Severity Of Lumbar Disc Degeneration Research Articles

Prevalence of and factors associated with stenotic thoracic ligamentum flavum hypertrophy

IntroductionStenotic thoracic ligamentum flavum hypertrophy can cause leg and/or low back pain similar to that caused by lumbar spinal stenosis. However, the thoracic spine may occasionally be overlooked in patients...

Correlation of Magnetic Resonance Imaging findings with Clinical Grading in Lumbar Disc Degeneration: A Cross-sectional Study

Introduction: Low Back Pain (LBP) is the most common musculoskeletal symptom encountered on a daily basis in clinical practice and has a significant impact on healthcare resources. Magnetic Resonance Imaging (MRI) is the most sensitive tool for diagnosing spinal degenerative disease and has proven to be a standard imaging modality for its evaluation. Assessment of the correlation between clinical and radiological severity of lumbar disc degeneration will help in better management of the LBP patients. Aim: To determine the correlation between the clinical and radiological severity of lumbar disc degeneration in non surgical LBP patients. Materials and Methods: This observational, cross-sectional study was conducted at the Department of Radiology and Imaging, Sagar Hospitals, Bengaluru, Karnataka, India, from December 2019 to June 2021. A total of 90 patients with LBP who were referred for MRI evaluation were included. Modified Oswestry questionnaire was given to the patients and the clinical severity of the LBP was quantified. Patients with disc degeneration were evaluated on MRI based on six parameters viz., T2-signal intensity, Disc Extension Beyond Interface (DEBIT), annular fissure, modic changes, endplate integrity and osteophytes. Fisher's exact test was used for qualitative data to look into the association between clinical and MRI grades of severity. Correlation was assessed for continuous variables using Pearson correlation analysis. Results: The study included a total of 90 patients with LBP, with a mean age of 57±13.75 years with equal sex preponderance (45 (50%) male and 45 (50%) female). Clinically, 51 (56.7%) of the study population revealed moderate disability. On quantifying the MRI total score of disc degeneration, 65 (72.3%) of the patients were found to show mild degeneration. In terms of involvement of all the evaluated six MRI parameters, the L4-L5 disc was most commonly affected, followed by the L5-S1 disc. Disc desiccation 353 (78.45%) and osteophytes 336 (74.67%) were the most consistently observed variations. Disc bulges 251 (55.78%) were the next most frequently observed parameter in disc degeneration. Conclusion: The correlation between the clinical and radiological severity of disc degenerative disease was found to be weakly positive and statistically insignificant. Disc desiccation, osteophytes and disc bulges were the most commonly observed parameters that contributed to lumbar degenerative disease.

Impact of dyslipidemia on the severity of symptomatic lumbar spine degeneration: A retrospective clinical study.

Lumbar intervertebral disc degeneration (IVDD) is an important cause of low back pain or sciatica, and metabolic factors play an important role. However, little is known about the relationship of dyslipidemia to the risk of intervertebral disc degeneration (IVDD). This study aimed to assess the impact of serum lipid levels on the severity of lumbar disc degeneration and to investigate its association with endplate inflammation. We conducted a case retrospective study in which a total of 302 hospitalized Chinese patients were recruited, of whom 188 (112 males and 76 females; mean age: 51.66 years) were without underlying disease, while the remaining 114 patients (51 males and 63 females; mean age: 62.75 years) had underlying diseases. We examined fasting serum lipid levels for total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Magnetic resonance imaging (MRI) was used to determine endplate inflammation. Pfirrmann grading and Weishaupt grading were used to evaluate the severity of intervertebral disc degeneration and facet joint degeneration, respectively. There was no difference in age, gender, and general BMI between the two groups (P > 0.05), but there were significantly high levels in TC, LDL-C, and LDL-C/HDL-C (P = 0.04, P = 0.013, P = 0.01, respectively). TG and HDL-C showed no significant difference (P = 0.064, P = 0.336, respectively). The multivariate logistic regression model showed that age was a risk factor for the occurrence of endplate inflammation. In the group without underlying diseases, age, but not other indicators, was a risk factor for the occurrence of endplate inflammation (P < 0.01), In the group with underlying diseases, none of the patient indicators was directly related to the occurrence of endplate inflammation (P > 0.05). A nonlinear machine learning model was used to measure the contribution of each factor to the disease outcome and to analyze the effect between the top three contributing factors and the outcome variables. In patients without underlying diseases, the top three factors contributing to the severity grading of intervertebral disc degeneration were age (32.9%), high-density lipoproteins (20.7%), and triglycerides (11.8%). For the severity grading of facet joint degeneration, the top three contributing factors were age (27.7%), high-density lipoproteins (19.4%), and triglycerides (14.6%). For patients with underlying diseases, the top three factors contributing to intervertebral disc degeneration were age (25.4%), BMI (15.3%), and low-density lipoprotein/high-density lipoprotein ratio (13.9%). In terms of degree classification for facet joint degeneration, the top three contributing factors were age (17.5%), BMI (17.2%), and total cholesterol (16.7%). This study shows that age, high-density lipoprotein, and triglycerides affect the degree of degeneration in patients with symptomatic lumbar degeneration without underlying diseases. Age and BMI are two major factors affecting the severity of degeneration in patients with underlying diseases, and dyslipidemia is a secondary factor. However, there is no clear association between dyslipidemia and the occurrence of endplate inflammation in either group.

