Bone loss induced by dietary magnesium reduction to 10% of the nutrient requirement in rats is associated with increased release of substance P and tumor necrosis factor-alpha.
Bone loss induced by dietary magnesium reduction to 10% of the nutrient requirement in rats is associated with increased release of substance P and tumor necrosis factor-alpha.
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DOI：
10.1093/jn/134.1.79
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
R. Rude;H. Gruber;H. Norton;Livia Y. Wei;A. Frausto;B. Mills
中科院分区：
文献类型：
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作者：
R. Rude;H. Gruber;H. Norton;Livia Y. Wei;A. Frausto;B. Mills
膳食镁摄入量与骨质疏松症有关。先前的研究表明，严重的镁缺乏[营养需求量（NR）的0.04%]导致啮齿动物模型的骨质疏松症。我们评估了更温和的饮食镁限制（10%的NR）对骨和矿物质代谢的影响，在6个月的实验期间，大鼠。分别于2、4、6个月检测血清镁、钙、甲状旁腺激素（PTH）、1，25-二羟维生素D、碱性磷酸酶、骨钙素和尿吡啶啉。收集股骨和胫骨进行矿物质含量测量、微计算机断层扫描、组织形态计量学和免疫细胞化学定位。到2个月时，严重的镁缺乏症已经发展为显著的低镁血症和骨镁含量下降高达51%。这些特征持续6个月的研究。在所有时间点，镁缺乏大鼠的血清钙略高于对照组，但有显著性差异。在2个月，血清甲状旁腺素镁缺乏大鼠升高，但显着下降，在6个月的对照组大鼠中，甲状旁腺素上升。血清1，25-二羟维生素D在4和6个月时显著低于对照组。血清碱性磷酸酶和骨钙素的显著下降表明成骨细胞活性降低。组织形态计量学显示骨体积和骨小梁厚度减少。这一点得到了微计算机断层扫描分析的证实，该分析还表明，镁缺乏大鼠的小梁体积、厚度和数量显著降低。与对照组相比，破骨细胞数量随时间增加，破骨细胞覆盖的骨表面和侵蚀表面也增加，提示骨吸收增加，但成骨细胞数量无差异。骨吸收的增加可能是由于TNF-α的增加，因为破骨细胞中TNF-α的免疫细胞化学定位在2个月时比对照组高199%，4个月时高75%，6个月时高194%。TNF-α的差异可能是由于P物质造成的，2个月时单核细胞中的P物质比对照组高250%，4个月时高266%。这些数据表明，镁摄入量为NR的10%的大鼠引起骨质流失，这可能是继发于P物质和TNF-α的释放增加。
Dietary Mg intake has been linked to osteoporosis. Previous studies have demonstrated that severe Mg deficiency [0.04% of nutrient requirement (NR)] results in osteoporosis in rodent models. We assessed the effects of more moderate dietary Mg restriction (10% of NR) on bone and mineral metabolism over a 6-mo experimental period in rats. At 2, 4 and 6 mo, serum Mg, Ca, parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D, alkaline phosphatase, osteocalcin and urine pyridinoline were measured. Femurs and tibiae were collected for measurement of mineral content, microcomputerized tomography, histomorphometry, and immunocytochemical localization. By 2 mo, profound Mg deficiency had developed as assessed by marked hypomagnesemia and up to a 51% reduction in bone Mg content. These features continued through 6 mo of study. Serum Ca was slightly but significantly higher in Mg-deficient rats than in controls at all time points. At 2 mo, serum PTH was elevated in Mg-deficient rats but was significantly decreased at 6 mo in contrast to control rats in which PTH rose. Serum 1,25-dihydroxy-vitamin D was significantly lower than in controls at 4 and 6 mo. A significant fall in both serum alkaline phosphatase and osteocalcin suggested decreased osteoblast activity. Histomorphometry demonstrated decreased bone volume and trabecular thickness. This was confirmed by microcomputerized tomography analysis, which also showed that trabecular volume, thickness and number were significantly lower in Mg-deficient rats. Increased bone resorption was suggested by an increase in osteoclast number over time compared with controls as well as surface of bone covered by osteoclasts and eroded surface, but there was no difference in osteoblast numbers. The increased bone resorption may be due to an increase in TNF-alpha because immunocytochemical localization of TNF-alpha in osteoclasts was 199% greater than in controls at 2 mo, 75% at 4 mo and 194% at 6 mo. The difference in TNF-alpha may be due to substance P, which was 250% greater than in controls in mononuclear cells at 2 mo and 266% at 4 mo. These data demonstrated that a Mg intake of 10% of NR in rats causes bone loss that may be secondary to the increased release of substance P and TNF-alpha.