OPG and sRANKL Serum Concentrations in Osteopenic, Postmenopausal Women After 2-Year Genistein Administration

Abstract

RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1-5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood. We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49-67 yr) with a femoral neck BMD <0.795 g/cm(2) and no significant comorbid conditions after 24-mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D(3). All patients received dietary instruction in an isocaloric fat-reduced diet. In comparison with placebo, sRANKL level was lower (p < 0.001 versus placebo) and OPG higher in genistein recipients (p < 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = -0.021, 95% CI, -0.020 to -0.022; placebo = +0.004, 95% CI, 0.003-0.005; difference = -0.020, 95% CI, -0.015 to -0.025, p < 0.001). Our findings suggest that genistein plus calcium and vitamin D(3) as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL-OPG balance after 24 mo of treatment.