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.
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