Folic Acid and B Vitamins to Prevent Fracture in Women

描述（由申请人提供）：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来源。前瞻性研究发现，血浆同型半胱氨酸水平升高的女性发生骨质疏松性骨折（包括髋部骨折）的风险显著增加。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，即通过膳食补充叶酸、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。女性的抗氧化治疗（妇女抗氧化心血管研究[WACS]）试验，由NHLBI资助，是一项随机、双盲、安慰剂对照的抗氧化维生素试验（维生素C、维生素E和β-胡萝卜素）和B族维生素（叶酸、维生素B6和维生素B12）用于预防入组时年龄大于或等于40岁的女性卫生专业人员的心血管事件，既存心血管疾病（CVD）或大于或等于3个冠状动脉风险因素的患者。我们提出的研究，叶酸和B维生素，以防止妇女骨折，将验证和分类的妇女报告的骨折在叶酸/维生素B6/维生素B12臂的WACS。我们保守地预测，在7.4年的治疗期间，将在5，442名女性中验证约700例非脊柱骨折，提供足够的力量来检测骨折风险总体降低19%。利用现有的存档标本，我们将进行一项巢式病例队列研究，以测试叶酸和B族维生素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，我们将使用保存的血浆来检验叶酸和B族维生素治疗通过改变骨转换率来影响骨折风险的假设。我们将测量骨形成标志物（P1 NP）和骨吸收标志物（CTX）的血浆水平变化，并探讨代谢率的变化是否可以解释膳食补充剂对骨折风险的影响。这项研究是一种具有成本效益的方法，可以确定一种安全廉价的营养干预是否能大幅降低骨折风险，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.