The Clinical Significance of the Modic Changes Grading Score.

Cross-sectional retrospective observational study. To evaluate the reliability and clinical utility of the Modic changes (MC) grading score. Patients from the Danish national spine registry, DaneSpine, scheduled for lumbar discectomy were identified. MRI of patients with MC were graded based on vertical height involvement: Grade A (<25%), Grade B (25%-50%), and Grade C (>50%). All MRIs were reviewed by 2 physicians to evaluate the reliability of the MC grade. Of 213 patients included, 142 patients had MC, 71 with MC-1 and 71 with MC-2; 34% were Grade A, 45% were Grade B, and 21% were Grade C. MC grade demonstrated substantial intra-rater (κ = .68) and inter-rater (κ = .61) reliability. A significantly higher proportion (n = 40, 57%) of patients with MC-1 had a severe MC grade compared to patients with MC-2 (n = 30, 43%, P < .001). Severe MC grade was associated with the presence of severe lumbar disc degeneration (DD) (Pfirrmann grade = V, P = .024), worse preoperative ODI (52.49 vs 44.17, P = .021) and EQ-5D scores (.26 vs .46, P = .053). MC alone including type was not associated with a significant difference in patient-reported outcomes (P > .05). The MC grade score was demonstrated to have substantial intra- and inter-observer reliability. Severe MC grade was associated with both severe DD and MC type, being more prevalent in patients with MC-1. The MC grade was also significantly associated with worse disability and reduced health-related quality of life. Results from the study suggest that MC grade is more clinically important than MC type.

Is There Any Relationship between Plasma IL-6 and TNF-α Levels and Lumbar Disc Degeneration? A Retrospective Single-Center Study.

Intervertebral disc degeneration (IDD) is one of the most common degenerative diseases all over the world. A growing number of studies have proved that large amounts of cytokines are produced during the development of IDD, and the inflammatory responses induced by these cytokines aggravate the occurrence and development of the disc degeneration. In this retrospective single-center study, a total of 182 lumbar spine cases were retrospectively reviewed between July 2020 and October 2021. An appropriate cutoff value was found for discriminating severity of IDD by William rank-sum test and locally weighted scatterplot smoothing algorithm. The cumulative grade was also calculated by summing Pfirrmann grades for all lumbar spine intervertebral discs. It was found that high-score group (total score > 18) plasma interleukin-6 (IL-6) concentration was significantly higher than that of the low-score group (total score ≤ 18) (9.6 ± 1.75 vs. 5.40 ± 0.61 pg/ml, p = 0.002), tumor necrosis factor-α (TNF-α) following the same trend (5.27 ± 1.48 vs. 2.97 ± 0.23, p = 0.006), which was most pronounced in the upper lumbar intervertebral discs (L1-3). In the entire sample, preoperative IL-6 concentration was significantly higher than that of the postoperation (p < 0.001), while the TNF-α was the opposite (p = 0.039). It was also found that there were significant differences in the two groups with respect to age and hypertension (p < 0.001 and p = 0.037). In conclusion, this study preliminarily indicated the relationship between IL-6 and TNF-α and the severity of lumbar disc degeneration.

