Growth Hormone and Insulin-like Growth Factor-I Treatment for Metabolic Bone Diseases

Abstract

The growth hormone (GH) and insulin-like growth factor-I (IGF-I) regulatory system, which includes endocrine/paracrine/autocrine effects of IGF-I, is involved in determining bone size, length, density, and architecture of the mature mammalian skeleton. This chapter reviews the evidence for and against the use of these peptides in bone diseases such as osteoporosis. The regulation of growth hormone secretion from the pituitary is complex and involves the elaboration of discrete neurosecretory peptides from the hypothalamus. Somatostatin (SMS), a small but ubiquitous polypeptide, inhibits GH synthesis and secretion, thereby tightly controlling GH production. GH secretion is pulsatile due to episodic release of GHRH, and circadian, with the highest pulse amplitude occurring between 02:00 and 06:00. Growth hormone has direct and indirect effects on bone, depending on age and skeletal maturity. Substantial differences between the direct and indirect effects of GH on the osteoblast partially explain changes in skeletal responsiveness to GH and IGF-I. Intermittent (daily or three times weekly) injections of rhGH results in a prolonged and sustained GH profile with resultant catch-up growth evident during the first year of treatment. The skeletal response to GH depends on several factors including GH secretory status, pretreatment IGF-I levels, pretreatment height velocity, and GH dosage. The treatment of adult GHD is a relatively new option for patients with low BMD. Short-term treatment with rhGH leads to a decrease in adiposity and an increase in lean body mass in adults. The majority of adult patients treated with rhGH have either idiopathic GHD or a history of previous central nervous system (CNS)/pituitary-hypothalamic tumors. Early trials with rhGH replacement therapy examined changes in muscle mass, muscle strength, and body fat. Daily administration of subcutaneous rhGH to GHD patients produced a marked rise in serum IGF-I and an increase in muscle mass and basal metabolic rate.