Although age-related bone loss is a universal problem, the bone loss that is associated with ovarian hormone deficiency at menopause is by far the commonest cause of osteoporosis and in 25% to 30% of aging women the bone loss results in major orthopedic problems. Beyond the consensus that postmenopausal osteoporosis is related to ovarian hormone deficiency, there is a lack of agreement on its pathogenesis. However, the different theories of postmenopausal bone loss that have been proposed share in common a linkage of an imbalance in the calcium regulating hormones to an imbalance in bone remodeling that favors bone resorption as a result of ovarian hormone deficiency. Therefore, a rational therapy for the disease is a regimen that promotes net bone formation and thereby reverses the remodeling defect caused by lack of ovarian hormones. It is the applications' longterm goal to advance our basic understanding of the pathogenesis of ovarian hormone deficiency bone loss, and contribute in enlarging the pool of therapeutic alternatives available for combating the disease. The hypothesis to be tested in this proposal is that age-related bone loss due to ovarian hormone deficiency can be reduced or prevented by stimulating net bone formation and intestinal calcium absorption. To test the hypothesis, we will determine the efficacy of the following treatment regimens in reducing or preventing ovarian hormone deficiency bone loss: 1) Parathyroid hormone; 2) Combination treatment with parathyroid hormone and calcitonin; 3) Combination treatment with parathyroid hormone and 1,25(OH)2 vitamin D; 4) Somatomedin C and 5) Determine the mechanism by which the treatment regimens of Specific Aims 1 to 4 act to reduce or prevent ovarian hormone deficiency bone loss. A newly characterized rat model of ovarian hormone deficiency will be used in these studies and the analyses to be carried out to fulfill the above objectives are grouped under the following headings: (i) Physical measurements of bone; (ii) Bone chemistry; (iii) Bone histomorphometry and bone cell dynamics; (iv) Intestinal calcium absorption; (v) Intestinal receptors for 1,25(OH)2 vitamin D; (vi) Renal function and kidney excretion of calcium, phosphorus and hydroxyproline; (vii) Serum calcium, phosphorus, alkaline phosphatase, total proteins, albumin and globulin, (viii) Serum calcium regulating hormones and sex hormones (parathyroid hormone, calcitonin, 25(OH) vitamin D, 1,25(OH)2 vitamin D, estradiol and progesterone).

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG007572-01
Application #
3118711
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1988-04-01
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Kalu, D N; Arjmandi, B H; Liu, C C et al. (1994) Effects of ovariectomy and estrogen on the serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3. Bone Miner 25:135-48
Arjmandi, B H; Salih, M A; Herbert, D C et al. (1993) Evidence for estrogen receptor-linked calcium transport in the intestine. Bone Miner 21:63-74
Kalu, D N; Salerno, E; Liu, C C et al. (1993) Ovariectomy-induced bone loss and the hematopoietic system. Bone Miner 23:145-61
Salih, M A; Liu, C C; Arjmandi, B H et al. (1993) Estrogen modulates the mRNA levels for cancellous bone protein of ovariectomized rats. Bone Miner 23:285-99
Kalu, D N; Salerno, E; Higami, Y et al. (1993) In vivo effects of transforming growth factor-beta 2 in ovariectomized rats. Bone Miner 22:209-20
Joffe, I; Katz, I; Jacobs, T et al. (1992) 17 beta-estradiol prevents osteopenia in the oophorectomized rat treated with cyclosporin-A. Endocrinology 130:1578-86
Liu, C C; Kalu, D N; Salerno, E et al. (1991) Preexisting bone loss associated with ovariectomy in rats is reversed by parathyroid hormone. J Bone Miner Res 6:1071-80
Kalu, D N (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175-91
Kalu, D N; Salerno, E; Liu, C C et al. (1991) A comparative study of the actions of tamoxifen, estrogen and progesterone in the ovariectomized rat. Bone Miner 15:109-23
Kalu, D N; Liu, C C; Salerno, E et al. (1991) Skeletal response of ovariectomized rats to low and high doses of 17 beta-estradiol. Bone Miner 14:175-87

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