Introduction. Vertebral compression fractures are the most common type of osteoporotic fracture. Though 89% of clinical fractures occur anteriorly, it is challenging to replicate these ex vivo with the underlying intervertebral discs (IVDs) present. Furthermore, the role of disc degeneration in this mechanism is poorly understood. Understanding how disc morphology alters vertebral strain distributions may lead to the utilisation of IVD metrics in fracture prediction, or inform surgical decision-making regarding instrumentation type and placement. Aim. To determine the effect of disc degeneration on the vertebral trabecular bone strain distributions in axial compression and flexion loading. Methods. Eight cadaveric thoracolumbar segments (T11-L3) were prepared (N=4 axial compression, N=4 flexion). µCT-based digital volume correlation was used to quantify trabecular strains. A bespoke loading device fixed specimens at the resultant displacement when loaded to 50N and 800N. Flexion was achieved by adding 6° wedges. Disc degeneration was quantified with Pfirrmann grading and T2 relaxation times. Results. Anterior axial strains were 80.9±39% higher than the posterior region in flexion (p<0.01), the ratio of which was correlated with T2 relaxation time (R. 2. =0.80, p<0.05). In flexion, the central-to-peripheral axial strain ratio in the endplate region was significantly higher when the underlying IVDs were non-degenerated relative to degenerated (+38.1±12%, p<0.05). No significant differences were observed in axial compression. Conclusion. Disc degeneration is a stronger determinant of the trabecular strain distribution when flexion is applied. Load transfer through non-degenerate IVDs under flexion appears to be more centralised, suggesting that disc degeneration predisposes flexion-type compression fractures by shifting high strains anteriorly. Conflicts of interest. The authors declare none. Sources of funding. This work was funded by the Engineering & Physical Sciences Research Council (EP/V029452/1), and Back-to-Back

Purpose of study and background. Degeneration of the intervertebral disc is a strong contributor of low back pain. Studies have shown that both, mechanical unloading and overloading, lead to disc degeneration. This is intuitively clear if one considers that an intervertebral disc essentially is a poro-elastic material embedded with cells, which depend on fluid flow for the transport of nutrients and waste products. As such, mechanical loading is also required for regeneration. It is unclear, however, how much loading is beneficial or detrimental for the healthy or degenerated disc. Methods and Results. We developed a loaded disc culture system for the long-term study of disc physiology. This way we could control both the mechanical and biochemical conditions. If no loading was applied, about half of the cells died within a week. Cells died under a low dynamic loading regime after three weeks. A diurnal loading regime rescued cell viability, gene expression profile and mechanical behavior of the discs. Both static and dynamic overloading induced damage to the discs and led to catabolic and inflammatory gene expressions. Conclusion. Intervertebral discs need a certain dosage of mechanical loading to remain viable. Under overloading, cells deform, change gene expression and become degenerative. The matrix is also remodeled, thereby further decreasing the hydrostatic pressure on the cells and increasing their deformation. This induces a vicious circle of disc degeneration, which needs to be reversed in order to repair the disc. The loaded disc culture system also allows evaluating new therapies for disc degeneration. There are no conflicts of interest. Funded by ZonMW program “Alternatives for live animal testing”, grant #11400090;. BioMedical Materials Program, grant # P2.01 IDiDas; Dutch Arthritis Funds, personal grant KSE

Background

Intervertebral disc degeneration (DD) is a complex age-related condition that constitutes the main risk factor for disabling back pain. DD is assessed using different traits extracted from MR imaging (MRI), normally combined to give summary measures (e.g. Pfirmann score). The aetiology of DD is poorly understood and despite its high heritability (75%), the precise genetic predisposition is yet to be defined. Genome wide association study (GWAS) is used to discover genetic variants associated with a disease or phenotype. It tests variants across the whole genome. It requires large samples to provide adequate but unfortunately there is poor availability of spine imaging data due to the high cost of MRI. We have adopted new methods to examine different MRI traits independently and use the information of those traits to boost GWAS power using specialized statistical software for jointly analyse correlated traits.

