title: Leptin may play a role in bone microstructural alterations in obese children.
abstract: BACKGROUND
  Bone mass is low and fracture risk is higher in obese children. Hormonal changes in relation to skeletal microstructure and biomechanics have not been studied in obese children.
  
  
  OBJECTIVE
  The objective of the study was to ascertain the relationships of obesity-related changes in hormones with skeletal microstructure and biomechanics.
  
  
  METHODS
  High resolution peripheral quantitative computed tomography (HR-pQCT) was used to compare three-dimensional cortical and trabecular microstructure and biomechanics at load-bearing and nonload bearing sites in obese and lean children. The relationship between leptin, adiponectin, testosterone, estrogen, osteocalcin and sclerostin and skeletal microstructure was also determined.
  
  
  METHODS
  The study was conducted at a tertiary pediatric endocrine unit in the United Kingdom.
  
  
  METHODS
  Obese and lean children were matched by gender and pubertal stage.
  
  
  RESULTS
  Radial cortical porosity (mean difference -0.01 [95% CI: -0.02, -0.004], P = .003) and cortical pore diameter (mean difference -0.005 mm [95% CI: -0.009, -0.001], P = .011) were lower in obese children. Tibial trabecular thickness was lower (mean difference -0.009 mm [95% CI: -0.014, -0.004], P = .003), and trabecular number was higher (mean difference 0.23 mm(-1) [95% CI: 0.08, 0.38], P = .004) in obese children. At the radius, fat mass percentage negatively correlated with cortical porosity (r = -0.57, P < .001) and pore diameter (r = -0.38, P = .02) and negatively correlated with trabecular thickness (r = -0.62, P < .001) and trabecular von Mises stress (r = -0.39, P = .019) at the tibia. No difference was observed in the other biomechanical parameters of the radius and tibia. Leptin was higher in obese children (805.3 ± 440.6 pg/ml vs 98.1 ± 75.4 pg/ml, P < .001) and was inversely related to radial cortical porosity (r = 0.60, 95% CI: [-0.80, -0.30], P < .001), radial cortical pore diameter (r = 0.51, 95% CI [-0.75, -0.16], P = .002), tibial trabecular thickness (r = 0.55, 95% CI: [-0.78, -0.21], P = .001) and tibial trabecular von Mises stress (r = -0.39, 95% CI: -0.65, 0.04, P = .02).
  
  
  CONCLUSIONS
  Childhood obesity alters radial and tibial microstructure. Leptin may direct these changes. Despite this, the biomechanical properties of the radius and tibia do not adapt sufficiently in obese children to withstand the increased loading potential from a fall. This may explain the higher incidence of fracture in obese children.
authors.affiliation: Department of Paediatric Endocrinology (P.D., D.K.), Sheffield Children's NHS Foundation Trust, Sheffield, S10 2TH, United Kingdom; School of Health and Related Research (R.M.J.), The Mellanby Centre for Bone Research (M.P., J.W., N.B., R.E.), Academic Unit of Bone Metabolism, and Centre for Computational Imaging and Simulation Technologies in Biomedicine, Department of Mechanical Engineering (Z.A.T., A.F.F.), University of Sheffield, Sheffield, S10 2TN, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Dimitri
authors.forename: R M
authors.initials: RM
authors.lastname: Jacques
authors.forename: M
authors.initials: M
authors.lastname: Paggiosi
authors.forename: D
authors.initials: D
authors.lastname: King
authors.forename: J
authors.initials: J
authors.lastname: Walsh
authors.forename: Z A
authors.initials: ZA
authors.lastname: Taylor
authors.forename: A F
authors.initials: AF
authors.lastname: Frangi
authors.forename: N
authors.initials: N
authors.lastname: Bishop
authors.forename: R
authors.initials: R
authors.lastname: Eastell
mesh_terms: D015502:Absorptiometry, Photon; D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D015519:Bone Density; D002648:Child; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood* / Q000000981:diagnostic imaging; D011884:Radius / Q000000981:diagnostic imaging*; D013739:Testosterone / Q000097:blood; D013977:Tibia / Q000000981:diagnostic imaging*
chemical_list: D052242:Adiponectin; D004967:Estrogens; D020738:Leptin; D013739:Testosterone