title: Body mass index of girls in health influences menarche and skeletal maturation: a leptin-sympathetic nervous system focus on the trunk with hypothalamic asymmetric dysfunction in the pathogenesis of adolescent idiopathic scoliosis?
abstract: Lower body mass index (BMI) and lower circulating leptin levels have been reported in girls with AIS. In this paper we evaluate skeletal sizes and asymmetries by higher and lower BMI subsets about the means for each of three groups of girls age 11-18 years: 1) normals, 2) school screening referrals, and 3) preoperative girls. Higher and lower BMI subsets, likely to have separated subjects with higher from those with lower circulating leptin levels, identify: 1) girls with relatively earlier and later menarche; 2) trunk width size greater in the higher than in the lower BMI subset, of all three groups; 3) abnormal upper arm length (UAL) asymmetries (right minus left) in the lower BMI subset of the preoperative girls; and 4) in thoracic AIS of screened and preoperative girls, Cobb angle and apical vertebral rotation each significantly and positively correlate with UAL asymmetry in the lower BMI subset but not in the higher BMI subset. In preoperative girls, the lower BMI subset shows the combination of relatively reduced pelvic width and abnormal UAL asymmetry, suggesting that both are linked to lower circulating leptin levels. An earlier puberty with hormonal changes provides a plausible explanation for the larger trunk width at the shoulders and pelvis especially at the younger ages in the higher BMI subsets. At the shoulders, this widening is driven by the ribcage which, in human evolution was acquired with decoupling of head and trunk movements required for efficient bipedal gait. The UAL asymmetry patterns within the groups and BMI subsets are not explained by hormonal mechanisms. It is hypothesized that 1) normal trunk widening of the thoracic cage by hormones in human adolescence is supplemented via the sympathetic nervous system under leptin-hypothalamic control influenced by energy stores (metabolic fuel); and 2) hypothalamic dysfunction with altered hypothalamic sensitivity to leptin through a SNS-driven asymmetric effect may create skeletal length asymmetries in upper arms, ribs, ilia and vertebrae, and initiate AIS. Additional mechanisms acting in the spine and trunk may be required for AIS to progress including 1) somatic nervous system dysfunction, 2) biomechanical spinal growth modulation, and 3) osteopenia.
authors.affiliation: Centre for Spinal Studies and Surgery, Nottingham University Hospitals Trust, Queen's Medical Centre Campus, Nottingham, UK.
authors.forename: R G
authors.initials: RG
authors.lastname: Burwell
authors.forename: R K
authors.initials: RK
authors.lastname: Aujla
authors.forename: A S
authors.initials: AS
authors.lastname: Kirby
authors.forename: P H
authors.initials: PH
authors.lastname: Dangerfield
authors.forename: A
authors.initials: A
authors.lastname: Moulton
authors.forename: A A
authors.initials: AA
authors.lastname: Cole
authors.forename: F J
authors.initials: FJ
authors.lastname: Polak
authors.forename: R K
authors.initials: RK
authors.lastname: Pratt
authors.forename: J K
authors.initials: JK
authors.lastname: Webb
mesh_terms: D000293:Adolescent; D000886:Anthropometry; D002648:Child; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000473:pathology*; D020738:Leptin / Q000502:physiology*; D008572:Menarche / Q000502:physiology*; D010865:Pilot Projects; D011859:Radiography; D012016:Reference Values; D012307:Risk Factors; D012600:Scoliosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D012737:Sex Factors; D012741:Sexual Maturation / Q000502:physiology*; D012863:Skeleton; D013564:Sympathetic Nervous System / Q000502:physiology*; D013904:Thoracic Vertebrae
chemical_list: D020738:Leptin