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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR036066-07
Application #
3157468
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1985-08-01
Project End
1996-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Wright, N M; Papadea, N; Veldhuis, J D et al. (2002) Growth hormone secretion and bone mineral density in prepubertal black and white boys. Calcif Tissue Int 70:146-52
Bell, N H; Williamson, B T; Hollis, B W et al. (2001) Effects of race on diurnal patterns of renal conservation of calcium and bone resorption in premenopausal women. Osteoporos Int 12:43-8
Bell, N H; Morrison, N A; Nguyen, T V et al. (2001) ApaI polymorphisms of the vitamin D receptor predict bone density of the lumbar spine and not racial difference in bone density in young men. J Lab Clin Med 137:133-40
Awumey, E M; Mitra, D A; Hollis, B W et al. (1998) Vitamin D metabolism is altered in Asian Indians in the southern United States: a clinical research center study. J Clin Endocrinol Metab 83:169-73
Wright, N M; Papadea, N; Wentz, B et al. (1997) Increased serum 1,25-dihydroxyvitamin D after growth hormone administration is not parathyroid hormone-mediated. Calcif Tissue Int 61:101-3
Wright, N M; Papadea, N; Willi, S et al. (1996) Demonstration of a lack of racial difference in secretion of growth hormone despite a racial difference in bone mineral density in premenopausal women--a Clinical Research Center study. J Clin Endocrinol Metab 81:1023-6
Bell, N H; Gordon, L; Stevens, J et al. (1995) Demonstration that bone mineral density of the lumbar spine, trochanter, and femoral neck is higher in black than in white young men. Calcif Tissue Int 56:11-3
Wright, N M; Renault, J; Willi, S et al. (1995) Greater secretion of growth hormone in black than in white men: possible factor in greater bone mineral density--a clinical research center study. J Clin Endocrinol Metab 80:2291-7
Bell, N H (1995) 25-Hydroxyvitamin D3 reverses alteration of the vitamin D-endocrine system in blacks. Am J Med 99:597-9
Bell, N H; Hollis, B W; Shary, J R et al. (1994) Diclofenac sodium inhibits bone resorption in postmenopausal women. Am J Med 96:349-53

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