Risk Factor For Disc Degeneration Research Articles

Inhibitory Effect of Insulin Treatment on Apoptosis of Intervertebral Disc Cells in a Streptozotocin-Induced Diabetic Rat Model.

Experimental study using a streptozotocin (STZ)-induced diabetic rat model. This study aims to investigate whether insulin treatment could attenuate disc cell apoptosis and matrix degradation in a STZ-induced diabetic rat model. Diabetes is a significant risk factor for disc degeneration due to excessive apoptosis of disc cells and matrix degradation. However, no studies were noted to demonstrate the inhibitory effect of insulin treatment on the apoptosis of disc cells and matrix degradation in diabetic patients. Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs). Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group. The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

Amyloid protein aggregation in diabetes mellitus accelerate intervertebral disc degeneration

Diabetes is one of the risk factors for disc degeneration, but the exact mechanism is still unclear. Misfolding and aggregation of human islet amyloid polypeptide (hIAPP) is an important factor in diabetes. hIAPP proteins misfold from monomers to β-sheet-rich oligomers, destroy the permeability of the cell membrane and cause abnormal cell function and death. Under the pathological state of diabetes, hIAPP oligomers can promote the expression and secretion of the inflammatory factor IL-1β, while IL-1β-mediated inflammatory response is the pathogenesis basis of intervertebral disc degeneration. Thus, amyloid hIAPP aggregation accelerates disc degeneration in the pathological state of diabetes.

Mechano growth factor attenuates mechanical overload-induced nucleus pulposus cell apoptosis through inhibiting the p38 MAPK pathway.

Mechanical overload is a risk factor of disc degeneration. It can induce disc degeneration through mediating cell apoptosis. Mechano growth factor (MGF) has been reported to inhibit mechanical overload-induced apoptosis of chondrocytes. The present study is aimed to investigate whether MGF can attenuate mechanical overload-induced nucleus pulposus (NP) cell apoptosis and the possible signaling transduction pathway. Rat NP cells were cultured and subjected to mechanical overload for 7 days. The control NP cells did not experience mechanical load. The exogenous MGF peptide was added into the culture medium to investigate its protective effects. NP cell apoptosis ratio, caspase-3 activity, gene expression of Bcl-2, Bax and caspase-3, protein expression of cleaved caspase-3, cleaved PARP, Bax and Bcl-2 were analyzed to evaluate NP cell apoptosis. In addition, activity of the p38 MAPK pathway was also detected. Compared with the control NP cells, mechanical overload significantly increased NP cell apoptosis and caspase-3 activity, up-regulated gene/protein expression of pro-apoptosis molecules (i.e. Bax, caspase-3, cleaved caspase-3 and cleaved PARP) whereas down-regulated gene/protein expression of anti-apoptosis molecule (i.e. Bcl-2). However, exogenous MGF partly reversed these effects of mechanical overload on NP cell apoptosis. Further results showed that activity of the p38 MAPK pathway of NP cells cultured under mechanical overload was decreased by addition of MGF peptide. In conclusion, MGF is able to attenuate mechanical overload-induced NP cell apoptosis, and the p38 MAPK signaling pathway may be involved in this process. The present study provides that MGF supplementation may be a promising strategy to retard mechanical overload-induced disc degeneration.

Asymmetry between the superior and inferior endplates is a risk factor for lumbar disc degeneration.

