Bondu Joseph Dian, Seshadri M S, Selvakumar R, Fleming Jude Joseph
1Department of Clinical Biochemistry, Christian Medical College, Vellore, Tamil Nadu 632004 India.
2Department of Endocrinology, Christian Medical College, Vellore, Tamil Nadu, India.
Indian J Clin Biochem. 2019 Jan;34(1):60-67. doi: 10.1007/s12291-017-0709-7. Epub 2017 Nov 13.
We investigated the combined effect of fluoride exposure and Vitamin D deficiency in causing bone damage as a precursor to development of Fluorotoxic Metabolic Bone Disease. Thirty-six male Sprague-Dawley rats were divided into 6 groups of six; 3 groups received a Vitamin D deficient diet whereas the other 3 received a Vitamin D adequate diet. Serum total 25-hydroxyvitamin D (25OHD), calcium, phosphorus, creatinine, Alkaline phosphatase (ALP), albumin, Parathyroid hormone (PTH), Osteocalcin and C terminal telopeptide (CTx) were measured following exposure to varying levels of fluoride in drinking water (< 1.0, 15 and 50 ppm). Full body Dual-energy X-ray Absorptiometry (DXA) scans were used to examine changes in bone morphology pre and post exposure to fluoride. Renal tubular function was assessed using serum creatinine and urine Cystatin C. Histopathological examination of sections of bone and kidney tissues were also performed. Prior to fluoride exposure, DXA scans revealed a significant decrease in Bone Mineral Density (BMD) and Bone Mineral content (BMC) ( < 0.05) but a significant increase in fat mass ( < 0.05) and fat percentage ( < 0.01) among Vitamin D deficient rats, with no significant change in biochemical parameters. Following exposure to fluoride, BMD was significantly increased ( < 0.05) in both groups with a corresponding increase in serum ALP, bone fluoride content, Osteocalcin, CTx and urine fluoride with increasing levels of fluoride exposure. Serum creatinine calcium and phosphate and urinary cystatin C levels showed no significant changes. Light microscopy examination revealed mild thickening and increased osteoid in 80% of the Vitamin D deficient rats exposed to high levels of fluoride but renal tubular changes were found only in one experimental and one control animal. Fluoride deposited in rat bone affects both osteoblastic and osteoclastic activity. Also, these effects are accentuated in the presence of Vitamin D deficiency.
我们研究了氟暴露与维生素D缺乏共同作用导致骨损伤作为氟中毒性代谢性骨病发展先兆的情况。将36只雄性斯普拉格-道利大鼠分为6组，每组6只；3组给予维生素D缺乏饮食，另外3组给予维生素D充足饮食。在饮用不同水平氟化物（<1.0、15和50 ppm）后，测定血清总25-羟基维生素D（25OHD）、钙、磷、肌酐、碱性磷酸酶（ALP）、白蛋白、甲状旁腺激素（PTH）、骨钙素和C端肽（CTx）。使用全身双能X线吸收法（DXA）扫描检查氟暴露前后的骨形态变化。使用血清肌酐和尿胱抑素C评估肾小管功能。还对骨组织和肾组织切片进行了组织病理学检查。在氟暴露前，DXA扫描显示维生素D缺乏大鼠的骨矿物质密度（BMD）和骨矿物质含量（BMC）显著降低（<0.05），但脂肪量（<0.05）和脂肪百分比（<0.01）显著增加，生化参数无显著变化。氟暴露后，两组的BMD均显著增加（<0.05），血清ALP、骨氟含量、骨钙素、CTx和尿氟随氟暴露水平增加而相应增加。血清肌酐、钙、磷和尿胱抑素C水平无显著变化。光学显微镜检查显示，80%暴露于高剂量氟的维生素D缺乏大鼠出现轻度增厚和类骨质增加，但仅在一只实验动物和一只对照动物中发现肾小管变化。沉积在大鼠骨骼中的氟会影响成骨细胞和破骨细胞的活性。此外，在维生素D缺乏的情况下，这些影响会更加明显。