Introduction. Risk factors for disc degeneration depend on how the condition is defined, i.e. on the specific disc degeneration “phenotype”. We present evidence that there are two major and largely-distinct types of disc degeneration. Methods. The relevant research literature was reviewed and re-interpreted. Evidence. In the . upper. lumbar and thoracic spine, disc degeneration is closely associated with endplate defects and with inflammatory changes in the vertebral bodies. It has a relatively high heritability (i.e. a strong genetic influence), and its incidence does not increase markedly with age. In the . lower. lumbar spine, disc degeneration is closely associated with radial fissures and nucleus herniation. Here it has a relatively low heritability, and a correspondingly stronger association with mechanical loading, and its incidence increases steadily throughout life. Mechanical experiments on cadaveric spines show that endplate fracture and nucleus herniation can be caused by compressive loading, and by bending combined with compression, respectively. Both lesions cause an immediate decompression of the nucleus, so that it becomes difficult to create subsequently the other lesion in the same disc. This suggests distinct phenotypes. Interpretation. The two types of disc degeneration are not entirely distinct, because disc herniation sometimes occurs at upper lumbar levels. Nevertheless, it may be useful to recognise two phenotypes when it comes to explaining and treating discogenic pain. Some other common disc changes (such as water loss and bulging) are attributable to ageing rather than degeneration, whereas disc narrowing probably represents a final common pathway for both types of disc degeneration. Conflicts of Interest. None. Source of Funding. None. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

Introduction. Delamination of the annulus fibrosus is an early feature of disc degeneration, and it allows individual lamellae to collapse into the nucleus, or to bulge radially outwards. We . hypothesise. that delamination is driven by high gradients of compressive stress in the annulus. Methods. 102 thoracolumbar motion segments (T8-9 to L5-S1) were dissected from 42 cadavers aged 19–92 yrs. Each specimen was subjected to 1 kN compression, while intradiscal compressive stresses were measured by pulling a pressure transducer along the disc's mid-sagittal diameter. Stress gradients were measured, in the anterior and posterior annulus, as the average rate of increase in compressive stress (MPa/mm) between the nucleus and the region of maximum stress in the annulus. Average nucleus pressure was also recorded. Disc degeneration was assessed macroscopically on a scale of 1–4. Results. Compared to grade 2 discs, moderately degenerated grade 3 discs showed increased stress gradients in the annulus, especially in the posterior annulus where they increased by an average 106%. Nucleus pressure showed minimal changes. However, comparing grade 3 discs with severely degenerated grade 4 discs showed that nucleus pressure fell by 47%, while stress gradients showed little or no further change. Discussion. The results support our hypothesis. In early disc degeneration, a minor reduction in nucleus pressure is sufficient to generate high stress gradients in the annulus. These shear adjacent lamellae, causing delamination and allowing internal displacement of nucleus. As disc degeneration progresses, nucleus migration causes severe decompression, and compressive loading is transferred increasingly to the neural arch. Conflicts of Interest. None. Source of Funding. None. This abstract has not been previously published in whole or in part; nor has it been presented previously at a national meeting

