Bone loss and the increasing incidence of osteoporosis is an accompaniment of aging. Women undergo two phases of bone loss—a slow phase with a linear decrease in bone, continuing into old age, and a superimposed, accelerated transient phase beginning at menopause caused by estrogen deficiency. The slow phase in the development of osteoporosis has been attributed to alteration of age-related factors resulting in impaired osteoblast function and bone formation. These include growth hormone (GH) and insulin-like growth factor 1 (IGF-1), both major determinants of adult bone mass, that decrease with advancing age and are lower in women with established osteoporosis.
The beneficial effects of GH on bone metabolism and BMD have been shown in, adult GH-deficient (AGHD) patients. Target organ insensitivity to the effects of PTH resulting in increased circulating PTH and abnormal PTH secretion contributes to the development of osteoporosis in AGHD. GH replacement (GHR) in AGHD patients has been shown to increase bone and renal PTH receptor or target cell sensitivity to the effects of PTH and simultaneously restore PTH secretory rhythm, increase bone turnover markers, 1,25-dihydroxy vitamin D [1,25(OH)2D] concentration, and Ca absorption/reabsorption, thus contributing to the positive effects of GH on bone.
Postmenopausal women with osteoporosis have high circulating PTH concentrations with abnormal PTH circadian rhythm and may consequently be insensitive to the effects of PTH, although this has not been shown conclusively. The decline in GH/IGF-1 with aging may contribute to these PTH related abnormalities through mechanisms similar to that observed in untreated AGHD. GH has been previously administered to healthy elderly women and women with postmenopausal osteoporosis and increases in bone turnover and BMD have been shown. However, the mechanisms by which GH exerts its beneficial effects on bone in established postmenopausal osteoporosis remain unexplained. We therefore studied the effects of 12 mo of GH administration on PTH secretory pattern, PTH sensitivity, and bone mineral metabolism in postmenopausal women with established osteoporosis.