title: Does adiposity status influence femoral cortical strength in rodent models of growth hormone deficiency?
abstract: Growth hormone (GH)-deficiency is usually associated with elevated adiposity, hyperleptinemia, and increased fracture risk. Since leptin is thought to enhance cortical bone formation, we have investigated the contribution of elevated adiposity and hyperleptinemia on femoral strength in rodent models of GH deficiency. Quantification of the transpubertal development of femoral strength in the moderately GH-deficient/hyperleptinemic Tgr rat and the profoundly GH-deficient/hypoleptinemic dw/dw rat revealed that the mechanical properties of cortical bone in these two models were similarly compromised, a 25-30% reduction in failure load being entirely due to impairment of geometric variables. In contrast, murine models of partial (GH antagonist transgenic) and complete (GH receptor-null) loss of GH signaling and elevated adiposity showed an impairment of femoral cortical strength proportionate to the reduction of GH signaling. To determine whether impaired femoral strength is exacerbated by obesity/hyperleptinemia, femoral strength was assessed in dw/dw rats following two developmental manipulations that elevate abdominal adiposity and circulating leptin, neonatal monosodium glutamate (MSG) treatment, and maintenance on an elevated fat diet. The additional impairment of femoral strength following MSG treatment is likely to have resulted from a reduction in residual activity of the hypothalamo-pituitary-GH-IGF-I axis, but consumption of elevated dietary fat, which did not reduce circulating IGF-I, failed to exacerbate the compromised femoral strength in dw/dw rats. Taken together, our data indicate that the obesity and hyperleptinemia usually associated with GH deficiency do not exert a significant influence over the strength of cortical bone.
authors.affiliation: School of Biosciences, Cardiff University, Museum Ave., Cardiff, CF10 3AX, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Stevenson
authors.forename: B A J
authors.initials: BA
authors.lastname: Evans
authors.forename: E F
authors.initials: EF
authors.lastname: Gevers
authors.forename: C
authors.initials: C
authors.lastname: Elford
authors.forename: R W J
authors.initials: RW
authors.lastname: McLeod
authors.forename: M J
authors.initials: MJ
authors.lastname: Perry
authors.forename: M M
authors.initials: MM
authors.lastname: El-Kasti
authors.forename: K T
authors.initials: KT
authors.lastname: Coschigano
authors.forename: J J
authors.initials: JJ
authors.lastname: Kopchick
authors.forename: S L
authors.initials: SL
authors.lastname: Evans
authors.forename: T
authors.initials: T
authors.lastname: Wells
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D015519:Bone Density / Q000502:physiology*; D004195:Disease Models, Animal; D005269:Femur / Q000502:physiology*; D013006:Growth Hormone / Q000172:deficiency* / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D020738:Leptin; D013006:Growth Hormone