Osteomalacia is a process whereby the mineralization of bone is impaired. Aluminum has been implicated as a cause of this clinical disorder, but the mechanism by which aluminum induces a defect in the mineralization of bone has yet to be established. The osteomalacia associated with aluminum deposition in bone is a disease model of particular interest because defective mineralization of bone occurs despite normal concentrations of calcium and phosphorus in serum. It is the purpose of this proposal to study the formation and mineralization of bone in the presence and absence of aluminum using in vitro tissue culture techniques. The putative actions of aluminum as an inhibitor of the synthesis of new bone collagen and as a physical-chemical inhibitor of mineralization will be evaluated. The response of bone tissues to parathyroid hormone and to 1,25 dihydroxyvitamin D will also be studied to investigate the role of alterations in the response of bone to these hormones during exposure to aluminum as potential mechanisms to explain the skeletal toxicity of aluminum. The results of the proposed studies should further our understanding of the processs of bone matrix formation and calcification and how these are altered by exposure to aluminum. Such investigations are relevant to the clinical bone disease observed in patients with chronic renal failure who currently are exposed to aluminum as part of their therapeutic regimen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035470-02
Application #
3157199
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1986-02-01
Project End
1989-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kasai, K; Hori, M T; Goodman, W G (1991) Transferrin enhances the antiproliferative effect of aluminum on osteoblast-like cells. Am J Physiol 260:E537-43
Goodman, W G; O'Connor, J (1991) Aluminum alters calcium influx and efflux from bone in vitro. Kidney Int 39:602-7
Salusky, I B; Foley, J; Nelson, P et al. (1991) Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease. N Engl J Med 324:527-31
Goodman, W G; Salusky, I B (1991) Evolution of secondary hyperparathyroidism during oral calcitriol therapy in pediatric renal osteodystrophy. Contrib Nephrol 90:189-95
Goodman, W G; Duarte, M E (1991) Aluminum: effects on bone and role in the pathogenesis of renal osteodystrophy. Miner Electrolyte Metab 17:221-32
Coburn, J W; Mischel, M G; Goodman, W G et al. (1991) Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis 17:708-11
Salusky, I B; Coburn, J W; Nelson, P et al. (1990) Prospective evaluation of aluminum loading from formula in infants with uremia. J Pediatr 116:726-9
Kasai, K; Hori, M T; Goodman, W G (1990) Characterization of the transferrin receptor in UMR-106-01 osteoblast-like cells. Endocrinology 126:1742-9
Salusky, I B; Goodman, W G; Horst, R et al. (1990) Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients. Am J Kidney Dis 16:126-32
Oppenheim, W L; Namba, R; Goodman, W G et al. (1989) Aluminum toxicity complicating renal osteodystrophy. A case report. J Bone Joint Surg Am 71:446-52

Showing the most recent 10 out of 14 publications