Growth hormone (GH)/insulin like growth factor (IGF) axis and insulin are key determinants of bone remodeling. Homozygous mutations in the GH releasing hormone receptor (GHRHR) gene (GHRHR) are a frequent cause of genetic isolated GHD (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.
PATIENTS AND 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 and CrossLaps), IGF-I, glucose, and insulin were measured and homeostasis model assessment of insulin resistance (HOMAIR) was calculated.
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 osteocalcin, but insulin (p = 0.01), HOMAIR (p = 0.01) and CrossLaps (p = 0.01) were lower in MUT/N. There was no correlation between osteocalcin and glucose, osteocalcin and HOMAIR in the140 individuals as a whole or in the separate MUT/N or N/N groups.
The present study suggests that one allele mutation in the GHRHR gene has a greater impact on energy metabolism than on bone quality.