The Association of Lumbosacral Transitional Vertebrae with Low Back Pain and Lumbar Degenerative Findings in MRI: A Large Cohort Study.

STUDY DESIGN: A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966). OBJECTIVE: To evaluate the association of lumbosacral transitional vertebrae (LSTV) with low back pain (LBP) and associated degenerative findings using magnetic resonance (MR) imaging. SUMMARY OF BACKGROUND DATA: LSTV is a common finding with a prevalence of 10% to 29%. LSTV causes biomechanical alterations leading to accelerated lumbar degeneration. However, its association with degenerative findings on MRI and LBP is unclear. METHODS: One thousand four hundred sixty eight lumbar spine MRI scans from the NFBC1966 acquired at a mean age of 47 years were assessed for the presence of LSTV and degenerative changes. Castellvi classification was utilized to identify LSTV anatomy. Additionally, 100 controls without LSTV were collected. Self-reported LBP with a duration of more than 30 days in the past year was deemed clinically relevant. For the statistical analyses, chi square test, independent samples t test and multinomial logistic regression analyses were used. RESULTS: LSTV was found in 310 (21.1%) subjects. After adjusting for age, sex, and disc degeneration (DD) sum, subjects with Castellvi type III reported prolonged LBP significantly more frequently than the controls (odds ratio [OR] = 8.9, P = 0.001). We observed a higher prevalence of facet degeneration (FD) at all levels from L3/L4 to L5/S1 in type I, and L3/L4 to L4/L5 in types II-IV. DD was more prevalent at L4/L5 in types II-IV. Disc protrusion/extrusion occurred more frequently at L3/L4 and L4/L5 in type II, and at L3/L4 in type III. Castellvi type II had a higher prevalence of type 1 Modic changes at levels from L3/L4 to L4/L5. CONCLUSION: LSTVs were a common finding within this study, and Castellvi type III LSTVs were associated with LBP. Degenerative findings were associated with LSTV anatomy and occurred more commonly above the transitional level.Level of Evidence: 3.

Lumbosacral transitional vertebrae are associated with lumbar degeneration: retrospective evaluation of 3855 consecutive abdominal CT scans.

OBJECTIVES: To assess the prevalence of lumbosacral transitional vertebra (LSTV) and associated spinal degenerative changes on abdominal CT scans in Caucasian population. MATERIAL AND METHODS: A total of 3855 abdominal CT scans of the year 2017 from a single hospital were retrospectively assessed for LSTV, disc degeneration (DD), and facet joint degeneration (FD). An age- and sex-matched 150-subject control group without LSTV was picked at random. Multivariable logistic regression was used for the analysis. RESULTS: LSTV was found in 1101 (29%) scans: Castellvi type I in 68%, type II in 16%, type III in 13%, and type IV in 3% of scans. Age- and sex-adjusted prevalence of DD was significantly higher in Castellvi type II and III groups at multiple lumbar levels, and in IV group at L4/5 than in control group (p < 0.001-0.034). At L5/S1, the prevalence of DD was significantly higher in the control group than in type II, III, or IV groups (p < 0.001-0.017). After combining Castellvi types II, III, and IV into one group, significant differences were found at all lumbar levels except L2/3 (p < 0.001-0.016). Prevalence of FD was significantly higher at L4/5 in Castellvi groups I, II, and III than in the control group (p < 0.001-0.002). When Castellvi types II, III, and IV were combined into one group, significant differences were found at lumbar levels L2/3, L3/4, and L4/5 (p < 0.001-0.021). CONCLUSION: Lumbosacral vertebrae of Castellvi types II, III, and IV are associated with greater lumbar degeneration, warranting meticulous evaluation of spinal anatomy, even on CT. KEY POINTS: • Lumbosacral transitional vertebra is a common incidental finding on abdominal CT scans with a high prevalence of 29%. • When assessing whole lumbar spine, lumbosacral vertebrae of Castellvi types II, III, and IV were associated with greater lumbar degeneration, warranting careful evaluation of the lumbar spine on abdominal CT scans.

Intervertebral Disc Biology: Genetic Basis of Disc Degeneration.

PURPOSE OF REVIEW: This review aims to highlight recent advances in understanding the genetic basis of intervertebral disc degeneration (IDD). RECENT FINDINGS: It has been known for some time that IDD is highly heritable. Recent studies, and in particular the availability of agnostic techniques such as genome-wide association studies, have identified new variants in a variety of genes which contribute to the risk of IDD and to back pain. SUMMARY: A variety of genetic variants are involved in IDD. Some are shared with variants predisposing to back pain, but few have been identified reliably in either phenotype. Further research is required to explain fully the high heritability and how the genetic variants influence cell biology to lead to IDD.

