Juhani H. Määttä

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 Schmorls 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

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

AbstractLow back pain (LBP) is the worlds 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.

Association of Modic changes with health-related quality of life among patients referred to spine surgery

Abstract Background and purpose Modic changes (MC) are bone marrow and vertebral endplate lesions seen in magnetic resonance imaging (MRI) which have been found to be associated with low back pain (LBP), but the association between MC and health-related quality of life (HRQoL) is poorly understood. The aim of this study was to assess the relationship between MC and HRQoL among patients referred to spine surgery. Methods The study population consisted of 181 patients referred to lumbar spine surgery in Northern and Eastern Finland between June 2007 and January 2011. HRQoL was assessed using RAND-36 health survey. Lumbar MC were evaluated and classified into ‘No MC’, ‘Type I’ (Type I or I/II), and ‘Type II’ (Type II, II/III or III). Results In total, 84 patients (46%) had MC. Of these, 37% had ‘Type I’ and 63% ‘Type II’. Patients with MC were older, more likely females, had longer duration of LBP and a higher degree of disc degeneration than patients without MC. The total physical component or physical dimensions did not differ significantly between the groups. The total mental component of RAND-36 (P = 0.010), and dimensions of energy (P = 0.023), emotional well-being (P = 0.012) and emotional role functioning (P = 0.016) differed significantly between the groups after adjustments for age and gender. In the mental dimension scores, a statistically significant difference was found between ‘No MC’ and ‘Type II’. Conclusions Among patients referred to spine surgery, MC were not associated with physical dimensions of HRQoL including dimension of pain. However, ‘Type II’ MC were associated with lower mental status of HRQoL. Implications Our study would suggest that Type II MC were associated with a worse mental status. This may affect the outcome of surgery as it is well recognized that patients with depression, for instance, have smaller improvements in HRQoL and disability. Thus the value of operative treatment for these patients should be recognized and taken into consideration in treatment. Our study shows that MC may affect outcome and thus clinicians and researchers should be cognizant of this and take this into account when comparing outcomes of surgical treatment in the future. A longitudinal study would be needed to properly address the relationship of MC with surgical outcome.

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 ± 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. 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

Intervertebral Disc Biology: Genetic Basis of Disc Degeneration

Purpose of ReviewThis review aims to highlight recent advances in understanding the genetic basis of intervertebral disc degeneration (IDD).Recent FindingsIt 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.SummaryA 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.

The Association of Modic Changes and MRI Phenotypes of the Lumbar Spine: A Population-Based Study

Introduction Low back pain is the worlds most disabling condition. Modic changes (MC) are associated with low back pain. These changes are spinal phenotypes that represent vertebral endplate and adjacent marrow changes on MRI. MC are classified into three main types (type I, type II, and type III) and mixed types (type I/II and II/III). Due to methodological biases in previous studies, the morphology, involvement of MC, and their association with other spinal phenotypes remain speculative. As such, the aim of this study was to evaluate the relationship of MC with other spinal MRI phenotypes in a large-scale population-based study. Materials and Methods Based on the Hong Kong Disc Degeneration Cohort of Southern Chinese, we assessed the T1- and T2-weighted MRIs of 1,604 subjects (62.4% females; mean age: 49 years) from L1 to S1. The MC assessment included the presence, type, vertical height, and axial area of MC. MC were evaluated as type I, type I/II, type II, type II/III, and type III. Types were regrouped in the analyses as “type I” (types I and I/II) and “type II” (types II and II/III). Very small MC, such as MC in only one sagittal plane, were excluded. Additional imaging phenotype findings were assessed (disc bulges/extrusions, Schmorl nodes, disc degeneration). Disc degeneration was based on the Pfirrmann classification. A degenerative disc disease (DDD) score was tabulated, which represented the global severity of disc degeneration of the lumbar spine. The lumbar spine was further stratified to upper (L1-L4) and lower (L4-S1) regions. Results The prevalence of MC was 24.7% (“type I”: 6.3%, “type II”: 15.5%). Of all MC, 77% were at L4-S1. Subjects with MC were older (mean age: 53 vs. 48 years, p < 0.001) and had higher DDD scores (p < 0.001). “Type I” MC were more common at lower lumbar levels (p = 0.021), were less likely to be located only in the anterior region (p = 0.017), and were more associated with disc bulges/extrusions (p < 0.001) in comparison to “type II” MC. MC of the lower lumbar levels were not commonly noted only in the anterior region, involved more likely only the left or right endplate and had a higher prevalence of disc bulges/extrusions and disc degeneration in comparison to upper lumbar levels (p < 0.001). Large MC (≥2/3 of the axial area) were more likely located at lower lumbar levels (83 vs. 73%, p = 0.001) and had a higher prevalence of disc bulge/extrusion (83 vs. 72%, p = 0.001) and Schmorl node at the affected level (52 vs. 39%, p < 0.001) compared with smaller MC. Conclusion Based on one of the largest population-based studies, our findings strengthen the belief that MC are clearly associated with disc pathology, such as disc degeneration, disc bulges/extrusions, and endplate abnormalities (e.g., Schmorl nodes). MC type- and level-related findings in relation to additional MRI phenotypes were also identified. This study further refines the phenotypic classification of MC, which if standardized can have immense utility in studies assessing the role of biomarkers (e.g., genetics) in relation to clinically relevant spinal changes. Acknowledgments The study has been supported by AOSpine Research Network Exchange Award. Disclosure of Interest None declared

The Prognostic Role of Modic Changes for Lumbar Discectomy: A Prospective Study

Introduction There is a controversy regarding the prognostic role of Modic changes (MCs) for lumbar discectomy. The aim of this study was to evaluate whether Modic changes affect the results of lumbar discectomy 1 year after surgery. Materials and Methods The study population consisted of 180 sciatica patients from Northern and Eastern Finland who underwent discectomy. Pain intensity (low back and leg pain) and disability on Oswestry Disability Index (ODI) were evaluated preoperatively and 1 year after surgery. Lumbar MCs on magnetic resonance imaging were classified into: “No MC,” “Type I” (Type I or I/II), and “Type II” (Type II, II/III, or III). The analyses were performed using the analysis of covariance (ANCOVA) with adjustments for age, gender, and disk degeneration (DD) sum score. Results At baseline, 83 (46%) patients had MCs. Of MCs, 33% were Type I. Patients with MCs were older, more likely female and had a higher degree of DD than patients without MCs. Patients with Type I MCs had smaller improvement in ODI than patients with No MC (p = 0.045) or Type II MCs (p = 0.037). The improvements in low back and leg pain were similar than in ODI but the differences were not significant. Conclusion Type I MCs indicated a poorer prognosis of lumbar discectomy. The previous contradictory results may be due to smaller study sample sizes. Patients with ‘Type I’ MCs had smaller disability improvement than patients without MCs or with Type II MCs 1 year after discectomy. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared