Relatively lower body mass index is associated with an excess of severe truncal asymmetry in healthy adolescents: Do white adipose tissue, leptin, hypothalamus and sympathetic nervous system influence truncal growth asymmetry?

<p>Abstract</p> <p>Background</p> <p>In healthy adolescents normal back shape asymmetry, here termed truncal asymmetry (TA), is evaluated by higher and lower subsets of BMI. The study was initiated after research on girls with adolescent idiopathic scoliosis (AIS) showed that higher and lower BMI subsets discriminated patterns of skeletal maturation and asymmetry unexplained by existing theories of pathogenesis leading to a new interpretation which has therapeutic implications <it>(double neuro-osseous theory)</it>.</p> <p>Methods</p> <p>5953 adolescents age 11–17 years (boys 2939, girls 3014) were examined in a school screening program in two standard positions, standing forward bending (FB) and sitting FB. The sitting FB position is thought to reveal intrinsic TA free from back humps induced by any leg-length inequality. TA was measured in both positions using a Pruijs scoliometer as angle of trunk inclinations (ATIs) across the back at each of three spinal regions, thoracic, thoracolumbar and lumbar. Abnormality of ATIs was defined as being outside 2 standard deviations for each age group, gender, position and spinal region, and termed <it>severe </it>TA.</p> <p>Results</p> <p>In the sitting FB position after correcting for age,<it>relatively lower BMIs </it>are statistically associated with a greater number of severe TAs than with relatively higher BMIs in both girls (thoracolumbar region) and boys (thoracolumbar and lumbar regions).</p> <p>The relative frequency of severe TAs is significantly higher in girls than boys for each of the right thoracic (56.76%) and thoracolumbar (58.82%) regions (p = 0.006, 0.006, respectively). After correcting for age, smaller BMIs are associated with more <it>severe TAs </it>in boys and girls.</p> <p>Discussion</p> <p>BMI is a surrogate measure for body fat and circulating leptin levels. The finding that girls with relatively lower BMI have significantly later menarche, and a significant excess of TAs, suggests a relation to energy homeostasis through the hypothalamus. The hypothesis we suggest for the pathogenesis of severe TA in girls and boys has the same mechanism as that proposed recently for AIS girls, namely: severe TAs are initiated by a <it>genetically-determined selectively </it>increased hypothalamic sensitivity (up-regulation, i.e. increased sensitivity) to leptin with asymmetry as an adverse response to stress (hormesis), mediated bilaterally mainly to the growing trunk via the sympathetic nervous system <it>(leptin-hypothalamic-sympathetic nervous system (LHS) concept)</it>. The putative autonomic dysfunction is thought to be increased by any lower circulating leptin levels associated with relatively lower BMIs. Sympathetic nervous system activation with asymmetry leads to asymmetries in ribs and/or vertebrae producing severe TA when beyond the capacity of postural mechanisms of the somatic nervous system to control the shape distortion of the trunk. A test of this hypothesis testing skin sympathetic responses, as in the Rett syndrome, is suggested.</p

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans