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.
