The purpose of the investigations proposed in this competing renewal application is to determine the means by which increases in bone mass and decreases in rates of bone formation and turnover occur in blacks and contribute to or are responsible for the low incidence of osteoporosis and fractures in them, to investigate the effects of the menopause and aging on bone and mineral metabolism in blacks and to investigate the pathogenesis of senile or type II osteoporosis in blacks. The hypotheses to be investigated are a) that bone resorption rate is lower in blacks than in whites and results from altered osteoclast function caused by diminished production of bone-resorbing cytokines by peripheral monocytes and bone cells and is accompanied by diminished skeletal response to parathyroid hormone, b) that the greater bone mass in blacks results not only from a reduction in skeletal remodeling but from altered osteoblast function: differences in the amount of growth factors produced by osteoblasts or stored in bone, their binding proteins or some combination, c) that loss of estrogen production at the menopause in black women results in enhanced bone resorption that is caused by increased production of cytokines by peripheral monocytes and osteoblasts and is associated with increased bone resorption and bone loss and that these changes are reversed by Premarin, d) that aging blacks are unable to adapt to a low calcium diet because of an age-related decline in the renal production of 1,25- dihydroxyvitamin D and have increases in the rate of skeletal remodeling and, e) that impaired renal production of 1,25-dihydroxyvitamin D is important in the pathogenesis of senile osteoporosis in blacks. The results of these studies should provide new and useful information concerning the pathogenesis of osteoporosis in blacks and could lead to new methods that can be used for the diagnosis, treatment and prevention of the disease.
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