Endplate pathology plays an important role in the development of lumbar disc degeneration. Previous research paid little attention to differences between the superior and inferior endplates as a possible risk factor for disc degeneration. The purpose of this study was to test the hypothesis that asymmetry between the superior and inferior endplates is a risk factor for the development of lumbar disc degeneration. A total of 134 patients with lumbar disc herniation (LDH) and 100 healthy adults ("Controls") underwent magnetic resonance imaging scans. Each disc was categorized as non-degenerated (Pfirrmann grades I-II) or degenerated (Pfirrmann grades III-V) and get the following three groups: "Degenerated LDH" discs (n = 145), "Non-degenerated LDH" discs (n = 525) and "Non-degenerated Control" discs (n = 500). On mid-sagittal image, the lumbar endplate morphology could be categorized into three types: Flat, concave, and irregular. Superior and inferior endplates of a given disc were "symmetric" if both were of the same type, and "asymmetric" if they were of different types. The proportion of asymmetric endplates at L4-5 was higher in the "Degenerated LDH" discs group (47%) than in the "Non-degenerated LDH" discs group (21%) or "Non-degenerated Control" discs group (7%) (p < 0.05). At L5-S1 the proportions were 73%, 55%, and 38% (p < 0.05). Asymmetry of superior and inferior endplates in the mid-sagittal plane is a risk factor for lumbar disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2469-2475, 2018.

Vertebral Endplate Defect as Initiating Factor in Intervertebral Disc Degeneration: Strong Association Between Endplate Defect and Disc Degeneration in the General Population.

Cross-sectional study of spine magnetic resonance in a population, predominantly female, sample. To determine the relationship between vertebral endplate defect and intervertebral disc degeneration (DD) in general population. 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. 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. 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). 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. 2.

Influence of lifestyle characteristics and VDR polymorphisms as risk factors for intervertebral disc degeneration: a case\u2013control study

BackgroundIntervertebral disc degeneration (DD) is an important cause of low back pain and its precise aetiology is not fully understood, being attributed to cumulative environmental, biomechanical and genetic effects. The vitamin D plays a key role in regulation of calcium homeostasis and bone mineralization, exerting its biological activities by binding to a high-affinity receptor (VDR). Polymorphisms in VDR gene were previously associated with DD process, however with conflicting results. Here, we aimed to investigate the influence of lifestyle characteristics and VDR TaqI, BsmI, ApaI and FokI polymorphisms as risk factors for DD process.MethodsRetrospective case–control study involving 231 participants: 119 with confirmed DD and 112 healthy controls. Genotyping of VDR polymorphisms was performed by PCR–RFLP and real-time PCR using TaqMan methodology. All patients answered a questionnaire regarding lifestyle characteristics, such as educational level, pain localization, smoking habits, engagement of physical activity, postural and load weight at work and familial history of disc degeneration. The variables were compared between groups and adjusted by age and gender.ResultsThe case group was composed by 52% female and 48% male and the mean age was 40.0 years old, while in the control group 79% was female and 21% male and the mean age was 32.0 years old. Although gender distribution and mean age were different between groups, in the control group all participants were less than 45 years old and there was a prevalence of women in both groups. The factors that could be possibly associated to DD in the Brazilian population studied included smoking habits (26% in cases and 9% in controls, p = 0.003), lack of engagement in physical activity (observed in 77% of cases and 62% of controls, p = 0.018), and loading weight during work routine (58% in cases and 24% in controls, p ≤ 0.001). However, after adjusting by age and gender, only smoking habits remained associated to disc degeneration (p = 0.027). Considering the educational level, 35.2% of cases and 15.6% of controls had only the Elementary School, and 5.5% of DD group and 28.6% of control group had completed College (p = 0.025). In addition, educational level was directly associated to load weight at work (p = 0.012). Regarding VDR polymorphisms, no significant difference in genotype and allele frequencies between groups was observed. The haplotype analysis revealed that the combined wild-type alleles of TaqI, ApaI and FokI polymorphisms—TGT—was observed in a higher frequency in control group (p = 0.039).ConclusionThe findings suggested that smoking habits was a risk factor for disc degeneration in the population studied. Single analysis revealed no significant effects of VDR polymorphisms in disc degeneration process, while the combination of wild-type alleles of TaqI, ApaI and FokI polymorphisms, TGT haplotype, decreased the risk of the disease.

