Risk Of Lumbar Disc Degeneration Research Articles

Biomechanical response of lumbar intervertebral disc in daily sitting postures: a poroelastic finite element analysis

This study aims to establish and validate a poroelastic L4–L5 finite element model to evaluate the effect of different sitting postures and their durations on the mechanical responses of the disc. During the sustained loading conditions, the height loss, fluid loss and von-Mises stress gradually increased, but the intradiscal pressure decreased. The varying rates of aforementioned parameters were more significant at the initial loading stage and less so at the end. The predicted values in the flexed sitting posture were significantly greater than other postures. The extended sitting posture caused an obvious von-Mises stress concentration in the posterior region of the inter-lamellar matrix. From the biomechanical perspective, prolonged sitting may pose a high risk of lumbar disc degeneration, and therefore adjusting the posture properly in the early stage of sitting time may be useful to mitigate that. Additionally, upright sitting is a safer posture, while flexed sitting posture is more harmful.

Association between single-nucleotide polymorphism rs145497186 related to NDUFV2 and lumbar disc degeneration: a pilot case–control study

ObjectiveThe association between the single-nucleotide polymorphisms (SNPs) rs28742109, rs12955018, rs987850, rs8093805, rs12965084 and rs145497186 related to gene named NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2) and lumbar disc degeneration (LDD) was preliminary investigated in a small sample size.MethodsA total of 46 patients with LDD and 45 controls were recruited at Qilu Hospital of Shandong University, and each participant provided 5 mL peripheral venous blood. NA was extracted from the blood of each participant for further genotyping. The frequency of different genotypes in the case group and control group was determined, and analysis of the risk of LDD associated with different SNP genotypes was performed. The visual analogue scale (VAS) scores of the patients’ degree of chronic low back pain were calculated, and the relationship between VAS scores and SNPs was analysed.ResultsAfter excluding the influence of sex, age, height, and weight on LDD, a significant association between SNP rs145497186 related to NDUFV2 and LDD persisted (P = 0.006). Simultaneously, rs145497186 was found to be associated with chronic low back pain in LDD populations.ConclusionNDUFV2 rs145497186 SNP could be associated with susceptibility to LDD and the degree of chronic low back pain.

Multiple variants in collagen genes are associated with the susceptibility to lumbar disc herniation in the Chinese population.

Lumbar disc herniation (LDH) is an important cause of back pain and sciatica, but its aetiology is not fully understood. Single-nucleotide polymorphisms (SNPs) in specific collagen genes are known to increase the risk of lumbar disc degeneration. We performed a case-control study among the Chinese Han population to investigate whether genetic variations in collagen genes were associated with the risk of LDH or not. We genotyped SNPs selected from 1000 Genome Projects using Agena MassARRAY technology. Three hundred and eighty-four LDH cases were compared with 384 controls of similar age, using the odds ratio and 95% confidence interval to calculate the susceptibility in several genetic models. Our results revealed that subjects with the rs6122316-C variant of the COL9A3 gene had a higher likelihood of LDH than subjects with the allele T variant in both the codominant and recessive models. In addition, after gender stratification analysis, we found significant associations between rs16970089 and rs740024 and LDH risk in females. Age stratification analysis illustrated that rs16970089 and rs6122316 were also correlated with LDH risk in people over 50years. The smoking stratification illustrated that rs2071358 and rs740024 had an increased association with LDH risk in smokers. And after drinking stratification, we also observed the significance between rs740024 and LDH risk. Variants in genes for COL1A1, COL9A3 and COL2A1 significantly influence the risk of LDH. Large and well-designed studies are needed to confirm and explain these conclusions. These slides can be retrieved under Electronic Supplementary Material.

Long non-coding RNA zinc finger antisense 1 expression associates with increased disease risk, elevated disease severity and higher inflammatory cytokines levels in patients with lumbar disc degeneration.

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646–0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1β (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.

