Endocrine Abstracts (2004) 7 P4

The role of the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis in the aetiology of male idiopathic osteoporosis

MBR Patel1, NK Arden1, L Masterson1, DIW Phillips1, R Swaminathan2, HE Syddall1, PJ Wood3, C Cooper1 & RIG Holt4

1Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton, UK; 2Department of Clinical Pathology, St Thomas' Hospital, London, UK; 3Chemical Pathology, Southampton University Hospital NHS Trust, Southampton, UK; 4Department of Endocrinology & Metabolic Programming, University of Southampton, Southampton, UK.

Growth hormone (GH) has profound anabolic effects on bone, but its use as a treatment for patients with osteoporosis has only resulted in small increases in BMD. The low serum IGF-I demonstrated in men with idiopathic osteoporosis may be important in the aetiology of this disease and has been attributed to GH hypo-secretion, though there are conflicting reports of this. Insensitivity to the actions of GH has also been suggested. We studied the GH-IGF-I axis in otherwise healthy men with osteopaenia to look for evidence to support either or both of these hypotheses.

28 healthy 60-70 year old men with low, intermediate or normal BMD were selected from the well-characterised Hertfordshire Cohort Study. GH secretion was measured directly from an overnight urine collection. GH reserve was assessed physiologically with a bicycle exercise test and pharmacologically with a glucagon stimulation test. Hepatic IGF-I production was investigated using the GH-IGF-I generation test.

Serum IGF-I was reduced in subjects with low BMD (p=0.009). There was no difference in mean urinary GH according to subject BMD. GH reserve was comparable by both physiological and pharmacological methods across the groups. The association of GH reserve and serum IGF-I differed between groups, being attenuated in the low BMD group (p=0.03 for interaction). There was no significant difference in IGF-I generation capacity in response to recombinant human GH, regardless of BMD group.

The relationship between low serum IGF-I and reduced BMD demonstrated here is consistent with previous studies. GH secretion and reserve in low BMD subjects appear to be comparable with normal controls. There was a suggestion of GH insensitivity in low BMD subjects. The source of low serum IGF-I in male idiopathic osteoporosis could in part be attributable to resistance to endogenous GH.

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