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Study Design: Animal laboratory study., Objective: This study investigated the effects of Cutibacteriumacnes and Staphylococcusepidermidis on the lumbar discs of rabbits, as well as the outcomes of combined infection., Summary of Background Data: Many studies have indicated that bacterial infections are associated with lumbar disc degeneration (LDD). The most commonly cultured bacteria from disc tissues are C. acnes and S. epidermidis ., Methods: New Zealand white rabbits (n=40) were randomly divided into control, C. acnes , S. epidermidis , and C. acnes plus S. epidermidis ( i.e. , combined) groups. All groups except the control were injected with 25 μL of saline at L4-L5 and 25 μL of bacteria (1×10 7 CFU/mL) at L5-L6. All injections were performed under x-ray guidance. Weight measurements, haematological evaluations, and magnetic resonance imaging were performed after 4, 8, and 12 weeks. Histological examination and gene expression detection were performed 12 weeks after surgery., Results: Inflammatory factors in the blood and weight did not differ among the groups after 4, 8, and 12 weeks ( P >0.05). However, after 4 weeks, LDD occurred in the C. acnes group, and discitis occurred in the S. epidermidis and combined groups, all of which worsened after 8 weeks. After 12 weeks, the nucleus pulposus (NP) protruded and compressed the spinal cord in the C. acnes group, and tissue staining showed decreased NP tissue and cartilaginous endplate fracture. In the S. epidermidis and combined groups, the discitis was more confined, but tissue staining revealed a significant decrease in NP tissue, and loss of the normal disc structure., Conclusions: In the early stage of infection in rabbits, C. acnes caused LDD, and S. epidermidis caused discitis. Coinfection with C. acnes and S. epidermidis caused discitis but was more limited in scope than infection with S. epidermidis alone., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: TNFAIP8 and TIPE2 belong to TNFa-induced protein 8 (TNFAIP8/TIPE) family. They control apoptosis and direct leukocyte migration. Nucleus pulposus cell loss is a hallmark of intervertebral disc degeneration in response to injury, and inflammation may cause pain. Here, we examined the effects of TNFAIP8/TIPE2 deficiency on the intervertebral discs in mice with these genes deleted., Design: Tail intervertebral discs in Tnfaip8 or Tipe2 single and double knockout mice ( Tnfaip8 -/- , Tipe2 -/- , and Tnfaip8/Tipe2 dko) , and wild-type controls were injured. The spine motion segments were stained with safranin O to reveal proteoglycans. Macrophages were identified by immunostaining, and selected inflammatory marker and collagen gene expression was examined by Real Time PCR., Results: The injured tail intervertebral discs of Tnfaip -/- , Tipe2 -/- , and Tnfaip8/Tipe2 dko mice all displayed higher levels of proteoglycans than wild-type controls. Fewer macrophages were found in the injured intervertebral discs of Tipe2 -/- and Tnfaip8/Tipe2 dko mice than wild type. Il6 , Adam8 , and Col1 gene expression was downregulated in the injured intervertebral discs of Tnfip8/Tipe2 dko mice., Conclusions: TNFAIP8 and TIPE2 loss of function ameliorated proteoglycan loss and inflammation in the injured intervertebral discs. They may serve as molecular targets to preserve disc structure and reduce inflammation., Competing Interests: Ethical approval statement: All animal use in this study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Pennsylvania, Philadelphia, PA. The authors have no financial or other conflict of interest. All authors approved the final version of the manuscript submitted. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Observational serial computed tomography (CT) analysis of the lumbar spine in a normal-aging population., Objective: To assess the natural history of the intradiscal vacuum phenomenon (IDVP) and its role in disc degeneration., Background: The natural history of disc degeneration is well described but our understanding of the end stage of pathogenesis remains incomplete. Magnetic resonance imaging loses accuracy with advanced degeneration, becoming hyporesonant and indistinct. Cadaveric specimens display adaptive changes in the disc with loss of the hydrostatic capacity of the nucleus, increased intradiscal clefts, and endplate impermeability. IDVP is associated with advanced disc degeneration and CT is the optimal modality to visualize this, yet these insights remain unreported., Patients and Methods: Patients only included historic CT abdomen scans of those over 60 years of age without acute or relevant spinal pathology, with a diagnosis of at least one level with IDVP on the original CT scan, and all of whom had a similar scan >7 years later. A history of clinically significant back pain was also recorded., Results: CT scans included 360 levels in 29 males and 31 females (mean: 68.9 y), displaying 82 levels of IDVP, with a second scan included after a mean of 10.3 years. Most levels displayed the same level of severity (persisted, 45) compared with where some progressed (26), regressed (8), and fused (3; P < 0.01). There was also an increased incidence, 37/60 (62%) of developing IDVP at another level. Disc heights were reduced with increased severity of IDVP. A record of back pain was evident in 31/60 patients, which was not significantly worse in those with worsening severity or additional level involvement over the study period., Conclusion: As disc degeneration advances, the associated IDVP persists in most cases, displaying a plateauing of severity over long periods, but rarely with progression to autofusion., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective, case series., Objective: To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH., Background: Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this "self-healing" phenomenon remains poorly understood, particularly in the context of multilevel herniations., Methods: A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatory-modulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH., Results: Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH ( P <0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects ( P =0.001), L4/L5 superior endplate defects ( P =0.012), and L4/L5 inferior endplate defects ( P =0.020) on MRI. No other differences in MRI phenotypes ( e.g. Modic changes, osteophytes, etc .) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH., Conclusions: Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with single-level LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected., Level of Evidence: Level 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Prospective observational study., Objective: To determine the prevalence of isolated thoracic degeneration on magnetic resonance imaging (MRI), demographic factors and imaging features, as well as the patient-reported quality of life outcomes associated with this condition., Summary of Background Data: Thoracic intervertebral discs are least susceptible to disc degeneration (DD) and may represent a manifestation of "dysgeneration." These discs may never be hydrated from the beginning and seem hypointense on MRI., Patients and Methods: A population-based MRI study of 2007 volunteers was conducted. Each disc from C2/3 to L5/S1 was measured by Pfirrmann and Schneiderman grading. Disc herniation, Schmorl node (SN), high-intensity zones (HIZ), and Modic changes were studied. DD was defined by Pfirrmann 4 or 5. patient-reported quality of life scores, including a 36-item short-form questionnaire and visual analog scale for low back pain, were recorded. Subjects were divided into "isolated thoracic degeneration" (only thoracic segment) and "tandem thoracic degeneration" (thoracic with other segments). The association between imaging findings and isolated thoracic degeneration was determined using multivariate logistic regression., Results: The mean age of the subjects was 50.0 ± 0.5 and 61.4% were females (n = 1232). Isolated thoracic degeneration was identified in 2.3% of the cohort. Factors associated with isolated thoracic degeneration included lower age, C6/7 HIZ, T8/9 HIZ, and T8/9 SN. Factors associated with tandem thoracic degeneration included L4/5 posterior bulging. The thoracic and lumbar tandem degeneration group demonstrated higher bodily pain, despite a lower visual analog scale, and a higher physical component score of the 36-item short form., Conclusions: Isolated thoracic degeneration demonstrated an earlier age of onset, mostly involving the mid-thoracic region (T5/6-T8/9), and in association with findings such as SN. Subjects with tandem thoracolumbar degeneration had less severe lumbar DD and low back pain as compared with those with isolated lumbar degeneration. This paints the picture of "dysgeneration" occurring in the thoracic and lumbar spine., Level of Evidence: 1., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lumbar herniated nucleus pulposus (L-HNP) is a condition in which fibroblasts escape due to degenerative changes or external forces in the intervertebral disc, causing neurological symptoms by compressing the dura mater or nerve root., Objectives: The purpose of this study is to analyze and compare the effectiveness, economic feasibility, and safety of using an integrated medical service critical pathway (CP) in L-HNP patients., Methods: This single-center prospective observational study will be performed at Kyung Hee University Medicine Hospital and Kyung Hee University Korean Medicine Hospital. The inclusion criteria are a diagnosis of L-HNP on magnetic resonance imaging or computed tomography scans, age under 80 years, a visual analog scale score of 7 or higher for either lower back pain or lower extremity pain. The included 102 participants will be classified into 6 groups (n = 17 in each group): CP application with conservative treatment; CP application with open discectomy; CP application with intrabody fusion; conservative treatment without CP application; open discectomy without CP application; and interbody fusion without CP application. We will collect data on the visual analog scale, ODI, SF-36, and EQ-5D-3L scores; number of admission days; medical staff satisfaction; patients health service satisfaction; waiting time for consultations; use of pain relievers; and CP application and completion rates., Conclusion: In future, this study is expected to serve as a basis for follow-up studies on the development and application of CPs in integrated medical services for various diseases, including lumbar herniated nucleus pulposus., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Herniation of the thoracic intervertebral disc (HTD) is a rare disease that accounts for <1% of all disc herniations. Physicians may make diagnostic errors due to the variable clinical features and limited experience of HTD. In this report, we present 2 unusual cases of HTD., Patient Concerns: A 72-year-old woman (case 1) visited our pain clinic because of chronic abdominal discomfort with visible bulging on the left side. Atrophy of the abdominal wall muscle and quadratus lumborum was observed. The therapeutic effect of interfascial plane block to exclude the possibility of truncal neuropathy following muscular atrophy was temporary. The other patient, a 75-year-old man (case 2) complained of aggravation of previously diagnosed postherpetic neuralgia. An extension of the previously symptomatic area of the forward upper dermatome was observed. Radiofrequency treatment on the symptomatic dorsal root ganglion failed to relieve symptoms., Diagnoses: Two patients underwent magnetic resonance imaging of the spine for further evaluation. The patients were diagnosed with multilevel HTD and foraminal herniated disc, compatible with their symptoms and without myelopathy., Interventions: Two patients were conservatively treated with a fluoroscopy-guided transforaminal epidural block., Outcomes: The 2 patients experienced significant pain reduction up to 50% on a numeric rating scale after repeated treatment., Lessons: Multilevel HTD of the mid- to lower-thoracic spine may present as abdominal bulging with atrophy of the abdominal wall muscles. We also report another case of concomitant symptomatic thoracic radiculopathy from HTD and postherpetic neuralgia at the adjacent level. Thoracic transforaminal epidural block may be considered a conservative therapeutic approach for HTD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to investigate the relationship between cervical region subcutaneous fat tissue thickness and the presence and level of cervical intervertebral disc degeneration (IVDD)., Methods: Magnetic resonance imaging examinations of patients referred to our clinic for the investigation of neck pain were evaluated retrospectively. A total of 300 women aged 30-40 years were included in the study. The presence and level of IVDD were evaluated for each patient. The cervical subcutaneous fat tissue thickness was also measured., Results: IVDD was determined as Grade 1 for 88 patients (29.3%), Grade 2 for 56 patients (18.6%), Grade 3 for 82 patients (27.3%), Grade 4 for 60 patients (20%), and Grade 5 for 14 patients (4.6%). Subcutaneous fat tissue thickness was higher in patients with cervical disc degeneration (mean: 6.28 ± 0.19 mm) than in those without cervical disc degeneration (mean: 5.33 ± 0.18 mm) (P = .001). There was a positive correlation between the degree of cervical disc degeneration and subcutaneous fat tissue thickness ( = 0.001, r = 0.245)., Conclusion: An increase in the cervical fat tissue thickness is a predisposing factor for the development of degeneration of the intervertebral disc. There is a close relationship between subcutaneous fat tissue thickness and the degree of degeneration., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: Porcine intervertebral discs (IVDs) were excised and then drilled to simulate degeneration before being electrically stimulated for 21 days while undergoing mechanical loading. The discs were then analyzed for gene expression and morphology to assess regeneration., Objective: The purpose of this study was to investigate the effectiveness of the electrical stimulation of IVD treatment as an early intervention method in halting the progression of degenerative disc disease using an ex-vivo porcine model., Summary of Background Data: Treatments for degenerative disc disease are limited in their efficacy and tend to treat the symptoms of the disease rather than repairing the degenerated disc itself. There is a dire need for an early intervention treatment that not only halts the progression of the disease but contributes to reviving the degenerated disc., Methods: Lumbar IVDs were extracted from a mature pig within 1 hour of death and were drilled with a 1.5 mm bit to simulate degenerative disc disease. Four IVDs at a time were then cultured in a dynamic bioreactor system under mechanical loading for 21 days, two with and two without the electrical stimulation treatment. The IVDs were assessed using histological analysis, magnetic resonance imaging, and quantitative reverse transcriptase polymerase chain reaction to quantify the effectiveness of the treatment on the degenerated discs., Results: IVDs with electrical stimulation treatment exhibited extensive annular regeneration and prevented herniation of the nucleus pulposus (NP). In contrast, the untreated group of IVDs were unable to maintain tissue integrity and exhibited NP herniation through multiple layers of the annulus fibrosus. Gene expression showed an increase of extracellular matrix markers and antiinflammatory cytokine interleukin-4 (IL-4), while decreasing in pro-inflammatory markers and pain markers in electrically stimulated IVDs when compared to the untreated group., Conclusion: The direct electrical stimulation application in NP of damaged IVDs can be a viable option to regenerate damaged NP and annulus fibrosus tissues., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To gain better insight into the magnetic resonance imaging (MRI) appearance of morphological intervertebral disc (IVD) details, such as annular and nucleus pulposus dimensions, by comparing contemporaneously obtained MRI and postdiscogram computed tomography (CT) scans of nondegenerated IVDs., Methods: Axial T2-weighted images and same-day postdiscography CTs, acquired after the MRI, of 26 normal-appearing lumbar IVDs (control IVDs at discography) were compared. The location and extent of central hyperintense zone on MRI and the extent of contrast distribution on CT relative to the IVD width (in anteroposterior [AP] and lateral planes) were assessed, with difference in measures between the modalities used to provide apparent inner annulus thickness and to estimate dimensions of also the outer annulus and location of nucleus pulposus., Results: The mean (SD) extent of contrast distribution on CT discograms (53.1% [6.6%] and 58.1% [8.7%] of AP and lateral IVD width) was smaller than (P < 0.001 for both), and correlated weakly (r = 0.31 and 0.32 for AP and lateral planes) with corresponding measurements (58.4% [5.3%] and 65.7% [5.9%], respectively) for central hyperintense zone at MRI. The center of contrast opacification on CT discograms was located posterior to that of central T2 hyperintense zone on MRI in AP (P < 0.01), without any difference in lateral direction (P = 0.60)., Conclusions: Normal-appearing lumbar IVDs are supported by outer annulus of larger relative thickness anteriorly, seen on both modalities. The shown discrepancy between the central T2 hyperintense zone and contrast distribution on CT discogram might reflect the inner annulus or structural changes within the borderzone nucleus and annulus. The exact nucleus size and inner annulus thickness could not be established due to a variable permeation of contrast across the central hyperintense zone on T2-weighted images., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Genetic cross-over study of intervertebral disc degeneration (IDD) and its associated risk factors., Objective: The purpose is to identify molecular biomarkers that may be involved in the IDD process and to provide effective recommendations in combination with drug analysis via systems biology methods., Summary of Background Data: The pathogenesis and genetic links of IDD are still unclear. Related research is mainly based on a single data set or gene, and the impact of related risk factors on IDD is often ignored., Methods: Identifying disease-associated biomarkers and therapeutic targets through a systems biology approach that Integrative network-based gene and multi-omics analysis. In this study, the differential expression of genes was analyzed through NCBI datasets, followed by enrichment analysis. The central protein was identified through the establishment of protein-protein interaction (PPI) network. Key genes were screened out by VENN diagram and reasonable suggestions were put forward based on gene-chemical drug analysis., Results: The IDD database analysis revealed 669 differentially expressed genes (DEGs) which were 22, 26, 168, 5, 38, 36, and 16 common DEGs with AG, SM, DEP, NAD, CED, OB, and HFD, respectively. GO and KEGG enrichment analysis may reveal the pathway by which these DEGs were involved. PPI network identified 10 central proteins including CCNB1, RETN, HMMR, BUB1, MPO, OIP5, HP, KIF11, BUB1B, and CDC25A. Three key genes BUB1, BUB1B, and CCNB1 were screened out and their expression might be related to the pathogenesis of IDD. According to the three chemical Dexamethasone, Nicotine, and Resvera-trol obtained from the analysis of genes-chemical drugs, reasonable treatment suggestions were put forward., Conclusion: Genetic association between IDD and risk factors in the general population was revealed by association network. Important gene-related molecular pathways and chemical drugs closely related to IDD have been found. Further study can provide guidance for the treatment and prognosis of IDD.Level of Evidence: N/A., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Case-control studies by examining the lumbar spine computed tomography (CT) findings focusing on the spinous processes."Passing spine" was defined as a lumbar degenerative change observed on CT images. In contrast, kissing spine, which is also an image finding, has been acknowledged as an established clinical condition. Therefore, we compared the passing spine group and the kissing spine group to investigate whether the 2 groups belong to a similar disease group; this would help explain the clinical and imaging characteristics of patients with passing spine.Previous studies have described the gradual increase in the height and thickness of the lumbar vertebral spinous processes that can occur in individuals aged >40 years, and reported that this progressive degeneration can lead to a condition termed "kissing spine."We examined the CT imaging of 373 patients with lumbar spinal disease and divided patients into 2 groups, the kissing spine (K) group and the passing spine (P) group, and compared the clinical (age, sex, presence/absence of lower extremity pain) and imaging data (localization of kissing or passing spine, intervertebral disc height at the level of kissing or passing spine, lumbar lordosis (LL) angle, presence/absence of vacuum phenomenon (VP) in the intervertebral discs and spondylolisthesis at the level of kissing or passing spine between the 2 groups.Compared with patients with kissing spine, patients with passing spine had an increased incidence of lower extremity pain, lower intervertebral disc height at the level of passing spine, relatively static LL, and VP commonly observed in the intervertebral discs at the level of passing spine.Because the clinical and imaging characteristics of patients with passing spine are different from those of patients with kissing spine, passing spine might be a pathological condition distinct from kissing spine., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: The cartilage endplate plays an important role in the stress distribution and nutrition metabolism of the intervertebral disc. The healing morphology of the endplate after spinal fracture and its effect on the intervertebral disc degeneration are still unclear.This was a retrospective study. Patients with traumatic single-level thoracolumbar fractures treated in our orthopedic trauma service center from June 2011 to May 2019 were included and the relevant data were collected from the medical records. Based on combined computed tomography and MRI images, the endplate injury status was determined (no endplate injury, unilateral and bilateral endplate injury). According to the location of the injury, endplate injury was further divided into endplate central injury and endplate peripheral injury. The degree of posttraumatic disc lesions and disc degeneration during follow-up were classified based on the Sander classification and the Pfirrmann classification, respectively. According to the T1 image of MRI at the final follow-up, the healing morphology of endplates was determined and classified. Univariate analyses and correlation analyses were performed to evaluate the within- and between-group differences.There were in total 51 patients included in this study. Cartilage endplate fracture was significantly closely related to the degree of degeneration of the intervertebral disc (P = .003). Injuries in different parts of the endplate have no significant effect on the intervertebral disc degeneration (P = .204). The healing morphology after endplate fracture significantly affected the degree of intervertebral disc degeneration (P = .001). The comparisons of groups showed that the effects of irregular healing and traumatic Schmorl nodes on disc degeneration were not statistically significant, but were significantly significant with increased curvature.These results suggest that the irregular healing and the traumatic Schmorl nodes are closely related to intervertebral disc degeneration. The presence and severity of the endplate injury can provide valuable information for individualized clinical decision-making processes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: mRNA analysis., Objective: The aim of this study was to identify differentially expressed genes (DEGs) in disc degeneration, analyze the potential biological functions of DEGs, and screen for a new target to prevent the degeneration., Summary of Background Data: Intervertebral disc degeneration (IDD) is an irreversible process and causes long-term heavy socioeconomic burdens. Existing and therapies under development are unable to prevent disc degeneration in a safe and effective manner. Therefore, elucidating the potential mechanism underlying degeneration and the development of new targets for IDD therapy are urgently required., Methods: Nucleus pulposus (NP) cells from mild and severe IDD (Ctrl and IDD groups) were separated, and DEGs of the two groups were identified with mRNA microarray analysis, followed by bioinformatics analysis.Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to verify the microarray results. Gene over-expression and silencing technologies were used to study the role of plant homeodomain finger protein 6 (PHF6). qRT-PCR and western blot analyses were used to detect the expressions of collagen II (COL2), matrix metalloproteinases 13 (MMP13), and ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS4)., Results: The study identified 377 up- and 116 downregulated DEGs in NP cells from two groups. These DEGs were mainly involved in cellular and metabolic processes and enriched in immune system and nucleotide metabolism pathways. Upregulated PHF6, with the highest verified fold change, was significantly increased in the IDD group. Over-expressing PHF6 in Ctrl NP cells significantly inhibited the expression of COL2 and enhanced the expressions of MMP13 and ADAMTS4, whereas silencing PHF6 in IDD NP cells reversed such expression alterations., Conclusion: Upregulated PHF6 caused IDD by promoting extracellular matrix degradation; therefore, PHF6 could be developed as a potential novel target to prevent the degeneration. Our DEG profiling of NP cells from IDD patients provided a database to identify the key genes involved in IDD., Level of Evidence: N/A.