Facet joint malorientation as a cause of disc degeneration and prolapse in cases with backache: A radiological analysis

Background: Facet tropism is defined as asymmetry between the left and right vertebral facet-joint angles, with one joint having a more sagittal orientation than the other. The goals of the present investigation were to examine the association between facet tropism and disc degeneration as well as disc herniation to determine the relationship between increased sagittal orientation of the facet joint. It is postulated that non-coherent movements of facets on either side leads to an altered biomechanical stress which has to be borne by the anterior structure that is the disc this leading to disc degeneration and earlier prolapse. Methods: Axial and sagittal sections of MRI of the L4 L5 levels of 49 symptomatic adults aged between 20 to 60 years has been taken and their disc degeneration was classified from the T1 and T2 weighted MRI scans and facet tropism was graded as Mild (6-10 degrees), Moderate (11-15 degrees), Severe (>15 degrees). Results: It was observed from our study that the greater the grades of disc degeneration was found in patients with higher degrees of mal-orientation. There is a 5.893 times risk of dis degeneration in the cases of malorientation of the facet joint. There was no significant difference between the male and female population with regard to face tropism as a risk factor for disc degeneration. Conclusion: In our present study the association between the facet tropism as a risk factor for degeneration is positively established. The alteration in the biomechanical forces in the cases of facet tropism thus has led to faster disc degeneration.

Association Between Lumbar Spine Sagittal Alignment and L4-L5 Disc Degeneration Among Asymptomatic Young Adults.

Cross-sectional observational study on the relationship between the degrees of disc degeneration and sagittal alignment in asymptomatic healthy individuals. This study sought to determine whether the sagittal spine alignment subtype is related to the prevalence of lumbar disc degeneration. Sagittal balance and spinopelvic parameters might be risk factors for disc degeneration. A total of 70 asymptomatic participants (36 women and 34 men) without regular physical activity were categorized according to the four subtypes of sagittal alignment proposed by Roussouly. All participants underwent magnetic resonance imaging of the lumbar spine (1.5T) and panoramic radiography of the spine. The degree of disc degeneration was graded using T2-weighted images according to the Pfirrmann classification. Spinopelvic parameters and vertebral curvatures were measured on digital panoramic radiographs using Surgimap software. Interobserver analyses for the Pfirrmann classification and spinopelvic parameters were assessed using the weighted Kappa and intraclass correlation coefficient (ICC), respectively. The Kappa associated with disc degeneration classification was 0.79 (95% confidence intervals 0.72-0.87). The ICCs were excellent, with small confidence intervals for all spinopelvic parameters. The type II group (flat lordosis) showed a higher frequency of degenerated discs at L4-L5 (P = 0.03) than the type IV group (long and curved lumbar spine). No significant differences in disc degeneration were observed among the four subtypes at the other disc levels. We found a negative, moderate correlation between the spinopelvic parameters and the occurrence of disc degeneration in the type II group. The Roussouly subtype II sagittal alignment is significantly associated with disc degeneration at L4-L5 in asymptomatic young adults. Our results support the hypothesis that spinal sagittal alignment plays a role in early disc degeneration. 3.

Interplay between Genetic Risk Factors and Protective Mechanisms for Intervertebral Disc Degeneration in Mice

