The effect of high parathyroid hormone levels on the development of aluminum-induced osteomalacia in the rat.
A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat.
Felsenfeld
A J
AJ
Department of Medicine, Wadsworth Veterans Administration, Los Angeles, CA 90073.
Machado
L
L
Rodriguez
M
M
D000535:Aluminum / Q000097:blood; D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis; D010018:Osteomalacia / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010281:Parathyroid Hormone; D000535:Aluminum