P146. Smoking is associated with poorer fusion, functional outcomes and lower satisfaction in non-diabetic patients undergoing single-level transforaminal lumbar interbody fusion

BACKGROUND CONTEXT Smoking is associated with increased risk of lumbar disc degeneration and inhibition of lumbar spinal fusion. There is conflicting data on the role of smoking on spinal surgery outcomes with some studies demonstrating that smokers tend to have poorer functional outcomes and satisfaction scores postoperatively, whereas others have demonstrated no significant associations between smoking and surgery outcomes. On a biomolecular level, smoking can negatively influence spinal fusion surgical outcomes through impedance of angiogenesis needed for fusion healing through vasoconstriction and interference of metabolic mediators that normally facilitate angiogenesis and osteogenesis. Previous studies suggest diabetes and smoking have a synergistic effect that contributes to poorer spinal surgery outcomes. However, relationship between non-diabetic smokers, fusion outcomes and patient reported outcomes is not well understood. PURPOSE This study seeks to examine if smoking influences patient-reported outcomes and fusion rates in patients undergoing a single level transfoaminal lumbar interbody fusion (TLIF) in non-diabetic patients. METHODS Prospectively collated data of 187 non-diabetic patients who underwent single level TLIF in an institution from 2012 to 2014 was reviewed. Smokers and non-smokers were identified. All patients were assessed pre-and postoperatively at 6 months and 2 years using the numberical pain rating scale (NPRS back and leg pain), Oswestry Disability Index (ODI), Short-Form 36 Physical and Mental Component Scores (SF-36 OCS and MCS) and North American Spine Society (NASS) score for neurogenic symptoms. Student's T-test and Chi-square test was used to compare parametric and proportion-based outcomes respectively between smokers and non-smokers. Multivariate logistic regression analysis was used to evaluate for any confounding factors. RESULTS Patients with smoking history were significantly younger and predominantly male as opposed to non-smokers. There were no significant differences in ODI, Sf-36 PCS/MCS and back/leg pain between smokers and non-smokers at 6 months and 2 years. However, significantly less smokers were satisfied with their surgical outcomes at 2-year follow up (p=0.003). In addition, there was a significant difference in fusion grades at 2 years postoperative (p=0.048) between smokers and non-smokers with poorer fusion rates in smokers. There was a trend toward greater minimal clinically important difference (MCID) attainment rates of SF-36 OCS in non-smokers as compared to smokers (84% vs 68%, p=0.05). Multivariate analysis performed showed patients with nil co-morbidities were likely to have better fusion outcomes (p=0.04) and hypertensive patients more likely to experience poorer fusion outcomes (p=0.02). CONCLUSIONS Smokers in our cohort were approximately 10 years younger than non-smokers, possibly explaining the deleterious effects of smoking on early development of lumbar spinal pathology. Smoking was associated with lower satisfaction and poorer radiological fusion after single-level TLIF. Non-diabetic ex-smokers and smokers with spinal pathology should be counselled accordingly preoperatively regarding their expectations post-surgery, in particular the likelihood of having poorer functional and satisfaction outcomes as well as poorer radiological fusion. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Association of CILP, COL9A2 and MMP3 Gene Polymorphisms with Lumbar Disc Degeneration in an Indian Population.

Lumbar disc degeneration (LDD) is a multifactorial disorder caused by genetic and environmental factors. Polymorphisms in several structural and inflammatory genes like collagens, aggrecan, matrix metalloproteinases are associated with the risk of disc degeneration. In this study, we analyzed the role of a few important single nucleotide polymorphisms in cartilage intermediate layer protein (CILP), collagen 9A2 (COL9A2) and matrix metalloproteinase 3 (MMP3) genes in LDD from an Indian population. Two hundred patients with LDD and 200 healthy controls were recruited for the study. Genotyping was performed by allelic discrimination assay. The rs2073711 polymorphism (CILP gene - GG genotype) was associated with reduced risk of LDD in the Indian population (OR = 0.43, p = 0.016). The rs591058 polymorphism (MMP3 gene - TT genotype) is found to be associated with lower risk among women (OR = 0.34, p = 0.041). No significant association was found between COL9A2 polymorphism rs7533552 and the risk of LDD. We conclude that the CILP gene polymorphism (rs2073711) is associated with a lower risk of LDD, the MMP3 (rs591058) gene polymorphism is associated with LDD among women, and the TT genotype confers a lower risk of LDD.