Summary Statement. Spinal flexibility in bending and axial torque has been shown to exhibit very modest changes with advancing disc degeneration. This study is the first to address the possible relationship in pure anterior shear and no clear relationship was observed. Introduction. Disc degeneration (DD) is a risk factor for low back pain. Stable or unstable spine segments may be treated with an isolated decompression or instrumented stabilization, respectively. The effect of DD on spinal flexibility has been addressed by several groups in bending but not in shear; a highly relevant load direction in the lumbar spine is anterior shear. The objective of our study was to determine the effect of DD on anterior translation and specimen stiffness under shear loading in an in vitro model of degenerative spondylolisthesis. Methods. Magnetic resonance images were obtained for human cadaveric lumbar FSUs (N=30). Disc degeneration was assessed with the Pfirrmann five-point grading scale. Three surgeons independently graded the discs and the grade common to at least two of the surgeons was assigned to that specimen. Each specimen was then tested in three sequential states: intact, facet destabilization, and disc destabilization, with the latter two states representing the clinical scenario of degenerative lumbar spondylolisthesis. The specimens were loaded with a constant 300 N axial compressive force, representing body weight, combined with a cyclic anterior shear force (5–250 N). Vertebral translation was tracked with an optoelectronic motion capture system. Kruskal-Wallis ANOVA and multiple comparison Dunn's tests were performed to determine the effect of DD on anterior translation and specimen stiffness. Results. There was only one specimen with disc grade V, and it was grouped with specimens with disc grade IV for the statistical analyses. DD had no effect on anterior translation or specimen stiffness for the intact and disc destabilization conditions. In the facet destabilization condition, specimens with disc grade II translated more than those with disc grades IV and V (p=0.03). Stiffness increased with DD in the facet destabilization condition (ANOVA p=0.04; Dunn's test was not significant). However, we re-analyzed the data with each surgeon's disc grades and found no significant differences in any of the specimen conditions for all three surgeons. Discussion. In the original data analysis, the translation results showed a trend to reduced anterior translation in shear with advancing degeneration only in the facet destabilization condition. These results suggest that shear stiffness of an intact specimen is not affected by overall degeneration, except in the case where the facets are not competent to resist load. In the subsequent data analyses, no significant effects were found. These findings indicate the sensitivity of the analyses to the assignment of disc grade. There are numerous disc grading scales reported in the literature and it is not clear which scale best defines disc degeneration. We are continuing to assess our methods to determine the most appropriate method of defining disc degeneration by disc grade

Purpose & Relevance: To examine the prevalence of degenerative findings in the thoracic spine in a population sample of adult men. Normative data on thoracic degenerative findings provide an essential reference for related observations in patients. Methods & Results: Qualitative and quantitative assessments of thoracic disc degeneration were obtained from MRI (levels T6-L1) for general population sample of 532 men aged 25–70 years. Qualitative assessments of disc degeneration were performed by an experienced spine surgeon and custom-made software was used to acquire quantitative assessments. Descriptive statistics were acquired using SPSS. Moderate or severe disc bulging was present in at least one disc in 7.9% of subjects, with bulging most common at the two lowest levels. The prevalence of disc herniations was 0.8%. Moderate or severe disc height narrowing was present in 2.7% to 9.7% by disc level with 22.4% of subjects having at least one narrowed disc. Four or more wedged vertebrae (≥ 5°) were present in 68 subjects and 13 (2.4%) had coexisting Schmorl’s nodes. Seven subjects (1.3%) met more stringent criteria for Scheuermann’s disease, with three or more wedged vertebrae, endplate changes, sclerosis and disc height narrowing. Of the variables examined, disc signal intensity correlated highest with age (r= 0.31–0.40, depending on disc level). Conclusion: The prevalence of disc degeneration appears lower in the thoracic spine than previously reported in the lumbar spine. However, one-fifth of the subjects have markedly narrowed discs, which have been associated with symptom history in the lumbar spine. Disc signal intensity is the finding most highly associated with age

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’

Mechanical function and failure of intervertebral discs. In a healthy disc, the nucleus pulposus acts like a pressurised fluid which is restrained by tensile stress within the annulus. With increasing age, the nucleus becomes more fibrous, and biochemical changes cause the whole disc to become less elastic, and more yellow in colour. Mechanically, the hydrostatic nucleus shrinks with age, and concentrations of compressive stress appear in the posterior annulus. Experiments on cadaveric spines have shown that healthy discs can prolapse when loaded severely or repetitively in bending and compression, and that internal disruption of the disc probably follows damage to the vertebral endplates. However, mechanical loading is not necessarily harmful to living discs: on the contrary, moderate repetitive loading may lead to disc hypertrophy rather than injury. Disc degeneration. Degeneration represents some mechanical or biological “insult” superimposed on normal ageing. A defining feature of “degeneration” should be structural failure of the annulus or endplate, because all degenerated discs exhibit structural failure whereas many old discs do not. Degeneration creates high stress concentrations within the annulus. Paradoxically, severe degeneration can lead to gross disc narrowing and reduced stresses in the annulus, presumably because it is “stress shielded” by the apophyseal joints. Animal experiments show that disc degeneration always follows mechanical disruption. In some cases, it may possibly precede it. Disc degeneration and back pain. Pain-provocation studies have shown that severe and chronic back pain often originates in the posterior annulus fibrosus, and can be elicited by relatively moderate mechanical pressure. Anatomical studies indicate that the outer annulus is supplied with complex and free nerve endings from the mixed sinuvertebral nerve. MRI and discographic studies show that back pain is closely correlated with structural features of disc degeneration such as radial fissures and prolapse, although age-related changes in composition are clinically irrelevant. The stress-shielding of severely degenerated discs (see above) suggests that discogenic pain may be most closely associated with intermediate stages of degeneration. The localised stress concentrations found in degenerated cadaveric discs have been directly linked to low back pain in living people. Medico-legal implications. The widely-held belief that a disc will not prolapse unless it is degenerated is no longer compatible with the scientific evidence. Severe loading, which in life usually arises from vigorous muscle contractions, can injure normal discs. On the contrary, it seems likely that severely degenerated discs are too fibrous to prolapse, and that many of the cell-mediated changes associated with disc prolapse occur after prolapse, rather than before. However, genetic inheritance is important in disc degeneration and prolapse, suggesting that some discs are more vulnerable than others to mechanical loading. The nature of this vulnerability is largely unknown, but is likely to involve genetic weaknesses in composition, and previous fatigue damage. It would be desirable to distinguish between these last two factors, but this is likely to prove difficult in practice

