate and a fluid constricted sclerotic cartilage endplate. Predicted NP fluid velocity increased for the calcified CEP and decreased for the calcified + less permeable CEP. Decreased NP fluid velocity was prominent in the axial direction through the CEP due to a less permeable path available for fluid flux. Fluid pressure and maximum principal stress in the NP were predicted to increase in both cases of CEP sclerosis compared to the healthy case. The porous medium predictions of this analysis agree with the hypothesis that CEP sclerosis decreases fluid flow out of the NP, builds up fluid pressure in the NP, and increases the stress concentrations in the NP solid matrix.

Facet Tropism in Lumbar Spine and Cervical Spine: A Systematic Review and Meta-Analysis.

BACKGROUND: Facet tropism (FT) refers to the difference in the orientation of facet joints with respect to each other in the sagittal plane. FT leads to unequal biomechanical forces on facet joint and intervertebral disc during rotation and other physiologic movements. Most of the studies have reported the incidence of FT in the lumbar spine to vary between 40% and 70%, with L4-5 level being the most commonly afflicted level. The objective of this study was to find the association between FT and various lumbar and cervical degenerative disorders. METHODS: A systematic search of PubMed was performed with the keywords "facet tropism" and "facet asymmetry." Data for meta-analysis were extracted from the studies to obtain pooled impact of FT on lumbar disc herniation (LDH) and lumbar degenerative spondylolisthesis (LDS). RESULTS: Eighty-two articles were included in the systematic review and 18 studies had the required data to be included in the meta-analysis. The pooled standard mean difference between FT angles in patients with or without LDH was 0.31 with (P = 0.04). The pooled odds ratio for FT in patients with LDH was 3.27 with (P = 0.02). Subgroup analysis showed that there is no significant difference in the L3/4, L4/5, and L5S1 subgroups. The pooled standard mean difference between FT angles in patients with or without LDS was 0.54 (P = 0.009). CONCLUSIONS: FT is significantly associated with LDH and LDS along with various other lumbar and cervical degenerative diseases.

Degeneration alters structure-function relationships at multiple length-scales and across interfaces in human intervertebral discs.

Intervertebral disc (IVD) degeneration and associated back pain place a significant burden on the population. IVD degeneration is a progressive cascade of cellular, compositional, and structural changes, which results in a loss of disc height, disorganization of extracellular matrix architecture, tears in the annulus fibrosus which may involve herniation of the nucleus pulposus, and remodeling of the bony and cartilaginous endplates (CEP). These changes to the IVD often occur concomitantly, across the entire motion segment from the disc subcomponents to the CEP and vertebral bone, making it difficult to determine the causal initiating factor of degeneration. Furthermore, assessments of the subcomponents of the IVD have been largely qualitative, with most studies focusing on a single attribute, rather than multiple adjacent IVD substructures. The objective of this study was to perform a multiscale and multimodal analysis of human lumbar motion segments across various length scales and degrees of degeneration. We performed multiple assays on every sample and identified several correlations between structural and functional measurements of disc subcomponents. Our results demonstrate that with increasing Pfirrmann grade there is a reduction in disc height and nucleus pulposus T2 relaxation time, in addition to alterations in motion segment macromechanical function, disc matrix composition and cellular morphology. At the cartilage endplate-vertebral bone interface, substantial remodeling was observed coinciding with alterations in micromechanical properties. Finally, we report significant relationships between vertebral bone and nucleus pulposus metrics, as well as between micromechanical properties of the endplate and whole motion segment biomechanical parameters, indicating the importance of studying IVD degeneration as a whole organ.

Biomechanical effects of reconstruction of the posterior structures after laminectomy with an individualized poly-ether-ether-ketone (PEEK) artificial lamina.

BACKGROUND: Laminectomy is a traditional method for treating lumbar diseases; however, the destruction of the posterior structures may cause postoperative symptoms. An individualized poly-ether-ether-ketone (PEEK) artificial lamina was designed to reconstruct the posterior structures after laminectomy. This study aimed to explore the biomechanical effects of reconstruction of the posterior structures with an individualized PEEK artificial lamina using validated finite element models. OBJECTIVE: To examine the biomechanical effects of individualized PEEK artificial lamina on postlaminectomy lumbar. METHODS: A finite element (FE) model of L3-5 was developed based on computed tomography images. Four surgical models (laminectomy, artificial lamina alone, ligament reconstruction, and osseointegration) were constructed, representing different stages of L4 artificial lamina implantation. The range of motion (ROM), intradiscal pressure (IDP), stresses in the annulus fibrosus at the surgical level and cephalad adjacent level, and stresses in the artificial lamina and screws were measured. RESULTS: The ROM, IDP, and stresses in the annulus fibrosus of the different artificial lamina models decreased compared to those of the laminectomy model at both surgical and adjacent levels for all motion patterns, most notably in the osseointegration model. In addition, the results of the stresses in the implants showed that the artificial lamina could enhance the lumbar isthmus and disperse the abnormally concentrated stresses after laminectomy. CONCLUSION: The application of a PEEK artificial lamina has the potential to stabilize the postlaminectomy lumbar spine and prevent adjacent segment disease (ASD) and iatrogenic lumbar deformities, resulting in a reduction in the incidence of post-lumbar surgery syndrome.

