Effect of aluminium on the development of hyperparathyroidism and bone disease in the azotaemic rat.
Aluminium toxicity in dialysis patients is associated with a relative parathyroid hormone (PTH) deficiency as well as osteomalacia. In-vitro studies of parathyroid cells have shown that aluminium inhibits PTH secretion. However, only limited data are available on how aluminium affects the development of hyperparathyroidism in the azotaemic animal. Four groups of azotaemic rats were studied; in each group, renal failure was induced by a two-stage 5/6 nephrectomy, after which rats were studied for 40 days. In three groups hyperparathyroidism was stimulated by the use of a high phosphorus (1.2%) diet (HPD). The four groups were (1) HPD; (2) HPD + high-dose aluminium (HDAL)--1.5 mg of aluminium was administered intraperitoneally (IP) 5 days per week; (3) HPD + low-dose aluminium (LDAL)--0.5 mg of aluminium was administered IP 5 days per week; and (4) moderate phosphorus (0.6%) diet (MPD); the MPD group was used to control hyperparathyroidism and thus provide a comparison of PTH levels and azotaemic bone disease. After 40 days, the serum PTH level was higher (P < 0.05) in the HPD + HDAL group (37 +/- 2 pmol/l) than the HPD, HPD + LDAL, and MPD groups (24 +/- 3, 28 +/- 4, and 6 +/- 1 pmol/l respectively). The correlation between serum PTH and calcium, serum PTH and phosphorus, and serum calcium and phosphorus was significant for the four groups (P < 0.02); however, the relationship between serum PTH and calcium, and between serum calcium and phosphorus was altered in the HPD + HDAL group (serum aluminium 30.8 +/- 2 mumol/l). Aluminium administration induced a decrease (P < 0.05) in the bone formation rate and the adjusted apposition rate, and an increase (P < 0.05) in osteoid volume and the mineralization lag time. Despite aluminium administration, diet-induced hyperparathyroidism resulted in an increase (P < 0.05) in the osteoblast surface. In conclusion, in the azotaemic rat (1) aluminium did not slow the development nor decrease the magnitude of hyperparathyroidism; (2) aluminium appeared to alter the relationship between serum PTH and calcium, and between serum calcium and phosphorus; (3) hyperparathyroidism changed the expression of aluminium-induced bone disease and may afford the bone some protection against the toxic effects of aluminium.
Felsenfeld
A J
AJ
Department of Medicine, Wadsworth VA Medical Center, Los Angeles, CA 90073.
Machado
L
L
Bover
J
J
Trinidad
P
P
Rodriguez
M
M
D000535:Aluminum / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001847:Bone Diseases / Q000209:etiology*; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006961:Hyperparathyroidism / Q000209:etiology*; D008297:Male; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D016226:Phosphorus, Dietary / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000097:blood / Q000150:complications*
D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary; D010758:Phosphorus; D000535:Aluminum; D002118:Calcium