Collagen IX gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis

BackgroundAn increasing number of studies have investigated associations between collagen IX alpha 2 chain (COL9A2) and collagen IX alpha 3 chain (COL9A3) gene polymorphisms and the risk of lumbar disc degeneration (LDD). However, these studies have yielded contradictory results. The purpose of this meta-analysis is to investigate the association between the collagen IX gene polymorphisms (rs12077871, rs12722877, rs7533552 in COL9A2; rs61734651 in COL9A3) and LDD.MethodsAll relevant articles were collected from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). The last electronic search was performed on September 1, 2017. The allele/genotype frequencies were extracted from each study. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of associations under the five comparison genetic models. Statistical analysis was performed by Review Manager (RevMan) 5.31 software.ResultsThe meta-analysis of 10 case-control studies, including 2102 LDD cases and 2507 controls, indicated that COL9A2 gene (rs12077871, rs12722877, rs7533552) and COL9A3 gene (rs61734651) polymorphisms were not associated with LDD (rs12077871: T vs. C, OR = 1.85, 95% CI = 0.87–3.91, P = 0.11; rs12722877: G vs. C, OR = 0.83, 95% CI = 0.69–1.01, P = 0.06; rs7533552: G vs. A, OR = 1.11, 95% CI = 0.98–1.25, P = 0.09; rs61734651: T vs. C, OR = 1.57, 95% CI = 0.51–4.84, P = 0.43). The Egger text and the Begg funnel plot did not show any evidence of publication bias.Conclusionrs12077871, rs12722877, and rs7533552 variants in COL9A2 and rs61734651 variant in COL9A3 were not significantly associated with a predisposition to LDD. Large-scale and well-designed studies are needed to confirm this conclusion.

VDR and GC gene polymorphisms modulate the risk of lumbar disc degeneration in Iran

ObjectiveLumbar disc degeneration (LDD) occurs commonly in humans. Vitamin D metabolic and signaling pathway plays a significant role in intervertebral disc degeneration. The aim of this study was to evaluate the influence of the genetic polymorphism in the two key genes of 1,25-(OH)2-D3 pathway, VDR (vitamin D receptor) and GC (group-specific component), in LDD development. Patients and MethodsTwo single-nucleotide polymorphisms, VDR rs2228570 (FokI) and GC rs7041, were genotyped in 180 patients with LDD and 230 healthy individuals. Genomic DNA was extracted from whole peripheral blood. VDR and GC genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ResultsA significant difference in genotype distributions of rs2228570 in VDR and rs7041 in GC gene were observed between cases and controls (P = .01 and. 005, respectively). The VDR AA homozygous genotype was seen in 30(16.7%) patients with LDD and 20(8.7%) controls (codominant model: OR = 2.48; 95% CI 1.30–4.73, P = .005) with an estimated approximately 2.5-fold risk of developing LDD in individuals with this genotype. Moreover, higher grades of disc degeneration were more related to VDR A allele. The minor allele of GC rs7041 was associated with a decreased risk of LDD (OR = 0.69; 95% CI 0.44–0.82, P = .001). ConclusionIn conclusion, our results suggest for the first time that the genetic variants of VDR and GC genes contribute to genetic predisposition to LDD in Iran. These findings need further validation in the large multicenter case-control studies.

Vitamin D receptor gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis.

