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SECOND INTERNATIONAL SYMPOSIUM
ON THE ROLE OF SOY
IN PREVENTING AND TREATING CHRONIC DISEASESeptember 15-18, 1996
Brussells, Belgium
SCIENTIFIC PROGRAM
(Oral Abstracts)Soy and Bone Health
Systematic Administration of Genistein Partially Prevents Bone Loss in Ovariectomized Rats in a Non-Estrogen-Like Mechanism
Fanti, O., M.C. Faugere, Z. Gang, J. Schmidt, D. Cohen, H.H. Malluche, Department of Internal Medicine, University of Kentucky and VA Medical Centers, Lexington, KY, USA.Recent epidemiological studies have suggested that the incidence of postmenopausal osteoporosis is lower in Asia than in the Western world. One of the possible explanations of this difference hinges on the large intake of phytoestrogen-rich soybean products by Asian women. To test the hypothesis that phytoestrogens prevent the bone loss associated with cessation of ovarian function, we studied 2-month-old female rats subjected to ovariectomy (OVX) or sham operation (SHAM), fed a casein-based diet and injected daily with subcutaneous (s.c.) vehicle or genistein, i.e., the most abundant and best characterized soybean phytoestrogen. All rats were sacrificed 21 days after surgery.
The first experiment utilized bone mineral density (BMD) of the whole tibias, primarily an index of the mineral content of compact bone, to establish the dose of genistein that is effective at preventing post-OVX bone loss. Thirty rats were divided in 5 groups of 6 animals each: SHAM and vehicle (SHAM-VE), OVX and vehicle (OVX-VE), or OVX and genistein at the following doses: 1 g/g b.w. (OVX-G-1), 5 g/g b.w. (OVX-G-5), or 25 g/g b.w. (OVX-G-25). BMD was lower in the OVX-VE than in the SHAM-VE rats and treatment with both 5 and 25 g genestein reduced the OVX-associated loss of BMD.
SHAM-VE OVX-VE OVX-G-1 OVX-G-5 OVG-G-25
BMD (mg/cm2) 196+/-3a 187+/-2b 186+/-4b 192+/-3b 191+/-2c
UTERUS (mg) 478+/-75a 149+/-25b 108+/-7b 157+/-17b 221+/-9c
Different letters indicate statistical difference.
The 1 mg/g dose did not protect from loss of BMD. Compared to the SHAM-VE, the uterus size was equally reduced in the OVX-VE, OVX-G-1 and OVX-G-5 rats, while it was 22% larger in the OVX-G-25 than in the OVX-VE. Urinary excretion of genestein measured by HPLC was approximately 100 mg/day in the OVX-G-5 rats, i.e., 10% of the injected dose, but it was undetectable in the OVX-VE rats.A second experiment utilized trabecular bone histomorphometry of the distal femur, as well as tibial BMD and indirect parameters of bone turnover to attempt to elucidate the mechanism by which genistein protects from post-OVX bone loss. Forty rats were divided in 4 groups of 10 animals each: SHAM and vehicle (SHAM-VE), SHAM and genistein 5 mg/g b.w. (SHAM-GEN), OVX and vehicle (OVX-VE), or OVX and genistein 5 mg/g b.w. (OVX-GEN). When compared with the SHAM-VE rats, the OVX-VE rats displayed lower BMD and trabecular bone volume (TBV), markedly increased osteoblast and osteoclast cell number (#), increased serum osteocalcin (OC - marker of bone formation) and increased 24o urine pyridinium cross-links (Dpd - marker of bone resorption), confirming that the immediate post-OVX period is characterized by rapid bone loss and increased bone turnover with predominant bone resorption.
SHAM-VE SHAM-GEN OVX-VE OVX-GEN
BMD (mg/cm2) 201+/-2a 200+/-1a 191+/-2b 196+/-2c
TBV(%) 7.7+/-0.7a 7.9+/-0.7a 3.3+/-0.2b 5.2+/-0.4c
Osteoblast # 170+/-54a 126+/-24b 511+/-72b 635+/-128c
Osteoclast # 130+/-23a 104+/-22a 277+/-32b 262+/-30c
OC (ng/ml) 48+/-3a 56+/-3b 56+/-2b 64+/-2c
Dpd (pmol/mg creat) 4.4+/-0.2b 4.7+/-0.5a 5.4+/-0.3b 5.7+/-0.4bGenistein protected from the post-OVX loss of TBV and BMD as much as in the first experiment and it caused further increment of serum OC and of the osteoblast #, but no change of urine Dpd or of osteoclast #. This suggests that the effect of genistein is geared primarily to stimulation of bone formation. In summary, we have shown that: (1) s.c. genistein reduces both trabecular and compact bone loss after OVX, (2) the amount of genistein excreted by our rats is similar to that recovered in humans after oral intake of the compound; and (3) the effect of genistein seems to depend on stimulation of bone formation rather than suppression of bone resorption. In conclusion, genistein, a constituent of soy products, protects from the bone loss associated with cessation of ovarian function. The mechanism of action of genistein appears to differ from that of estrogens, since the protective effect of estrogen on bone is characterized by suppression of bone turnover, bone cellularity, serum OC and urinary Dpd.
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