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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 绝经后妇女骨折的风险急剧增加。雌激素替代疗法通过减少骨质流失来降低这种风险，但会引起潜在的副作用并增加患癌症的风险。 在短期研究中，大豆异黄酮已被证明可以减少绝经后和绝经后妇女的腰椎骨质流失，且无有害影响。 目前尚不清楚大豆异黄酮预防更年期妇女骨质流失的长期安全性、有效性和最佳剂量。 我们假设长期补充大豆蛋白可以安全地减少绝经后妇女的骨丢失，其有益效果是剂量依赖性的。 为了检验这一假设，400名绝经早期的健康绝经后妇女将在四个美国研究中心（贝勒医学院、格鲁吉亚大学、爱荷华州州立大学和加州大学@ Davis）参加一项为期2年的随访、随机、双盲、安慰剂对照研究。这些妇女中有三分之一将接受安慰剂;三分之一将接受80 mg/天的补充剂;其余三分之一将接受120 mg/天的补充剂。 所有女性在研究期间都将接受钙和维生素D补充剂。 将在基线、6个月、12个月和24个月进行临床访视，以监测补充维生素B2的安全性。 为了监测安全性，将在每次临床访视时进行临床血液化学和全面体格检查。 将在基线时和每年间隔进行乳房X线检查、巴氏涂片检查和粪便愈创木脂检查。 为了监测疗效，将在基线和每年间隔测量全身和局部骨矿物质含量（BMC）和骨矿物质密度（BMD）以及骨代谢的生化标志物。 BMC和BMD将通过双能X线吸收法（DXA）测量。 将在基线时和每年间隔时测量胆甾酮及其代谢物的血液浓度，以监测依从性、肠道吸收效率和剂量反应性。 每组约133名女性的样本量将使我们能够检测到腰椎BMC和BMD每年分别增加4.1%和2.2%，α水平为0.05，功效为0.8。 样本量还将允许我们检测血清骨钙素1.0 ng/mL、血清骨特异性碱性磷酸酶（BAP）2.0 U/L和血清脱氧尿苷酸交联（Dpd）5.9 nmol/L的差异。 这将是第一个全国性的研究，以确定天然大豆维生素补充剂的安全性，有效性和最佳剂量，以防止绝经后妇女的骨质流失。 如果我们的假设是正确的，大豆异黄酮可能提供一个安全的替代雌激素替代治疗和预防妇女骨质疏松症。

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.