Introduction: Disc degeneration is consistent with advancing age and in many cases is associated with back pain and restricted mobility. The traditional surgical treatment for chronic back pain has been spinal fusion to immobilize the painful level. Long-term studies, however, suggest that fusion actually promotes degeneration at adjacent levels. One of the hallmarks of disc degeneration is aggregation of chondrocytes in the nucleus of chondrones, and more recently apoptosis has been implicated as a factor controlling the longevity of the cells. Recent research suggests that it may be possible to restore normal function to degenerate discs by introducing a fresh population of cells. This study investigated the potential for autologous costal chondrocyte implantation to prevent lumbar disc degeneration after annular injury in the sheep. Methods: the lumbar spines of eight adult sheep were exposed. In four animals, full thickness annular incisions were made in three alternate discs. No annular incisions were made in the other four sheep. A minimum of 500 mg of cartilaginous tissue was harvested from the twelfth rib of all animals. Tissue was cultured in vitro and the chondrocytes were labelled with a fluorescent marker for retrospective identification. After six weeks the chondrocytes were injected into the lower two alternate discs of all animals, leaving the uppermost discs and those untouched as internal controls. The animals were killed at intervals from three to twenty-four weeks and MRI, plain x-ray, histology and immunocytochemistry were evaluated. Results: MRI at twelve and twenty-four weeks showed apparent preservation of all incised discs that had been transplanted with autologous chondrocytes. Histology revealed clusters of viable chondrocytes of normal appearance within the nucleus. These cells stained positive for the fluorescent label. The same cells and the surrounding matrix were also positive for collagen type II. Serial X-ray measurements suggested that progressive disc degeneration was arrested in the discs that received autologous costal chondrocytes. Discussion: This pilot study showed evidence that cultured autologous costal chondrocytes remained viable and produced extracellular matrix following transplantation into normal and degenerate discs. In contrast to other studies that have used mesenchymal stem cells or chondrocytes harvested directly from discs, this study demonstrated success with cells from a source other than the disc. Costal cartilage is a convenient source of cells for transplantation and this technique warrants further investigation as a potential treatment for degenerative disc disease