Introduction Intervertebral disc degeneration is a major cause of back pain. It is clear that there is a significant genetic contribution to the susceptibility of an individual-to-disc degeneration. Study in Hong Kong population cohort for disc degeneration cohort showed that while approximately 90% of the people will develop some form of disc degeneration by the age of 50 years, there are individuals who showed no indication of disc degeneration by MRI, suggesting the possibility of “protective factors,” either genetic and/or environmental. We have previously shown that Aspirin, an extracellular matrix protein, is a genetic risk factor of disc degeneration. Furthermore, our unpublished data have revealed that transgenic mice (ASPN-tg) overexpressing human ASPN gene in cartilage and disc tissues results in an accelerated or abnormal differentiation of cells in the mouse nucleus pulposus that could enhance initiation of disc degeneration. It is possible to study protective genes in humans using case–control association studies, but this would require the collection of a very large cohort of “protected” individuals. Another approach is to study in animal models and map the identified loci to the human genome. In mice, there are “super healer” strains (e.g., LG/J) with superior healing potentials of damaged tissues including ear elastic cartilage and hyaline cartilage of synovial joints, and potential genetic loci for improved joint cartilage repair have been identified in these mice. Materials and Methods Using the LG/J mice as a source of “protective” genes, we aim to perform sequential backcross of the ASPN-tg mice in C57 background to an LG/J background and compare the degenerative outcome in each generation. Our hypothesis is that if there is a protective or modulating effect, this will be reflected in histological analysis of the tail discs, coupled with the use of specific molecular analysis of differentiation markers for the different population of nucleus pulposus (NP) cells. Results Our data showed that ASPN-tg in successive backcross generations to LG/J background showed progressive improvement in the repair potential to ear punch wound compared with the parental strain, ASPN-tg/C57, for the repair of a 2 mm through-and-through ear punch wound. This is our positive indicator for the presence of “healing” genes in corresponding F1, F2, and F3 generations for the repair of damages to ear cartilage. In the NP for the backcrossed mice at F3, histological and immunostaining of cells in the NP showed fewer or absence of clusters of small round-shaped cells and Brachyury/Sox-9 positive chondrocyte-like cells were observed in ASPN-tg/C57 mice, suggesting there are genes in the LG/J background that reduces the risk or susceptibility to disc degeneration. Conclusion Our study reveals that genetic components in mice with a genetic background for better wound healing can provide protection against the morphological changes to chondrocyte-like cells in the NP that we use as an indicator of disc degeneration in intervertebral discs, induced by enhanced expression of ASPN in NP cells. Further investigation is needed to map the protective genes and study their functional impact on genetic risk factors to provide mechanistic insight for this protection or modulation of disc degeneration.

Advanced glycation end products in degenerative nucleus pulposus with diabetes

Diabetes mellitus (DM) has been clinically proved as a risk factor of disc degeneration, and the accumulation of advanced glycation end products (AGEs) is known to be potentially involved in diabetes. The purpose of this study is to investigate the effect of AGEs in the degeneration process of diabetic nucleus pulposus (NP) in rats and humans. Diabetic NP cells from rat coccygeal discs were treated with different concentrations of AGEs (0, 50, and 100 µg/ml) for 3 days, and mRNA expressions of MMP-2 and RAGE were measured by real-time RT-PCR. In addition, conditioned medium from NP cells was used to analyze protein expression of MMP-2 activity and ERK by gelatin zymography and Western blot. These experiments were repeated using human intervertebral disc samples. The immunohistochemical expression of AGEs was significantly increased in diabetic discs. In response to AGEs, an increase of MMP-2, RAGE, and ERK at both mRNA and protein expression levels was observed in diabetic NP cells. The findings suggest that AGEs and DM are associated with disc degeneration in both species. Hyperglycemia in diabetes enhances the accumulation of AGEs in the NP and triggers disc degeneration.

Biological Response of the Intervertebral Disc to Repetitive Short-Term Cyclic Torsion

