Although the effect of GH on linear growth in GH-deficient children has long been known, more recent technical advances in measurement of bone turnover markers and bone densitometry have allowed the investigation of osteoblast activity and bone density in this population. A number of studies have shown that in vitro observations, demonstrating positive GH effects on osteoblasts, can be applied to GH-deficient children receiving GH replacement. A study of GH-deficient patients, ages 11-19, who received increasing doses of GH in 2-wk blocks, showed increases in serum levels of osteocalcin (28) and the carboxyterminal propeptide of Type 1 procollagen (29). These findings are indicative of increased osteoblast activity and increased synthesis of collagen in bone occurring in a dose-dependent manner in response to GH treatment.
Subsequent studies have evaluated both bone formation markers and bone density. Twenty-two GH-deficient children were studied while receiving GH either three or six times per week for six months (30). Under both treatment protocols, significant increases in serum osteocalcin were seen. Only with more frequent dosing, however, did bone density increase at the ultradistal radius, a region consisting principally of trabecular bone. In a similar study, 26 GH-deficient patients were studied during 12 mo of GH administration. These patients showed significant increases in the carboxyterminal propeptide of Type 1 procollagen and in bone density at the distal third of the radius, a measure of cortical bone density (31). The increase in bone density was significant whether normalized for chronologic age, statural age, or bone age.
Although the primary purpose of GH treatment of GH-deficient children is to stimulate linear growth, GH administration also increases bone density in this population. When taken together with the finding that adults with a history of childhood-onset GH deficiency are osteoporotic, these data suggest that GH plays an important physiologic role in the attainment of peak bone mass.
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