Purpose: To evaluate the long term clinical outcomes as well as radiological changes in distal unfused mobile segments and to evaluate factors that may predispose to distal disc degeneration and/or poor outcome. Method: 151 mobile segments in 85 patients (65 female), mean age 43.2 (range 21–68), were studied. Curve type, number of fused levels and pelvic incidence were recorded. Clinical outcome was measured using the Whitecloud function scale and disc degeneration using the UCLA disc degeneration score. Spinal balance, local segmental angulations and lumbar lordosis were measured pre- and post-operatively as well as at the most recent follow up – mean 9.3 years (range 7–19). Results: 62% of patients had a good or excellent outcome. 11 had a poor outcome of which 10 underwent extension of fusion – 5 for pain alone, 3 pain with stenosis and 2 pseudarthroses. Pre-operative disc degeneration was often asymmetric and was slightly greater in older patients. Overall, there was a significant deterioration in disc degeneration (p< 0.0001) that did not correlate with clinical outcome. Disc degeneration correlated with the recent sagittal balance (Anova F=14.285, p< 0.001) and the most recent lordosis (Anova F=4.057, p=0.048). The post-operative sagittal balance and local L5-S1 sagittal angulation correlated to L4 and L5 degeneration respectively. There was no correlation between degeneration and age, pre-operative degenerative score, pelvic incidence, sacral slope, number of fused levels or distal level of fusion. Conclusion: Disc degeneration does occur below an arthrodesis for scoliosis in adults which does not correlate with clinical outcome. The correlation of loss of sagittal balance with disc degeneration may be as a result of degeneration causing the loss of balance or vice versa i.e. sagittal imbalance causing degeneration. Immediate post-operative imbalance correlates with degeneration of the L4/5 disc, which may imply the latter

Osteoporotic fractures are associated with bone loss following hormonal changes and reduced physical activity in middle age. But these systemic changes do not explain why the anterior vertebral body should be such a common site of fracture. We hypothesise that age-related degenerative changes in the intervertebral discs can lead to abnormal load-bearing by the anterior vertebral body. Cadaveric lumbar motion segments (mean age 50 ± 19 yrs, n = 33) were subjected to 2 kN of compressive loading while the distribution of compressive stress was measured along the antero-posterior diameter of the intervertebral disc, using a miniature pressure-transducer. “Stress profiles” were obtained with each motion segment positioned to simulate a) the erect standing posture, and b) a forward stooping posture. Stress measurements were effectively integrated over area in order to calculate the force acting on the anterior and posterior halves of the disc ( . 1. ). These two forces were subtracted from the applied 2 kN to determine the compressive force resisted by the neural arch. Discs were sectioned and their degree of disc degeneration assessed visually on a scale of 1–4. In motion segments with non-degenerated (grade 1) discs, less than 5% of the compressive force was resisted by the neural arch, and forces on the disc were distributed evenly in both postures. However, in the presence of severe disc degeneration, neural arch load-bearing increased to 40% in the erect posture, and the compressive force exerted by the disc on the vertebral body was concentrated anteriorly in flexion, and posteriorly in erect posture. In severely degenerated discs, the proportion of the 2 kN resisted by the anterior disc increased from 18% in the erect posture to 58% in the forward stooped posture. Disc degeneration causes the disc to lose height, so that in erect postures, substantial compressive force is transferred to the neural arch. In addition, the disc loses its ability to distribute stress evenly on the vertebral body, so that the anterior vertebral body is heavily loaded in flexion. These two effects combine to ensure that the anterior vertebral body is stress-shielded in erect postures, and yet severely loaded in flexed postures. This could explain why anterior vertebral body fractures are so common in elderly people with degenerated discs, and why forward bending movements often precipitate the injury

Introduction. Primary cilia are singular structures containing a microtubule-based axoneme which are believed to not only be mechanosensitive but also to co-ordinate many cell functions via signalling pathways including Hedgehog and Wnt. Primary cilia have previously been described on cells of mouse intervertebral discs (IVDs), but not in bovine or human IVDs. Our aim was to examine primary cilia in these species. Methods. Nucleus pulposus cells were obtained from cows with no overt disc degeneration and patients following spine surgery (for herniations and/or degenerative disc disease) and cultured until confluent before maintaining with or without serum for 24h. Primary cilia were visualised with antibodies to the axoneme (acetylated α-tubulin and Arl13b) and/or the basal body (pericentrin) using fluorescent secondary antibodies and ≥200 cells per sample were counted. Results. Primary cilia were detected in the majority of disc cells (81.2±4.1% and 54.8±28.7% with and without serum depletion, respectively, in bovine and 78.9±0.3% and 89.8±7.4% in human cells). Some cilia demonstrated abnormalities, such as bulbous tips or breaks in the axonome. Conclusion. This is the first report of primary cilia being present on human and bovine IVD cells. There remain many other aspects to be investigated, for example, their length has been shown to alter in osteoarthritic chondrocytes. If this, or the incidence of abnormalities, differs in cells from normal and abnormal discs, it could suggest new pathways of disc degeneration, as these organelles are key to so many cell functions. Conflicts of interest: None. Supported by the Orthopaedic Institute Ltd