In vitro study of the biological response of the intervertebral disc (IVD) to cyclic torsion by using bovine caudal IVDs. To evaluate the biological response of the IVD to repetitive cyclic torsion of varying magnitudes at a physiological frequency. Mechanical loading is known to be a risk factor for disc degeneration (DD) but the role of torsion in DD is controversial. It has been suggested that a small magnitude of spinal rotation decreases spinal pressure, increases spinal length, and enhances nutrition exchange in the IVD. However, athletes who participate actively in sports involving torsional movement of the spine are frequently diagnosed with DD and/or disc prolapse. Bovine caudal discs with end plates were harvested and kept in custom-made chambers for in vitro culture and mechanical stimulation. Torsion was applied to the explants for 1 hour/day over four consecutive days by using a servohydraulic testing machine. The biological response was evaluated by cell viability, metabolic activity, gene expression, glycosaminoglycan content, and histological evaluation. A significantly higher cell viability was found in the inner annulus of the 2˚ torsion group than in the static control group. A trend of decreasing metabolic activity in the nucleus pulposus with increasing torsion magnitude was observed. Apoptotic activity in the nucleus pulposus significantly increased with 5˚ torsion. No statistical significant difference in gene expression was found between the three torsion angles. No visible change in matrix organization could be observed by histological evaluation. The IVD can tolerate short-term repetitive cyclic torsion, as tested in this study. A small angle of cyclic torsion can be beneficial to the IVD in organ culture, possibly by improving nutrition and waste exchange, whereas large torsion angle may cause damage to disc in the long term.

RADIOGRAPHIC AND MAGNETIC RESONANCE IMAGING FINDINGS IN DEGENERATIVE DISC OF THE LUMAR SPINE

Objective: This study was conducted to describe the patterns of radiographic and MRI changes in subjects with degenerative disc of the lumbar spine. Materials and Method: a cross-sectional study was done in a sample of 212 individuals who had been diagnosed degenerative disc on MRI sagittal T2 FSE. The degree of degeneration was classified into 5 grades according to Pfirrmann’s classification. All individuals underwent clinical examination, lumbar conventional radiograph and lumbar MRI using 0.23T Open MRI system. Peridiscal lesions such as discal herniation, thecal sac compression, canal stenosis, vertebral osteochondrosis, Modic change and Schmorl’s node were also included in this study. Results: The result showed the proportion of subjects with lumbar disc degeneration by age. The rate was highest in the age group ³ 50 (45.4%) and lowest in the age group &lt;30 (12.7%). There was no significant difference between male and female (χ2 = 2,42; p=0,12). The most common finding of lumbar radiograph was osteophytes (77.4%; p&lt;0.001). There was a correlation between age, osteophytes, disc space narrowing with the degree of degeneration. Cut-off value for age was estimated &gt; 47 (Se=73.4%, Sp=76.1%) with area under ROC curve was 0.806. The most usually affected level was found to be L4-L5 (31.8%). Most of degenerated disc were classifies as grade III (59.5%). Subjects with 1 or 2 degenerative levels made the definitely higher rate compared to 4 or 5 levels. Common peridiscal lesions were disc herniation, canal stenosis, thecal sac compression, vertebral osteochodrosis, Modic change and Schmorl’s node (respectively). Conclusion: The prevalent rate and degree of disc degeneration increased by age meaning that age is risk factor for disc degeneration. Lumbar radiograph and MRI are useful in the evaluation of degenerative disc disease. Key words: lumbar intervertebral disc degeneration, magnetic resonance imaging.

Risk Factors for Disc Degeneration

Risk Factors for Disc Degeneration

A Vertebral Fracture in Childhood Is Not a Risk Factor for Disc Degeneration but for Schmorl’s Nodes

