MAGNESIUM DEFICIENCY INDUCED OSTEOPOROSIS

这项建议的目的是增加我们对镁(Mg)耗竭在骨质疏松症病因中的作用的了解。膳食镁摄入量与衰老和绝经后骨质疏松症的骨量和/或骨丢失有关。镁缺乏会导致大鼠骨骼生长减少，骨质减少，骨骼脆性增加。在缺镁大鼠中观察到骨形成减少和骨吸收增加。我们假设镁缺乏会导致骨质疏松症的发生。镁缺乏对骨骼的不利影响的机制(S)尚不清楚，但可能涉及全身激素或局部调节骨细胞活动的因素。人体镁缺乏会导致低钙血症、血清1，25(OH)2-维生素D水平降低、甲状旁腺激素(PTH)分泌受损以及肾脏和骨骼对PTH的抵抗。在动物模型中镁的消耗也显示出类似的结果。然而，与其他物种不同的是，缺镁大鼠患的是高钙血症，而不是低钙血症。因此，无法对缺镁大鼠的骨骼和矿物质代谢变化进行外推。需要一种不同的镁缺乏引起的骨质疏松症模型。我们建议建立一种缺镁致衰老雌性小鼠骨质疏松的模型。我们将造成3周和6周的膳食镁缺乏，并评估血清镁、钙和甲状旁腺素的变化。将评估骨组织形态计量学和骨镁、钙、磷含量。细胞因子与骨质疏松症的发生有关，镁缺乏的大鼠的血清水平也很高。因此，我们将测定血清I1-1β和TNFpha水平，并对骨组织进行I1-1β、I1-6的免疫组织化学染色。和肿瘤坏死因子α。这些研究应该证实我们的假设，即镁缺乏会导致骨质疏松症，并探索可能的机制。如果得到证实，将建议进行未来的实验，以进一步确定确切的机制。这一结果可能对预防骨质疏松症有重要意义。

The objective of this proposal is to increase our understanding of the role of magnesium (Mg) depletion in the etiology of osteoporosis. Dietary Mg intake has been associated with bone mass and/or bone loss in aging and postmenopausal osteoporosis. Mg depletion in the rat results in decreased bone growth, osteopenia and increased skeletal fragility. Decreased bone formation and increased bone resorption has been observed in the Mg depleted rat. We hypothesize that Mg depletion results in the development of osteoporosis. Mechanism(s) for the adverse effect of Mg deficiency on the skeleton is unclear but may involve systemic hormones or local factors regulating bone cell activity. Mg depletion in humans results in hypocalcemia, low serum 1,25(OH)2-vitamin D levels and impaired parathyroid hormone (PTH) secretion as well as renal and skeletal resistance to PTH. Mg depletion in animal models shows similar findings. The Mg deficient rat however, unlike other species, develops hypercalcemia rather than hypocalcemia. Extrapolation of alterations in bone and mineral metabolism in the Mg deficient rat cannot therefore be made to humans. A different model of Mg deficiency-induced osteoporosis is needed. We propose to develop a model of Mg deficiency-induced osteoporosis in the aging female mouse. We will induce dietary Mg deficiency for 3 and 6 weeks and assess changes in serum Mg, calcium and PTH. Bone histomorphometry and bone Mg, calcium and phosphorous content will be evaluated. Cytokines are implicated in the development of osteoporosis and serum levels are known to be high in the Mg deficient rat. We will therefore measure serum levels of I1- 1beta and TNFalpha and perform immunohistochemical staining of bone for I1-1beta, I1-6. And TNFalpha. These studies should substantiate our hypothesis that Mg depletion contributes to osteoporosis and explore possible mechanisms. If substantiated, future experiments will be proposed to further define exact mechanisms. The results may have important implications on the prevention of osteoporosis.