Summary Statement. DNA damage induced by systemic drugs or local γ-irradiation drives disc degeneration and DNA repair ability is extremely important to help prevent bad effects of genotoxins (DNA damage inducing agents) on disc. Introduction. DNA damage (genotoxic stress) and deficiency of intracellular DNA repair mechanisms strongly contribute to biological aging. Moreover, aging is a primary risk factor for loss of disc matrix proteoglycan (PG) and intervertebral disc degeneration (IDD). Indeed, our previous evidences in DNA repair deficient Ercc1−/Δ mouse model strongly suggest that systemic aging and IDD correlate with nuclear DNA damage. Thus the aim of the current study was to test whether systemic or local (spine) genotoxic stress can induce disc degeneration and how DNA repair ability could help prevent negative effects of DNA damage on IDD. To test this hypothesis a total of twelve Ercc1−/Δ mice (DNA repair deficient) and twelve wild-type mice (DNA repair competent) were challenged with two separate genotoxins to induce DNA damage, i.e. chemotherapeutic crosslinking agent mechlorethamine (MEC) and whole-body gamma irradiation. Local effects of gamma irradiation were also tested in six wild-type mice. Methods. Ercc1. −/Δ. mice (n=6) and their wild-type littermates were chronically exposed to genotoxic stress beginning at 8 wks of age by subcutaneous administration of a subtoxic dose of MEC (8 μg/kg once per week for 6 weeks). Similarly, six Ercc1. −/Δ. mice and their wild-type littermates were exposed to genotoxic stress by whole-body administration of ∼10% radiotherapeutic dose of ionizing radiation (0.5 Gy 1x per week for 10 weeks). A third set of wild-type mice (n=6) were exposed to one shot local spine irradiation at 0, 6, and 10 Gy at 22 weeks old and sacrificed 10 weeks later. Histological staining for proteoglycan (Safranin O) and collagen (Masson's Trichrome), PG synthesis (. 35. S-sulfate incorporation) and GAG content (DMMB assay), disc ADAMTS4, aggrecan and its fragments terminating in NITEGE-. 373. (immunohistochemistry (IHC)) were analyzed. Cellular senescence markers (p16) and apoptosis (TUNEL assay) were also measured. Results. Histological staining revealed substantial reduction in matrix collagen, proteoglycan, and endplate cellularity in the discs of MEC-exposed and irradiated mice. IHC analysis showed decreased aggrecan and increased levels of ADAMTS4 and NITEGE-. 373. containing aggrecan proteolytic fragments. Disc PG synthesis was reduced 2–3 folds in MEC-treated mice and irradiated mice. Locally irradiated mice showed similar effects on disc matrix. Expression of p16 as well as apoptosis significantly increased in MEC-treated and irradiated mice. The overall effect of the treatments on disc matrix and endplate cartilage was more severe in Ercc1−/Δ mice than wild-type mice. Discussion/Conclusion. MEC and IR treatment resulted in loss of disc matrix proteoglycan and collagen in adult wild-type and Ercc1−/Δ mice. The finding that loss of matrix proteoglycan was greater in the DNA repair deficient mice strongly supports the conclusion that DNA damage can drive disc degeneration and DNA repair ability is extremely important to help prevent these effects. Results of this work suggest that patients treated with genotoxic drugs (i.e. long-term cancer survivors) may be at increased risk of IDD

