The candidate has completed one year of clinical training in nephrology and two years of research, during which she has demonstrated a clear determination to pursue a career in clinical investigation. She has been first author on 3 major publications, each concerning a different aspect of metabolic bone disease and involving separate patient populations. She has shown great interest in the problem of aluminum-related bone disease and in the more fundamental questions of bone formation. The proposed research will study a rat-model of aluminum-induced osteomalacia as well as human osteoporosis. The first project will aim to produced osteomalacia and low bone formation by daily intraperitoneal injections of aluminum. The ability of various agents (1,25(OH)2 vitamin D, desferrioxamine, 24,25(OH)2 vitamin D, and fluoride) to ameliorate or to treat the osteomalacia will be evaluated by examination of histologic bone sections, tetracycline labelling, bone chemical measurements, and serum chemical and hormone determinations. The influence of chronic renal failure will be studied by repeating the experiments in rats with partial nephrectomies. The relationship between aluminum and parathyroid hormone will be studied by giving aluminum to rats with low, normal, and high parathyroid hormone levels. The studies of human osteoporosis will involve bone histologic studies on biopsies from osteoportic patients enrolled in a trial of 1,25(OH)2 vitamin D. Tetracycline lables will be quantitated as an index of bone formation. The histologic data will be correlated to serum biochemical measurements, to bone mass measurements, to bone chemical determinations, and to clinical response to the drug. The environment at the University of Washington is well suited for these studies and for further training of the candidate. Dr. Sherrard is an established bone histomorphometrist with extensive experience in renal osteodystrophy. Dr. Chesnut has already conducted several major clinical trials in osteoporosis. This institution is unique in the country in its capacity to evaluate bone mass by biopsy, single and dual-beam photon densitometry, total body calcium by neutron activation, and computerized tomography. Dr. Brunell's laboratory performs chemical measurements of bone samples. Finally, Dr. Howard runs a bone research laboratory which utilizes methods of bone cell culture and tissue culture. Animal studies needing carefully controlled diets or surgery such as parathyroidectomy or nephrectomy have been done for years in this facility. All those investigators are enthusiastic about training the candidate.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Clinical Investigator Award (CIA) (K08)
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Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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University of Washington
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Ott, S M; Chesnut 3rd, C H (1989) Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 110:267-74