SAFETY, EFFICACY, & OPTIMAL DOSAGE OF SOY ISOFLAVONES TO PREVENT OSTEOPOROSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Risk for bone fracture increases dramatically in women after menopause. Estrogen replacement therapy reduces this risk by reducing bone loss but introduces potential side effects and increased risk of cancer. Soy isoflavones have been shown to reduce lumbar spine bone loss in peri- and postmenopausal women in short-term studies with no harmful effects. The long-term safety, efficacy, and optimal dosage of soy isoflavones to prevent bone loss in menopausal women are not known. We hypothesize that long-term soy isoflavone supplementation safely reduce bone loss in postmenopausal women and the beneficial effect is dose dependent. To test this hypothesis, 400 healthy postmenopausal women in their early years of menopause will be enrolled in a 2-year follow-up, randomized, double-blind, placebo-controlled study at four U.S. study sites (Baylor College of Medicine, University of Georgia, Iowa State University, and University of California @ Davis). One-third of these women will receive a placebo; one-third will receive isoflavone supplementation at 80 mg/day; and the remaining one-third will receive isoflavone supplementation at 120 mg/day. All women will receive calcium and vitamin D supplementation during the study. Clinic visits at baseline, 6, 12, and 24 months will be carried out to monitor the safety of isoflavone supplementation. To monitor safety, clinical blood chemistries and complete physical examinations will be performed at each clinic visit. Mammograms, Pap smears, and stool guaiac tests will be performed at baseline and at annual intervals. To monitor efficacy, total-body and regional bone mineral content (BMC) and bone mineral density (BMD) as well as biochemical markers of bone metabolism will be measured at baseline and at annual intervals. BMC and BMD will be measured by dual-energy x-ray absorptiometry (DXA). Blood concentrations of isoflavones and their metabolites will be measured at baseline and at annual intervals to monitor compliance, intestinal absorption efficiency, and dose responsiveness. The sample size of ~133 women per group will allow us to detect increases in lumbar spine BMC and BMD of 4.1% per year and 2.2% per year, respectively with an alpha level of 0.05 and a power of 0.8. The sample size also will allow us to detect differences in serum osteocalcin of 1.0 ng/mL, in serum bone-specific alkaline phosphatase (BAP) of 2.0 U/L, and in serum deoxypyrindinoline crosslink (Dpd) of 5.9 nmol/L. This will represent the first National study to determine the safety, efficacy, and optimal dosage of natural soy isoflavone supplementation to prevent bone loss in postmenopausal women. If our hypothesis is correct, soy isoflavones may provide a safe alternative to estrogen replacement therapy for the treatment and prevention of osteoporosis in women.