Investigating the role of the growth hormone-insulin-like growth factor (GH-IGF) axis as a determinant of male bone mineral density (BMD).
BACKGROUND
The GH-IGF axis has profound effects on bone metabolism and may be important in the etiology of idiopathic osteoporosis. Serum IGF-I is often low in men with osteoporosis, which may be attributable to GH hypo-secretion or hepatic GH insensitivity. We studied the GH-IGF axis in depth to look for evidence to support these hypotheses.


METHODS
28 healthy 60- to 70-year-old men with low, intermediate, or normal BMD were studied. GH secretion was measured by overnight urine collection. GH reserve was assessed by exercise and glucagon stimulation tests. Hepatic IGF-I production was investigated using a GH-IGF-I generation test. Data were analyzed using Pearson's correlation coefficient, linear regression, and analysis of variance.


RESULTS
Serum IGF-I was reduced in subjects with low BMD (P = 0.009). There was no difference in GH secretion or reserve between the groups. Overall, GH reserve and IGF-I were positively related but this was attenuated in the low BMD group. However, no statistically significant difference in IGF-I generation capacity between BMD groups was found.


CONCLUSIONS
Men with reduced BMD have low IGF-I but normal GH secretion and reserve. Our data suggested, but could not confirm, hepatic resistance to GH as a mechanism for this association.
Patel
M B R
MB
MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton SO16 6YD, UK.
Arden
N K
NK
Masterson
L M
LM
Phillips
D I W
DI
Swaminathan
R
R
Syddall
H E
HE
Byrne
C D
CD
Wood
P J
PJ
Cooper
C
C
Holt
R I G
RI
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling; D015444:Exercise; D005934:Glucagon / Q000008:administration & dosage; D013006:Growth Hormone / Q000378:metabolism / Q000652:urine*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008099:Liver / Q000737:chemistry*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon