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Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_15 | Pages 4 - 4
1 Oct 2014
Hughes M Bernard J
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Costoplasty remains useful in the treatment of adolescent idiopathic scoliosis, rib hump and associated chest wall deformities. However traditional costoplasty increases morbidity and blood loss. We examine the feasibility and possible effectiveness of a more conservative costoplasty using an animal model. 4 fresh half Ovine rib cages from separate animals were obtained, stored at +4 °C and warmed to room temperature before testing. Each rib cage was randomly assigned to group 1, 2, 3 or 4. Ribs 2–10 were dissected out for testing. The ribs then underwent stepwise deconstruction according to their group. Beginning at the convexity, removing first the convex cortex, then the cancellous, then the cranial and caudal cortices to leave just the concave cortex. Testing for stiffness was by three-point bending on the concave side of each rib with the rib fixed at the head of the rib and 5 cm from the resected area. The ribs were deformed at a constant rate of 0.5 mm.sec . −. 1 up to a maximum load of 9.99 kg or until fracturing. Then stress was plotted against strain to find the Young's modulus of each group and statistics carried out with an ANOVA test. The ribs in each group were as follows: Group 1= control, group 2= 30 mm long convex side cortical bone removed 10 mm from lateral tubercle, group 3= convex, cortical and cancellous bone removal and group 4= removal of convex, caudal and cranial cortices with cancellous removal. The Young's Modulus of the groups were: 1= 3.38 N-m (+/− 0.84), 2= 2.65 N-m (+/− 1.58), 3= 1.55 N-m (+/− 0.55) and 4= 0.74 N-m (+/− 0.55). Groups 3 and 4 were significantly less stiff than group 1 (p< 0.01.) No ribs in groups 1, 2 and 4 fractured under the maximum load. 5/8 ribs in group 3 fractured before the maximum load was administered. By deconstructing the rib down to only the concave side it becomes significantly more flexible by approximately 4.5 times than the control Ribs. Coupled with its increase in flexibility it still retains its ability to withstand up to 10 kg of load without fracture. It may be possible to perform a costoplasty whilst preserving ventilatory integrity. This may improve rib hump correction, and curve correction due to increased flexibility of the stiff thoracic cage


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 49 - 49
1 Jun 2012
Grivas TB Vasiliadis ES Khaldi L Kaspiris A Kletsas D
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Introduction

The response of the intervertebral disc to asymmetric forces may accelerate degeneration through changes in the matrix. Macroscopically, the disc sustains structural changes that may play a part in the progression of a scoliotic curve. Molecularly, disc degeneration is the outcome of the action of matrix metalloproteases (MMPs), members of a family of enzymes that bring about the degradation of extracellular matrix components. In this study we measured in vivo the expression of MMPs in a rat scoliotic intervertebral disc and studied the effect of the degree of the deformity on their production.

Methods

Asymmetric forces were applied in the intervertebral disc between the ninth and tenth vertebrae at the base of a rat tail with the use of a mini Ilizarov external fixator, under anaesthesia. Animals were categorised into three groups according to the degree of the deformity. In group I, the deformity that was applied on the intervertebral disc was 10°, in group II 30°, and in group III 50°. All the animals used were female Wistar rats before adulthood, to take into account the effect of growth for the study of intervertebral disc changes. The intact intervertebral discs outside the fixator were used as controls. After the rats' death on day 35, the tails were prepared and analysed with an immunohistochemical protocol for chromogenic detection and location of MMPs 1 and 12 in tissue sections of the intervertebral discs.


Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc. Cite this article: Bone Joint Res 2013;2:169–78


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_10 | Pages 30 - 30
1 Oct 2019
Snuggs J Rustenberg C Emanuel K Partridge S Sammon C Smit T Le Maitre C
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Purpose of study and background. Low back pain affects 80% of the population at some point in their lives with 40% of cases attributed to intervertebral disc (IVD) degeneration. A number of potential regenerative approaches are under investigation worldwide, however their translation to clinic is currently hampered by an appropriate model for testing prior to clinical trials. Therefore, a more representative large animal model for IVD degeneration is needed to mimic human degeneration. Here we investigate a caprine IVD degeneration model in a loaded disc culture system which can mimic the native loading environment of the disc. Methods and Results. Goat discs were excised and cultured in a bioreactor under diurnal, simulated-physiological loading (SPL) conditions, following 3 days pre load, IVDs were degenerated enzymatically for 2hrs and subsequently loaded for 10 days under physiological loading. A PBS injected group was used as controls. Disc deformation was continuously monitored and changes in disc height recovery quantified using stretched-exponential fitting. Histological staining was performed on caprine discs to assess extracellular matrix production and immunohistochemistry performed to determine expression of catabolic protein expression. The injection of collagenase and cABC induced mechanical behavior akin to that seen in human degeneration. A decrease in collagens and glycosaminoglycans (GAGs) was seen in enzyme injected discs, which was accompanied by increased cellular expression for degradative enzymes and catabolic cytokines. Conclusion. This model provides a reproducible model of IVD degeneration which mimics human degeneration. This model allows the testing of biomaterials and other potential treatments of IVD degeneration on a scale more representative of the human disc. There are no conflicts of interest. Funded by MRC and Versus Arthritis


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 46 - 46
1 Jun 2012
Wise C Sharma S Gao X Londono D Mauldin KN Brandon J King V Zhang D Gordon D Herring J
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Introduction. Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity, affecting about 3% of school-aged children worldwide. This disorder occurs in otherwise healthy children who bear no obvious deficiencies in the components of the spinal column itself. The cause of AIS is poorly understood, as is implied by the name. Lesions of the bony composition of the vertebrae, the vertebral endplates, the paraspinous muscles, or the neurological system each have been proposed to explain disease pathogenesis. Progress has been hampered by the absence of an obvious AIS animal model. Consequently we have used genetic studies in human populations to identify factors underlying AIS susceptibility. The complex inheritance and population frequency of AIS suggest that many genetic factors are involved in this disease. To search comprehensively for such factors we previously undertook the first genome-wide association study (GWAS) of AIS susceptibility in a cohort of 419 families in Texas, USA. We found that chromosome 3 SNPs in the proximity of the CHL1 gene yielded strongest results, which we replicated in additional cohorts (rs10510181 OR 1·49, 95% CI 1·29–173, p=2·58×10–8). CHL1 is of interest because it encodes an axon guidance protein and is functionally related to the ROBO3 gene that causes hereditary gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Here we expanded the study to 702 Texas families. Methods. We tested more than 327 000 single-nucleotide polymorphisms (SNPs) across all human autosomes for association with disease. Results. Results of the study in 702 Texas families yielded evidence for association with SNPs in a second axon guidance gene, DSCAM, which encodes a protein in the same structural and functional class with Chl1 and Robo3 (rs2222973 combined OR 0·59, 95% CI 0·48–0·74; p=1·46×10–6). We additionally found AIS associations with loci in CNTNAP2, whose protein product interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Conclusions. These data support genetic variation in axon guidance genes as risk factors in AIS. Our results provide new insight into disease pathogenesis and suggest that late-onset scoliosis may be correlated with secondary neurological development