Introduction: Percutaneous endoscopic lumbar disectomy (PELD) is one of the most popular minimally invasive techniques of spinal surgery in recent years. At present, there are 2 main surgical approaches in PELD: foraminal approach and interlaminar approach. What's more, foraminoplasty is a necessary step for both approaches. However, there are few biomechanical studies on the formation of different parts of the intervertebral foramen. The aim of this study is to explore the effects of different foraminoplasty methods on the biomechanics of the corresponding and adjacent segments of the lumbar through a 3-dimensional finite element model analysis., Methods: We established a normal 3-dimensional finite element mode of L3 to L5, simulated lumbar percutaneous endoscopy by doing cylindrical excision of bone whose diameter was 7.5 mm on the L5 superior articular process and the L4 inferior articular process, respectively, so that we obtained 3 models: the first one was normal lumbar model, the second one was the L4 inferior articular process shaped model, and the third one was the L5 superior articular process shaped model. We compared the biomechanics of the intervertebral disc of L3/4 and L4/5 when they were in the states of forward flexion, backward extension, left and right flexion, and left and right rotation on specific loading condition., Discussion: If the outcomes indicate the trial is feasible and there is evidence that one of the foraminoplasty technique may make few differences in biomechanics of corresponding lumbar intervertebral disc, we will proceed to a definitive trial to test the best way to foraminplasty, which could make biomechanical influence as little as possible., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900026973. Registered on September 27, 2019.