Association between severe lumbar disc degeneration and self-reported occupational physical loading.

ObjectivesOccupational physical loading has been reported to be associated with intervertebral disc degeneration. However, previous literature reports inconsistent results for different vertebral levels. The aim of our study was to investigate the association between lumbar disc degeneration (LDD) at different vertebral levels and the self‐reported physical loading of occupation.MethodsThe study population consisted of 1,022 postmenopausal women and was based on the prospective Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. The severity of LDD was graded from T2‐weighted MRI images using the five‐grade Pfirrmann classification. Five intervertebral levels (L1–L2 to L5–S1) were studied (total 5110 discs). The self‐rated occupational physical loading contained four groups: sedentary, light, moderate, and heavy.ResultsThe heavy occupational physical loading group had higher odds for severe LDD at the L5–S1 vertebral level (OR 1.86, 95% CI: 1.19–2.92, p = .006) in comparison with the sedentary work group. A clear trend of increasing disc degeneration with heavier occupational loading was also observed at the L5–S1 level. Age, smoking, and higher body mass index (BMI) were associated with more severe LDD. Leisure‐time physical activity at the age of 11–17 years was associated with less severe LDD. Controlling for confounding factors did not alter the results.ConclusionsThere appears to be an association between occupational physical loading and severe disc degeneration at the lower lumbar spine in postmenopausal women. Individuals in occupations with heavy physical loading may have an increased risk for work‐related disability due to more severe disc degeneration.

Is There Any Association between the Severity of Disc Degeneration and Low Back Pain?

Objective To access the possibility that higher degrees of disc degeneration lead to higher levels of pain and dysfunction. Methods Magnetic resonance imaging (MRI) scans of 85 patients with low back pain lasting for more than 12 weeks were evaluated, and the degree of disc degeneration was quantified according to the Pfirrmann grading system. The Pfirrmann degree in each disc space from L1-L2 to L5-S1, the maximum degree of Pfirrmann (Pfirrmann-max) between the lumbar discs, and the sum of Pfirrmann (Pfirrmann-sum) degrees were correlated (through the Spearman test) with the Oswestry Disability Index (ODI) and the Visual Analogical Scale (VAS) for pain. Results In total, 87% of the patients had moderate to severe lumbar disc degeneration measured by Pfirrmann-max, and the most degenerated discs were L4-L5 and L5-S1. There was a week to moderate correlation regarding the Pfirrmann-max (r = 0,330; p = 0.002) and the Pfirrmann-sum (r = 0,266; p = 0,037) and the ODI, and the Pfirrmann scores in L1-L2 were correlated with the ODI and the VAS. Conclusion Patients with chronic idiopathic low back pain frequently have moderate to severe lumbar disc degeneration, which has a negative impact on the quality of life of the patients. Low degrees of degeneration in L1-L2 might be related with higher degrees of pain and of functional disability.

The association of lumbar intervertebral disc degeneration and lumbar spinal stenosis on magnetic resonance imaging with body mass index in overweight and obese adults in Indian population

Aims: To investigate the association of being overweight or obese with the presence, extent, and severity of lumbar disc degeneration and lumbar spinal stenosis on magnetic resonance imaging (MRI) in adults in the Indian population.Study Design: Level 4, Cross-sectional studyPlace and duration of study: Department of Orthopaedics, SVP Hospital, Ahmedabad between February 2019 and October 2019. Methodology: A population-based cross-sectional study of 500 Indian volunteers was conducted. Subjects underwent radiographic and clinical assessment, and weight and height were measured. T2-weighted MRIs of the lumbar spine were obtained. The presence, extent, and severity of disc degeneration and additional radiographic and clinical parameters were assessed. Asian-modified body mass index (BMI) (kg/m2) categories were used.Results: The study included 305 men and 195 women (mean age 50.59 years). Disc degeneration was noted in 450 (90%) subjects. BMI was significantly higher in subjects with disc degeneration (mean 29.18 kg/m2) than in subjects without degeneration (mean 23.66 kg/m2). A significant increase in the number of degenerated levels, global severity of disc degeneration, and end-stage disc degeneration with lumbar spinal stenosis was noted with elevated BMI, in particular in overweight and obese subjects. End-stage disc degeneration with disc space narrowing was significantly more pronounced in obese subject.Conclusion: Our findings, to systematically assess lumbar disc degeneration and lumbar spinal stenosis on MRI, indicated a significant association between the presence, extent, and global severity of disc degeneration and lumbar spinal stenosis with BMI (>23 kg/m2) in overweight and obese adults.

