Miroestrol (MR) is a highly active phytoestrogen isolated from tuberous root of Pueraria candollei
var. mirifica (PM). Modulatory effects of PM and MR on osteoprotegerin (OPG) and receptor
activator of nuclear factor kappa B ligand (RANKL) mRNAs which are bone-specific genes were
investigated in ovariectomized female ICR mice. After ovariectomy, expression of OPGmRNA was
suppressed but that of RANKL was induced. Estradiol benzoate (E2) recovered OPG expression to
the level comparable to the shamwhile that of RANKLwas suppressed in ovariectomizedmice. PM
crude extract (PME) significantly down-regulated the expression of RANKLmRNAwith no change
in the OPG level whereasMR elevated the expression of OPGmRNAwith lowering level of RANKL
mRNA, resulting in the increasedOPG/RANKL ratio, and consequently lead to lowering progression
of osteoporosis at molecular level. These findings revealed potential of PME and MR on bone loss
prevention via increasing the ratio of OPG to RANKL (osteoformation/osteoresorption) in liver of
ovariectomized mice. Therefore, using PME and MR as alternative hormone replacement therapy
of E2might be beneficial recommended due to advantageous on regulation of osteoporosis related
genes.