Endocrine Abstracts

The observation that acquired GnRH deficiency and estrogen deficiency leads
to decreased bone mass in young women was critical evidence that
hypothalamic/pituitary disorders could impact on bone metabolism in adults.
A three-fold risk of fractures in adults with growth hormone deficiency
(GHD) has led to the investigation of the role of the GH/IGF-I axis in bone
metabolism. Two human experimental models, acquired GHD and acquired GH
resistance due to severe weight loss have been used to understand the
physiology of the GH/IGF-I/bone axis. In GHD men, administration of GH for
18 mo increases bone mass. When GH is discontinued, bone density, in
contrast to lean body and fat mass does not return to pre-treatment baseline
but continues to increase. Therefore, differential responses to GH are
tissue and cell specific. Duration of therapy and physiological GH
administration are key considerations. IGF-I mediates many of the metabolic
actions of GH, although GH may have direct effects upon bone, independent of
IGF-I. In fasting and undernutrition, IGF-1 levels are low and GH levels are
high. This has led to the concept of acquired GH resistance in adults. In
patients with anorexia nervosa, rhIGF-I administered short-term stimulates
bone formation without affecting resorption. Spine BD is significantly
decreased in over 50 percent of such patients. To test the hypothesis that
resistance to GH effects on bone could be overcome by administration of
IGF-I, women with anorexia nervosa were treated for 9 mo with rhIGF-I (30
mcg/kg/BID) or placebo, with or without gonadal steroid replacement. Bone
density in IGF-I treated patients was significantly increased vs. controls.
The relative contributions of GH, circulating and locally produced IGF-I to
bone metabolism remain to be determined. In a reverse experimental paradigm,
patients with GH secreting tumors treated with a GH receptor antagonist to
decrease circulating IGF-I, showed decreased markers of bone formation
including PICP, and osteocalcin, consistent with IGF-I effects. Central and
autocrine/paracrine regulated GH and IGF-I are important stimulators of bone
formation via complex neuroendocrine/bone interactions.