How is spinal range of motion affected by disc- and facet degeneration and spinopelvic anatomy?

BackgroundWe aimed to investigate how disc- and facet joint degeneration relate to ROM and spinopelvic alignment parameters. Their interrelation, however, is not yet understood, although eminent in patient specific modeling approaches and surgical decision making. Further is not yet sufficiently understood whether spinal alignment parameters relate to the degenerative states. MethodsThe ROM of lumbar spinal segments was quantified using flexion/extension radiographs of 90 patients. The grades of degeneration of discs (IDD, Pfirrmann grades, n=440) and facet joints (FJD, Weishaupt classification, n=406) were assessed in CT and MRI scans. ResultsThe grade of IDD was significantly related to changes in ROM (p<0.01) whereas no association was observed with the amount of FJD. Grade V IDD was associated with a significant decrease in motion (p<0.01) compared to all other IDD grades (II-IV), which did not differ significantly among each other. The combined occurrence of IDD and FJD revealed the largest angular segmental ROM in segments with the lowest IDD (II) and lowest FJD (0). The lowermost ROM was present in fused segments (control), followed by those with severe IDD (V). In combination with FJD, the destabilizing effect of initial IDD was only observed if FJD was already in an advanced state. ConclusionsWhile the degree of facet joint degeneration seems not significantly associated with limitations in spinal motion, severe lumbar disc degeneration limits segmental motion, nearly equal to spinal fusion. This should affect counseling patients undergoing spinal fusion with questions on the probability of adjacent segment degeneration compared to the natural course.

Indirect foraminal decompression and improvement in the lumbar alignment after percutaneous cement discoplasty.

Percutaneous cement discoplasty (PCD) is a minimally invasive surgical procedure, that can provide a segmental stabilizing and indirect decompression effect in case of severely degenerated discs characterized by vacuum phenomenon. The objective of this study was to evaluate the effects of PCD on spinopelvic radiological parameters and their associations with the clinical outcome. Retrospective analysis of prospectively collected dataset of 28 patients (112 lumbar segments) who underwent single- or multilevel PCD was performed. Spinopelvic, intrasegmental and intersegmental parameters were measured on lumbar X-rays pre-, postoperatively and 6months after the surgery. Correlations between radiological parameters and clinical outcome data were determined. Sacral slope significantly increased (p < .001), and pelvic tilt (p < .05) was decreased after the PCD procedure. Segmental and total lordosis (p < .05, p < .05) disc and foraminal height showed significantly increase (p < .001, p < .001) after procedure. Pain and disability (ODI) significantly decreased due to PCD. An association was found between postoperative increase in SS and improvement in ODI (r = 0.39, p < .05). The change in low back pain was correlated with segmental scoliosis correction (p < .001). Moderate correlation was detected between the increase in disc height and ODI (p < .05) as well as leg pain (p < .01). PCD is an effective minimally invasive technique to treat axial pain and disability related to severe lumbar disc degeneration. Our study shows that an improvement in lumbar alignment and a significant indirect foraminal decompression could be achieved with the procedure. These changes can significantly contribute to the pain relief and increase in the patients' functional capacity. These slides can be retrieved under Electronic Supplementary Material.

The potential effect of type 2 diabetes mellitus on lumbar disc degeneration: a retrospective single-center study

