title: The consequences of growth hormone-releasing hormone receptor haploinsufficiency for bone quality and insulin resistance.
abstract: OBJECTIVE
  Growth hormone (GH)/insulin-like growth factor (IGF) axis and insulin are key determinants of bone remodelling. Homozygous mutations in the GH-releasing hormone receptor (GHRHR) gene (GHRHR) are a frequent cause of genetic isolated GH deficiency (IGHD). Heterozygosity for GHRHR mutation causes changes in body composition and possibly an increase in insulin sensitivity, but its effects on bone quality are still unknown. The objective of this study was to assess the bone quality and metabolism and its correlation with insulin sensitivity in subjects heterozygous for a null mutation in the GHRHR.
  
  
  METHODS
  A cross-sectional study was performed on 76 normal subjects (68·4% females) (N/N) and 64 individuals (64·1% females) heterozygous for a mutation in the GHRHR (MUT/N). Anthropometric features, quantitative ultrasound (QUS) of the heel, bone markers [osteocalcin (OC) and CrossLaps], IGF-I, glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA(IR) ) was calculated.
  
  
  RESULTS
  There were no differences in age or height between the two groups, but weight (P = 0·007) and BMI (P = 0·001) were lower in MUT/N. There were no differences in serum levels of IGF-I, glucose, T-score or absolute values of stiffness and OC, but insulin (P = 0·01), HOMA(IR) (P = 0·01) and CrossLaps (P = 0·01) were lower in MUT/N. There was no correlation between OC and glucose, OC and HOMA(IR) in the 140 individuals as a whole or in the separate MUT/N or N/N groups.
  
  
  CONCLUSIONS
  This study suggests that one allele mutation in the GHRHR gene has a greater impact on energy metabolism than on bone quality.
authors: Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors: Miburge B
authors: MB
authors: Gois
authors: Roberto
authors: R
authors: Salvatori
authors: Manuel H
authors: MH
authors: Aguiar-Oliveira
authors: Francisco A
authors: FA
authors: Pereira
authors: Carla R P
authors: CR
authors: Oliveira
authors: Luiz A
authors: LA
authors: Oliveira-Neto
authors: Rossana M C
authors: RM
authors: Pereira
authors: Anita H O
authors: AH
authors: Souza
authors: Enaldo V
authors: EV
authors: Melo
authors: Francisco J A
authors: FJ
authors: de Paula
mesh_terms: D000328:Adult; D000368:Aged; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling / Q000235:genetics* / Q000502:physiology; D001938:Brazil; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D013006:Growth Hormone / Q000172:deficiency; D057895:Haploinsufficiency; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015675:Osteocalcin / Q000097:blood; D018013:Receptors, Neuropeptide / Q000172:deficiency / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000172:deficiency / Q000235:genetics*
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D015675:Osteocalcin; D013006:Growth Hormone; C048250:somatotropin releasing hormone receptor