Strong association between vertebral endplate defect and Modic change in the general population.

Modic change (MC) is considered an independent risk factor for low back pain (LBP) but its aetiology remains unclear. In this cross-sectional, large-scale population-based study we sought to characterise associations between endplate defect (ED) and MC in a population sample of broad age range. The study population consisted of 831 twin volunteers (including 4155 discs and 8310 endplates) from TwinsUK. Lumbar T2-weighted MR images were coded for ED and MC. Total endplate (TEP) score was calculated at each intervertebral disc while receiver operating curves (ROC) were calculated to define critical endplate values predictive of MC. MC was detected in 32.1% of the subjects, with a significantly higher prevalence at lower lumbar levels (3.5% at L1/2-L3/4 vs. 15.9% at L4/5-L5/S1, p < 0.001). TEP score was strongly and independently associated with MC at each lumbar level (risk estimates from 1.49 to 2.44; all p ≤ 0.001) after adjustment for age, sex, BMI and twin pairing. ROC analysis showed a TEP score cut-off of 6 above which there was a significantly higher prevalence of MC. In conclusion, ED were strongly associated with MC at every lumbar level. These findings support the hypothesis that endplate defect is a major initiating factor for the cascade of events that may include disc degeneration (DD) and MC.

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

STUDY DESIGN: Cross-sectional study of spine magnetic resonance in a population, predominantly female, sample. OBJECTIVE: To determine the relationship between vertebral endplate defect and intervertebral disc degeneration (DD) in general population. SUMMARY OF BACKGROUND DATA: 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. METHODS: The study population comprised 831 twin volunteers from TwinsUK (mean age 54 ±â€Š8 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: 2.

The relationship between Modic changes and intervertebral disc degeneration.

BACKGROUND: Recent reported results have added to the weight of evidence supporting association between disc degeneration and Modic changes. Endplate or Modic changes are also associated with increased body mass index. The most recent study from Teichtahl et al. titled 'Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height - a 3.0 T-MRI study' showed associations of Modic changes with quantitatively measured reduced disc height and fat mass index. However, there were some facts, which we would like to address in this Correspondence to their article. DISCUSSION: The different components of intervertebral disc degeneration such as loss of disc height and disc signal intensity have already been shown associated with endplate changes - but not disc height if it is assessed using newer more precise methods of quantitation of disc height. A possible protective effect of different adiposity distribution in the body to Modic change development would be of interest if observed in a longitudinal study in the future. Modic changes have been associated with different components of intervertebral disc degeneration such as loss of disc height and disc signal intensity previously. The influence of body fat distribution on endplate changes would be interesting to study longitudinally.

Refined Phenotyping of Modic Changes: Imaging Biomarkers of Prolonged Severe Low Back Pain and Disability.

Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese.We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting ≥30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors.In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P < 0.001) and greater degree of disc degeneration (P < 0.001) than non-MC subjects. In adjusted models, any MC (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.01-2.18), MC affecting whole anterior-posterior length (OR 1.62, 95% CI 1.04-2.51), and MC affecting 2/3 posterior length (OR 2.79, 95% CI 1.17-6.65) were associated with prolonged severe LBP. Type I MC tended to associate with pain more strongly than type II MC (OR 1.80, 95% CI 0.94-3.44 vs OR 1.36, 95% CI 0.88-2.09, respectively). Any MC (OR 1.47, 95% CI 1.04-2.10), type II MC (OR 1.56, 95% CI 1.06-2.31), MC affecting 2/3 posterior length (OR 2.96, 95% CI 1.27-6.89), and extensive MC (OR 1.95, 95% CI 1.21-3.15) were associated with disability. The strength of the associations increased with the number of MC.This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP.

Phenotype profiling of Modic changes of the lumbar spine and its association with other MRI phenotypes: a large-scale population-based study.