BackgroundDiabetes mellitus (DM) and low back pain which is mainly caused by degeneration of the intervertebral discs (IVDs) both are major public health problem worldwide. The present study was designed to investigate the association between type 2 diabetes mellitus (T2D) and severity of lumbar disc degeneration (LDD).MethodsWe retrospectively reviewed patients with low back pain visiting our spine clinic in 2014. Low back pain patients all have the lumbar MRI imaging and no previous treatment. One hundred fifty patients without T2D (group A) and 622 patients with T2D meeting the criteria were included. Sex, age, body mass index (BMI), high blood pressure (HBP), history of smoking, alcohol use, and duration of T2D were recorded. Patients with T2D were assigned to a well-controlled group (group B, n = 380) and a bad-controlled group (group C, n = 242). In group B, T2D duration of 148 patients was ≤ 10 years (group B1) and 232 patients > 10 years (group B2). In group C, T2D duration of 100 patients was ≤ 10 years (group C1) and 142 patients > 10 years (group C2). The severity of LDD was evaluated using the five-level Pfirrmann grading system. Data were analyzed using SPSS 19.0.ResultsDemographic data except age showed no difference among groups (P > 0.5). Compared to patients without T2D, patients with T2D showed more severe disc degeneration after removal of age effects (P < 0.05). From L1/2 to L5/S1, the average Pfirrmann scores between groups A and B1 showed no difference(P > 0.05); groups B2, C1, and C2 showed higher average Pfirrmann scores than group A (P < 0.05). Groups B2 and C2 showed higher average Pfirrmann scores than groups B1 and C1 (P < 0.05). Groups C1 and C2 showed higher average Pfirrmann scores than groups B1 and B2 (P < 0.05). From L1/2 to L5/S1, the severity of LDD was highly positively related to T2D duration both in groups B and C (P < 0.05).ConclusionsT2D duration > 10 years and a bad control of T2D were risk factors for LDD. The longer T2D duration was, the more severe disc degeneration would be.

Association of collagen I, IX and vitamin D receptor gene polymorphisms with radiological severity of intervertebral disc degeneration in Southern European Ancestor.

Several genomic loci have been previously found to be associated with intervertebral disc degeneration, so far. Data are mostly derived from northern European countries whereas data derived from Southern European Ancestor are limited. This study aimed to evaluate the association between radiological disease severity of lumbar disc degeneration and certain genetic loci in a sample of participants from Southern Europe. Seventy-five patients with mild to severe lumbar disc degeneration and 25 healthy controls were enrolled into the study. In each subject, each lumbar intervertebral disc was separately examined to obtain a total radiological score for disease severity. In addition, single-nucleotide polymorphisms of predefined genetic samples were analyzed in all participants: COL1A1 Sp1, COL9a2 Trp2, COL9a3 Trp3, and VDR TaqI. Degeneration scores were significantly worse in cases with COL1A1 Sp1, COL9a3 Trp3, and VDR TaqI mutations; however, COL9a2 Trp2 mutation was not associated with a difference in the severity of disc degeneration. In addition, subjects with mutation in more than one gene sample (n = 20) had significantly worse degeneration scores than the remaining study participants (n = 80) (17.70 ± 2.72 vs. 21.81 ± 1.81, p < 0.001). Single-nucleotide polymorphisms occurring in COL1A1, COL9a3 and VDR genes seem to be associated with the development of lumbar disc degeneration in this cohort, possibly with even more pronounced association when multiple mutations are present in the same individual. By further prospective twin studies in associated genes and analyses of their relationship with environmental factors in an internationally sampled large cohort will make a more clear-minded conclusion about their association with disc degeneration, which would yield better appreciation and clinical planning of some predisposed people for these pathologies.

Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model

Background ContextChronic low back pain is debilitating and difficult to treat. Depending on the etiology, responses to treatments vary widely. Although chronic low back pain is frequently related to intervertebral disc degeneration, the relationship between disc degeneration severity and clinical symptoms are still poorly understood.In humans, studies investigating the relationship between disc degeneration severity and low back pain are limited by the difficulty of obtaining disc samples from well-characterized patients and pain-free controls. We have previously described the secreted protein, acidic, rich in cysteine (SPARC)-null mouse model of chronic low back pain. SPARC is a matricellular protein involved in regulating the assembly and composition of extracellular matrix. The SPARC-null mice develop age-dependent disc degeneration of increasing severity accompanied by behavioral signs suggestive of axial low back pain, radiating leg pain, and motor impairment. The existence of this model allows for examination of the relationships between clinical symptoms in vivo and pathological signs of disc degeneration ex vivo. PurposeThe goal of this study was to explore the relationship between behavioral signs of pain and the severity of lumbar disc degeneration using the SPARC-null mouse model of disc degeneration-related low back pain. Study DesignThis study used a cross-sectional, multiple-cohort behavioral and histological study of disc degeneration and behavioral symptoms in a mouse model of low back pain associated with disc degeneration. MethodsSPARC-null and wild-type control mice ranging from 6 to 78 weeks of age were used in this study. The severity of disc degeneration was determined by ex vivo analysis of the lumbar spine using colorimetric histological staining and a scoring system adapted from the Pfirrmann scale. Behavioral signs of axial low back pain, radiating leg pain, and motor impairment were quantified as tolerance to axial stretching in the grip force assay, hypersensitivity to cold or mechanical stimuli on the hindpaw (acetone and von Frey tests), and latency to fall in the rotarod assay, respectively. ResultsThe SPARC-null mice exhibited decreased tolerance to axial stretching, hindpaw cold hypersensitivity, and motor impairment compared with age-matched control mice. The severity of disc degeneration increased with age in both SPARC-null and control mice and by 78 weeks of age, the same proportion of lumbar discs were abnormal in SPARC-null and control mice. However, the degree of degeneration was more severe in the SPARC-null mice. In both SPARC-null and control mice, tolerance to axial stretching but not hindpaw cold sensitivity correlated with disc degeneration severity. Motor impairment correlated with degeneration severity in the SPARC-null mice only. ConclusionsThese data suggest that internal disc disruption contributes to axial low back pain and motor impairment but not to radiating leg pain. These results have implications for the optimization of mechanism-based treatments strategies.

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.

Genetic susceptibility of lumbar degenerative disc disease in young Indian adults.

Although the exact mechanisms that lead to degenerative disc disease (DDD) are not well understood, a significant genetic influence has been found. Focusing on DDD that occurs in young adults can be valuable in determining the exact role of genetic predisposition to DDD. Patients (<40 years) with lumbar disc degeneration were evaluated with MRI imaging (1.5 Tesla) and genetic association analysis for 58 single nucleotide polymorphism (SNP) of 35 candidate genes was performed. Disc degeneration of individual discs of lumbar spine from L1 to S1 was graded by Pfirrmann's grading. The subjects were stratified into two groups based on Total Disc Degenerative Score (TDDS). Based on TDDS, the severity of DDD was classified as mild (Group A: TDDS <10) and severe (Group B: TDDS >10). 695 Indian subjects including 308 with mild TDDS and 387 with severe TDDS were studied. The mean age of the patients was 29.6 ± 6.9 years in group A and 31.7 ± 6.1 in group B (p < 0.05). Five of the 35 candidate genes viz., rs1337185 of COL11A (p = 0.02), rs5275 (p = 0.03) and rs5277 (p = 0.05) of COX2, rs7575934 of IL1F5 (p = 0.04), rs3213718 of CALM1 (p = 0.04) and rs162509 of ADAMTS5 (p = 0.04) were found to be significantly associated with severe TDDS. The study identifies specific SNP associations of five genes in young adults with severe lumbar disc degeneration. These five genes (COL11A1, ADAMTS5, CALM1, IL1F5 and COX2) have different functions in the matrix metabolism, intracellular signalling and inflammatory cascade. This shows that disc degeneration is a complex disease with an intricate interplay of multiple genetic polymorphisms.

Association between bone mineral density and lumbar disc degeneration

ObjectivesHigher vertebral bone mineral density (BMD) has been found to be related with lumbar disc degeneration (LDD), while relationship between femoral neck BMD and LDD remains controversial. The aim of our research was to study the relationship between LDD and BMD of the lumbar spine and femoral neck. Study designThe study population consisted of 168 postmenopausal women (aged 63.3–75.0 years, mean 68.6 years) from the prospective OSTPRE and OSTPRE-FPS study cohorts. The severity of LDD was graded from T2-weighted MRI images using the five-grade Pfirrmann classification. Four vertebral levels (L1-L4) were studied (total 672 discs). The association between lumbar BMD and Z-score and the severity of LDD was studied separately for each vertebral level with AN(C)OVA analysis, using potential confounders as covariates. ResultsHigher lumbar BMD and Z-score were associated with more severe LDD at all studied levels (L1-L4): between L4-L5 disc and L4 BMD (p=0.044) and L4 Z-score (p=0.052), between L2-L3 disc and L3 BMD (p=0.001) and at all other levels (p<0.001). The mean degeneration grade of the studied discs was associated with the mean L1-L4 BMD and Z-score (p<0.001). Statistical significance of any result did not alter after controlling for confounding factors. There was no significant association between femoral neck BMD and LDD. ConclusionsHigher lumbar BMD/Z-score were associated with more severe LDD. There was no significant association between femoral neck BMD and disc degeneration. Femoral neck BMD may be a more reliable measurement for diagnosing osteoporosis in postmenopausal women with degenerative changes in the lumbar spine.

