In the absence of any generally accepted scientific theory for the etiology of idiopathic scoliosis, treatment remains pragmatic with a very incomplete scientific basis. The International Federated Body on Scoliosis Etiology (IBSE)  introduced the Electronic Focus Group (EFG) as a means of increasing debate of knowledge on important topics. The text for this debate was written by Dr Ian Stokes who addresses the concept of mechanical modulation of vertebral body growth in the pathogenesis of progressive adolescent scoliosis generally attributed to the Hueter-Volkmann or Delpech effect [1–25] in which constant pathologic strong pressure inhibits endochondral longitudinal growth while reduced compression accelerates growth [2–4]; pressure exerted eccentrically causes an active change in the direction of growth [2, 5–7]. Brace treatment is based on this effect although the efficacy of bracing continues to be debated and questioned [26–39] while exercises are not even considered by many clinicians. Guidelines for the conservative management of scoliosis by physical therapy, intensive rehabilitation and brace treatment have been published recently [37, 38]; on evidence-based medicine [40, 41] bracing and exercises gave a grade of evidence C (level of evidence IV) (i.e. expert committee reports or opinions and/or clinical experience of respected authorities indicating that directly applicable clinical studies of good quality are absent). Since it is generally recognized that multi-level arthrodesis of the spine is not a desirable outcome, currently there is renewed interest in modifying vertebral growth by early surgical interventions [42–44] including stapling and, in young children, fusionless scoliosis surgery  which is being evaluated experimentally in animals [46–48].
The mechanical modulation of vertebral growth in the presumed asymmetrically loaded spine with scoliosis was described by Stokes as a 'vicious cycle' and interpreted by his vicious cycle hypothesis of pathogenesis [3, 4]. Roaf  had previously used the term 'vicious circle' to describe the effects of gravity on thoracic vertebral endplate physes in Scheuermann's disease whatever the primary cause of that deformity. The implication is that independent of whether a scoliosis is congenital, neuromuscular, or idiopathic, mechanical factors become predominant relative to initiating factors during rapid adolescent growth, when the risk of curve progression is greatest [49–51]. While qualitatively attractive, the validity of this mechanical stress-growth relationship hypothesis remains to be proven. Proof requires quantitative information about the loading state of the spine with scoliosis, consequential growth alterations and geometrical changes all of which are addressed here.
The Statement of this EFG is drawn from biomechanical studies that Dr Stokes has pursued in recent years relating to a mathematical simulation of the vicious cycle hypothesis for the pathogenesis of adolescent scoliosis. A frontal plane model was designed because very little is known about the details of how the loads are transmitted through the spine in three-dimensions. The model, involving geometric recursive/growth analysis, tested whether (1) the calculated loading asymmetry of a growing spine with scoliosis created by a neuromuscular activation strategy, together with (2) the measured bone growth sensitivity to altered compression could explain (3) the observed rate of scoliosis progression during adolescent growth. The model assumes that (1) a pre-existing scoliosis curve of unknown etiology initiates the mechanically modulated alteration of growth that in turn causes worsening of the scoliosis, (2) everything else is anatomically and physiologically 'normal', and (3) loading sustained over a substantial proportion of the day modulates endochondral bone growth, whereas transient loading does not. The forces due to muscle activation are generally of greater magnitude than forces due to superimposed body weight . The simulations employ newly-available data on the magnitude of asymmetric loading imposed on the spine as a function of the scoliosis curve, and of the resulting mechanically altered vertebral growth. The effects of intervertebral disc wedging were included only indirectly by prior knowledge of their relationship to vertebral wedging. The findings are consistent with the vicious cycle hypothesis of pathogenesis namely that in progressive adolescent idiopathic scoliosis (AIS) frontal plane vertebral body wedging during growth results from asymmetric neuromuscular loading.
The research engenders controversy, including:
Are the results applicable to humans who lack ossified vertebral body epiphyses and have "ring" apophyses?
Are there separate initiating (? discal, vertebral, costal or neuromuscular) and progressive (mechanical and non-mechanical) factors for AIS pathogenesis?
Are vertebral endplate physes normal when the growth modulation starts?
Whether healthy adolescents can spontaneously generate asymmetrical vertebral growth and deformity by inappropriate neuromuscular activation strategies.
Do the findings have relevance to treatment? Or, is the resurrection of exercise programs for AIS a step too far?
Why does asymmetric loading on the spine from pelvic tilt scoliosis not lead to curve progression?
Does movement asymmetry of both hips during gait cause idiopathic scoliosis?
Why do normal sagittal spinal curves not progress from front-back asymmetric vertebral loading?
Might not patients with severe curves have, in addition to the hypokyphosis, a slightly postero-lateral asymmetric load on endplate physes?
Do neurogenic thoracic scolioses result from different skeletal pathomechanisms than those that evoke thoracic AIS?
In some conditions why does curve progression occur without evidence to suggest that the cause is asymmetric loading?
Do the relative anterior spinal overgrowth (RASO) and other biologic concepts of structural scoliosis contribute to curve progression?
Does the vertebral body wedging in progressive lumbar AIS result from:
secondary neuromuscular dysfunction [this paper],
primary neuromuscular imbalance [12, 19, 22, 53, 54],
relative anterior spinal overgrowth (RASO) due to -
primary skeletal change [12, 55, 56] with uncoupled endochondral-membranous bone formation [55, 56], or
uncoupled neuro-osseous growth between the anterior spinal column and spinal cord [57–60],
calcification of cartilage endplates [61, 62],
resorption by osteoclasts , or
osteopenia [64–67], possibly due to maturational abnormalities in cell differentiation – recently suggested by studying calcium channel isoforms in the membranes of platelets and osteoblasts from patients with AIS .
Do methods and findings from recent research on mechanotransduction in articular cartilage have relevance to the vertebral growth plate chondrocytic phenotype?
Is the adjective "vicious" appropriate for Dr Stokes' biomechanical hypothesis of pathogenesis?
A new speculative concept is proposed namely of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. It explains the developmental onset of AIS in morphological, biomechanical and molecular terms and is complementary to a vascular concept of pathogenesis [69–71]. What is not controversial is the need to test the Dr Stokes' hypothesis using additional factors not only in the current model but also in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. An urgent challenge is to be able to distinguish the factors that predict whether a curve is progressive or not.
The vertebral body growth modulation process is one type of the biologic phenomenon of mechanotransduction [72–75]. In this phenomenon a single physical parameter – force – is converted into a response that is the basis for a plethora of fundamental biologic processes known to occur in many tissues including skeletal tissues [76, 77], muscles, tendons and ligaments [78, 79]. There is recent evidence that cells from distinct regions of intervertebral discs of cattle tails differ in their mechanosensitivity as revealed by gene expression . The finding that extracellular matrix genes are upregulated by cyclical mechanical strain suggests that such genes are possible targets for novel therapeutic intervention .
In sum, this EFG aims to explore what may be learnt about the etiopathogenesis of AIS by IBSE members debating via e-mail Dr Stokes' biomechanical spinal growth modulation experiments on progressive adolescent scoliosis. Biomechanical, biological and clinical issues are discussed, a novel hypothesis formulated and recent relevant research on AIS etiopathogenesis is considered.