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 21 - 21
1 Jun 2012
Zaidman A Zaidman MN Mikhailovsky M Suzdalov V Zavyalova EL Sadovoy MA
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Introduction. Type 1 neurofibromatosis is a serious hereditary disease in which mainly skin, nervous, muscular, and bone systems are damaged. In bone systems the most common deformities are thoracic kyphosis and scoliosis. Data for morphological changes in the structural components of spine in neurofibromatosis are scarce. Thus our study aimed to investigate morphological changes in structural components of the spine in NF1 neurofibromatosis. Methods. Growth plates, intervertebral discs, and fragments of vertebral bodies from deformed and adjacent segments of the spine were obtained from 15 patients aged 10–14 years with scoliosis (Cobb angle 90–120°) caused by neurofibromatosis. Preoperative examination included MRI study of the spine and brain to exclude intracanal masses, and radiographic study of the spine. Patients did not present any neurological symptoms. All children underwent anterior release and interbody fusion. Structural spinal components from children aged 12–14 years collected at forensic autopsy were used as controls. Tissues were investigated by conventional histochemical and ultrastructural methods. The levels of aggrecan and NF1 gene expression were studied with the PCR method. Results. The study of growth plate and intervertebral disc specimens removed during surgery for scoliosis in neurofibromatosis showed a clear boundary between their convex and concave sides. Both growth plate and intervertebral disc in convex side retain their architectonic and histochemical characteristics. The concave side of the growth plate is presented by small chondroblasts densely spaced without a definite orientation and surrounded by homogeneous matrix, which is made up of chondroitin sulphates. These embryonic-type chondroblasts are poorly differentiated. Chondroblasts proliferate beyond the growth plate. Proliferating cells invade into vertebral body and are bordered by thin bone lamellae, causing the scalloping of vertebral body as a radiological symptom of the pathology. Changes occurring in the intervertebral disc are of considerable interest. Concave-side disc is characterised by isolated proliferation zones containing poorly differentiated chondroblasts and fibroblasts, and neurinoma-like masses. Bone trabeculae inside a concave-side vertebra are passing the stage of osteogenesis imperfecta. Detected morphological changes in spinal structures are consistent with findings of Stevenson, who registered cartilage and bone deficiencies in animal model (mice with NF1 genemutation). Thus, morphological studies testify to structural disorder in concave side of the growth plate, but unchanged regularities and stages of chondroblast differentiation and adequate osteogenesis in the convex side. NF1 gene regulates the growth, differentiation, and proliferation of chondroblasts at the early stage of embryogenesis. Gene inactivation at a somite stage results in altered development of definitive spinal structures. Continued growth with adequate proliferation, differentiation, osteogenesis, and topochemical characteristics occurs in the convex-side growth plate, and growth disorder in the concave-side part with continued load cause growth asymmetry and development of spinal deformity. Scoliosis associated with neurofibromatosis is notable for deformity progression and pseudoarthrosis development after surgery. Deformity progression (modulation) should be considered in connection with disorder in osteogenic potency of osteoblasts. Conclusions. The causal factor of spinal deformity development in NF1 neurofibromatosis is NF1 gene mutation. Inactivation of NF1 gene results in disorder in chondrogenesis and osteogenesis within structurally altered zones. A continued load causes development of scoliotic spinal deformity


Bone & Joint Open
Vol. 3, Issue 5 | Pages 348 - 358
1 May 2022
Stokes S Drozda M Lee C

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 172 - 179
1 Feb 2023
Shimizu T Kato S Demura S Shinmura K Yokogawa N Kurokawa Y Yoshioka K Murakami H Kawahara N Tsuchiya H

Aims

The aim of this study was to investigate the incidence and characteristics of instrumentation failure (IF) after total en bloc spondylectomy (TES), and to analyze risk factors for IF.

Methods

The medical records from 136 patients (65 male, 71 female) with a mean age of 52.7 years (14 to 80) who underwent TES were retrospectively reviewed. The mean follow-up period was 101 months (36 to 232). Analyzed factors included incidence of IF, age, sex, BMI, history of chemotherapy or radiotherapy, tumour histology (primary or metastasis; benign or malignant), surgical approach (posterior or combined), tumour location (thoracic or lumbar; junctional or non-junctional), number of resected vertebrae (single or multilevel), anterior resection line (disc-to-disc or intravertebra), type of bone graft (autograft or frozen autograft), cage subsidence (CS), and local alignment (LA). A survival analysis of the instrumentation was performed, and relationships between IF and other factors were investigated using the Cox regression model.


Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Methods

An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 547 - 552
1 Mar 2021
Magampa RS Dunn R

Aims

Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy.

Methods

We carried out a retrospective review of a single surgeon’s prospectively maintained database of cases in which TcMEP monitoring had been used between 2010 and 2017. The upper limbs were used as the control. A true alert was recorded when there was a 50% or more loss of amplitude from the lower limbs with maintained upper limb signals. Patients with true alerts were identified and their case history analyzed.