Menopause is associated with lumbar disc degeneration: a review of 4230 intervertebral discs

Objective The main objective of this study was to investigate, in a population of normal postmenopausal women, the association between menopause and severity of lumbar disc degeneration from the first lumbar to the first sacral vertebra on magnetic resonance imaging.Methods Between January 2010 and May 2013, 846 normal women and 4230 intervertebral discs were retrospectively analyzed. Age, height, weight and years since menopause (YSM) were recorded. Disc degeneration was evaluated using the modified Pfirrmann grading system.Results Compared to premenopausal and perimenopausal women, postmenopausal women had more severe disc degeneration after removal of age, height and weight effects (p < 0.0001). Postmenopausal women were divided into six subgroups for every 5 YSM. When YSM was below 15 years, there was a significant difference between every two groups, i.e. groups 1–5 YSM, 6–10 YSM and 11–15 YSM (p < 0.01). A positive trend was observed between YSM and severity of disc degeneration, respectively, i.e. L1/L2 (r = 0.235), L2/L3 (r = 0.161), L3/L4 (r = 0.173), L4/L5 (r = 0.146), L5/S1 (r = 0.137) and all lumbar discs (r = 0.259) (p < 0.05 or 0.01). However, when YSM was above 15, there was no difference, i.e. groups 16–20 YSM, 21–25 YSM and 26–30 YSM (p > 0.05), and the significance correlation also disappeared (p > 0.05).Conclusion Menopause is associated with disc degeneration in the lumbar spine. The association almost entirely occurred in the first 15 years since menopause, suggesting estrogen decrease may be a risk factor for lumbar disc degeneration.

MMP 7, CALM 1, and Cox 2 Genes Influence Genetic Susceptibility of Lumbar Degenerative Disc Disease in Young Adults—Analysis of 58 Single Nucleotide Polymorphisms in 580 Individuals Based on Total Degenerative Disc Score

Introduction Although the exact mechanisms that lead to degenerative disc disease (DDD) are not well understood, a significant genetic influence has been found. Focusing on DDD that occurs in young adults can be valuable in determining the exact role of genetic predisposition to DD. The present study was undertaken to assess the association between single nucleotide polymorphisms (SNPs) of candidate genes in a cohort of young Indian adults. Materials and Methods We selected young patients (age &lt; 40 years) with lumbar disc degeneration and evaluated them with MRI and genetic association studies for 58 SNPs of 35 candidate genes. Disc degeneration of individual discs of lumbar spine from L1 to S1 was quantified by Pfirrmann grading in MRI images (1.5 T). The subjects were stratified into three groups based on a total degenerative disc score (TDDS). TDDS was developed by adding the individual scores of Pfirrmann grading of all the five lumbar discs. Based on the TDDS, the severity of DDD among the subjects was classified as mild (TDDS &lt; 10), moderate (TDDS of 10-15), and severe (TDDS &gt; 15). The patients were classified into three groups so that the extreme confounding patients in the mild and severe TDDS groups will automatically fall into the moderate TDDS group. For the final association analysis, only the results of mild (the unaffected, control group) and severe TDDS groups (affected, case group) were compared and analyzed. Results The study population comprised 580 subjects including 308 patients with mild TDDS, 211 patients with moderate TDDS, and 61 patients with severe TDDS. There was no significant difference in the gender difference and the mean age of the both groups. Three of the 35 candidate genes showed significant association with severe TDDS. SNPs, viz., rs1940044 of MMP (matrix metalloproteinase 7), rs2300496 SNP and rs3213718 SNPs of CALM1 (calmodulin), and rs5277 of COX 2 (cyclooxygenase) were found to be significantly associated with severe TDDS. Among the previously reported candidate genes, our analysis in the young Indian population had revealed that SNPs of COL 9, SKT, CHST 3, CILP, IGFR, SOXp, BMP, MMP 2-12, ADH2, IL1RN, AGC 1, ADAMTS5, NGFB, GLI, HHIP, TAC1, and IL1B were not significantly associated with severe TDDS. [Table: see text] Conclusion This is the first of its kind in studying the genetic aspects of disc degeneration in the young adults. The study identifies specific SNP associations of three genes (MMP 7, CALM 1, and COX2) in young adults with severe lumbar disc degeneration. Genes involved in matrix degradation (MMP), intracellular signaling (CALM), and inflammation (COX 2) were associated with early disc degeneration indicating that DDD is a complex disease with an intricate interplay of multiple genetic polymorphisms. Disclosure of Interest None declared

