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Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

R Geoffrey Burwell1*, Peter H Dangerfield234, Alan Moulton5 and Theodoros B Grivas6

Author Affiliations

1 Centre for Spinal Studies and Surgery, Nottingham University Hospitals Trust, Queen's Medical Centre Campus, Derby Road, Nottingham, NG7 2UH, UK

2 University of Liverpool, Ashton Street, L69 3GE, UK

3 Staffordshire University, Leek Road, Stoke-on-Trent, ST4 2DF, UK

4 Royal Liverpool Children's Hospital, Eaton Road, Liverpool, L12 2AP, UK

5 Department of Orthopaedic Surgery, King's Mill Hospital, Sutton Road, Mansfield NG17 4JL, UK

6 Department of Trauma and Orthopedics, "Tzanio" General Hospital, Tzani and Afendouli 1 st, Piraeus 18536, Greece

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Scoliosis 2011, 6:26  doi:10.1186/1748-7161-6-26

Published: 2 December 2011


Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening, genetic, epigenetic, biochemical, metabolic phenotypes and pharmacogenomic research to identify susceptible individuals at risk and modulate abnormal molecular pathways of AIS. The potential of epigenetic-based medical therapy for AIS cannot be assessed at present, and must await new research derived from the evaluation of epigenetic concepts of spinal growth in health and deformity. The tenets outlined here for AIS are applicable to other musculoskeletal growth disorders including infantile and juvenile idiopathic scoliosis.