To examine the association between Vitamin D receptor (VDR) gene polymorphisms and lumbar disc degeneration (LDD) predisposition. A comprehensive literature search was conducted to identify all the relevant studies. The allele/genotype frequencies were extracted from each study. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (CI) to assess the strength of the association between the VDR gene polymorphisms and LDD risk. Statistical analysis was performed using RevMan 5.31 software. A total of 23 case-control studies (1835 cases and 1923 controls) were included in this systematic review. For the TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) polymorphisms of VDR gene, nine studies, seven studies, and five studies, were eventually included in the meta-analysis, respectively. There was no evidence that the VDR gene polymorphisms (TaqI, FokI, ApaI) had significant associations with LDD risk.(for TaqI allelic comparison, OR=1.07, 95% CI 0.81-1.40, p=0.64; for FokI allelic comparison, OR=1.23, 95% CI 0.83-1.82, p=0.31; for ApaI allelic comparison, OR=0.79, 95% CI 0.55-1.14, p=0.20). For stratified analyses by ethnicity and study design, no significant associations were found in Caucasian population and Asian population, as well as the population-based studies and hospital-based studies under all genetic models. TaqI, FokI, and ApaI polymorphisms of VDR gene were not significantly associated with the predisposition of LDD. Large-scale and well-designed international studies are needed to further analyze this field.

Association between ADAMTS-4 gene polymorphism and lumbar disc degeneration in Chinese Han population.

Low back pain (LBP) is a common health problem and many LBP are caused by lumbar disc degeneration (LDD). ADAMTS-4 (a disintegrin and metalloprotease with thrombospondin motifs-4), also known as aggrecanse-1, plays a core role in degeneration of extracellular matrix in LDD. To investigate the association between ADAMTS-4 genetic polymorphism and LDD, we genotyped SNPs in and around ADAMTS-4. We recruited 482 sporadic cases of LDD and 496 healthy controls from Chinese Han population. Five SNPs were selected and phenotyped by the Sequenom MassARRAY system. Allelic, genotypic, and haplotypic association was performed. Rs4233367 (c.1877 C>T), which located in exon of ADAMTS-4 showed significant association with LDD. The T allele conferred a lower risk of LDD with an OR of 0.69 and TT genotype is at nearly one-fifth of the risk compared to CC genotype. Other tested SNPs didn't show significant difference between the case and control groups. The SNP rs4233367 in the exon of ADAMTS-4 gene may be associated with lumbar disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:860-864, 2016.

Association of the Polymorphism of TRAIL with the Risk and Severity of Lumbar Disc Degeneration in Chinese Han Population

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis of various normal and tumor cells. Apoptosis plays an important role in the development of lumbar disc degeneration (LDD). The aim of this study was to determine whether the 1595C/T polymorphism of the TRAIL gene is associated with the increased risk and severity of LDD in the Chinese Han population. This study consisted of 312 patients with LDD and 196 healthy controls. The grade of disc degeneration was determined according to Schneiderman's classification for magnetic resonance imaging (MRI). The genotype frequency of the 1595C/T polymorphism was in agreement with the Hardy-Weinberg equilibrium (p=0.278). Patients with LDD had significantly lower frequencies of CT and TT genotypes compared with normal controls (p<0.001). In addition, a lower frequency of the T allele was found in patients with LDD than normal controls (p<0.001). Unconditional logistic regression analysis revealed that CT and TT genotypes were both significantly associated with a reduced risk of LDD compared with the CC genotype (p<0.001; odds ratio [OR] 0.327; 95% confidence interval [95% CI] 0.217-0.493 and p<0.001; OR 0.393; 95% CI 0.234-0.661, respectively). Furthermore, the T allele was significantly associated with a decreased risk of LDD compared with the C allele (p<0.001; OR 0.483; 95% CI 0.369-0.633). In addition, the CT and TT genotypes, as well as the T allele, were associated with lower degenerative grades of LDD compared with the CC genotype and the C allele, respectively (p=0.008 and p=0.001, respectively). The 1595C/T polymorphism of TRAIL may be adversely associated with the risk and severity of LDD in the Chinese Han population.

