Abstract
Aluminum (Al) accumulation in renal failure is an etiological factor in the pathogenesis of low turnover bone disease. Aluminum-induced impairment of mineralization has been related to a reduced extent of active bone-forming surface. The present study investigated the effect of fluoride, a potent stimulator of osteoblast number, on the toxicity of aluminum in rats with renal failure (Nx). ...
Abstract
Aluminum (Al) accumulation in renal failure is an etiological factor in the pathogenesis of low turnover bone disease. Aluminum-induced impairment of mineralization has been related to a reduced extent of active bone-forming surface. The present study investigated the effect of fluoride, a potent stimulator of osteoblast number, on the toxicity of aluminum in rats with renal failure (Nx). Following a large parenteral aluminum load (3.2 mg/kg x day) over a period of nine weeks, bone histomorphometry of vertebral cancellous bone revealed a severe low-turnover osteodystrophy as evidenced by a fall in osteoblastic osteoid surfaces and mineral apposition rates. Concurrent administration of fluoride [20 mg/liter (F20) or 40 mg/liter (F40) supplied with the drinking water] resulted in a significant increase in the number of osteoblasts (Nx+Al+F40 vs. Nx+Al, 33.75 +/- 2.83 vs. 1.81 +/- 0.43 mm-1, P less than 0.001) together with an overall reduced deposition of aluminum in bone (469.3 +/- 24.6 vs. 592.2 +/- 28.3 micrograms/g, P less than 0.01). However, there was an increase in the fraction of osteoid surface exhibiting stainable aluminum at the bone-osteoid interface (70.7 +/- 7.1 vs. 44.3 +/- 6.0%, P less than 0.005). Fluoride-exposed rats accumulated a significantly larger osteoid volume, suggesting an exacerbation of the osteomalacic lesion, and furthermore, dynamic histomorphometric parameters remained depressed. These results indicate that fluoride has a distinct effect on the pattern of aluminum deposition in bone. In addition, fluoride antagonizes the aluminum-induced reduction in osteoblast number but provides no amelioration of the impaired mineralization in aluminum-intoxicated rats. Thus, in this model a decrease in the extent of osteoblast surface does not account for the development of aluminum-related bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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