BACKGROUND CONTEXT: Modic changes (MC) are associated with low back pain. They represent vertebral endplate and adjacent vertebral marrow changes on magnetic resonance imaging (MRI), classified into three types. Because of small sample sizes, patient cohorts, and limited phenotype assessment, the morphology and involvement of MC and their association with other spinal phenotypes remain speculative. PURPOSE: We addressed and proposed a phenotypic profiling of MC and their relationship with lumbar MRI phenotypes in a large-scale population-based study. STUDY DESIGN/SETTING: A cross-sectional study of the Hong Kong Disc Degeneration Cohort. PATIENT SAMPLE: The study population consisted of 1,546 Southern Chinese volunteers. OUTCOME MEASURES: Topographical and morphological dimensions of MC, presence of disc degeneration (DD) and displacement, and Schmorl nodes were evaluated. METHODS: Axial T1-weighted and sagittal T2-weighted MRIs (3T) were assessed. RESULTS: Females were 62.4% (mean age, 49 years). The overall prevalence of MC was 21.9% (6.3% Type I and 15.5% Type II). Of all MC, 76% were located at the two lowest lumbar levels. Modic changes at the two lowest lumbar levels were more commonly located laterally (p<.001), less commonly anteriorly (p<.001), and were more extensive horizontally (p=.006) but not in vertical height compared with the upper levels. Type I MC were less common in the anterior part (p=.022), larger in size (height p=.004), and affected more likely the whole horizontal plane (p=.016) than Type II MC. Modic changes were associated with disc displacement, Schmorl nodes, and DD at the affected level (all p<.001), and the strength of association increased with the size of the lesion. Type I MC were associated more strongly with disc displacement (p=.008) and DD (p=.022) than Type II MC. CONCLUSIONS: Our large-scale MRI study is the first to definitely note that MC were size- and type-dependently significantly associated with disc pathology and endplate abnormalities. Our phenotype profiling of MC may have clinical utility.

ISSLS Prize Winner: Vertebral Endplate (Modic) Change is an Independent Risk Factor for Episodes of Severe and Disabling Low Back Pain.

STUDY DESIGN: Longitudinal cohort study of twins representative of the general population. OBJECTIVE: To assess the relationship between Modic change (MC) and severe, disabling low back pain (LBP), features of intervertebral disc degeneration (DD) and incident MC during 10-year follow-up. SUMMARY OF BACKGROUND DATA: MC describes vertebral endplate and bone marrow lesions visible on magnetic resonance imaging (MRI). MC has been associated with DD. It remains unclear whether MC causes LBP independently or through association with DD. Moreover, association of MC with severe, disabling LBP is uncertain. METHODS: Volunteers were recruited from the TwinsUK register to MRI and interview between 1996 and 2000 with a subset attending for follow-up a decade later. MC, DD (evaluated by loss of disc height and signal intensity, presence of disc bulge and anterior osteophytes) and Schmorl's nodes (SN) were determined on T2-weighted lumbar MR scans. RESULTS: Complete data were available for 823 subjects at baseline and 429 at follow-up. Mean age at baseline was 54.0 years (range 32-70) with 96% females. The prevalence of MC was 32.2% at baseline and 48.7% at follow-up. Subjects with MC were older (P < 0.001) and more overweight (BMI: P = 0.026, weight: P < 0.001). At both baseline and follow-up, more subjects reporting severe LBP demonstrated MC (subjects with MC vs. without MC: 35.0% vs. 16.4% respectively, P < 0.001 at baseline; and 35.1% vs. 20.0% respectively, P < 0.001 at follow-up). In multivariable analyses, MC remained significantly associated with episodes of severe, disabling LBP (OR 1.58; 95% CI 1.04-2.41) after adjustment for age, BMI, DD, and SN at baseline. Loss of disc height and disc signal intensity were independently associated with prevalent MC at baseline, and disc height and disc bulge with incident MC during follow-up. CONCLUSION: MC is an independent risk factor for episodes of severe and disabling LBP in middle-aged women. These observations support further work aimed at identifying the precise histology underlying MC. LEVEL OF EVIDENCE: 2.

Vertebral endplate change as a feature of intervertebral disc degeneration: a heritability study.

PURPOSE: To study the prevalence of vertebral endplate or Modic change (MC), the progression of MC over a 10-year follow-up and the heritability of MC prevalence in a classical twin study. METHODS: The study population was recruited from TwinsUK register between 1996 and 2000. MC was evaluated from T2-weighted lumbar magnetic resonance imaging (MRI) at baseline and follow-up. Heritability was estimated using variance components analysis. Baseline MRI with appropriate data was available for 831 twins and follow-up for 436 twins. In total, both baseline and follow-up imaging were available for 347 twins. RESULTS: Mean age of the study population was 54.1 years (range 45.7-62.5) and females comprised 96%. The prevalence of MC at baseline was 32.1% and at follow-up 48.4%. The incidence of MC during the 10-year follow-up was 21.6% and was highest at L4-5 and L5-S1. MC regressed totally in 3.5% of twins. Twins with prevalent MC at baseline demonstrated a higher incidence of MC at upper lumbar levels during follow-up compared to twins without baseline MC (p = 0.009). Probandwise concordance rates were higher in monozygotic (0.56) than dizygotic twin pairs (0.39) suggestive of familial influence. Heritability of MC prevalence was estimated at 30 (16-43) %. CONCLUSIONS: The results suggest that MC is generally progressive in middle age and furthermore is heritable. Since MC is associated with disc degeneration, which is also heritable, further work on potential shared mechanisms is needed.