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Grant Abstract

Grant Number: 5P50AT000477-10

Abstract: DESCRIPTION (provided by applicant): Several types of botanical products containing isoflavones are being marketed as an alternative to estrogen replacement therapy to prevent osteoporosis in postmenopausal women. Estrogen suppresses bone resorption and may increase calcium absorption. Efficacy of isoflavones on bone health has mixed results, which may depend on the dose and interaction of isoflavones and the ability of individuals to produce equol. Specific Aim 1 is to determine the dose response of effect of genistein and the interaction with other soy isoflavones on calcium absorption and bone resorption in postmenopausal women who are equol vs. nonequolproducers. We will use 41Ca, a long-lived isotope, to label the skeleton and an Accelerator Mass Spectrometry (AMS) to monitor perturbations by diet. This innovative approach to study bone resorption is a direct measure of bone resorption in contrast to biochemical markers of bone turnover and traditional calcium kinetics, rapid compared to studying changes in bone density, and not invasive as is bone histomorphometry. We are able to systematically determine the effect of various types and dosages of isoflavone-containing botanical products sequentially in the same postmenopausal women for their effectiveness in suppressing bone resorption by measuring changes in 41Ca excretion in the urine. Preliminary evidence indicates that kudzu root, marketed as an estrogen replacement, reduces bone loss, which may relate to an unusual isoflavone, puerarin. Specific Aim 2 is to measure the dose response effect of genistein, kudzu, and equol on bone and bone quality in an ovariectomized rat model. Specific Aim 3 is to study metabolism of isoflavones in soybeans and kudzu. We have developed the ability to prepare C-14 and C-13 labeled plant tissue culture. By gavaging purified or crude fractions to rats with implanted microdialysis probes, we can follow the metabolic fate of bioactive compounds throughout the body. Minute quantities can be traced with AMS and microNMR.

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