A longitudinal study of the effect of genistein on bone mass and bone architecture in an innovative perimenopausal mouse model
In this experiment the effect of genistein (GEN), a soy-derived isoflavone, was assessed in a novel murine model treated with the ovotoxic chemical vinyl-chlorohexene diepoxide (VCD) to gradually induce a menopausal state in which bone changes were monitored. This ovary-intact model more accurately represents the hormonal transition to menopause experienced by human females, as opposed to an ovariectomized (OVX) animal model which only simulates surgical menopause, a medical procedure responsible for <13% of menopause in women. VCD-treated mice and OVX mice were fed a casein-based diet, either with or without the addition of genistein (0.4g GEN/kg diet), and plasma concentrations reached levels documented in humans habitually consuming a soy diet. Significant positive treatment effects were observed in OVX mice fed GEN versus OVX controls in the proximal tibia (i.e., total and subcortical bone mineral density and bone area increased) based on longitudinal in vivo peripheral computed tomography. High resolution micro-computed tomography of excised bones revealed that trabeculae of the fifth vertebral body and cortical bone in the midshaft of the femur were significantly thicker in OVX mice fed GEN versus OVX mice on a phytoestrogen-free diet. The difference in cortical thickness attributed to GEN in ovariectomized mice translated to an increase in the peak load withstood by the femur during three-point mechanical testing. In the transition to menopause, VCD-treated mice in this experiment did not lose an amount of bone that was statistically significantly different from the sham controls, making the assessment of GEN effects under these circumstances impossible. VCD-treated mice exhibited a trend towards higher concentrations of circulating androgens which may have substantially contributed to the attenuation of bone loss, rendering the role of GEN non apparent. The magnitude of bone loss due to VCD-treatment in skeletally mature mice was not known prior to this experiment, however, with the data generated from this study it should be possible to plan a more focused investigation of this animal model in the future. Prospective power calculations suggest streamlining the experiment so there are less groups, and focusing in on the vertebral trabeculae region in VCD-treated mice, would be most advantageous. ^
Connie M. Weaver, Purdue University.
Health Sciences, Nutrition
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