HIGH FLUORIDE INTAKES CAUSE OSTEOMALACIA AND DIMINISHED BONE STRENGTHIN RATS WITH RENAL DEFICIENCY

Renal insufficiency is known to increase plasma fluoride levels, which may increase the risk of fluorosis and osteomalacia, The purpose of t his study was to determine the effects of fluoride on skeletal fragili ty and mineralization in renal-deficient animals, We evaluated the ske leton of rats with surgically induced renal deficiency (4/5 nephrectom y) that were chronically exposed to fluoridated water at concentration s of 0, 5, 15, and 50 ppm for a period of 6 months, The chosen fluorid e doses caused plasma fluoride levels equivalent to those in humans co nsuming fluoridated water levels of 0, 1, 3, and 10 ppm, respectively, Animals with renal deficiency drank about 60% more water and excreted 85% more urine than control animals, Glomerular filtration rate (GFR) was decreased 68% and plasma BUN was increased fourfold in rats with renal deficiency, Plasma fluoride was strongly correlated with 1/GFR a nd was greatly increased by renal deficiency in all animals consuming fluoridated water, There was a strong positive, nonlinear relationship between plasma fluoride and bone fluoride levels, suggesting nonlinea r binding characteristics of fluoride to bone, The amount of unmineral ized osteoid in the vertebral bone was related to the plasma fluoride levels, Vertebral osteoid volume was increased over 20-fold in animals with renal deficiency that received 15 or 50 ppm fluoride, suggesting osteomalacia, Should osteomalacia be defined as a tenfold increase in osteoid volume, there appeared to be a threshold plasma fluoride leve l of about 20 mu mol/L, above which osteomalacia was observed consiste ntly, This plasma fluoride level was not achieved in control rats rega rdless of fluoride intake, nor was it achieved in renal-deficient rats receiving 0 or 5 ppm fluoride, A fluoride concentration of 50 ppm red uced femoral bone strength by 11% in control rats and by 31% in renal- deficient rats, Vertebral strength also was decreased significantly in renal-deficient rats given 50 ppm fluoride, In conclusion, fluoridate d water in concentrations equivalent to 3 and 10 ppm in humans, caused osteomalacia and reduced bone strength in rats with surgically-induce d renal deficiency. (C) 1996 by Elsevier Science Inc.