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Effects of the Phytoestrogen Genistein on the Circulating Soluble Receptor Activator of Nuclear Factor B Ligand-Osteoprotegerin System in Early Postmenopausal Women

Department of Biomedical Sciences (A.C.), Section of Pharmacology, University of Modena and Reggio Emilia, 41100 Modena, Italy; Department of Clinical and Experimental Medicine and Pharmacology (A.C., D.A., M.A.I., H.M., A.B., F.S.), Section of Pharmacology, and Departments of Internal Medicine (G.S., A.R., S.B., N.F.), Obstetrical and Gynecological Sciences (R.D., F.C.), and Biochemical Physiological and Nutritional Sciences (E.B.A., R.M.), School of Medicine, University of Messina, 98125 Messina, Italy

Address all correspondence and requests for reprints to: Professor Francesco Squadrito, M.D., Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Azienda Ospedaliera Universitaria "G. Martino," Torre Biologica 5 degree Piano, Via Consolare Valeria, 98125 Messina, Italy. E-mail: francesco.squadrito{at}unime.it.

We investigated the serum levels of both receptor activator of nuclear factor B ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) in postmenopausal healthy women after a 1-yr therapy with genistein, (n = 30; 54 mg/d), hormone replacement therapy (n = 30; 1 mg/d 17ß-estradiol combined with norethisterone acetate) and placebo (n = 30). By comparison with placebo, the soluble RANKL (sRANKL)/OPG ratio was lower in the genistein group (-69 ± 7%; P < 0.01 vs. placebo 81 ± 24%) and in hormone replacement therapy-treated women (-11 ± 2%; P < 0.01 vs. placebo). A positive correlation (r = 0.63; P < 0.01) was found between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in urinary deoxypyridinoline, a bone resorption marker. A negative correlation was observed between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in femoral neck bone mineral density (r = -0.7; P < 0.01). Our findings suggest that the sRANKL-OPG system may mediate the beneficial effects of genistein on bone remodeling in postmenopausal women.

Abbreviations: BMD, Bone mineral density; CV, coefficient of variation; ER, estrogen receptor; HRT, hormone replacement therapy; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor B ligand; sRANKL, soluble RANKL.

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