Only a small number of studies have evaluated the effects of GH administration on bone density in women with postmenopausal osteoporosis and elderly men. The sample sizes of these studies have typically been small and overall fail to demonstrate a positive effect of GH on bone density. Aloia et al. (49) performed a series of three studies evaluating the effectiveness of GH in the treatment of post-menopausal osteoporosis. The first of these included eight patients who received pituitary-derived human GH for up to 12 mo (49). Bone resorption increased as measured by urine hydroxyproline, and bone density of the radius decreased. A subsequent study compared 24 mo of combination treatment with GH and calcitonin to calcitonin alone in 25 post-menopausal women, and showed a deleterious effect of the addition of GH on radial bone density (50). The third study compared a regimen of alternating GH and calcitonin to calcitonin alone in 14 women over 24 mo, and showed no significant difference in bone density between the two groups (51).
Marcus and coworkers also investigated the effect of GH administration on bone turnover and bone mass in elderly subjects in two studies. In the first study, the effects of seven days of GH administration on bone turnover markers was examined in 12 women and six men over age 60, and both osteocalcin and hydroxyproline increased (52). In a subsequent placebo-controlled study, bone density did not change in the group receiving GH, but decreased significantly in the placebo group (53). Although these data suggest a possible protective effect of GH on bone density, the group was too small at the conclusion of the study, owing to a high dropout rate, to reach a meaningful conclusion. These data also highlight the potential high side effect profile of GH, particularly in high doses in an elderly population.
Rudman et al. (54) studied 21 elderly men with low levels of IGF-1, who, based on the investigator's previous work, were assumed to produce low levels of endogenous GH. This initial randomized trial demonstrated a small increase in lumbar bone density in the group treated with GH. However, when the study was expanded to include 45 subjects followed for up to 21 mo, a significant increase in bone density could no longer be demonstrated (55). Because serum levels of IGF-1 have not been subsequently shown to separate GH sufficient and GH deficient patients, it remains unclear whether elderly patients diagnosed as GH-deficient on the basis of low IGF-1 levels may benefit from GH replacement.
Although GH administration to post-menopausal women and elderly adults does exert an effect on bone turnover, studies have failed to show a definite effect on bone density. It does not appear that a sufficient number of studies with large patient populations have been performed to rule out a possible benefit of GH in age-related or post-menopausal osteoporosis. Studies of GH in combination with a potent antiresorptive agent such as alendronate might be a productive future direction for this area of research. Long term studies of GH administration in GH-sufficient subjects, however, would have to be carefully designed to ensure that consequences of GH excess are not encountered.
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