Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.

Background: Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. Objective: To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Design: Randomized, double-blind, placebo-controlled trial. Setting: 3 university medical centers in Italy. Patients: 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. Intervention: After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n 191) or 54 mg of genistein (n 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. Measurements: The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. Results: At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. 0.053 g/cm2 [CI, 0.058 to 0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. 0.037 g/cm2 [CI, 0.044 to 0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P 0.002) and discontinued the study. Limitations: The study did not measure fractures and had limited power to evaluate adverse effects. Conclusion: Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women.