Aggrecan Variable Number of Tandem Repeat Polymorphism and Lumbar Disc Degeneration

Data on the association between the ACAN (encoded for aggrecan core protein) variable number of tandem repeat (VNTR) polymorphism and lumbar disc degeneration are conflicting, so we performed a meta-analysis. Aggrecan is involved in the shock absorbing function of the lumbar disc; we performed a meta-analysis to assess the association between ACAN VNTR and lumbar degeneration. To perform a meta-analysis, we searched for studies published until September 2012, using electronic databases (PubMed, EMBASE, and China National Knowledge Infrastructure). Eight studies involving 965 cases of lumbar disc degeneration and 982 control subjects were identified. Assessment for eligibility and extraction of data were performed by 2 independent investigators. We extracted allele frequency for each study. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (CI) to assess the strength of the association between the ACAN VNTR polymorphism and lumbar disc degeneration risk. Results from the allele model suggested an increased risk of lumbar disc degeneration for the shorter alleles carriers compared with the normal alleles and longer alleles (OR = 1.54, 95% CI: 1.04-2.30, P = 0.03). In subgroup analysis by ethnicity, significant increased risks were found among Asians with shorter alleles (OR=1.65, 95% CI: 1.17-2.33, P = 0.004). Our results suggest an increased risk of shorter alleles compared with normal alleles and longer alleles against lumbar disc degeneration among populations especially among Asian descent. Such association may not be statistically significant in European populations.

Joint Laxity Negatively Correlates With Lumbar Disc Degeneration in Young Adults

Cross-sectional study of preselected cohort of patients with neck pain. To determine the association between joint laxity and lumbar disc degeneration in young adults. Joint laxity is known to be closely related with orthopedic injuries and disease; however, studies about the relationship between spinal disorder and joint laxity are lacking. Patients aged 30 to 40 years, seen at the outpatient clinic of our hospital for the evaluation of neck pain, who had magnetic resonance imaging of the cervical spine with routine inclusion of T2-weighted sagittal plane of the whole spine were included in the study. The Beighton and Horan criteria was used for the assessment of joint laxity. Logistic regression analysis was performed to estimate the odds ratio for lumbar disc degeneration in patients with joint laxity, and other variables including age, sex, body mass index, physical workload, neck pain (visual analogue scale score), and related disability (neck disability index score), and sagittal alignment. A total of 101 patients were enrolled in the study: 34 patients with joint laxity and 67 patients without joint laxity. There were no differences in age, body mass index, physical workload, neck pain (visual analogue scale score), and neck disability index score between the 2 groups, but there was a significant difference in sex ratio (P < 0.001). Patients with joint laxity showed increased lumbar lordosis (P = 0.004) and increased sacral slope (P = 0.003) but without significant difference in pelvic incidence (P = 0.084). In univariate analysis, presence of joint laxity (Beighton score ≥4) as well as positive results of thumb (P = 0.016) and elbow (P = 0.047) tests were significantly associated with decreased risk for lumbar disc degeneration. Presence of joint laxity remained significant after multivariate adjustment for sex and lumbar lordosis (odds ratio = 0.373, P = 0.040). Increased joint laxity was closely associated with lower prevalence of lumbar disc degeneration in young adults, and the increased lumbar lordosis associated with joint laxity might explain the decreased risk of lumbar disc degeneration. 2.

Disc degeneration after disc herniation: are we accelerating the process?

Study design: Systematic review.Study rationale: Disc degeneration is a common process starting early in life. Often disc herniation is an early step in disc degeneration, which may cause pain or stenosis. How quickly this subsequent disc degeneration occurs following a disc herniation and subsequent surgical treatment and whether certain spinal procedures increase the rate of degeneration remain unclear.Objectives: To investigate the risk of subsequent radiographic disc degeneration following discectomy, discography, and conservative care in patients with a first-time diagnosed herniated nucleus pulpous (HNP) and to ascertain whether this risk in these defined groups changes over time.Methods: A systematic review of pertinent articles published up to June 2012. Key articles were searched to identify studies evaluating the risk of subsequent radiographic disc degeneration following treatment for HNP. Studies that included patients undergoing secondary surgery for disc herniation or that did not use a validated classification system to measure the severity of disc degeneration were excluded. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus.Results: From a total of 147 possible citations, three cohort studies (class of evidence III) met our inclusion criteria and form the basis for this report. The risk of subsequent lumbar disc degeneration following standard discectomy was significantly greater compared with both microdiscectomy (48.7% vs 9.1%) and asymptomatic controls (90% vs 68%) in two studies with mean follow-ups of 5.5 and 25.3 years, respectively. Following conservative care for first-time HNP in the third study, the risk of progression of lumbar disc degeneration was 47.6% over the first 2 years of follow-up and 95.2% over the next 6 years of follow-up. In the same study, the risk of lumbar disc degeneration was shown to increase incrementally over the course of the 8-year follow-up, with all patients showing signs of degeneration at final examination.Conclusion: Standard discectomy in first-time lumbar HNP may increase the risk of subsequent same-level lumbar disc degeneration compared with microdiscectomy as seen in one low-quality study. However, disc degeneration is likely a natural, temporal consequence following HNP, as demonstrated in a second low-quality study. The overall strength of evidence for the conclusions is very low.

