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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 绝经后女性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，但会带来潜在的副作用和增加癌症的风险。短期研究表明，大豆异黄酮能减少围绝经期和绝经后妇女的腰椎骨丢失，且无不良影响。大豆异黄酮类预防绝经后妇女骨质流失的长期安全性、有效性和最佳剂量尚不清楚。我们假设长期补充大豆异黄酮会安全地减少绝经后妇女的骨丢失，其有益效果是剂量依赖的。为了验证这一假设，400名处于绝经早期的健康绝经后妇女将在四个美国研究地点(贝勒医学院、佐治亚大学、爱荷华州立大学和加州大学戴维斯分校)参加为期两年的随机、双盲、安慰剂对照研究。其中三分之一的女性将接受安慰剂；三分之一的女性将接受每天80毫克的异黄酮补充剂；其余三分之一的女性将接受每天120毫克的异黄酮补充剂。在研究期间，所有女性都将接受钙和维生素D的补充。将在基线、6个月、12个月和24个月进行临床访问，以监测异黄酮类补充剂的安全性。为了监测安全性，每次就诊时都会进行临床血液化学检查和全面的身体检查。乳房X光检查、巴氏涂片和大便愈创木酚检查将在基线和每年一次的间隔进行。为了监测疗效，将在基线和每年间隔测量全身和局部骨矿含量(BMC)和骨密度(BMD)以及骨代谢的生化指标。采用双能X射线骨密度仪(DXA)测量BMC和BMD。将在基线和每年间隔测量异黄酮类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响应性。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分别以每年4.1%和2.2%的速度增加，α水平为0.05，幂为0.8。样本量还将使我们能够检测血清骨钙素为1.0 ng/毫升、血清骨特异性碱性磷酸酶为2.0U/L和血清脱氧吡喹啉交联物为5.9nmol/L的差异。这将是第一项确定天然大豆异黄酮补充剂预防绝经后妇女骨丢失的安全性、有效性和最佳剂量的全国性研究。如果我们的假设是正确的，大豆异黄酮可能为治疗和预防女性骨质疏松症提供一种安全的替代雌激素替代疗法。

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.