Study Design: A biomechanical analysis correlating internal disc strains and tissue damage during simulated repetitive lifting., Objective: To understand the failure modes during simulated safe and unsafe repetitive lifting., Summary of Background Data: Repetitive lifting has been shown to lead to lumbar disc herniation (LDH). In vitro studies have developed a qualitative understanding of the effect of repetitive loading on LDH. However, no studies have measured internal disc strains and subsequently correlated these with disc damage., Methods: Thirty human cadaver lumbar functional spinal units were subjected to an equivalent of 1 year of simulated repetitive lifting under safe and unsafe levels of compression, in combination with flexion (13-15°), and right axial rotation (2°) for 20,000 cycles or until failure. Safe or unsafe lifting were applied as a compressive load to mimic holding a 20 kg weight either close to, or at arm's length, from the body, respectively. Maximum shear strains (MSS) were measured, and disc damage scores were determined in nine regions from axial post-test magnetic resonance imaging (MRI) and macroscopic images., Results: Twenty percent of specimens in the safe lifting group failed before 20,000 cycles due to endplate failure, compared with 67% in the unsafe group. Over half of the specimens in the safe lifting group failed via either disc protrusion or LDH, compared with only 20% via protrusion in the unsafe group. Significant positive correlations were found between MRI and macroscopic damage scores in all regions (rs > 0.385, P < 0.049). A significant positive correlation was observed in the left lateral region for MSS versus macroscopic damage score (rs = 0.486, P < 0.037) and MSS versus failure mode (rs = 0.724, P = 0.018, only specimens with disc failure). Pfirrmann Grade 3 discs were strongly associated with subsequent LDH (P = 0.003)., Conclusion: Increased shear strains were observed in the contralateral side to the applied rotation as disc injury progressed from protrusion to LDH. Larger compressive loads applied to simulate unsafe lifting led to frequent early failure of the endplate, however, smaller compressive loads at similar flexion angles applied under safe lifting led to more loading cycles before failure, where the site of failure was more likely to be the disc. Our study demonstrated that unsafe lifting leads to greater risk of injury compared with safe lifting, and LDH and disc protrusion were more common in the posterior/posterolateral regions., Level of Evidence: N/A.

Study Design: Experimental study with human mesenchymal stem cells (MSCs) and intervertebral disc (IVD) tissue samples., Objective: This study aimed to characterize the effect of MSC homing on the Tie2-positive IVD progenitor cell population, IVD cell survival, and proliferation., Summary of Background Data: Homing of human MSCs has been described as potential alternative to MSC injection, aiming to enhance the regenerative capacity of the IVD. IVD cells expressing Tie2 (also known as CD202b or Angiopoietin-1 receptor TEK tyrosine kinase) represent a progenitor cell population with discogenic differentiation potential. However, the fraction of Tie2-positive progenitor cells decreases with aging and degree of IVD degeneration, resulting in a potential loss of the IVD's regenerative capacity., Methods: Human MSCs, isolated from vertebral bone marrow aspirates, were labeled and seeded onto the endplate of bovine IVDs and human IVD tissue. Following MSC migration for 5 days, IVD cells were isolated by tissue digestion. The fractions of Tie2-positive, dead, apoptotic, and proliferative IVD cells were evaluated by flow cytometry and compared to untreated IVDs. For human IVDs, 3 groups were investigated: nondegenerated (organ donors), IVDs of patients suffering from spinal trauma, and degenerative IVD tissue samples., Results: MSC homing enhanced the fraction of Tie2-positive IVD cells in bovine and human IVD samples. Furthermore, a proliferative response and lower fraction of dead cells were observed after MSC homing in both bovine and human IVD tissues., Conclusion: Our findings indicate that MSC homing enhances the survival and regenerative capability of IVD cells, which may be mediated by intercellular communication. MSC homing could represent a potential treatment strategy to prevent the onset of the degenerative cascade in IVDs at risk such as IVDs adjacent to a fused segment or IVDs after herniation., Level of Evidence: N/A.

Study Design: Prospective longitudinal study., Objective: The aim of this study was to evaluate long-term degenerative changes in intervertebral discs in the thoracic spine in healthy asymptomatic subjects., Summary of Background Data: Longitudinal magnetic resonance imaging (MRI) studies of intervertebral disc degeneration have been reported for the cervical and lumbar but not the thoracic spine., Methods: In this longitudinal study (average follow-up 10.0 ± 0.6 years), we assessed degenerative changes in the thoracic spine of 103 volunteers (58 men) of 223 healthy volunteers in the initial MRI study of the thoracic spine (follow-up rate 46.2%). The mean age at the initial study was 45.0 ± 11.5 years (24-77 years). Initial and follow-up thoracic-spine MRIs were graded for the following 4 factors of degenerative changes: decrease in signal intensity of intervertebral disc (DSI), posterior disc protrusion (PDP), anterior compression of dura and spinal cord (AC), and disc-space narrowing (DSN) from T1-2 to T12-L1. We assessed associations between changes in MRI grade and demographical factors such as age, sex, body mass index, smoking habits, sports activities, and disc degeneration in the cervical spine., Results: MRIs revealed that 63.1% of the subjects had degenerative changes in the thoracic intervertebral discs that had progressed at least one grade during the follow-up period. DSI progressed in 44.7% of subjects, PDP in 21.4%, and AC in 18.4% during the 10-year period. No DSN progression was seen. DSI was frequently observed in the upper thoracic spine (T1-2 to T4-5). Disc degeneration was relatively scarce in the lower thoracic spine (T9-10 to T12-L1). PDP was frequently observed in the middle thoracic spine (T5-6 toT8-9). We found significant associations between DSI and cervical-spine degeneration (P = .004) and between AC and smoking (P = .04)., Conclusion: Progressive thoracic disc degeneration, observed in 63.1% of subjects; was significantly associated with smoking and with cervical-spine degeneration., Level of Evidence: 2.

Lumbar 3-joint complex degeneration is a multifactorial, pathological process. Previous studies included insufficient quantitative analyses to prove the relationship between disc degeneration and facet joint osteoarthritis (OA). We assessed the correlation between intervertebral disc and lumbar facet joint degeneration using computed tomography (CT) and magnetic resonance imaging (MRI) parameters.A total of 152 participants who underwent conventional MRI and CT in the clinostat position were included in this study. The presence of lumbar disc degeneration was identified using the Pfirrmann grading system, and the presence of lumbar facet joint degeneration was identified using the Weishaupt grading system. Facet tropism was defined as a divergence more than 7° between the facet joint angles of both sides at the same segment. The intervertebral disc heights were also measured.Most facet joint OA probably appeared at the segment with intervertebral disc degeneration of more than grade III. Facet joint OA was significantly exacerbated with the progression of disc degeneration grade. The intervertebral height significantly decreased with the progression of facet joint degeneration grades, except for grades 0 and 1.Our current study found that each individual joint degeneration influences the other 2 in the lumbar 3-joint complex. Facet tropism was significantly associated with lumbar disc degeneration. Narrowing of the intervertebral disc height probably aggravates the facet joint degeneration further at the same level.

