Folic Acid and B Vitamins to Prevent Fracture in Women

描述(申请人提供)：骨质疏松性骨折是老年人残疾的主要原因，也是世界各地医疗费用的主要贡献者。前瞻性研究发现，血浆同型半胱氨酸升高的女性患骨质疏松性骨折的风险大大增加，包括髋部骨折。下一步是测试降低同型半胱氨酸水平是否会降低骨折的风险。我们建议使用一项正在进行的随机试验来检验这一假设，即通过饮食补充叶酸、维生素B6和维生素B12来降低血浆同型半胱氨酸水平将降低女性非脊柱骨折的风险。女性抗氧化剂疗法(女性抗氧化剂心血管研究[WACS])试验由NHLBI资助，是一项关于抗氧化维生素(维生素C、维生素E和β-胡萝卜素)和维生素B(叶酸、维生素B6和维生素B12)的随机、双盲、安慰剂对照试验，用于预防登记时年龄大于或等于40岁、既有心血管疾病(CVD)或大于或等于3个冠状动脉危险因素的女性健康专业人员的心血管事件。我们提出的名为叶酸和B维生素预防女性骨折的研究将对WACS中叶酸/维生素B6/维生素B12部门的女性报告的骨折进行验证和分类。我们保守地预测，在7.4年的治疗期间，5442名女性中将有大约700名非脊柱骨折得到验证，这提供了足够的力量来检测到骨折风险总体降低19%。利用现有的存档标本，我们将进行嵌套病例队列研究，以测试叶酸和维生素B治疗对非脊柱骨折风险的影响是否取决于基线血浆同型半胱氨酸水平，或者取决于叶酸或维生素B12水平。研究发现，同型半胱氨酸除了影响骨密度外，还会增加骨折的风险。因此，我们将使用存档的血浆来检验这一假设，即叶酸和维生素B的治疗通过改变骨转换率来影响骨折风险。我们将测量血浆骨形成标记物(P1NP)和骨吸收标记物(CTX)水平的变化，并探索周转变化是否可以解释饮食补充对骨折风险的影响。这项拟议的研究是一种成本效益高的方法，可以确定安全和廉价的营养干预是否能显著降低骨折风险，并了解这种影响的机制。

DESCRIPTION (provided by applicant): Osteoporotic fractures are a leading cause of disability in older adults, and a major contributor to medical care costs around the world. Prospective studies have found that women with elevated plasma homocysteine have a substantially increased risk of osteoporotic fractures, including hip fractures. The next step is to test whether lowering homocysteine levels will reduce the risk of fractures. We propose to use an ongoing randomized trial to test the hypothesis that reducing plasma homocysteine levels by dietary supplementation with folic acid, vitamin B6, and vitamin B12 will reduce the risk of non- spine fractures in women. The Antioxidant Therapy in Women (Women's Antioxidant Cardiovascular Study [WACS]) Trial, funded by NHLBI, is a randomized, double-blind, placebo-controlled trial of antioxidant vitamins (vitamin C, vitamin E, and beta-carotene) and B vitamins (folic acid, vitamin B6, and vitamin B12) for the prevention of cardiovascular events among female health professionals aged more than or equal to 40 years at enrollment, who had either pre-existing cardiovascular disease (CVD) or greater than or equal to 3 coronary risk factors. Our proposed study, Folic Acid & B Vitamins to Prevent Fractures in Women, will validate and classify fractures that were reported by women in the folic acid/vitamin B6/vitamin B12 arm of WACS. We conservatively project that about 700 non-spine fractures will be validated among 5,442 women during 7.4 years of treatment, providing sufficient power to detect a 19% overall reduction in fracture risk. Utilizing existing archived specimens, we will perform a nested case-cohort study to test whether the effects of treatment with folic acid and B vitamins on risk of non-spine fracture depends on baseline plasma levels of homocysteine, or alternatively by levels of folate or vitamin B12. Studies have found that homocysteine increases the risk of fracture by means besides influencing bone density. Thus, we will use archived plasma to test the hypothesis that treatment with folic acid and B- vitamins influences fracture risk by changing the rate of bone turnover. We will measure change in plasma levels of markers of bone formation (P1NP) and bone resorption (CTX) and explore whether changes in turnover may account for effects of the dietary supplementation on risk of fracture. The proposed study is a cost-effective approach to determining whether a safe and inexpensive nutritional intervention substantially reduces the risk of fracture and to understanding the mechanism of this effect.