Effects of growth hormone on bone and muscle.
The decade since the initial availability of recombinant growth hormone (GH) has seen an increase in our understanding of the effects of GH on muscle and bone. Adult GH deficiency (GHD) is associated with osteopenia, the severity of which is related to three factors: the timing, age of onset and severity of GHD. Epidemiological data suggest that this osteopenia is associated with an increased risk of fracture. The impact of GH replacement therapy on bone mineral density (BMD) appears to be related to a large number of interrelated factors, including the dose and duration of therapy, timing of onset of GHD, skeletal site, degree of osteopenia at baseline, and age and gender of the patient. Overall, the effect of GH replacement on BMD in the majority of patients is beneficial. As yet, however, no data are available that demonstrate a reduction in fracture rate following GH therapy. In comparison with normal individuals, GH-deficient individuals have reduced lean body mass and muscle strength, both of which increase within 12 months of GH therapy. Therefore, the effects of GH replacement on muscle and bone in GH-deficient individuals are significant and beneficial, although the longer-term effects of GH replacement in terms of reducing the number of fractures and prevention of frailty in old age are not yet established. The effects of GH on bone and muscle in GH-replete individuals have been studied less fully. While GH therapy modulates markers of bone resorption and formation, its effects in patients with idiopathic osteoporosis are disappointing, with oestrogen therapy or bisphosphonates proving to be more effective in post-menopausal women. To date, however, there have been no GH treatment trials of adequate duration (longer than 18 months), and it remains possible that longer-term trials may demonstrate more profound effects. The effects of GH therapy on muscle have been examined in normal elderly individuals. Generally, the doses used have been supraphysiological and associated with an unacceptable incidence of side-effects. GH therapy has resulted in an increase in lean body mass, but functional ability and strength have not improved in the majority of studies. Thus, clear-cut beneficial effects of GH on muscle and bone in GH-replete individuals have not been demonstrated. It seems unlikely that normal elderly individuals will benefit significantly from GH therapy, but frail individuals or those with musculoskeletal or neuromuscular pathology are potential candidates for study.