Observational cohort study. To evaluate by MRI whether a vertebral fracture during childhood is a risk factor for degeneration of adjacent discs. Several studies infer that trauma is a major cause of disc degeneration. Only 1 study has by magnetic resonance imaging (MRI) evaluated disc degeneration in children with a former thoracic or lumbar vertebral fracture. That study reported a 50% prevalence of degenerative disc changes 4 years after the fracture. However, due to the sparse literature, it is still unclear whether a vertebral fracture in childhood represents a risk factor for disc degeneration in a long-term perspective. Nine boys and 11 girls with a mean age of 12 years (range, 7-16 years) when sustaining a lumbar or thoracic vertebral fracture without neurologic deficits were examined at a mean of 40 years (range, 33-53 years) after the injury. Eighteen of the subjects had 1-column compression fractures, and 2 had Denis Type B burst fractures. All were mobilized without brace or surgery directly after being injured. A favorable long-term clinical and plain radiographic outcome has previously been reported for this cohort. In the present study, the intervertebral discs were evaluated with MRI by applying the Oner classification scheme. Degenerative disc changes were defined as loss of signal intensity on T2-weighted images with or without disc height reduction. Degenerative changes were not more prevalent in discs adjacent to the previously fractured vertebrae than in discs at a distance from those segments. However, there were more Schmorl's nodes at the disc levels adjacent to the earlier fractures. Stable vertebral fractures in childhood with no neurologic deficits at injury do not render more degenerative changes than can be expected according to age, but they are associated with more Schmorl's nodes at adjacent disc levels.

Lumbar Disc Degeneration: Epidemiology and Genetics

Research conducted over the past decade has led to a dramatic shift in the understanding of disc degeneration and its etiology. Previously, heavy physical loading-often associated with occupation-was the main suspected risk factor for disc degeneration, which was commonly viewed as a wear-and-tear phenomenon exacerbated by the precarious nutritional status of the disc. However, results of studies on twins suggest that physical loading specific to occupation and sport plays a relatively minor role in disc degeneration. Recent research indicates that heredity has a dominant role in disc degeneration, which would explain the variance of up to 74% seen in adult populations that have been studied to date. Since 1998, genetic influences have been confirmed by the identification of several gene forms associated with disc degeneration. This research is paving the way for a better understanding of the biologic mechanisms through which disc degeneration occurs, including specific interactions between genes and environment. Research into disc degeneration and genetics has become more limited by phenotypes or definitions and measures of disc degeneration than by DNA analysis. Standardized, universally accepted definitions of disc degeneration are lacking, in part due to limited knowledge of the process. The measurements that are selected depend on the method used to evaluate the disc and are often qualitative ordinal rating scales, lacking in precision. Although it is generally agreed that disc degeneration is common, the prevalence of specific findings is unclear. A review of the epidemiology of disc degeneration reveals wide-ranging prevalence estimates for various signs of disc degeneration in samples of the general population and in patients with back symptoms. The extreme variations in prevalence rates are likely largely due to inconsistencies in the definitions and measurements of disc degeneration. Such inconsistencies and inaccuracies impede epidemiologic research on disc degeneration.