Study Design: An in vivo and in vitro study of the correlation between Paraoxonase 1 (PON1) and intervertebral disc degeneration (IVDD)., Objective: The aim of this study is to clarify the expression and role of PON1 on the process of IVDD., Summary of Background Data: IVDD is responsible for most of the spinal degenerative diseases. Inflammation and oxidative stress can deteriorate the living environment of nucleus pulposus (NP) cells, leading to IVDD. PON1 is an enzyme reported to have anti-inflammatory and anti-oxidative effects. There is no study about the correlation of PON1 expression with IVDD., Methods: Immunohistochemical (IHC), hematoxylin and eosin (H&E) staining, and Western blot examined the expression of PON1 in 88 human disc samples (male: female 43: 45) and rat models (n = 5 each group). The level of PON1 is measured in the tumor necrosis factor (TNF)-α and oxidative stress (H2O2)-induced degenerative NP cell models using Western blot and reverse transcription-polymerase chain reaction (RT-qPCR). The TNF-α, interleukin (IL)-1β, Mito superoxide (SOX), aggrecan, and collagen II are detected in nucleus pulposus (NP) cells transfected with si-RNA of PON1 using Enzyme-Linked Immunosorbent Assay (ELISA), mitoSOX staining Western blot, and RT-qPCR., Results: The expression of PON1 is significantly suppressed in human and rat degenerative intervertebral discs. The level of PON1 is significantly decreased in TNF-α and oxidative stress (H2O2)-induced degenerative NP cell models. ELISA results show that the level of TNF-α and IL-1β obviously increased; Mito SOX staining indicates that the Mito SOX fluorescence significantly increased, and the expression of aggrecan and collagen reduced in NP cells transfected with si-RNA of PON1., Conclusion: Our study indicates that low PON1 expression is predictive of severe IVDD; PON1 plays an important role of keeping the homeostatic balance of intervertebral discs, and therapeutic approach regarding PON1 may be helpful to alleviate IVDD in the future., Level of Evidence: N/A.

Study Design: A rat puncture injury intervertebral disc (IVD) degeneration model with structural, biomechanical, and histological analyses., Objective: To determine if males and females have distinct responses in the IVD after injury., Summary of Background Data: Low back pain (LBP) and spinal impairments are more common in women than men. However, sex differences in IVD response to injury have been underexplored, particularly in animal models where sex differences can be measured without gender confounds., Methods: Forty-eight male and female Sprague Dawley rats underwent sham, single annular puncture with tumor necrosis factor α (TNFα) injection (1×), or triple annular puncture with TNFα injection (3×) surgery. Six weeks after surgery, lumbar IVDs were assessed by radiologic IVD height, spinal motion segment biomechanical testing, histological degeneration grading, second harmonic generation (SHG) imaging, and immunofluorescence for fibronectin and α-smooth muscle actin., Results: Annular puncture injuries significantly increased degenerative grade and IVD height loss for males and females, but females had increased degeneration grade particularly in the annulus fibrosus (AF). Despite IVD height loss, biomechanical properties were largely unaffected by injury at 6 weeks. However, biomechanical measures sensitive to outer AF differed by sex after 3× injury-male IVDs had greater torsional stiffness, torque range, and viscoelastic creep responses. SHG intensity of outer AF was reduced after injury only in female IVDs, suggesting sex differences in collagen remodeling. Both males and females exhibited decreased cellularity and increased fibronectin expression at injury sites., Conclusion: IVD injury results in distinct degeneration and functional healing responses between males and females. The subtle sex differences identified in this animal model suggest differences in response to IVD injury that might explain some of the variance observed in human LBP, and demonstrate the need to better understand differences in male and female IVD degeneration patterns and pain pathogenesis., Level of Evidence: N/A.

Study Design: Microstructural investigation of compression-induced herniation of ovine lumbar discs with and without added component of anterior-inferior slope., Objective: Does increased shear arising from a simulated component of motion segment slope imitating sacral slope weaken the lateral annulus and increase risk of overt herniation at this same region., Summary of Background Data: An increase in sacral slope secondary to lordosis and pelvic incidence increases shear stresses at the lumbosacral junction and has been associated with an increase in spondylolisthetic disorders and back injury. The small component of forward shear induced when a segment is compressed in flexion is suggested to cause differential recruitment of the lateral annular fibers leading to its early disruption followed by intra-annular nuclear tracking to the posterolateral/posterior regions. However, the influence of even greater forward shear arising from the added component of slope seen where pelvic incidence and lumbar lordosis are increased in the lower lumbar spine is less understood., Methods: Ovine motion segments were compressed at 40 mm/min up to failure; 9 with a horizontal disc alignment and 26 with a segment slope of 15° and then analyzed structurally., Results: All the horizontal discs failed (11.8 ± 2.4 kN) via vertebral fracture without any evidence of soft tissue failure even in the lateral aspects of the discs. The increased forward shear resulting from the slope decreased the failure load (6.4 ± 1.6 kN). The sloping discs mostly suffered mid-span, noncontinuous disruption of the lateral annulus with some extruding nuclear material directly from these same lateral regions., Conclusion: The increased level of forward shear generated in moderately sloping lumbar segments when compressed was abnormally damaging to the lateral regions of the disc annulus. This is consistent with the view that shear differentially loads the oblique-counter oblique fiber sets in the lateral annulus, increasing its vulnerability to early disruption and overt herniation., Level of Evidence: N/A.

Study Design: In vivo and in vitro studies of the role of miR-2355-5p and its possible targets in intervertebral disc degeneration (IVDD)., Objective: To elucidate the regulatory role of miR-2355-5p in IVDD and the underlying mechanisms., Summary of Background Data: IVDD, which is caused by multiple factors, is the main cause of lower back pain with or without extremity pain. However, the underlying cellular mechanisms of IVDD pathogenesis are not well elucidated. Cell hyper-proliferation, inflammation, and epidermal growth factor receptor activation have been implicated in IVDD. Up-regulated miR-2355-5p level was identified to associate with IVDD. ERRFI1 (the product of mitogen-inducible gene 6 [MIG6]) was known to inhibit epidermal growth factor receptor activation., Methods: We monitored the expression of miR-2355-5p and ERRFI1 in IVDD tissues and lipopolysaccharides (LPS)-treated nucleus pulposus (NP) cells. We explored the effects of ERFFI1 on NP cells proliferation and LPS-induced pro-inflammatory cytokines production. We searched the targets of miR-2355-5p and explored the effects of miR-2355-5p on NP cells proliferation and cytokines production., Results: We identified the up-regulation of miR-2355-5p and down-regulation of ERFFI1 in IVDD samples and LPS-treated NP cells. ERFFI1 inhibited NP cells proliferation and LPS-induced pro-inflammatory cytokine production. MiR-2355-5p targeted ERFFI1 and negatively regulated ERFFI1 expression. MiR-2355-5p regulated IVDD by targeting ERFFI1., Conclusion: MiR-2355-5p negatively regulated ERFFI1 and prevented the effects of ERRFI1 on inhibiting NP cells proliferation and inflammation., Level of Evidence: N/A.

Study Design: Reliability study., Objective: To evaluate the applicability and reliability of 9.4T magnetic resonance imaging (MRI) in the assessment of degenerative disc disease compared with 3T MRI., Summary of Background Data: MRI is a reliable indicator of biochemical changes in the intervertebral disc (IVD) including hydration status, proteoglycan content, and disc degeneration compared with anatomical and histological studies. High-field 9.4T MRI has been shown to provide superior resolution and anatomical detail. However, it has not been tested against current standard MRI techniques., Methods: Disc degeneration was initiated in 36 skeletally mature ewes 6 months prior to necropsy via validated surgical IVD injury models using either scalpel injury or drill-bit injury techniques at lumbar spine levels L2/3 and L3/4 with L1/2, L4/5, and L5/6 serving as control discs. All ex vivo IVDs were examined with 9.4T MRI and 3T MRI. All scans were analyzed using the Pfirrmann grading system by four independent observers. Intra- and interobserver reliability was assessed using kappa statistics and Spearman correlation., Results: Inter- and intraobserver agreement for 9.4T MRI was excellent, both at κ 0.91 (P < 0.001). Comparatively, 3T interobserver reliability demonstrated substantial agreement at κ 0.61 (P < 0.001). Complete agreement was obtained in 92.7% to 100% of discs at 9.4T compared with 69.7% to 83.1% at 3T. A difference of one grade or more occurred in 6.7% at 9.4T and 39.3% at 3T. 9.4T MRI scored 97.3% of discs as grade 1 to 2 compared with 71.3% at 3T. 3T MRI tended to over-score the extent of disc degeneration with 28.6% of discs scored as grade 3 or higher compared with 2.7% at 9.4T MRI., Conclusion: 9.4T MRI study of IVD degeneration using the Pfirrmann grading system demonstrated excellent inter- and intraobserver reliability. Comparatively, 3T MRI demonstrated a tendency to over score the extent of disc degeneration. This improved reliability of 9.4T MRI holds great potential for its clinical applications., Level of Evidence: 3.

Study Design: This is a cross-sectional study., Objective: To investigate the oblique corridor to the L1-S1 intervertebral disc space between the psoas muscle and the great vessels in cadaveric specimens bilaterally and the location of genitofemoral nerve and the diaphragmatic crura relative to the oblique corridor., Summary of Background Data: Although use of oblique lumbar interbody fusion is rapidly expanding, the morphometric data related to the procedure are limited., Methods: Twelve fresh-frozen full-torso cadaveric specimens were dissected to examine the oblique corridor to access the L1-S1 space in a static state and with mild retraction of the psoas. The level at which the genitofemoral nerve pierces from the psoas major and the diaphragmatic crura originate from the lumbar vertebral body was also investigated., Results: The mean width of oblique corridor in the static state and with mild psoas retraction, respectively, were as follows: on the right side: (L1-2) 13.33 and 16.75 mm; (L2-3) 15.42 and 21.42 mm; (L3-4) 16.58 and 22.67 mm; (L4-5) 12.75 and 21.17 mm; (L5-S1) 5.92 and 12.00 mm; on the left side: (L1-2) 16.75 and 19.67 mm; (L2-3) 18.50 and 25.33 mm; (L3-4) 20.58 and 28.00 mm; (L4-5) 18.17 and 26.08 mm; and (L5-S1) 5.83 and 12.00 mm. The level at which the genitofemoral nerve pierces from the psoas major was between L2 and L4. The diaphragmatic crura originates from L1 to L3., Conclusion: The oblique corridor allows access to the L1-L5 discs from both sides, but it is larger on the left side. The corridor between the iliac vessels and the psoas for L5-S1 is difficult to be applied clinically. Mild psoas retraction can moderately enlarge the oblique corridor. The genitofemoral nerve and diaphragmatic crura may be encountered in this approach and should be carefully observed., Level of Evidence: 5.

