The evolution of osteomalacia in the rat with acute aluminum toxicity

Abstract

Aluminum toxicity is the presumed cause of aluminum-associated osteomalacia. In animal models, osteomalacia has been produced after a prolonged course of aluminum. In the present study, rats with renal failure received 20 mg intraperitoneal aluminum during a 2 day period. This model allows sequential observations in the development of osteomalacia. Rats were sacrificed and studied 5, 12, 25, and 40 days after aluminum administration. No differences were observed in serum calcium, phosphorus, or creatinine as a consequence of aluminum administration. Compared with control rats, parathyroid hormone was decreased at 12 and 25 days. A direct correlation was present between plasma and bone aluminum at 12 days (r = 0.92, p less than 0.01), 25 days (r = 0.85, p less than 0.005), and 40 days (r = 0.88, p less than 0.001) but not 5 days after aluminum administration. Plasma aluminum peaked at 5 days (727 +/- 89 micrograms/liter, mean +/- SEM) and bone aluminum at 40 days (273 +/- 40 micrograms/g). Aluminum had profound effect on bone histology. At 5 days there was a decrease in osteoblast surface and osteoid surface; at 12 days osteoblast surface and osteoid surface returned to normal but osteoclast surface decreased. Subsequently there was a progressive increase in osteoid surface and osteoid volume. Bone formation rate measured at 12, 25, and 40 days was decreased at these intervals. In conclusion, (1) high plasma aluminum may be directly toxic to the osteoblast; (2) progressive osteoid accumulation is secondary to matrix (osteoid) deposition, which exceeds the depressed bone formation rate; (3) the progressive decrease in plasma aluminum and increase in bone aluminum suggest that bone has a high affinity for aluminum but may have a relatively slow rate of uptake at any given time; (4) aluminum may directly decrease parathyroid hormone; (5) the correlation between plasma and bone aluminum suggest an exchange is present; and (6) aluminum toxicity may independently affect the osteoblast and bone mineralization.

A Magnesium Based Phosphate Binder Reduces Vascular Calcification without Affecting Bone in Chronic Renal Failure Rats

“…osteomalacia or adynamic bone, which in the past has been seen with aluminum [10]–[12]. These effects were due to a direct interference of aluminum with bone mineralization, a direct effect on the osteoblast and the parathyroid glands [13]–[16]. In the present study, bone histomorphometric analyses were performed in CRF animals treated with CaMg to address this question.…”

“…Daily treatment with 750 and 375 mg/kg/day CaMg in adenine-induced uremic rats effectively regulated serum phosphorus and PTH concentrations without inducing any adverse effects on serum calcium levels and significantly reduced the development of aortic calcification [4]. As was the case in the past with aluminum [5], [6] and lanthanum carbonate [7], [8], some concern exists about the potential direct effect of magnesium carbonate on bone remodeling as this alkaline earth metal is absorbed and could possibly interfere with bone mineralization/formation. Although serum magnesium levels were only slightly increased in hemodialysis patients after being treated with CaMg for 24 weeks [3], evaluation of the effect of CaMg therapy on bone is needed.…”