Association of the polymorphism of DR4 with the risk and severity of lumbar disc degeneration in the Chinese Han population

Objective. Death receptor 4 (DR4), an apoptosis-associated gene, plays an important role in the pathophysiology of lumbar disc degeneration (LDD). The present study aimed to determine whether the C626G polymorphism (rs4871857) of the DR4 gene is associated with the risk and severity of LDD in the Chinese Han population. Methods. A total of 296 patients with LDD and 208 healthy controls were enrolled in this study. The grade of disc degeneration was determined according to Schneiderman's classification for MRI. The C626G polymorphism of DR4 was genotyped using polymerase chain reaction and the restriction fragment length polymorphism method. Results. The genotype frequency of the C626G polymorphism was in agreement with the Hardy-Weinberg equilibrium (p = 0.194). The frequencies of the 626CG and GG genotypes were higher among LDD patients compared with normal controls; however, the differences were not significant. Patients with LDD showed significantly higher frequencies of the G allele than normal controls (p = 0.023). Unconditional logistic regression analysis revealed that the G allele was significantly associated with an increased risk of LDD compared with the C allele (p = 0.025; OR 1.958; 95% CI 1.087–3.526). However, no association was found between the different genotypes and the risk of LDD. In addition, the 626CG and GG genotypes, as well as the G allele were associated with higher degenerative grades of LDD compared with the CC genotype and the C allele, respectively (p = 0.005 and p < 0.001, respectively). Conclusion. The C626G polymorphism of DR4 may be associated with the risk and severity of LDD in the Chinese Han population.

Disc degeneration of the lumbar spine in relation to overweight

To study the association between overweight and lumbar disc degeneration. Population-based 4-y follow-up magnetic resonance imaging (MRI) study. The subjects were 129 working middle-aged men selected to the baseline magnetic resonance imaging (MRI) study from a cohort of 1832 men representing three occupations: machine drivers, construction carpenters, and office workers. The selection was based on the paticipants' age (40-45 y) and place of residence. MR images of the lumbar spines were obtained at baseline and at 4-y follow-up. Signal intensity of the nucleus pulposus of the discs L2/L3-L4/L5 was visually assessed by two readers using the adjacent cerebrospinal fluid as an intensity reference. The weight (at age 25 and 40-45 y) and height of the subjects, history of car driving, smoking, and back injuries were assessed by questionnaire. Multiple regression analyses allowing for occupation, history of car driving, smoking, and back injuries showed that persistent overweight (body mass index (BMI) > or =25 kg/m(2) at both ages) associated strongly with an increased risk of the number of lumbar discs with decreased signal intensity of nucleus pulposus at follow-up, adjusted odds ratio (OR) being 4.3 (95% confidence intervals (95% CIs) 1.3-14.3). Overweight at young age (risk ratio (RR) 3.8; 95% CI 1.4-10.4) was a stronger predictor of an increase in the number of degenerated discs during follow-up than overweight in middle age (RR 1.3; 95% CI 0.7-2.7). The study provides evidence that the BMI above 25 kg/m(2) increases the risk of lumbar disc degeneration. Overweight at young age seems to be particularly detrimental.