Bone Metabolism During Chronic Growth Hormone Deficiency Experimental and Clinical Studies
Bone Metabolism During Chronic Growth Hormone Deficiency Experimental and Clinical Studies
European Endocrine Review 2006 - January 2006
Published: October 2008
Published: October 2008
Adult-onset growth hormone deficiency (AOGHD) is most often caused by pituitary or hypothalamic tumours or their treatment, and may serve as a model where the effect of chronic GH deficiency on skeletal metabolism can be studied. While the low bone mass in adults with childhoodonset GHD (CO-GHD) may be explained by deficient bone accretion during childhood, decreased bone mass in AO-GHD may be caused by imbalanced bone remodelling. These patients have secondary osteoporosis characterised by reduced bone mass, decreased bone turnover measured by biochemical markers and increased fracture risk. However, studies on the impact of GH substitution have yielded conflicting results, probably due to high doses and short treatment periods. Longer studies, with treatment periods of one year or more, have shown significant increases in bone mass and turnover.
GH plays a crucial role in the maintenance of bone mass in adults by regulating bone remodelling through a complex interaction of circulating GH, insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and locally produced IGFs and IGFBPs acting in an autocrine and paracrine way. The cellular basis for these interactions has been thoroughly studied, employing in vitro systems with isolated homogenous bone cell populations, and the molecular signalling pathways revealed. Furthermore, progress in genetic engineering has greatly increased the understanding of how GH controls somatic growth in vivo. The original somatomedin hypothesis originated in the 1950s in an effort to describe how somatic growth was regulated by the pituitary and that the effects of GH on target tissue were mediated by intermediate substances and not GH alone.1
At present, it appears clear that GH also may have direct effects on target tissues and that locally produced IGF-1 may mediate the effects of GH. The debate now largely concerns the importance of liver-derived IGF-1.2 This article focuses on recent work on the effect of GH/IGF on remodelling in patients with AO-GHD and experimental models characterised by decreased systemic levels of these proteins.
There are other papers that provide detailed reviews on GH and IGF signalling in vitro and the somatomedin hypothesis.3 The effects of GH and IGF-1/-2 on bone cells in vitro are briefly described in Figure 1.