Study Design: An in vitro magnetic resonance imaging (MRI) study., Objective: Investigate the potential of high-field MRI for producing higher quality images of the intervertebral disc (IVD) to better distinguish structural details., Summary of Background Data: Higher spatial and contrast resolution are important advantages when imaging the complex tissue structures in the spine such as the IVDs. However, at present it is challenging to capture the substructural details in the IVD such as the lamellae., Methods: Three MRI sequences; two-dimensional proton-density-weighted Turbo-Spin-Echo (PD-TSE), 2D T2-weighted Turbo-Spin-Echo (T2W-TSE) with fat-saturation (FS), and 3D Spoiled-Gradient-Echo (3D-GE), were modified based on the image quality and scan duration. IVDs of three intact cadaveric lumbar-spines (T12-S1, Age 83-94 yr) were imaged using these optimized sequences. Thereafter each IVD was transversely sectioned and the exposed surfaces were photographed. Landmark observations from corresponding MRI slices and photographs were compared to confirm the MRI captured morphology. The image quality was evaluated using signal-to-noise ratio (SNR), and relative-contrast values. Finally, the underlying tissue structures, including specific pathological features, were qualitatively compared between the MR images and photographs., Results: Observations from photographs and corresponding MRI slices matched well. The PD-TSE sequence had better overall SNR, but the relative contrast between the tissue types was relatively poor. The 3D-GE sequence had higher relative contrast between the IVD and bone, but not between annulus and nucleus regions. The T2W images provided the best relative contrast between the annulus and nucleus, however the standard deviations here were high. Structural details including fissures, vascular and granular tissue proliferation, and pathologies in the endplate region, were identifiable from the MR images obtained using the optimized sequences., Conclusion: The results demonstrate the potential of high-field MRI to capture the IVD structural details. Since the acquisition durations were within clinically acceptable levels, these methodological improvements have the potential to enhance clinical diagnostics., Level of Evidence: 4.

Study Design: Basic science study., Objective: To illustrate supplemental alpha-2 macroglobulin (α2 M) has beneficial effects on cartilaginous endplates (CEPs) that may slow the progression of intervertebral disc (IVD) degeneration., Summary of Background Data: CEPs play a vital role in progression of intervertebral disc degenerative diseases. However, the ideal and economic therapies for CEPs degeneration are still urgently required., Methods: Firstly, we confirmed degenerative CEP characters by H&E and Safranin O fast green staining and detected increasing level of α2 M and matrix metalloproteinase 13(MMP-13) in degenerative CEP by immunohistochemistry. Then, effects of exogenous α2 M on tumor necrosis factor alpha (TNF-α)-induced CEP catabolic enzyme and anabolic molecules were evaluated by qRT-PCR, Western blotting and ELISA in cultured CEP cells obtained from rats. Furthermore, suppression of α2 M on TNF-α-induced activation of NF-кB signaling pathway was measured by Western blotting and immunofluorescence. In addition, function of α2 M on TNF-α-treated ex vivo IVDs from rats lumbar IVDs was estimated by measuring the expression of MMP-13, Sox9, aggrecan, and type II collagen in CEP area., Results: Compared with normal CEP, level of α2 M was slightly increased in CEP from degenerative patients, whereas MMP-13 was sharply elevated. In vitro, α2 M inhibited expression and activity of MMP-3 or MMP-13 in a dose-dependent manner in rat CEP cells stimulated by TNF-α. The α2 M refrained phosphorylation of IκBα and inhibited nuclear translocation of p65. Finally, supplemental α2 M reduced expression of MMP-13, and promoted expression of Sox9, aggrecan, and type II collagen in CEP area of ex vivo IVDs cultured with TNF-α., Conclusion: α2 M is not sufficiently produced to inactivate higher concentrations of catabolic factor MMP-13 found in the degenerated CEP. Supplemental α2 M protects against the progression of IVD degeneration by inhibiting effects of proinflammatory cytokines., Level of Evidence: N/A.

Study Design: A laboratory study using a rabbit annular puncture model of intervertebral disc degeneration (IDD)., Objective: The aims of this study were to assess whether an amniotic suspension allograft (ASA) containing particulated human amnion and amniotic fluid derived cells regains intervertebral disc height and morphology and improves histologic scoring in a rabbit model of IDD., Summary of Background Data: In contrast to current surgical interventions for IDD, in which the primary goal is to relieve symptomatic pain, one novel strategy involves the direct injection of anabolic cytokines. Current therapies for IDD are limited by both the short half-life of therapeutic proteins and general decline in anabolic cell populations., Methods: Intervertebral discs in New Zealand white rabbits were punctured using 18-gauge needle under fluoroscopic guidance. Four weeks post-puncture, two groups of rabbits were injected with either ASA or a vehicle/sham control, while a third group was untreated. Weekly radiographs were obtained for 12 weeks to assess disc height index (DHI). Magnetic resonance imaging (MRI) T2 relaxation time was evaluated at weeks 4 and 12 to assess morphological changes. Histologic sections were evaluated on a semi-quantitative grading scale., Results: Before treatment at week 4, DHIs and normalized T2 relaxation times between the three groups were not significantly different. At week 12, ASA-treated rabbits exhibited significantly greater DHIs and MRI T2 relaxation times than vehicle and untreated control groups. The ASA group had higher mean histologic score than the vehicle group, which demonstrated extensive fiber disorganization and delamination with reduced proteoglycan staining on histology., Conclusion: Minimally invasive intervention with intradiscal injection of ASA was successful in reducing IDD in a reproducible rabbit model, with significant improvement in disc height and morphology when compared with vehicle and untreated control groups on radiographic and MRI analyses., Level of Evidence: N/A.

Study Design: An experimental study., Objective: The aim of this study was to determine the effect of polymethylmethacrylate (PMMA) augmentation on the adjacent disc., Summary of Background Data: Vertebral augmentation with PMMA reportedly may predispose the adjacent vertebra to fracture. The influence of PMMA augmentation on the adjacent disc, however, remains unclear., Methods: Using a retroperitoneal approach, PMMA augmentation was performed for 23 rabbits. For each animal, at least one vertebra was augmented with 0.2 to 0.3 mL PMMA. The disc adjacent to the augmented vertebra and a proximal control disc were studied using magnetic resonance (MR) imaging, histological and molecular level evaluation at 1, 3, and 6 months postoperatively. Marrow contact channels in the endplate were quantified in histological slices and number of invalid channels (those without erythrocytes inside) was rated. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to determine disc cell apoptosis., Results: On MR images, the signal and height of the adjacent disc did not change 6 months after vertebral augmentation. Histological scores of the adjacent disc increased over time, particularly for the nucleus pulposus. The adjacent disc had greater nucleus degeneration score than the control disc at 3 months (5.7 vs. 4.5, P < 0.01) and 6 months (6.9 vs. 4.4, P < 0.001). There were more invalid marrow contact channels in the endplate of augmented vertebra than the control (43.3% vs. 11.1%, P < 0.01). mRNA of ADAMTS-5, MMP-13, HIF-1α, and caspase-3 were significantly upregulated in the adjacent disc at 3 and 6 months (P < 0.05 for all). In addition, there were more TUNEL-positive cells in the adjacent disc than in the control disc (43.4% vs. 24.0%, P < 0.05) at 6 months postoperatively., Conclusion: Vertebral augmentation can induce early degenerative signs in the adjacent disc, which may be due to impaired nutrient supply to the disc., Level of Evidence: N/A.

Study Design: A longitudinal case-control animal model., Objective: The aim of this study was to investigate the inflammatory pathways active in the multifidus muscle after spontaneous intervertebral disc degeneration (IDD), and whether these IDD-related muscle changes can be ameliorated by exercise., Summary of Background Data: A pro-inflammatory response is present in the multifidus muscle after an intervertebral disc lesion and has been proposed to drive the structural alterations present during low back pain. However, it is not known whether spontaneous IDD produces an inflammatory response. Furthermore, exercise/physical activity produces a strong anti-inflammatory response, but its effectiveness in ameliorating inflammation in the multifidus is unknown. We assessed the inflammatory profile of the multifidus and the effectiveness of physical activity as a treatment using an animal model of spontaneous model of IDD., Methods: Wild-type and SPARC null mice that were sedentary or housed with a running wheel were used in this study. Multifidus muscle segments were harvested from L2-L6 from the mice at 9 months of age after they had undergone a magnetic resonance imaging (MRI) scan to determine levels with IDD. The inflammatory profile of the multifidus was examined using quantitative polymerase chain reaction (PCR) assays., Results: Spontaneous IDD in the SPARC-null mice caused a dysregulation of interleukin (IL)-1β, IL6, transforming growth factor-beta (TGFβ1), and adiponectin expression. More specifically, the proximity and degree of IDD was related to levels of IL-1β expression. Physical activity reduced the pro-inflammatory response to IDD in the multifidus. IL-1β, tumor necrosis factor (TNF), IL-10, adiponectin, and leptin levels were lower in the physically active group., Conclusion: These results reveal that spontaneous IDD causes dysregulation of the inflammatory pathways active in the multifidus muscle. These alterations were related to the severity of IDD and were prevented by physical activity., Level of Evidence: N/A.

Study Design: Given the results of previous in vitro investigations of the expression patterns of adiponectin and its receptors in healthy and degenerated intervertebral discs (IVDs), we studied the effects of adiponectin on tumor necrosis factor-alpha (TNF-α) production in degenerated nucleus pulposus (NP) cells and analyzed the association between adiponectin levels in IVD tissues and IVD Pfirrmann grades., Objective: The aim of this study was to investigate the potential role of adiponectin in the pathogenesis of IVD degeneration., Summary of Background Data: Adiponectin has been reported to be involved in physiologic and pathologic processes associated with bone and cartilage diseases. However, the expression profiles of adiponectin and its receptors in human IVD tissues and the function of adiponectin in the pathogenesis of IVD degeneration remain unknown., Methods: Real-time polymerase chain reaction, immunohistochemistry, and western blotting were performed to examine the expression levels of adiponectin, adiponectin receptors, and TNF-α in IVD tissues and isolated NP cells. The effects of adiponectin on TNF-α production in degenerated NP cells were detected by enzyme linked immunosorbent assay., Results: Adiponectin expression levels were downregulated, while adiponectin receptor 1 (adipoR1) and adipoR2 expression levels were upregulated in degenerated IVD tissues and degenerated NP cells compared with those in healthy IVD tissues and healthy NP cells. Moreover, we confirmed that TNF-α production by degenerated NP cells was downregulated by adiponectin administration in a dose- and time-dependent manner. Furthermore, our data showed that adiponectin levels in degenerated IVD tissues were inversely correlated with IVD Pfirrmann grades., Conclusion: These results indicated that adiponectin may play an anti-inflammatory role with respect to the maintenance of IVD homeostasis by downregulating TNF-α production., Level of Evidence: N/A.

Study Design: A study of mechanically induced herniation in punctured ovine discs followed by structural analysis., Objective: To investigate whether an annular puncture influences the path that herniation takes by providing direct passage for nucleus through the annulus and therefore whether it increases the risk of acute herniation from overload at the site of damage independent of any longer-term degeneration., Summary of Background Data: Ten years after treatment with discography both degenerative changes and frequency of herniation have been shown to increase compared to untreated discs. Although the effect of an annular puncture over time has been widely investigated the question of whether it increases the risk of acute herniation has not been resolved., Methods: The posterolateral annuli of healthy ovine lumbar discs were punctured with either a 25-gauge (n = 8) or a larger 18-gauge (n = 8) needle and then compressed in a flexed posture of 10° until initial indications of failure. The entire volume of the disc was visually assessed for structural damage by obtaining progressive, full transverse cross-sections of its entire height thus exposing all regions of the disc., Results: There was no association between the 25-gauge puncture and disc disruption and herniation. In contrast, nuclear material was observed to migrate through the 18-gauge needle puncture. Disruption of the lateral inner annulus was observed in 12 out of the 16 discs tested., Conclusion: The risk of acute herniation through the puncture site is dependent on the needle diameter used. Under the conditions employed the lateral inner annulus remains the site most vulnerable to disruption independent of the presence of a posterolateral puncture., Level of Evidence: N /A.

Study Design: Cross-sectional study of spine magnetic resonance in a population, predominantly female, sample., Objective: To determine the relationship between vertebral endplate defect and intervertebral disc degeneration (DD) in general population., Summary of Background Data: Precise understanding of the mechanisms leading to DD development is lacking. In a degenerating disc, mechanical and structural changes lead to further worsening of disc integrity. Increasing attention has been paid to vertebral endplate defects as having a possible role in the etiopathogenesis of DD., Methods: The study population comprised 831 twin volunteers from TwinsUK (mean age 54 ± 8 yr, 95.8% female). Lumbar T2-weighted magnetic resonance images were coded for endplate defects from 8310 endplates into six grades. Total endplate score (TEP score) was achieved by summing both endplate defect grades from the same disc level. DD was evaluated using two different classifications; Pfirrmann grading, and a quantitative trait for DD based on a 4-point grading system. Multivariable regression analysis was used to determine relationships between the traits of interest and the known risk factors for DD, age, and body mass index (BMI). A receiver operator curve for TEP score predicting DD was generated, and survival analysis paired with Cox proportional hazards models analysis performed., Results: There was statistically significant association between DD and age and BMI. These associations lost significance when TEP score was included as predictor in multivariable model. TEP score was strongly and independently associated at every lumbar disc level with DD (Pfirmann P≤0.001; 4-point grading systems P < 1e-16). A cut-off point score of 5 for TEP score was found above which there was a higher DD prevalence. Across all age subgroups, probabilities of having DD were significantly increased in those considered TEP score positive (≥5)., Conclusion: Our large, population-based study has shown that endplate defect was strongly and independently associated with DD at every lumbar disc level. These results provide a mechanism by which increasing age and BMI predispose to DD., Level of Evidence: 2.

Study Design: Human intervertebral disc (hIVD) cells were isolated from 41 surgically excised samples and assessed for their phenotypic alterations with age., Objective: Toward the design of novel anti-aging strategies to overcome degenerative disc disease (DDD), we investigated age-correlated phenotypic alterations that occur on primary hIVD cells., Summary of Background Data: Although regenerative medicine holds great hope, much is still to be unveiled on IVD cell biology and its intrinsic signaling pathways, which can lead the way to successful therapies for IDD. A greater focus on age-related phenotypic changes at the cell level would contribute to establish more effective anti-aging/degeneration targets., Methods: The study was subdivided in four main steps: i) optimization of primary cells isolation technique; ii) high-throughput cell morphology analysis, by imaging flow cytometry (FC) and subsequent validation by histological analysis; iii) analysis of progenitor cell surface markers expression, by conventional FC; and iv) statistical analysis and correlation of cells morphology and phenotype with donor age., Results: Three subsets of cells were identified on the basis of their diameter: small cell (SC), large cell (LC), and super LC (SLC). The frequency of SCs decreased nearly 50% with age, whereas that of LCs increased nearly 30%. Interestingly, the increased cells size was due to an enlargement of the pericellular matrix (PCM). Moreover, the expression pattern for CD90 and CD73 was a reflexion of age, where older individuals show reduced frequencies of positive cells for those markers. Nevertheless, the elevated percentages of primary positive cells for the mesenchymal stem cells (MSCs) marker CD146 found, even in some older donors, refreshed hope for the hypothetical activation of the self-renewal potential of the IVD., Conclusion: These findings highlight the remarkable morphological alterations that occur on hIVD cells with aging and degeneration, while reinforcing previous reports on the gradual disappearance of an endogenous progenitor cell population., Level of Evidence: N/A.

Study Design: Microstructural investigation of low frequency cyclic loading and flexing of the lumbar disc., Objective: To explore micro-level structural damage in motion segments subjected to low frequency repetitive loading and flexing at sub-acute loads., Summary of Background Data: Cumulative exposure to mechanical load has been implicated in low back pain and injury. The mechanical pathways by which cyclic loading physically affects spine tissues remain unclear, in part due to the absence of high quality microstructural evidence., Methods: The study utilized seven intact ovine lumbar spines and from each spine one motion segment was used as a control, two others were cyclically loaded. Ten motion segments were subjected to 5000 cycles at 0.5 Hz with a peak load corresponding to ∼30% of that required to achieve failure. An additional small group of segments subjected to 10,000 or 30,000 cycles was similarly analyzed. Following chemical fixation and decalcification samples were cryosectioned along one of the oblique fiber angles and imaged in their fully hydrated state using differential interference contrast optical microscopy. Structural damage obtained from the images was organized into an algebraic shell for analysis., Results: At 5000 cycles the disc damage was limited to inner wall distortions, evidence of stress concentrations at bridging-lamellae attachments, and small delaminations. The high-cycle discs tested exhibited significant mid-wall damage. There was no evidence of nuclear material being displaced., Conclusion: At this low frequency and without the application of sustained loading or a more severe loading regime, or maintaining a constant flexion with repetitive loading, it seems unlikely that actual nuclear migration occurs. It is possible that the inner-annular damage shown in the low dose group could disrupt pathways for nutrient diffusion leading to earlier cell death and matrix degradation, thus contributing to a cascade of degeneration., Level of Evidence: N/A.

Study Design: ADAMTS5-deficient and wild type (WT) mice were chronically exposed to tobacco smoke to investigate effects on intervertebral disc degeneration (IDD)., Objective: The aim of this study was to demonstrate a role for ADAMTS5 in mediating tobacco smoking-induced IDD., Summary of Background Data: We previously demonstrated that chronic tobacco smoking causes IDD in mice because, in part, of proteolytic destruction of disc aggrecan. However, it was unknown which matrix proteinase(s) drive these detrimental effects., Methods: Three-month-old WT (C57BL/6) and ADAMTS5 mice were chronically exposed to tobacco smoke (four cigarettes/day, 5 day/week for 6 months). ADAMTS-mediated cleavage of disc aggrecan was analyzed by Western blot. Disc total glycosaminoglycan (GAG) content was assessed by dimethyl methylene blue assay and safranin O/fast green histology. Vertebral osteoporosity was measured by microcomputed tomography. Human nucleus pulposus (hNP) cell cultures were also exposed directly to tobacco smoke extract (TSE), a condensate containing the water-soluble compounds inhaled by smokers, to measure ADAMTS5 expression and ADAMTS-mediated cleavage of aggrecan. Activation of nuclear factor (NF)-κB, a family of transcription factors essential for modulating the cellular response to stress, was measured by immunofluorescence assay., Results: Genetic depletion of ADAMTS5 prevented vertebral bone loss, substantially reduced loss of disc GAG content, and completely obviated ADAMTS-mediated proteolysis of disc aggrecan within its interglobular domain (IGD) in mice following exposure to tobacco smoke. hNP cell cultures exposed to TSE also resulted in upregulation of ADAMTS5 protein expression and a concomitant increase in ADAMTS-mediated cleavage within aggrecan IGD. Activation of NF-κB, known to be required for ADAMTS5 gene expression, was observed in both TSE-treated hNP cell cultures and disc tissue of tobacco smoke-exposed mice., Conclusion: The findings demonstrate that ADAMTS5 is the primary aggrecanase mediating smoking-induced disc aggrecanolysis and IDD. Mouse models of chronic tobacco smoking are important and useful for probing the mechanisms of disc aggrecan catabolism and IDD., Level of Evidence: N/A.