Demographic factors that influence human disc cell proliferation in vitro

Background context Although previous work has shown that greater age, greater disc degeneration, female gender, and surgical derivation of disc tissue had deleterious effects on cell proliferative potential, relatively little is known about the association between disc cell proliferation in vitro and clinical donor characteristics. Purpose To identify the relationships between donor characteristic and the in vitro proliferative potential of human disc cells from the annulus. Study design/setting Studies were approved by the human subjects Institutional Review Board. Donor data included donor source, ethnicity, age, gender, smoking history, height, weight, number of years of back pain, and Thompson score. Cells cultured from the annulus were tested for proliferation. Patient sample There were two study populations: 1) Comparison Group (32 control donors and 33 control surgical subjects; 60 Caucasians, 5 African-Americans). Cell proliferation, age, Thompson score, height, weight, and smoking history were statistically analyzed for control donors versus control surgical group. No significant differences were present, and these two groups were pooled to form the Comparison Group. 2) Nineteen subjects from the United Arab Emirates who underwent disc surgery. Outcome measures Linear models were fit to the data to determine the best prediction of cell proliferation as the outcome variable; multiple R-squared was used to determine model goodness of fit. Methods Control donor specimens were obtained from the National Cancer Institute Cooperative Human Tissue Network, and control donor surgical specimens from disc surgeries. A standardized cell proliferation assay was used to evaluate monolayer and three-dimensional agarose cell proliferation. Data were expressed as mean cpm[ 3H]-thymidine per microgram deoxyribonucleic acid±SEM. Standard statistical methods used the SAS system for data analysis. Results No differences were present in the Comparison Group versus the Middle Eastern group for mean Thompson score (both averaged grade III), mean age (44.3 vs. 43.0 years, respectively), gender, height, weight, length of time with back pain (1.9 years vs. 2.1 years respectively), or smoking history. Three-dimensional proliferation in agarose was not significantly different for the two groups. Monolayer proliferation, however, was significantly different (17,434±2,929 vs. 6,693±2,103, respectively), p=.019. Linear regression models were fit to the data to determine the best prediction using proliferation as the outcome variable. In the Middle Eastern group, monolayer cell proliferation bore a significant negative correlation to age (p=.02, r=−.32), whereas the Comparison Group showed no such relationship. The following equation was derived to fit these data: Log 10 of proliferation (cpm/μg deoxyribonucleic acid)=10.915–0.7919 (Middle Eastern ethnicity)–0.0296 (Age). The r 2 for this equation is 0.203 (ie, 20.3% of the change in proliferation is explained by age and Middle Eastern ethnicity). Middle Eastern ethnicity and age were significant in this equation (p=.04 and .0003, respectively). Conclusions Studies have shown that familial history, age, and smoking are important risk factors for disc degeneration in Arabic pedigrees. It is interesting that our present findings also point to age and familial history as important significant factors influencing monolayer proliferation. Further research is needed to identify the cellular basis for this influence on cellular proliferative capacity.

Lumbar Disc Degeneration

A literature review. To synthesize the scientific literature on the prevalence of lumbar disc degeneration and factors associated with its occurrence, including genetic influences. A literature review was conducted of the prevalence of disc degeneration. Studies of the etiology of disc degeneration were summarized, with particular attention given to studies of genetic influences. There are extreme variations in the reported prevalence of specific degenerative findings of the lumbar spine among studies, which cannot be explained entirely by age or other identifiable risk factors (e.g., prevalence figures for disc narrowing varied from 3% to 56%). It is likely that these variations are due, in great part, to inconsistencies in case definitions and measurements, which are impeding epidemiologic research on disc degeneration. Research conducted over the past decade has led to a dramatic shift in the understanding of disc degeneration and its etiology. Previously, heavy physical loading was the main suspected risk factor for disc degeneration. However, results of exposure-discordant monozygotic and classic twin studies suggest that physical loading specific to occupation and sport has a relatively minor role in disc degeneration, beyond that of upright postures and routine activities of daily living. Recent research indicates that heredity has a dominant role in disc degeneration, explaining 74% of the variance in adult populations studied to date. Since 1998, genetic influences have been confirmed by the identification of several gene forms associated with disc degeneration.

COL9A3 gene polymorphism and obesity in intervertebral disc degeneration of the lumbar spine: evidence of gene-environment interaction.

Cross-sectional. To evaluate the interaction between the COL9A3 gene polymorphism and persistent obesity in relation to lumbar disc degeneration. Obesity has been suggested to be a risk factor for disc degeneration. There is some indication for an association between collagen IX genes and lumbar disc disease characterized by sciatica. However, the interaction between those factors in their influences on the risk of disc degeneration has not been studied. Blood samples from 135 middle-aged men who had undergone magnetic resonance imaging (MRI) of the lumbar spine were analyzed for the presence of an arginine to tryptophan change in the COL9A3 gene (Trp3 allele). The men represented three occupations: 41 were machine drivers, 42 were carpenters, and 52 were office workers. The discs L2/L3-L5/S1 were evaluated on MRI, using decreased signal intensity of the nucleus pulposus, posterior disc bulges, and decreased disc height as signs of disc degeneration. Based on self-reports on body height and weight currently and at the age of 25 years, obesity history was classified as no obesity, persistent obesity, and other. Rothman's synergy index was used as a measure of interaction between two factors. The Trp3 allele and persistent obesity acted synergistically to increase the risk of dark nucleus pulposus, posterior disc bulge, and decreased disc height at L4/L5; of multilevel posterior disc bulges; and of decreased disc height. From 45% to 71% of disc degeneration among persistently obese individuals with the Trp3 allele could be attributed to the synergism of these two factors. The effect of obesity on lumbar disc degeneration seems to be modified by the collagen IX gene polymorphism, so that people who carry the Trp3 allele are at increased risk if they are persistently obese.

