EFFECT OF ALUMINUM ON THE DEVELOPMENT OF HYPERPARATHYROIDISM AND BONE-DISEASE IN THE AZOTEMIC 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 s ecretion. However, only limited data are available on how aluminium af fects the development of hyperparathyroidism in the azotaemic animal. Four groups of azotaemic rats were studied; in each group, renal failu re was induced by a two-stage 5/6 nephrectomy, after which rats were s tudied for 40 days. In three groups hyperparathyroidism was stimulated by the use of a high phosphorus (1.2%) diet (HPD). The four groups we re (1) HPD; (2) HPD + high-dose aluminium (HDAL)-1.5 mg of aluminium w as administered intraperitoneally (IP) 5 days per week, (3) HPD+low-do se 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 wa s used to control hyperparathyroidism and thus provide a comparison of PTH levels and azotaemic bone disease. After 40 days, the serum PTH l evel 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 pmo l/l respectively). The correlation between serum PTH and calcium, seru m 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 administrat ion, diet-induced hyperparathyroidism resulted in an increase (P<0.05) in the osteoblast surface. In conclusion, in the azotaemic rat (1) al uminium did not slow the development nor decrease the magnitude of hyp erparathyroidism; (2) aluminium appeared to alter the relationship bet ween serum PTH and calcium, and between serum calcium and phosphorus, (3) hyperparathyroidism changed the expression of aluminium-induced bo ne disease and may afford the bone some protection against the toxic e ffects of aluminium.