The Bone & Joint Journal
Vol. 95-B, Issue 2 | Pages 217 - 223
1 Feb 2013
Hwang CJ Lee JH Baek H Chang B Lee C

We evaluated the efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) in a mini-pig model of spinal anterior interbody fusion. A total of 14 male mini-pigs underwent three-level anterior lumbar interbody fusion using polyether etherketone (PEEK) cages containing porous hydroxyapatite (HA). Four groups of cages were prepared: 1) control (n = 10 segments); 2) 50 μg E-BMP-2 (n = 9); 3) 200 μg E-BMP-2 (n = 10); and 4) 800 μg E-BMP-2 (n = 9). At eight weeks after surgery the mini-pigs were killed and the specimens were evaluated by gross inspection and manual palpation, radiological evaluation including plain radiographs and micro-CT scans, and histological analysis. Rates of fusion within PEEK cages and overall union rates were calculated, and bone formation outside vertebrae was evaluated. One animal died post-operatively and was excluded, and one section was lost and also excluded, leaving 38 sites for assessment. This rate of fusion within cages was 30.0% (three of ten) in the control group, 44.4% (four of nine) in the 50 μg E-BMP-2 group, 60.0% (six of ten) in the 200 μg E-BMP-2 group, and 77.8% (seven of nine) in the 800 μg E-BMP-2 group. Fusion rate was significantly increased by the addition of E-BMP-2 and with increasing E-BMP-2 dose (p = 0.046). In a mini-pig spinal anterior interbody fusion model using porous HA as a carrier, the implantation of E-BMP-2-loaded PEEK cages improved the fusion rate compared with PEEK cages alone, an effect that was significantly increased with increasing E-BMP-2 dosage.

Cite this article: Bone Joint J 2013;95-B:217–23.


Bone & Joint 360
Vol. 3, Issue 2 | Pages 32 - 65
1 Apr 2014
Adams MA

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’.


Bone & Joint Research
Vol. 1, Issue 9 | Pages 198 - 204
1 Sep 2012
Iwase T Takebayashi T Tanimoto K Terashima Y Miyakawa T Kobayashi T Tohse N Yamashita T

Objectives

In order to elucidate the influence of sympathetic nerves on lumbar radiculopathy, we investigated whether sympathectomy attenuated pain behaviour and altered the electrical properties of the dorsal root ganglion (DRG) neurons in a rat model of lumbar root constriction.

Methods

Sprague-Dawley rats were divided into three experimental groups. In the root constriction group, the left L5 spinal nerve root was ligated proximal to the DRG as a lumbar radiculopathy model. In the root constriction + sympathectomy group, sympathectomy was performed after the root constriction procedure. In the control group, no procedures were performed. In order to evaluate the pain relief effect of sympathectomy, behavioural analysis using mechanical and thermal stimulation was performed. In order to evaluate the excitability of the DRG neurons, we recorded action potentials of the isolated single DRG neuron by the whole-cell patch-clamp method.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1292 - 1294
1 Sep 2012
Dabasia H Rahim N Marshall R

Neurogenic claudication is most frequently observed in patients with degenerative lumbar spinal stenosis. We describe a patient with lumbar epidural varices secondary to obstruction of the inferior vena cava by pathological lymph nodes presenting with this syndrome. Following a diagnosis of follicular lymphoma, successful chemotherapy led to the resolution of the varices and the symptoms of neurogenic claudication.

The lumbar epidural venous plexus may have an important role in the pathogenesis of spinal stenosis. Although rare, epidural venous engorgement can induce neurogenic claudication without spinal stenosis. Further investigations should be directed at identifying an underlying cause.


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1127 - 1133
1 Aug 2013
Lama P Le Maitre CL Dolan P Tarlton JF Harding IJ Adams MA

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus.

Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells.

In conclusion, it should not be assumed that degenerative changes always precede disc herniation.

Cite this article: Bone Joint J 2013;95-B:1127–33.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 62 - 67
1 Jan 2005
Peng B Wu W Hou S Li P Zhang C Yang Y

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres.

The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.