The overall objective of this proposal is to develop a safe and effective restoration of lost bone in postmenopausal osteoporosis, entailing intermittent treatment with slow release sodium fluoride (SR-NaF) and continuous calcium citrate (CaCit) supplementation, which avoids toxicity and problems of conventional fluoride therapy. The primary hypothesis to be tested is that intermittent application of SR-NAF with continuous Cacit supplementation provides safety of usage, maintains serum fluoride within the """"""""therapeutic window"""""""" during prolonged therapy, augments spinal bone mass persistently, and inhibits spinal fractures without exaggerating hip fractures. Validation of these predictions, suggested largely from a non- randomized trial, will be sought from a placebo-controlled randomized trial (SR-NAF 25 mg bid + CaCit 400 mg Ca bid vs. placebo + CaCit 400 mg Ca bid). 200 women with postmenopausal osteoporosis (100 in each group) will be followed for 4 years. The response to treatment will be quantitated by bone densitometry (whole body, ulnar head and shaft, proximal femur, L2-L4 whole spine and body), skeletal x-rays (read on electrostatic digitizing pad for fractures), and by in vivo reflection ultrasound analysis of ulnar head. The reflection ultrasound analysis is a new technique developed at Dallas to assess quantitatively and non- invasively the mechanical property of bone. The choice of ulnar head is justified by a strong correlation between bone density of L2-L4 and distal ulna, a fall in reflection ultrasound velocity at ulnar head with aging, and a lower velocity in osteoporotic individuals with spinal fractures than in osteopenic individual without fractures. The in Vivo ultrasound analysis is critical to confirm the finding in from the examination of iliac crest biopsy specimens that SR-NaF plus CaCit increases reflection ultrasound velocity and the material strength of bone.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR016061-22
Application #
3154873
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1976-05-01
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
22
Fiscal Year
1993
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

Showing the most recent 10 out of 46 publications