Study Design: In vitro study using rat intervertebral discs (IVDs)., Objective: To explore the alteration of annulus fibrosus collagen fibrils after loading on IVD and to investigate the degeneration pathogenesis at the nanoscale., Summary of Background Data: Abnormal loading can lead to IVD degeneration, but the precise mechanism has been hitherto elusive, especially at the nanoscale., Methods: A rat IVD loading model was used, which combined bending of the tail by 40° with compressive loading of 1.8, 4.5, and 7.2 N of the rat tail using an external fixation device. The structure and the elastic modulus of individual collagen fibrils within IVD Co8-Co9 was examined 2 weeks after loading at the nanoscale using atomic force microscopy., Results: Significant fibril disorder and a decrease in cell number within the annulus fibrosus after loading was observed at the microscale as judged by hematoxylin/eosin staining, suggesting initiation of rupture of the structure and degradation of the IVD. The annulus fibrosus collagen fibrils underwent a change in diameter and elastic modulus from 170 ± 18 to 310 ± 24 nm (P < 0.001) and 0.86 ± 0.12 to 1.27 ± 0.30 GPa (P = 0.003), respectively when measured on the concave side after a loading of 7.2 N. Thus the loading process resulted in a thickening and stiffening of collagen fibrils with a difference between the inner and outer layers., Conclusion: The results of the present study indicated that abnormal loading was not only associated with disorder at the microscale, but also alteration of the collagen fibrils at the nanoscale, possibly leading to changes in the mechanical and physiological environment around the cells of the annulus fibrosus., Level of Evidence: N/A.

Background: The aim of this study is to identify which possessed the best stem-cell-like characteristics in 3 kinds of cell in human degenerative intervertebral disc: NPSCs (nucleus pulposus-derived stem cells), AFSCs (annulus fibrosus-derived stem cells), or CESCs (cartilage endplate-derived stem cells)., Methods: We separated the disc samples obtained from 15 surgically treated patients with disc degenerative diseases into nucleus pulposus, annulus fibrosus, and cartilage endplate. After cultivating, we used the cell counting kit-8 to analysis the cell activity of 3 kinds of disc tissue-derived stem cell separately; different stem cells were defined with multilineage (osteogenic, chondrogenic, and adipogenic) differentiation. We extracted the total RNA and detected the expression of different lineage differentiation-related genes with the real-time polymerase chain reaction (RT-PCR)., Results: Cell morphology of NPSCs, AFSCs, and CESCs did not show significant difference. Cell proliferation capacity of NPSCs and AFSCs was stronger than that of CESCs. The differentiation outcomes showed that osteocyte-like cells were stained red by Alizarin red S, chondrocyte-like cells blue by toluidine blue, and adipocyte-like red by oil red O. The RT-PCR reflected that the expression of different lineage differentiation-related genes of AFSCs was stronger than NPSCs and CESCs., Conclusion: In conclusion, we found that the cell morphology was not significantly different among NPSCs, AFSCs, and CESCs. Both differentiation and RT-PCR tests demonstrated that AFSCs had the best stem-cell-like characteristics in the human degenerative intervertebral disc.

A 10-year-old girl with a 2-week history of atraumatic back pain presented to the emergency department with difficulty ambulating and a history of 2 episodes of urinary incontinence in the past week. Her examination was significant for pain with movement, tenderness to palpation in the lower thoracic spine, and no neurological deficits. In this case, the child was found to have a Schmorl node at T8 in the superior aspect of the vertebral body. Schmorl nodes are protrusions of the cartilage of the intervertebral disc through the vertebral body endplate and into the adjacent that is more commonly reported in the adult population. In this child, radiographic findings were normal, with no evidence of the Schmorl node. The diagnosis was made by magnetic resonance imaging. The child's symptoms significantly resolved with ibuprofen anti-inflammatory therapy. In children with atraumatic back pain lasting greater than 2 weeks with a sudden increase in severity and associated with a neurological deficit, advanced imaging is strongly recommended.

Study Design: We collected the samples of cervical intervertebral discs from patients with vertigo to examine the distribution and types of mechanoreceptors in diseased cervical disc., Objective: The aim of this study was to determine whether mechanoreceptors are distributed more abundantly in cervical discs from patients with cervical spondylosis, and whether they are related to vertigo., Summary of Background Data: Previous limited studies have found that normal cervical intervertebral discs are supplied with mechanoreceptors that have been considered responsible for proprioceptive functions. Several clinical studies have indicated that the patients with cervical spondylosis manifested significantly impaired postural control and subjective balance disturbance., Methods: We collected 77 samples of cervical discs from 62 cervical spondylosis patients without vertigo, 61 samples from 54 patients with vertigo, and 40 control samples from 8 cadaveric donors to investigate distribution of mechanoreceptors containing neurofilament (NF200) and S-100 protein immunoreactive nerve endings., Results: The immunohistochemical investigation revealed that the most frequently encountered mechanoreceptors were the Ruffini corpuscles in all groups of cervical disc samples. They were obviously increased in the number and deeply ingrown into inner annulus fibrosus and even into nucleus pulposus in the diseased cervical discs from patients with vertigo in comparison with the discs from patients without vertigo and control discs. Only three Golgi endings were seen in the three samples from patients with vertigo. No Pacinian corpuscles were found in any samples of cervical discs., Conclusion: The diseased cervical discs from patients with vertigo had more abundant distribution of Ruffini corpuscles than other discs. A positive association between the increased number and ingrowth of Ruffini corpuscles in the diseased cervical disc and the incidence of vertigo in the patients with cervical spondylosis was found, which may indicate a key role of Ruffini corpuscles in the pathogenesis of vertigo of cervical origin., Level of Evidence: 1.

Study Design: A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD., Objective: The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD., Summary of Background Data: Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive., Methods: Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed., Results: In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin α2β1 (upregulated) and α10β1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin α1, α2, α11, and β1 were upregulated, whereas α10 was downregulated. Similar activation of integrin signaling was observed., Conclusion: Static compression altered collagen and MMP expression, and promoted β1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force., Level of Evidence: N/A.

Study Design: Biomechanical evaluation using porcine spines., Objective: Compare the fixation strength of two currently used fusionless adolescent idiopathic scoliosis correction techniques following cyclic loading using porcine spines., Summary of Background Data: The ability of fusionless implants to control or correct scoliosis in a growing patient requires such implants to maintain spinal fixation. Because they cross the disc, motion may weaken fixation over time., Methods: Eight pig spines were divided into cycled segments (T10-T13) and uncycled segments (T7-T8, L2-L3). Initial range of motion (ROM) was determined in torsion, flexion-extension, and lateral bending (0.5°/s to 1.75 N·m).Staple group (n = 4): 6 mm parallel staples were inserted on the right anterolateral spine across each intervertebral disc. Cycled segments received six staples (three adjacent discs) and uncycled segments received four staples (two separate discs).Tether group (n = 4): 5.35 × 35 mm right anterolateral vertebral body screws were placed into each vertebra. Cycled segments received four screws and uncycled segments received four screws. Screws in cycled segments were connected with a flexible tether tensioned to straight alignment.ROM of instrumented cycled segments was measured, and then segments were loaded to the measured ROM in flexion-extension (2000 cycles), lateral bending (1000 cycles), and axial rotation (2000 cycles). Implants were axially loaded to failure. Parametric tests compared pre- to postimplant ROM; nonparametric tests compared staple to screw pullout strength; P < 0.05 was significant., Results: There were no differences in ROM before instrumentation between groups. ROM was not changed except tethers decreased left lateral bending (-6.2°). Although staple pullout was less than screw pullout for cycled and uncycled segments (P < 0.05 and P = 0.057, respectively), there was no difference in pullout strength with and without cyclic loading for either group (P = 0.4)., Conclusion: Tethers decreased lateral bending away from the tether. Screws had almost five times greater load to failure than staples. Five thousand cycles did not result in loosening of either staple or tether screws., Level of Evidence: N/A.

Study Design: High resolution imaging investigation of the failure of ovine lumbar intervertebral discs under complex loading., Objective: To investigate how different loading combinations influence the mechanism and extent of intervertebral disc failure., Summary of Background Data: Even though there has been extensive research on how an intervertebral disc fails under various conditions, failure mechanisms remain unclear. In addition, the influence of different loading directions on the mode and extent of failure under complex loading was never systematically investigated., Methods: Thirty ovine lumbar spinal segments were loaded in a newly developed, dynamic, 6-degree-of-freedom (6-DOF) disc loading simulator under five combinations of the following loading parameters: 0°-13° flexion, 0°-10° lateral bending, 0°-4° axial rotation, 0-800 N axial compression. A total of 1000 cycles at 2 Hz were done. After testing, imaging of the discs was performed in an ultra-high field magnetic resonance imaging (11.7 T) scanner and with a micro-computed tomography scanner., Results: A total of 13 large endplate junction failures (EPJFs) occurred, of which all but one maintained an intact cartilaginous endplate. Ten out of 13 EPJFs occurred caudally. Four solely annulus failures occurred affecting only the outer posterior annulus. A herniation was not observed. The maximum moments measured in any group (median) were 52.5 N · m flexion, 16.5 N · m lateral bending, and 14.0 N · m axial rotation., Conclusion: Complex loading protocols could lead to EPJFs (76%) and annulus failures (24%) in vitro. The combination of flexion, lateral bending, axial rotation, and axial compression bears the highest risk for caudal EPJF. Flexion without lateral bending and vice versa has the lowest risk for failure. Both axial compression and axial rotation seem to have a smaller influence than flexion and lateral bending. It seems that a herniation requires an additional failure of the cartilaginous endplate, likely initiated by further axial compressive load., Level of Evidence: 4.

Study Design: A single-center, prospective comparative study of prospectively collected outcomes, with a minimum 12 months follow-up., Objectives: The primary purpose of the study is to investigate the clinical, functional, and radiological outcomes of cervical total disc replacement (CTDR) in comparison with anterior cervical discectomy and fusion (ACDF) in the treatment of single-level cervical disc degenerative disease, prospectively., Summary of Background Data: CTDR has recently been an alternative to ACDF in cervical disc degenerative disease to preserve the motion at the treated level., Methods: This study included 34 patients, who underwent either single-level ACDF (n = 17) or single-level CTDR (n = 17) at C3 to C7 level for cervical disc degenerative disease between July 2012 to April 2014 with a minimum of 12 months of follow-up., Results: Neck disability index, visual analog scale, and neck-arm pain score showed significant difference between the two groups at final follow-up of 12 months. Modified orthopedic association score and Nurick scale also showed the Japanese significant difference between the two groups at final follow-up of 12 months. Odom criteria were not statistically significant between the two groups at final follow-up. The changes in overall cervical sagittal angle (CSA) were significantly different between the two groups. The segmental angle (SA) was maintained at a significantly higher value in the CTDR group than in the ACDF group during the follow-up period (P < 0.05). The range of motion of the cervical spine and the treated level was well maintained and improved in the CTDR group as compared with ACDF group and showed extremely statistically significant difference between the two groups., Conclusion: CTDR was found to be a safe, effective, better, and efficient alternative to the traditional ACDF. CTDR using Prestige LP cervical disc provided a statistically significant clinical, functional, and radiological outcomes between the two groups after 1-year follow-up., Level of Evidence: 2.

