High fluoride intakes cause osteomalacia and diminished bone strength in rats with renal deficiency.
High fluoride intakes cause osteomalacia and diminished bone strength in rats with renal deficiency.
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DOI：
10.1016/s8756-3282(96)00278-5
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发表时间：
1996-12
期刊：
影响因子：
4.1
通讯作者：
C. Turner;I. Owan;E. Brizendine;W. Zhang;M. Wilson;A. Dunipace
中科院分区：
文献类型：
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作者：
C. Turner;I. Owan;E. Brizendine;W. Zhang;M. Wilson;A. Dunipace
已知肾功能不全会增加血浆氟化物水平，这可能会增加氟中毒和骨软化症的风险。本研究的目的是确定氟化物对肾缺陷动物骨骼脆性和矿化的影响。我们评估了手术引起的肾功能不全（4 5 肾切除术）大鼠的骨骼，这些大鼠长期暴露于浓度为 0、5、15 和 50 ppm 的氟化水中 6 个月。所选择的氟化物剂量导致的血浆氟化物水平分别相当于人类饮用0、1、3和10 ppm氟化水的水平。与对照组动物相比，肾功能不全的动物多喝了约 60% 的水，排出的尿液多了 85%。肾虚大鼠的肾小球滤过率 (GFR) 降低 68%，血浆 BUN 增加四倍。血浆氟化物与 1/GFR 密切相关，并且在所有饮用氟化水的动物中，由于肾功能不全，血浆氟化物大大增加。血浆氟化物和骨氟化物水平之间存在很强的正非线性关系，表明氟化物与骨的非线性结合特征。椎骨中未矿化的类骨质的量与血浆氟化物水平有关。在接受 15 或 50 ppm 氟化物的肾功能不全的动物中，椎骨类骨质体积增加了 20 倍以上，表明存在骨软化症。如果将骨软化症定义为骨样体积增加十倍，则似乎存在约 20 μmol/L 的血浆氟化物阈值水平，高于该阈值则一致观察到骨软化症。无论氟化物摄入量如何，对照大鼠均未达到该血浆氟化物水平，接受 0 或 5 ppm 氟化物的肾缺陷大鼠也未达到该血浆氟化物水平。氟化物浓度为 50 ppm 时，对照大鼠的股骨强度降低了 11%，肾缺陷大鼠的股骨强度降低了 31%。给予 50 ppm 氟化物的肾缺陷大鼠的椎骨强度也显着下降。总之，人体中浓度相当于 3 ppm 和 10 ppm 的氟化水会引起骨软化，并降低手术引起的肾缺陷大鼠的骨强度。
Renal insufficiency is known to increase plasma fluoride levels, which may increase the risk of fluorosis and osteomalacia. The purpose of this study was to determine the effects of fluoride on skeletal fragility and mineralization in renal-deficient animals. We evaluated the skeleton of rats with surgically induced renal deficiency (4 5 nephrectomy) that were chronically exposed to fluoridated water at concentrations of 0, 5, 15, and 50 ppm for a period of 6 months. The chosen fluoride doses caused plasma fluoride levels equivalent to those in humans consuming 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 and 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 nonlinear binding characteristics of fluoride to bone. The amount of unmineralized 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 level of about 20 μmol/L, above which osteomalacia was observed consistently. This plasma fluoride level was not achieved in control rats regardless of fluoride intake, nor was it achieved in renal-deficient rats receiving 0 or 5 ppm fluoride. A fluoride concentration of 50 ppm reduced 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, fluoridated water in concentrations equivalent to 3 and 10 ppm in humans, caused osteomalacia and reduced bone strength in rats with surgically-induced renal deficiency.