Phytoestrogens Reduce Bone Loss and Bone Resorption in Oophorectomized Rats

Abstract

To examine a potential role for phytoestrogens in postmenopausal bone loss, the oophorectomized (OOX) rat model has been used in three studies to investigate the effects of the phytoestrogens coumestrol, zearalanol 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 micromol coumestrol or 3.1 mmol zearalanol twice per week, intramuscular) or, in the coumestrol study, an estrogen-treated group (28.1 nmol, intramuscular). In the isoflavone study, the rats were allocated to a control group, an estrogen treated group or a treatment group that received 131.25 mg of phytoestrogens per week incorporated into the nonpurified rat diet. Bone mineral density was measured globally and at the spine and femur at base line and 6 wk post-oophorectomy. In the coumestrol study, blood and urine samples were collected. Compared with the control group, rats receiving coumestrol and zearalanol had significantly reduced bone loss at all sites measured. The estrogen-treated group had significantly greater bone density than the control and the coumestrol-treated groups in the spine and global measurements. Coumestrol reduced urine calcium excretion and the bone resorption markers pyridinoline and deoxypyridinoline after 1 wk of treatment. Oral isoflavone phytoestrogens had no effect on oophorectomized rats including bone loss at the dose used. Thus, for the first time, the bioactivity of coumestrol and zearalanol in preventing bone loss has been demonstrated in a well-recognized model of postmenopausal bone loss.

Cross-species and interassay comparisons of phytoestrogen action.

“…Much higher oral doses (50-400 mg/kg/day) of IPR have been required to prevent bone loss in ovariectomized rats (138), doses that also produce plasma concentrations similar to the effective in vitro concentrations (139,140). COM also inhibits bone resorption in vitro (141) and is a more potent agent, preventing bone loss at oral doses of 1-2 mg/kg/day (142,143). Results with GEN, on the other hand, have been inconsistent.…”

Effect of some phytoestrogens on metabolism of rat adipocytes

“…Phytoestrogens were also found to participate in other events, e.g. cancer development [12], prevention of osteoporosis [2,3], corticosteroid synthesis disturbances, reduction of cardiovascular diseases [2], and the protection of LDL against oxidative modifications [11,14] [1]. One of the effects is the reduction of the inhibitory action of insulin on lipolysis [1].…”

The Phytoestrogen α-Zearalenol Reverses Endothelial Dysfunction Induced by Oophorectomy in Rats

“…This is supported by the observation that certain phytoestrogens, such as genistein, coumestrol, or zearalenol, are able to bind to the estrogen receptors and modulate a variety of estrogendependent processes (Stahl et al, 1998). Furthermore it has been suggested that ␣-zearalenol shows interesting bioactivity in preventing bone loss in a wellrecognized model of postmenopausal osteoporosis in the rat (Draper et al, 1997).…”

“…The treatment lasted 4 weeks. The doses of 17␤-estradiol and ␣-zearalenol were selected according to previous studies of the effects of both compounds in OVX rats (Draper et al, 1997;Squadrito et al, 1996). It has been suggested that the estrogenic potency of ␣-zearalenol relative to 17␤-estradiol is 50 times less (Everett et al, 1987).…”

“…Zearalenone is metabolized in the presence of NADPH and UDPglucuronosyltransferase into ␣-zearalenol and ␤-zearalenol (Jimenez and Mateo, 1997). Because ␣-zearalenol showed a greater ability to bind to estrogen receptors than both zearalenone and ␤-zearalenol (Fitzpatrick et al, 1989), the ␣-isomer has been tested successfully in a model of postmenopausal bone loss (Draper et al, 1997). In this model the phytoestrogen was able to reduce bone loss and resorption, likely by acting as an estrogen agonist.…”