Study Design: Neovascularization and expression of inflammatory cytokines were examined in Osteoprotegerin (Opg) knockout (KO) mice that show intervertebral disc (IVD) degeneration., Objective: The aim of this study was to clarify the pathological changes in lumbar IVD degeneration in Opg KO mice., Summary of Background Data: Osteoporosis is a controversial risk factor for IVD degeneration. Deletion of Opg resulted in IVD degeneration in mice. Neovascularization and inflammatory cytokines are key factors in IVD degeneration., Methods: Opg KO mice and their wild-type (WT) littermates were euthanized. Lumbar IVDs were harvested. Safranin O/Fast Green staining was performed to examine the pathological changes. Microcomputed tomographic (micro-CT) analysis was performed to determine the structural changes at the junction of lumbar IVD cartilage and vertebrae. Tartrate-resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Protein expression of vascular endothelial growth factor A (VEGF-A), CD31, VE-cadherin, CD 34, interleukin-1β (IL-1β), and tumor necrosis factors α (TNF-α) were analyzed by immunohistochemistry (IHC) assays. Gene expressions of IL-1β, IL-6, and TNF-α were analyzed by real-time polymerase chain reaction (RT-PCR)., Results: In 12-week-old Opg KO mice, new bone was formed in the endplate cartilage of lumbar IVDs and this became more obvious in 24-week-old Opg KO mice. Three-dimensional (3D) μCT reconstruction analyses showed that the edges of the L4 and L5 vertebrae were rugged with bone marrow cavities in it. Protein expression of VEGF-A, CD31, VE-cadherin, and CD34 was increased in the endplate and growth plate of lumbar IVDs of Opg KO mice. Gene expression of IL-1β, IL-6, and TNF-α as well as protein expression of IL-1β and TNF-α were highly expressed in the lumbar IVDs of Opg KO mice., Conclusion: Deletion of Opg leads to increased neovascularization and expression of inflammatory cytokines in the lumbar disc in Opg KO mice, which may play important roles in IVD degeneration., Level of Evidence: N/A.

Study Design: Prospective case series., Objective: Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station. The long-term objective of this project is to promote spine health and prevent spinal injury during space missions and here on Earth., Summary of Background Data: National Aeronautics and Space Administration (NASA) crewmembers have a 4.3 times higher risk of herniated IVDs, compared with the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in approximately 5 cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described., Methods: Six NASA crewmembers were imaged supine with a 3 Tesla magnetic resonance imaging. Imaging was conducted preflight, immediately postflight, and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle, and posterior sections of all lumbar levels. Repeated measures analysis of variance was used to determine significance at P < 0.05, followed by post-hoc testing., Results: Paraspinal lean muscle mass, as indicated by the FCSA, decreased from 86% of the total PSM cross-sectional area down to 72%, immediately after the mission. Recovery of 68% of the postflight loss occurred during the next 6 weeks, still leaving a significantly lower lean muscle fractional content compared with preflight values. In contrast, lumbar IVD heights were not appreciably different at any time point., Conclusion: The data reveal lumbar spine PSM atrophy after long-duration spaceflight. Some FCSA recovery was seen with 46 days postflight in a terrestrial environment, but it remained incomplete compared with preflight levels., Level of Evidence: 4.

Acquired torticollis is a common clinical finding in children evaluated in the pediatric emergency department. It may be the presentation symptom of different illnesses, such as trauma, muscle contraction, infections, or malignancies, and an accurate differential diagnosis is required to correctly identify the cause and choose the right treatment. Spondylodiscitis is a low-grade bacterial infection that involves intervertebral disks and the adjacent vertebral bodies. Spondylodiscitis of the cervical spine is unusual and may be a rare cause of torticollis. We report the case of a 4-year-old male patient admitted to the emergency department for a 5-day history of painful torticollis. Blood tests showed an elevated erythrocyte sedimentation rate. The radiograph of the cervical spine showed a thin fifth cervical soma. The magnetic resonance imaging of cervical spine showed the alteration of cervical vertebral bodies and intervertebral disks, suggesting the diagnosis of cervical spondylodiscitis. The patient recovered after endovenous antibiotic treatment. We suggest that cervical spondylodiscitis should be suspected and investigated by means of an magnetic resonance imaging in every case of unexplained torticollis with persisting symptoms.

Study Design: In-vivo ovine model of intervertebral disc degeneration (IVD) to evaluate treatment with stem cells., Objective: To determine if stem cells delivered to the nucleus pulposus (NP) or the annulus fibrosus (AF) of degenerated lumbar IVDs leads to improved indices of disc health., Summary of Background Data: Previous studies assessing the efficacy of stem cell injections into degenerated IVDs have reported positive findings. However, studies have been limited to small animals, targeting solely the NP, with short term follow-up., Methods: Mesenchymal precursor cells (MSC) were obtained from the iliac crest of 8-week-old sheep. IVD degeneration was induced by postero-lateral annulotomy at three lumbar levels in eight 2-year-old sheep. Six months later, each degenerated IVD was randomized to one of three treatments: Injection of MSC into (i) previously incised AF (AFI), (ii) NP (NPI), or (iii) no injection (negative control, NC). The adjacent IVD received injection of phosphate buffered saline into NP (positive control, PC). Radiographs and magnetic resonance imaging scans were obtained at baseline, 6, 9, and 12 months. Discs were harvested at 12 months for biochemical and histological analyses., Results: IVD degeneration was consistently observed postannulotomy, and characterized by reduced disc height index (DHI), disc height (DH), glycosaminoglycan (GAG) content, and increased grade of disc degeneration.Six months after stem cell injection, DHI and DH had recovered in AFI and NPI groups when compared with NC group (P < 0.01). Mean Pfirrmann grade improved from 3.25 to 2.67 (AFI group) and from 2.96 to 2.43 (NPI group). Mean histopathological grade improved for both AFI (P < 0.002) and NPI (P < 0.02) groups. Both AFI and NPI groups demonstrated spontaneous repair of the postero-lateral annular lesion., Conclusion: In this large animal model, injection of MSCs into the annulus fibrosus or the nucleus pulposus of degenerated IVD resulted in significant improvements in disc health., Level of Evidence: N/A.

Study Design: A biomechanical comparison among the intact C2 to C7 segments, the C5 to C6 segments implanted with fusion cage, and three different artificial disc replacements (ADRs) by finite element (FE) model creation reflecting the entire cervical spine below C2., Objective: The aim of this study was to analyze the biomechanical changes in subaxial cervical spine after ADR and to verify the efficacy of a new mobile core artificial disc Baguera C that is designed to absorb shock., Summary of Background Data: Scarce references could be found and compared regarding the cervical ADR devices' biomechanical differences that are consequently related to their different clinical results., Methods: One fusion device (CJ cage system, WINNOVA) and three different cervical artificial discs (Prodisc-C Nova (DePuy Synthes), Discocerv (Scient'x/Alphatec), Baguera C (Spineart)) were inserted at C5-6 disc space inside the FE model and analyzed. Hybrid loading conditions, under bending moments of 1 Nm along flexion, extension, lateral bending, and axial rotation with a compressive force of 50 N along the follower loading direction, were used in this study. Biomechanical behaviors such as segmental mobility, facet joint forces, and possible wear debris phenomenon inside the core were investigated., Results: The segmental motions as well as facet joint forces were exaggerated after ADR regardless of type of the devices. The Baguera C mimicked the intact cervical spine regarding the location of the center of rotation only during the flexion moment. It also showed a relatively wider distribution of the contact area and significantly lower contact pressure distribution on the core than the other two devices. A "lift off" phenomenon was noted for other two devices according to the specific loading condition., Conclusion: The mobile core artificial disc Baguera C can be considered biomechanically superior to other devices by demonstrating no "lift off" phenomenon, and significantly lower contact pressure distribution on core., Level of Evidence: N/A.

Study Design: Preclinical animal study., Objective: Determine the in vivo effects of platelet-derived growth factor BB (PDGF-BB) delivered in a thiol-modified hyaluronic acid (TMHA) hydrogel on intervertebral disk (IVD) degeneration., Summary of Background Data: IVD degeneration is a worldwide health concern and remains without an effective treatment. Several in vitro studies have demonstrated the potential of PDGF-BB, a primary component of platelet-rich plasma, as a therapy for IVD degeneration. Our hypotheses were that treatment of injured IVDs with PDGF would inhibit degeneration and that administration of PDGF in a TMHA hydrogel would improve its efficacy., Methods: IVD degeneration was induced using the rabbit annular puncture model. Four weeks after injury, IVDs were treated with either PDGF-BB or PDGF-BB delivered within a TMHA hydrogel. The efficacy of treatment was determined using x-ray, MRI, histology, and biomechanical testing., Results: At 4 weeks after treatment, cell apoptosis and deposition of matrix containing type III collagen a1 (Col3a1) was demonstrated in both the nucleus pulposus and annulus fibrosus, while this was inhibited by PDGF. At 8 weeks after treatment, disc area and MRI indices of injured IVDs treated with PDGF were significantly higher (P < 0.05) than those treated with the TMHA alone. Similarly, degenerative scores for saline- and TMHA-treated IVDs demonstrated significantly more degeneration (P < 0.05) than PDGF-treated IVDs at 8 weeks. Biomechanical assessments found fewer indicators of degeneration in PDGF-TMHA-treated IVDs at both 4 and 8 weeks post-treatment, compared to saline-, TMHA-, and PDGF-only-treated IVDs. Both PDGF- and PDGF-TMHA-treated IVDs also demonstrated a significant increase (P < 0.05) in compressive strength to failure, compared with controls at 8 weeks post-treatment., Conclusion: The results of this study suggest that PDGF-BB significantly decreases disc degeneration and when delivered in a TMHA gel scaffold, helps prevent both apoptosis and Col3 matrix production, while maintaining disc structure and biomechanical function., Level of Evidence: NA.