Matrix Metalloproteinase-3, Vitamin D Receptor Gene Polymorphisms, and Occupational Risk Factors in Lumbar Disc Degeneration

Lumbar disc degeneration (LDD) is a process that begins early in life, contributing to the development of low back pain. LDD is a consequence of a variety of factors, and its etiology remains poorly understood. Objectives to investigate occupational and genetic risk factors inducing lumbar disc degeneration, and to evaluate the possible association of genetic polymorphisms of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the severity of LDD in an Egyptian population. A case control study involving 84 LDD and 60 controls was carried out. Five types of work related factors were investigated by questionnaire, complete neurological examination for all subjects and MRI for the cases. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect polymorphisms in MMP-3 Promoter (-1,171 6A/5A) (rs 731236) and VDR-Apa (rs 35068180). We found that family history, back injury, smoking, high level of sitting, bending/twisting, physical workload, lifting, whole body vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2, 12.6, 2.5 and 3.1 respectively, p < 0.05). Cases that carry allele 5A and/or allele T were associated with LDD severity. LDD is closely associated in occurrence and severity with occupational, environmental risk factors and susceptibility genes namely MMP-3, and VDR (ApaI). This study throws light on the importance of screening for early detection of susceptible individuals and disease prevention.

Treatment outcome of chronic low back pain and radiographic lumbar disc degeneration are associated with inflammatory and matrix degrading gene variants: a prospective genetic association study

BackgroundInflammatory and matrix degrading gene variants have been reported to be associated with disc degeneration. Some of these variants also modulate peripheral pain. This study examines the association of these genetic variants with radiographic lumbar disc degeneration and changes in pain and disability at long-term after surgical and cognitive behavioural management.Methods93 unrelated patients with chronic low back pain (CLBP) for duration of >1 year and lumbar disc degeneration were treated with lumbar fusion or cognitive intervention and exercises. Standardised questionnaires included the Oswestry Disability Index (ODI) and Visual Analog Score (VAS) for CLBP, were filled in by patients both at baseline and at 9 years follow-up. Degenerative changes at baseline Magnetic Resonance Imaging and Computed Tomography scans, were graded as moderate and severe (N=79). Yield and quality of blood and saliva DNA was assessed by nano drop spectrophotometry. Eight SNPs in 5 inflammatory and matrix degrading genes were successfully genotyped. Single marker and haplotype association with severity of degeneration, number of discs involved, changes in ODI and VAS CLBP, was done using Haploview, linear regression and R-package Haplostats.ResultsAssociation analysis of individual SNPs revealed association of IL18RAP polymorphism rs1420100 with severe degeneration (p = 0.05) and more than one degenerated disc (p = 0.02). From the same gene two SNPs, rs917997 and rs1420106, were found to be in strong linkage disequilibrium (LD) and were associated with post treatment improvement in disability (p = 0.02). Haplotype association analysis of 5 SNPs spanning across IL18RAP, IL18R1 and IL1A genes revealed significant associations with improvement in disability (p=0.02) and reduction in pain (p=0.04). An association was found between MMP3 polymorphism rs72520913 and improvement in pain (p = 0.03) and with severe degeneration (p = 0.006).ConclusionsThe findings of the current study suggest a role of variation at inflammatory and matrix degrading genes with severity of lumbar disc degeneration, pain and disability.