The positive effects of GH on osteoblast proliferation and bone formation clearly manifest in humans. This has been illustrated by several studies of patients with GHD in whom the absence of GH is associated with diminished bone-density. A relative bone density deficit has been reported in children with GHD before the start of GH replacement therapy (17). However, these data are difficult to interpret because of the confounding variable of delayed skeletal maturation in such children.
Studies of adult patients with a history of childhood-onset GHD also demonstrate relative osteopenia compared to age-matched controls. Degerblad et al. (18) studied six young adults who had previously received GH replacement for GHD. Bone density of the proximal and distal forearm, primarily reflecting cortical and trabecular bone, respectively, was markedly diminished compared with healthy controls. A larger study of 30 GH-deficient men, 18-46 yr, reached a similar conclusion. Despite a history of GH replacement, bone density in the proximal forearm, distal forearm, and lumbar spine of these patients was significantly lower than normal (19). To determine whether pituitary deficiencies other than GH were responsible for the lower bone density seen in the patients, the eight patients with isolated GH deficiency were analyzed separately. In this subgroup, bone density at all sites remained below that of the normal controls, although because of the small sample size, this difference remained significant only at the distal forearm. These data indicate that the osteopenia seen in patients with childhood-onset GH deficiency is at least partly attributable to GHD.
It is uncertain why such patients have low bone density despite GH replacement during childhood. It is possible that GH treatment was initiated too late or at too low a dose to achieve normal peak bone mass. Furthermore, GH replacement is typically discontinued when growth slows or ceases. It is likely that GH plays a role in the continued accretion of bone mass seen in normal adolescents and young adults after linear growth is complete. Finally, withdrawal of GH therapy may lead to an ongoing loss of bone after peak bone mass has been achieved.
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