Free Iron, Estrogen and Postmenopausal Osteoporosis

本研究的目的是验证雌激素的损失导致骨中游离铁水平失控的假设，游离铁是自由基形成的强大催化剂，从而引起氧化损伤。 这会导致绝经后妇女骨质疏松症的发展，以及卵巢切除（ovx）的成年雌性大鼠骨质减少的发展。为此，将使用OVX大鼠模型。 将对6个月大的大鼠进行卵巢切除术，然后进行两个月的骨质减少期。 然后他们将接受三个月的治疗（1）雌激素，（2）铁螯合剂或（3）雌激素和铁螯合剂的组合。 在给药期结束时处死动物，并分别通过电子顺磁（EPR）和X射线吸收测定法（pDEXA和pOct）测定其游离铁和矿物质水平。使用的铁螯合剂将是我们实验室开发的，并已被证明具有有效去除骨中重金属的能力。 我们将使用的EPR技术也是在我们的实验室开发的。 我们相信，这个小而重要的项目将提供新的见解的机制，其中损失的雌激素导致骨质疏松症的发展。此外，这种新方法将允许重新评估雌激素的作用，并将加速开发用于预防或治疗骨质疏松症的新型药剂。

The goal of this study is to test the hypothesis that loss of estrogen results in loss of control of the levels of free iron in bone which are powerful catalysts for free radical formation, and thus cause oxidative damage. This results in the development of osteoporosis in man postmenopausal women as well as the development of osteopenia in ovariectomized (ovx) adult female rats. To do this, an ovx rat model will be used. Six month old rats will be ovariectomized, followed by a two month period for osteopenia to develop. They will then be treated for three months with (1) estrogen, (2) iron chelator or (3) a combination of estrogen and iron chelator. The animals will be sacrificed at the end of the treatment period and their free iron and mineral levels will be determined by electron paramagnetic (EPR) and x-ray absorptiometry (pDEXA and pOct) respectively. The iron chelator used will be one which has been developed in our laboratory and has been shown to have the ability to efficiently remove heavy metals from bone. The EPR techniques which we will use were also developed in our laboratory. We believe that this small but important project will provide novel insights into the mechanism by which loss of estrogens results in the development of osteoporosis. Moreover, this new approach will permit the reevaluation of the role of estrogen and will expedite the development of novel pharmaceutical agents for the prevention or treatment of osteoporosis.