Aluminum administration in the rat separately affects the osteoblast and bone mineralization.
Aluminum administration in the experimental animal results in osteomalacia as characterized by osteoid accumulation and decreased mineralization. Previous in vivo and in vitro studies have indicated that either aluminum directly inhibits mineralization or is toxic to the osteoblast. In the present study, PTH was continuously infused in rats with aluminum-induced osteomalacia to evaluate whether aluminum administration decreased mineralization without a concomitant decrease in osteoblasts. Four groups of rats were studied: chronic renal failure (CRF); CRF + aluminum (AL); CRF + PTH; and CRF + PTH + AL. Rats were sacrificed 5 and 12 days after aluminum or diluent administration; in the PTH groups, bovine PTH (1-34) was administered at 2 units/h via a subcutaneously implanted Alzet pump. Aluminum administration decreased osteoblast surface, increased osteoid accumulation, and produced a cessation of bone formation. The infusion of PTH alone increased osteoblast surface and bone formation. The simultaneous administration of aluminum and PTH resulted in an osteoblast surface intermediate between aluminum and PTH alone; however, despite a PTH-induced restoration of osteoblast surface, bone formation did not increase. These findings indicate (1) aluminum is toxic to osteoblasts and also directly inhibits mineralization even when osteoblasts are not decreased; (2) PTH is capable of increasing osteoblasts even in the presence of aluminum; and (3) despite a PTH-induced increase in osteoblast surface, mineralization of osteoid was not improved.
Rodriguez
M
M
Department of Medicine, Wadsworth VA Medical Center, Los Angeles, CA.
Felsenfeld
A J
AJ
Llach
F
F
D000535:Aluminum / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D009392:Nephrectomy; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects; D010018:Osteomalacia / Q000139:chemically induced / Q000517:prevention & control; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D010281:Parathyroid Hormone; D010758:Phosphorus; D003404:Creatinine; D000535:Aluminum; D002118:Calcium