Soy protein, rich in isoflavones (estrogen-like compounds), has been shown to prevent bone loss in ovariectomized rats. Short-term preliminary study results in perimenopausal women suggest a bone-sparing effect. Great interest in isoflavones as an alternative to hormone replacement therapy has emerged, yet the long-term efficacy of isoflavones on bone in humans is unknown. Our objective is to determine the three-year efficacy of isoflavone-rich soy extract in attenuating bone loss in postmenopausal women. The central hypothesis is that soy isoflavones will attenuate bone loss in these women by maintaining bone formation, which is modulated by growth factors and isoflavone metabolism. The rationale for this research is that current hormone therapy is fraught with adverse side effects, resulting in non-compliance. This randomized, double-blind, placebo-controlled clinical trial will examine the effects of two doses (80 or 120 mg daily) of isoflavone-rich soy extract on bone in non-osteoporotic postmenopausal women (N=234). The specific aims of this study are: 1) to determine the bone-preserving effects of isoflavones on lumbar spine bone mineral density (BMD); 2) to relate treatment-induced changes in BMD to changes in biochemical markers of bone turnover; 3) to identify potential mechanisms by which isoflavones prevent or modulate bone loss by measuring endogenous estrogens, sex hormone-binding globulin, insulin-like growth factor-I (IGF-I), urinary minerals, serum 25(OH)vitamin D, plasma isoflavones and their metabolites, and customary intake of isoflavone-containing soy; and, 4) to ascertain the safety of isoflavone-rich soy extract. Postmenopausal women will be recruited at two sites (117 at Iowa, 117 at California). Random effects repeated measures analyses will be used to characterize change in BMD as the primary outcome, estimate treatment-induced effects, and depict change in markers of bone turnover in relation to BMD change. We will use intent-to-treat for the primary test, but also account for potential modulators (reproductive hormones, IGF-I, plasma isoflavones) that affect bone, as indicated in specific aim 3.