Effect of fluoride on aluminum-induced bone disease in rats with renal failure.
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)
Ittel
T H
TH
Department of Internal Medicine II, R.W.T.H., Aachen, Germany.
Gruber
E
E
Heinrichs
A
A
Handt
S
S
Hofstädter
F
F
Sieberth
H G
HG
D000535:Aluminum / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001847:Bone Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D005459:Fluorides / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D008903:Minerals / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010018:Osteomalacia / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D008903:Minerals; D000535:Aluminum; D005459:Fluorides