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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.

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.