Introduction Disc replacement surgery is being investigated as an alternative to spinal fusion surgery in the hope that maintaining segment spinal motion will not only relieve pain, but also prevent or reduce the likelihood of symptomatic adjacent segment degeneration that is believed to be a consequence of fusion surgery. The aim of this study was to identify evidence in the medical literature that indicates whether or not spinal fusion surgery increases the likelihood of symptomatic adjacent segment degeneration compared to disc replacement surgery or natural history. Methods A search of the Cochrane Controlled Trials Register, Medline and reference lists of retrieved articles was performed. Search terms included arthroplasty replacement, spinal fusion, prognosis, controlled clinical trials and cohort studies, Studies were included if abstracts were available electronically, were published in the English language before1/3/2005 and involved humans. Levels of evidence were determined using the Oxford Centre for Evidence-Based Medicine criteria (. http://www.cebm.net/levels of evidence.asp. ). Discussion The majority of identified studies were case series of patients presenting with adjacent level disc degeneration following spinal fusion surgery (Level 4) and whilst indicating patients can develop adjacent level disc degeneration following fusion surgery, do not indicate the likelihood of doing so. Uncontrolled prospective cohort studies (Level 4) provide conflicting evidence. One retrospective cohort (Level 2b) studying comparing the incidence of adjacent disc degeneration following spinal fusion and discectomy or decompressive surgery alone found that the incidence of degeneration in the superior adjacent disc was increased in the fusion group, but was not associated with differences in functional outcome. No systematic reviews of inception cohort studies (Level 1) were identified. Conclusions Only poor quality evidence has been published to support the proposition that spinal fusion surgery is associated with an increased likelihood of developing symptomatic adjacent level disc degeneration. Long term follow-up of patients enrolled in prospective randomised controlled trials comparing outcomes of spinal fusion and disc replacement surgery is necessary to determine whether or not disc replacement surgery decreases the likelihood of any symptomatic adjacent level disc degeneration that can be attributed to spinal fusion surgery

Study Design: Experimental in vivo study on New Zealand White Rabbits. Summary of Background Data: We have developed an in-vivo rabbit model of lumbar disc degeneration. This model provides a defined loading of one single disc. However, the molecular mechanism that leads to mechanically-induced disc degeneration remains unclear. Objective: To investigate the process of mechanically induced disc degeneration in New Zealand White Rabbits with respect to remodeling on the gene and the level of protein expression. Subjects: Seven animals were treated with an external compression-device applying 200N on segment L3/4. Eight animals underwent sham surgery. Outcome Measures: After 28 days discs were harvested and cut into two pieces in a sagittal plain. One piece was used for protein analysis utilizing immunohistochemical protocols for collagen I, II and aggrecan. The other half of the disc was used for quantitative real-time RT-PCR to determine gene expression of selected matrix genes. Results: In the compression group matrix genes were upregulated: collagen I (6.46x; p=0,018), collagen II (2.14x), biglycan (2.97x; p=0,049), decorin (4.64x; p=0,043), aggrecan (1.2x), osteonectin (2.03x), fibronectin (3.48x), fibromodulin (2.6x; p=0,037). The MMP-13 gene could only be detected in compressed discs. Gene transcripts of the metalloproteinase-inhibitor TIMP-1 were 4.5 times upregulated (p=0,007). Immunohistochemical analysis revealed a decrease of aggrecan and collagen I. Conclusions: In our animal model mechanical loading caused degradation of the matrix proteins collagen I and aggrecan. Metalloproteinases like MMP-13 trigger this degenerative process. The elevated expression of matrix genes and TIMP-1 transcripts may characterize a mechanism of compensation

Objectives. A single degenerate intervertebral disc is suggested to promote rapid degeneration in its adjacent discs. We validated this hypothesis using discordant co-twin case-control design. Methods. 185 pairs of twins were selected from the TwinsUK database having cervical MRI scans at baseline and at follow-up, after 10 years. Isolated disc degeneration (IDD) was diagnosed in subjects having severe loss in disc height (graded 3/3) in a single disc, whilst discs immediately adjacent manifested little or no degeneration (graded 0 or 1). The controls' ‘adjacent discs’ were considered at the same levels as their affected co-twins. Results. Eight twin pairs fulfilled case/control criteria. At follow-up, no significant difference in adjacent disc degeneration between IDD cases and controls remained (p=0.69). Conclusions. Using a highly matched case-control design we did not find evidence that lone IDD has an adverse effect on the natural rate of adjacent disc degeneration in the cervical spine. No conflicts of interest. Acknowledgements. This study was supported by a grant from Globus Inc. Arthritis Research UK supported the imaging costs. TwinsUK. The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007–2013). The study also receives support from the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London