Investigation of Alterations in the Lumbar Disc Biomechanics at the Adjacent Segments After Spinal Fusion Using a Combined In Vivo and In Silico Approach.

The development of adjacent segment degeneration (ASD) is a major concern after lumbar spinal fusion surgery, but the causative mechanisms remain unclear. This study used a combined in vivo and in silico method to investigate the changes of anatomical dimensions and biomechanical responses of the adjacent segment (L3-4) after spinal fusion (L4-S1) in five patients under weight-bearing upright standing conditions. The in vivo adjacent disc height changes before and after fusion were measured using a dual fluoroscopic imaging system (DFIS), and the measured in vivo intervertebral positions and orientations were used as displacement boundary conditions of the patient-specific three-dimensional (3D) finite element (FE) disc models to simulate the biomechanical responses of adjacent discs to fusion of the diseased segments. Our data (represented by medians and 95% confidence intervals) showed that a significant decrease by - 0.8 (- 1.2, - 0.4) mm (p < 0.05) in the adjacent disc heights occurred at the posterior region after fusion. The significant increases in disc tissue strains and stresses, 0.32 (0.21, 0.43) mm/mm (p < 0.05) and 1.70 (1.07, 3.60) MPa (p < 0.05), respectively, after fusion were found in the posterolateral portions of the outermost annular lamella. The intradiscal pressure of the adjacent disc was significantly increased by 0.29 (0.13, 0.47) MPa after fusion (p < 0.05). This study demonstrated that fusion could cause alterations in adjacent disc biomechanics, and the combined in vivo and in silico method could be a valuable tool for the quantitative assessment of ASD after fusion.

Clinical efficacy of targeted injection of drugs in combination with ozone in treatment of lumbar disc protrusion.

To investigate the clinical efficacy of targeted injection of drugs surrounding the protruded lumbar disc in combination with the ozone in treatment of lumbar disc protrusion. Between January 2017 and January 2019, a total of 120 patients with lumbar disc protrusion were recruited in this study and divided into the control group and observation group, with 60 patients in each group. Patients in the control group received the ozone treatment, while those in the observation group additionally took the targeted injection of betamethasone surrounding the protruded lumbar disc. Following one month of treatment, we compared the short-term efficacy, joint range of motion in bending forward or backward of the lumbar disc, limb function, life quality and functional disturbance before and after treatment. In the observation group, the short-term effectiveness rate was higher than that in the control group (P<0.05), while after treatment, the joint range of motion in bending forward or backward of lumbar disc in the observation group was improved when comparing to the control group (P<0.05). After treatment, BI and Fugl-Meyer scale were all higher in the observation than those in the control group (P<0.05), with a lower Oswestry score (P<0.05). Targeted injection of betamethasone surrounding the protruded lumbar disc in combination with the ozone performs well in short-term efficacy, conducive to the improvement of the lumbar disc function and limb function and alleviation in function disturbance. Thus, this strategy is worthy of being promoted in clinical practice.

Disc wall structural abnormalities can act as initiation sites for herniation.

Both posture and loading rate are key factors in the herniation process and can determine the failure mechanism of the disc. The influence of disc structure on the herniation process has yet to be directly observed, thus the aim of this study was to test the hypothesis that discs containing greater levels of pre-existing disruption would be more vulnerable to herniation when subjected to severe levels of posture and loading. 30 ovine lumbar motion segments were subjected to combinations of 4 loading conditions (0 - 12° flexion,0 - 9° lateral bending, 0 - 4° axial rotation, 0-1500 N axial compression) for 1000 loading cycles at 2 Hz in a dynamic disc loading simulator. The discs were scanned in an ultra-high field MRI (magnetic resonance imaging, 11.7 T) prior to and following testing. 4 discs herniated and 7 discs suffered nucleus displacement. These discs contained pre-existing defects in the central dorsal annulus. Generally, following testing, discs contained more dorsal annulus disruption, including 7 discs which developed similar characteristic defects although these did not herniate. Overall, more severe complex postures produced more disruption. While more severe postures such as twisting and bending increased disc damage, these results are probably the first directly showing that naturally occurring defects in the disc can act as initiation sites for herniation. The clinical significance of these findings is that, in principle at least, MRI based techniques could be capable of identifying vulnerable discs, with the obvious caveat that further correlation with clinical techniques is required.