Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin

Abstract

This paper formulates a novel multifactorial Cascade Concept for the pathogenesis of adolescent idiopathic scoliosis (AIS). This Concept stems from the longitudinal findings of Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) who identified leptin body composition factors at 10 years of age associated with a scoliosis deformity found at 15 years. We interpret these findings in the light of some concepts for AIS pathogenesis. In particular, we speculate that the leptin body composition effect is linked to central nervous system development and the initiation of the asynchronous neuro-osseous growth mechanism that involves the creation of a neuraxis tether of relative anterior vertebral overgrowth. The latter mechanism in combination with age and gender-related anatomical variants of vertebral backward tilt (dorsal shear concept), human upright posture, adolescent growth factors, Hueter-Volkmann effect in vertebrae and vertebral bone mass abnormalities, lead to AIS, possibly both initiation and progression of scoliosis curvatures. Being multifactorial, while the Cascade Concept cannot be tested for all its components, some components should be testable by the method of numerical simulation.Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) also suggested the origin of scoliosis was in the embryonic stages of life from cell types, including adipocytes and osteoblasts, derived from the same progenitor cells, and myoblasts from mesodermal somites. The involvement of cell types from different developmental origins suggests a process acting in embryonic life at a similar time, probably environmental, as previously proposed from anthropometric studies. As a Complex disease, AIS will involve genetic, environmental and life style factors operating in development and growth; this possibility needs evaluating in epidemiological studies.

Low Body Mass Index for Early Screening of Adolescent Idiopathic Scoliosis: A Comparison Based on Standardized Body Mass Index Classifications

“…In a population with AIS, body composition measurements such as BMI, fat-free mass, and fat mass index were lower than those in the general population [31]. Although the precise molecular mechanism remains to be elucidated, Burwell et al [32] hypothesized that lower leptin levels are related to the initiation of asynchronous neuro-osseous growth, leading to tension in the neuraxis and tethered anterior vertebral growth. In contrast, low BMI was not associated with scoliosis in man adolescents.…”

Prevalence of Scoliosis in Elementary School Students Aged 8-11 Years

“…This is confirmed by some studies reporting that scoliotic children and adolescents had lighter body mass and greater height than normal adolescents of the same sex and age group (Wang, Wang, Zhu, Zhu, & Qiu, 2016;Ramírez et al, 2013). The anthropometric character of scoliosis patients is thought to be related to the pathophysiology of scoliosis, namely, the influence of leptin as well as somatic and autonomic nerve disharmony (Burwell et al, 2009;Burwell, Clark, Dangerfield, & Moulton, 2016).…”

“…As in the case of body height, our study also reported that scoliotic students had lower BMI than normal, but it was significant only in girls. Slenderness in scoliosis might be related to some mechanisms, pathophysiology of scoliosis involving leptin (Burwell et al, 2016;Liu et al, 2012), increased activity of the sympathetic nervous system (Burwell et al, 2009;Burwell et al, 2008a), and eating disorders (Smith, Latchford, Hall, Millner, & Dickson, 2002).…”

Etiopathogenesis of idiopathic scoliosis

“…The researchers speculated that the decreased circulating leptin is linked to the onset of the imbalanced neuroosseous growth mechanism that leads to relative anterior skeletal overgrowth. This mechanism in combination with other factors ,including anatomical differences of vertebrae ,bipedal posture, growth acceleration during puberty, Hueter-Volkmann law and decreased bone mass leads to the development of IS 39 .…”