Introduction and Aims: Lower back and/or leg pain is a symptom of a number of pathological conditions involving lumbosacral nerve roots. Disc herniation is one of the most common causes of LBP (after mechanical back pain). There is controversy regarding the progression of disc degeneration and/or lower back pain to symptomatic disc prolapse over time. Method: The aim of the study was to determine the natural progression of patients with lower back pain/disc degeneration established clinically and on MRI to symptomatic disc herniation over three to six years. Total of 970 patients who had an MRI scan between January 1998 and September 2000 were included in the study. Information about disc pathology, level and number of discs involved were recorded from MRI scan reports. A short questionnaire was sent to all patients. It contained 10 questions regarding current status of pain and neurology, any treatment in form of back injection and operation, current occupation and smoking status. Results: The collected data was analysed using standard statistics software (SPSS). The results will be discussed. Conclusion: The information provided by this study will be useful in judging the natural progression of lower back pain and/or disc degeneration to a symptomatic prolapse intervertebral disc. It will also be useful in medico-legal cases where patients had pre-existing disc degeneration and subsequently developed disc herniation over time

Introduction: The development of laboratory techniques in the last ten years has enabled the successful harvest, in vitro selection, culture and transplant of chondrocytes. The study proposes that transplantation of autologous chondrocytes prevents degeneration of the intervertebral disc following outer annular injury in an ovine model. Methods: Eight sheep were anaesthetised and five contiguous lumbar discs were exposed via a left-sided posterolateral approach. Four of the animals were given full thickness annular incisions in three alternate discs. No annular incisions were made in the other 4 sheep. Costal cartilage was harvested from the left twelfth rib of all animals. Tissue was cultured and the chondrocytes were labelled in vitro with CFSE for verification following transplantation. Six weeks later autologous cultured chondrocytes were injected into the lower two alternate discs of all animals, leaving the uppermost discs and those untouched in between as internal controls. Animals were sacrificed after three, six, twelve and twenty-four weeks. Results were based on X rays, histological, and immunocytochemical assessments. Results: Preliminary histological results up to three months showed viability of cultured chondrocytes and matrix production post transplantation. Serial X rays suggested that progressive disc degeneration was arrested in the treated discs. Discussion: In this pilot study we have shown that cultured autologous chondrocytes can remain viable long term in vivo. These preliminary results suggest that these transplanted chondrocytes have the ability to retard and possibly prevent disc degeneration following annular incision. Previous similar studies have reported the use of chondrocytes cultured from disc, whilst this study showed that chondrocytes from a source foreign to the disc can exert positive effects. The encouraging result from this pilot study needs to be further validated to realise its potential as a treatment for degenerative disc disease

INTRODUCTION: The development of laboratory techniques in the last ten years has enabled the successful harvest, in vitro selection, culture and transplant of chondrocytes. The study proposes that transplantation of autologous chondrocytes prevents degeneration of the intervertebral disc following outer annular injury in an ovine model. METHODS: Eight sheep were anaesthetised and five contiguous lumbar discs were exposed via a left-sided posterolateral approach. Four of the animals were given full thickness annular incisions in three alternate discs. No annular incisions were made in the other four sheep. Costal cartilage was harvested from the left twelfth rib of all animals. Tissue was cultured and the chondrocytes were labelled in vitro with CFSE for verification following transplantation. Six weeks later autologous cultured chondrocytes were injected into the lower two alternate discs of all animals, leaving the uppermost discs and those untouched in between as internal controls. Animals were sacrificed after three, six, twelve and twenty-four weeks. Results were based on X-rays, histological, and immunocytochemical assessments. RESULTS: Preliminary histological results up to three months showed viability of cultured chondrocytes and matrix production post transplantation. Serial X-rays suggested that progressive disc degeneration was arrested in the treated discs. DISCUSSION: In this pilot study we have shown that cultured autologous chondrocytes can remain viable long term in vivo. These preliminary results suggest that these transplanted chondrocytes have the ability to retard and possibly prevent disc degeneration following annular incision. Previous similar studies have reported the use of chondrocytes cultured from disc, whilst this study showed that chondrocytes from a source foreign to the disc can exert positive effects. The encouraging result from this pilot study needs to be further validated to realise its potential as a treatment for degenerative disc disease