The overall objective of this proposal is to test the hypothesis that calcium supplementation with calcium citrate would be more effective than calcium carbonate in preventing bone loss and the development of osteoporosis in postmenopausal women, because of its greater calcium bioavailability and alkali load, and its reduced risk for stone formation. This hypothesis will be tested by comparing the effects of long-term treatment (4 yrs) with the two calcium salts (1 and 2 g/day) in 192 postmsenopausal women without fractures (early post-menopause, late and elderly).
Aim I will assess pathophysiological consequences of calcium suplementation, in order to show that calcium treatment suppresses parathyroid function, inhibits bone resorption and produces a low turnovr state of bone. An assessment of bone mass in vivo will be obtained from single and dual photon absorptiometry and CT scan.
Aim 2 will seek to obtain histomorphometric confirmation from iliac crest biopsy in selected patients.
Aim 3 will pursue metabolic calcium balance in selected patients in order to show that improvement in calcium balance is correlated with hormonal-metabolic changes and with histomorphometric picture.
Aim 4 will assess potential complications of therapy. In particular, it will carefully perform urinary crystallization studies in order to show that calcium citrate therapy confers less stone-forming risk than calcium carbonate supplementation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR016061-18
Application #
3154870
Study Section
General Medicine B Study Section (GMB)
Project Start
1976-05-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
18
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Ruml, L A; Sakhaee, K; Peterson, R et al. (1999) The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study. Am J Ther 6:303-11
Mehta, S S; Oz, O K; Antich, P P (1998) Bone elasticity and ultrasound velocity are affected by subtle changes in the organic matrix. J Bone Miner Res 13:114-21
Zerwekh, J E; Padalino, P; Pak, C Y (1997) The effect of intermittent slow-release sodium fluoride and continuous calcium citrate therapy on calcitropic hormones, biochemical markers of bone metabolism, and blood chemistry in postmenopausal osteoporosis. Calcif Tissue Int 61:272-8
Zerwekh, J E; Antich, P P; Mehta, S et al. (1997) Reflection ultrasound velocities and histomorphometric and connectivity analyses: correlations and effect of slow-release sodium fluoride. J Bone Miner Res 12:2068-75
Wessels, M; Mason, R P; Antich, P P et al. (1997) Connectivity in human cancellous bone by three-dimensional magnetic resonance imaging. Med Phys 24:1409-20
Pak, C Y; Ho, A; Poindexter, J et al. (1996) Quantitation of incident spinal fractures: comparison of visual detection with quantitative morphometry. Bone 18:349-53
Pak, C Y; Adams-Huet, B; Sakhaee, K et al. (1996) Comparison of nonrandomized trials with slow-release sodium fluoride with a randomized placebo-controlled trial in postmenopausal osteoporosis. J Bone Miner Res 11:160-8
Pak, C Y; Sakhaee, K; Adams-Huet, B et al. (1995) Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial. Ann Intern Med 123:401-8
Reed, B Y; Zerwekh, J E; Sakhaee, K et al. (1995) Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res 10:1218-24
Rubin, C D; Reed, B; Sakhaee, K et al. (1994) Treating a patient with the Werner syndrome and osteoporosis using recombinant human insulin-like growth factor. Ann Intern Med 121:665-8

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