PHYTOESTROGENS REDUCE BONE LOSS AND BONE-RESORPTION IN OOPHORECTOMIZED RATS

To examine a potential role for phytoestrogens in postmenopausal bone loss, the oophorectomized (OOX) rat model has been used in three studi es to investigate the effects of the phytoestrogens coumestrol, zearal anol and a mixture of isoflavones on estrogen-dependent bone loss. In the studies of coumestrol and zearalanol, the rats were allocated to a control group, a phytoestrogen-treated group (1.5 mu mol coumestrol o r 3.1 mmol zearalanol twice per week, intramuscular) or, in the coumes trol study, an estrogen-treated group (28.1 nmol, intramuscular). In t he isoflavone study, the rats were allocated to a control group, an es trogen treated group or a treatment group that received 131.25 mg of p hytoestrogens per week incorporated into the nonpurified rat diet. Bon e mineral density was measured globally and at the spine and femur at base line and 6 wk post-oophorectomy. In the coumestrol study, blood a nd urine samples were collected. Compared with the control group, rats receiving coumestrol and zearalanol had significantly reduced bone lo ss at all sites measured. The estrogen-treated group had significantly greater bone density than the control and the coumestrol-treated grou ps in the spine and global measurements. Coumestrol reduced urine calc ium excretion and the bone resorption markers pyridinoline and deoxypy ridinoline after 1 wk of treatment. Oral isoflavone phytoestrogens had no effect on oophorectomized rats including bone loss at the dose use d. Thus, for the first time, the bioactivity of coumestrol and zearala nol in preventing bone loss has been demonstrated in a well-recognized model of postmenopausal bone loss.