RELATIVE EFFECTS OF RESISTANCE TRAINING, BODY WEIGHT, AND SPINE DEGENERATION IN LUMBAR BONE DENSITY

562 Several studies have shown that weight lifters have higher bone densities (BD). On the other hand, heavy lifting is one of the main suspected risk factors for disc degeneration, which includes sclerosis and osteophyte formation, both increasing BD measurement values without increasing bone strength. High body weight, often present in weight lifters, also contributes to higher BD. The goal of this study was to investigate the relative roles of resistance training and other determinants of lumbar vertebral BD. The subjects consisted of 117 former elite athletes including weight lifters, soccer players, endurance runners and shooters (mean age was 59 and range 45-68 years). Data on lifetime physical loading consisted of work, leisure and all sport activities from the age of 12 years, as collected through an extensive structured interview. Areal bone densities were measured at the L3 vertebra in lateral position using dual energy X-ray absorptiometry. Vertebral degeneration was evaluated from MR images obtained using a 1.5 tesla devise with surface coil. The stepwise multivariate model explained 24% of the total variance of BD. Age, although not significant, was included as an effect modifier and accounted for 1% of the variation. Other factors in the model were "lifetime mean" body weight, explaining 9%, disc height narrowing, adding 10%, and lifetime resistance training hours contributed 3% to the total variability explained in BD measurements. Recent weightlifting over the prior 12 months did not have contribute to the model. In conclusion, the role of lifetime resistance training in vertebral BD is significant, however, greater variability in BD among former top athletes was explained by higher body weight and spine degeneration, both of which are more common among weight lifters. Much of the increased BD in weight lifters that has been attributed to resistance training is likely due to the covariates of higher body weight and spine degeneration, neither of which are perceived as beneficial to health. Supported by Ministry of Education and Social Insurance Institution.

Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration.

A study in genetic epidemiology of disc degeneration, based on lifetime exposure data, findings on magnetic resonance imaging, and genotyping of intragenic markers. To pursue the potential correlation between common allelic variations in the vitamin D receptor locus and degeneration of the intervertebral disc. Familial aggregation has been observed in intervertebral disc degeneration, but the relative significance of the genetic component and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specify a genetic component and increase our understanding of the etiopathogenesis of disc degeneration. From the population-based Finnish Twin cohort, 85 pairs of male monozygotic twins were selected based on exposure to suspected risk factors for disc degeneration. Interview data were gathered on relevant lifetime exposures, and thoracic and lumbar disc degeneration was determined through quantitative and qualitative assessments of signal intensity on magnetic resonance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible associations were examined between disc degeneration measures and two polymorphisms of the coding region of the vitamin D receptor locus. Two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration. Quantitatively assessed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% worse in men with the Taql tt genotype and 4.5% worse in men with the Tt genotype, compared with signal intensity in men with the TT genotype (age adjusted P = 0.003). A similar pattern was found between disc signal intensity and Fokl genotypes; men with the ff and Ff genotypes had mean signal intensities that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively assessed signal intensity, bulging, and disc height were 4.0% and 6.9% worse in men with Ff and ff genotypes, respectively, when compared with those in men with the FF genotype (age-adjusted P = 0.029). Specific vitamin D receptor alleles were associated with intervertebral disc degeneration as measured by T2-weighted signal intensity, demonstrating for the first time, the existence of genetic susceptibility to this progressive, age-related degenerative process.