Vertebral Endplate Change as a Feature of Intervertebral Disc Degeneration: A Heritability Study

Abstract

Introduction Low back pain (LBP) is a common disorder in the western world and accounts for disability and considerable work absenteeism.1 Lumbar disc degeneration (DD) is associated with LBP.2 It has been suggested that different DD phenotypes should be “split” rather than “lumped” into a single phenotype (DD) so as to allow a more meaningful interrogation of the pathogenic processes underlying the constituent traits.3 One trait of special interest is vertebral endplate or Modic change (MC), which comprises vertebral endplate and bone marrow lesions seen on magnetic resonance imaging (MRI).4 This trait has been found to be associated with LBP in some,5 but not all studies.6 MC is classified into three different types: types I-III. Whether MC is entirely environmental in origin, or whether it is influenced by underlying genetic factors, has not been established. Our purpose was to study (1) the prevalence of MC, (2) the progression of MC over a 10-year follow-up, and (3) the heritability of MC prevalence in a classical twin study. Materials and Methods The study population was recruited from TwinsUK register between 1996 and 2000 when the baseline spine MRI study was performed as previously described7 and at follow-up a decade later.3 MC was evaluated from T2-weighted lumbar MRI. Both rostral and caudal endplates of each lumbar segment were coded using the same method at baseline and follow-up.8 The maximum depth and width of each MC was evaluated and the size index was calculated. Heritability was estimated using variance components analysis. MRI with appropriate data was available for 831 twins at baseline and for 436 twins at follow-up. In total, both baseline and follow-up imaging were available for 347 twins. Results Mean age of the study population at baseline 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 was 48.4%. The incidence of new MC at any level during the 10-year follow-up was 21.6% and was most frequent at L4-L5 and L5-S1. MC regressed totally in 3.5% of twins. The volume of the MC lesions increased during follow-up: the median MC size index summary score was 10.0 (interquartile range = 5.0-18.0) at baseline and 13.5 (interquartile range = 8.0-21.75) at follow-up ( p = 0.012). Twins with prevalent MC at baseline demonstrated a higher incidence of MC at upper lumbar levels compared with twins without baseline MC ( p = 0.015). 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 using variance components analysis to be 30 (16-43)%. Conclusion This is the first study to assess the heritability of MC. This study suggests that MC is heritable and progressive in middle age. Further work is needed to define the relationship of MC and lumbar DD. That MC shows a degree of heritability suggests that it is reasonable to search for genetic variants. Disclosure of Interest None declared References Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380(9859):2197–2223 Livshits G, Popham M, Malkin I, et al. Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis 2011;70(10):1740–1745 Williams FM, Popham M, Sambrook PN, Jones AF, Spector TD, MacGregor AJ. Progression of lumbar disc degeneration over a decade: a heritability study. Ann Rheum Dis 2011;70(7):1203–1207 Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR. Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 1988;166(1 Pt 1):193–199 Jensen TS, Karppinen J, Sorensen JS, Niinimäki J, Leboeuf-Yde C. Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain. Eur Spine J 2008;17(11):1407–1422 Lim CH, Jee WH, Son BC, Kim DH, Ha KY, Park CK. Discogenic lumbar pain: association with MR imaging and CT discography. Eur J Radiol 2005;54(3):431–437 Sambrook PN, MacGregor AJ, Spector TD. Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins. Arthritis Rheum 1999;42(2):366–372 Jensen TS, Sorensen JS, Kjaer P. Intra- and interobserver reproducibility of vertebral endplate signal (modic) changes in the lumbar spine: the Nordic Modic Consensus Group classification. Acta Radiol 2007;48(7):748–754