Azienda Ospedaliera Universitaria Policlinico G. Martino, University of Messina, Messina, Italy.
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. ClinicalTrials.gov registration number: NCT00355953.