Uric Acid, Vitamin C and Bone Health: The Framingham Study

尿酸、维生素 C 和骨骼健康：弗雷明汉研究

• 批准号: 8447230
• 负责人: Shivani Sahni
• 金额: $ 8.25万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-24 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447230
• 关键词: Abbreviations; Affect; Age-Related Bone Loss; Antioxidants; Applications Grants; Area; Ascorbic Acid; Bone Density; Chronic Disease; Clinical; Collagen; Compressive Strength; Cross-Sectional Studies; Data; Diet Modification; Effectiveness; Elderly; Food; Fracture; Frequencies; Future; Generations; Goals; Gout; Grant; Hip Fractures; Human; Hypertension; Hyperuricemia; Inflammation; Intake; Intervention; Intervention Trial; Lead; Link; Low Prevalence; Maintenance; Measures; Mediating; Mediation; Mediator of activation protein; Normal Range; Osteoporosis; Osteoporosis prevention; Oxidative Stress; Participant; Pathway interactions; Pharmaceutical Preparations; Physical activity; Physical activity scale; Physiological; Population; Production; Property; Public Health; Questionnaires; Reactive Oxygen Species; Risk; Role; Sampling; Sampling Studies; Serum; Supplementation; Testing; Uric Acid; Vertebral column; Water; Woman; Work; X-Ray Computed Tomography; aging population; bone; bone health; bone loss; bone strength; bone turnover; cohort; cone-beam computed tomography; cytokine; follow-up; indexing; member; men; novel therapeutics; public health relevance; spine bone structure; vertebra body

DESCRIPTION (provided by applicant): Osteoporosis is a major public health problem especially in the aging population. Uric acid may affect bone health. Recent evidence indicates that uric acid serves as an endogenous antioxidant at normal physiological ranges (3-7 mg/dL) and it has been associated with higher bone mineral density, lower bone turnover and lower prevalence of fractures in a large cross-sectional study of men. However, at elevated levels (hyperuricemia), uric acid may act as a prooxidant and contribute to inflammation. Oxidative stress and inflammation has been implicated as one of the etiologic pathways involved in bone loss. However, associations of elevated uric acid level with bone have not been studied. Vitamin C intake has a uricosuric effect. Therefore vitamin C may contribute to maintenance of uric acid concentrations in the normal physiological range, thereby supporting an antioxidant effect instead of a prooxidant effect on bone. Our previous work demonstrated that vitamin C (a powerful water soluble antioxidant) protects against bone loss and risk of hip fracture. Yet surprisingly not much is known about the inter-relation of vitamin C and uric acid with osteoporosis. Uric acid may provide a unique yet unexplored mechanism through which vitamin C may affect bone health. The proposed work will be able to examine the relation between uric acid concentrations in the normal range with bone health as well as potential deleterious effects of high levels of uric acid, which has not been previously studied. Therefore, the specific goal is to examine the relation of serum uric acid and bone health and to determine whether vitamin C may represent an important part of the potential biologic pathway involving uric acid and bone. The participants from the Framingham Original cohort and Generation Three (Gen3) cohort will comprise the study sample for the proposed grant. Of the cohort members, 3,003 men and women had serum uric acid samples collected and were followed for hip fracture. Of the Gen3 cohort, 1,781 men and women had vitamin C intake, serum uric acid and QCT bone measured at the same exam. We will use mediation/suppression analysis to examine if serum uric acid mediates the association of vitamin C intake with QCT bone measures in the Gen3 cohort. The results from this study have important clinical implications because hyperuricemia can be treated with drugs and dietary modification. This could provide new therapeutic strategies to decrease risk of osteoporosis. Furthermore, findings from this proposed R03 have the potential to lead to future intervention trials in older adults.

描述（由申请人提供）：骨质疏松症是一个主要的公共卫生问题，尤其是在老龄化人群中。尿酸可能会影响骨骼健康。最近的证据表明，在正常生理范围（3-7 mg/dl）处作为内源性抗氧化剂，并且在大型大型骨矿物质密度，较低的骨转换率和较低的骨折患病率与较大的大型横断面研究有关男人。然而，在升高的水平（高尿酸血症）下，尿酸可能是促氧化剂，并导致炎症。氧化应激和炎症已被认为是与骨质流失有关的病因学途径之一。然而，尚未研究尿酸水平升高的关联。维生素C摄入量具有尿清乳作用。因此，维生素C可能有助于在正常生理范围内维持尿酸浓度，从而支持抗氧化作用，而不是对骨骼的促氧化作用。我们以前的工作表明，维生素C（一种强大的水溶性抗氧化剂）可以防止骨质流失和髋部骨折的风险。然而，令人惊讶的是，关于维生素C和尿酸与骨质疏松症的关系并不多。尿酸可能会提供一种独特但未开发的机制，维生素C可能会影响骨骼健康。拟议的工作将能够检查正常范围内的尿酸浓度与骨骼健康的关系以及高水平的尿酸的潜在有害作用，而尿酸的潜在有害影响先前尚未进行过研究。因此，具体目标是 检查血清尿酸和骨骼健康的关系，并确定维生素C是否可能代表涉及尿酸和骨骼的潜在生物学途径的重要组成部分。弗雷明汉原始队列和第三代（GEN3）队列的参与者将构成拟议赠款的研究样本。在队列成员中，有3,003名男性和女性收集了血清尿酸样品，并接受了髋部骨折。在Gen3队列中，有1,781名男性和女性在同一检查中测量了维生素C摄入，血清尿酸和QCT骨。我们将使用介导/抑制分析来检查血清尿酸是否介导了GEN3队列中维生素C摄入量与QCT骨测量的关联。这项研究的结果具有重要的临床意义，因为高尿酸血症可以用药物和饮食改性治疗。这可以提供新的治疗策略，以降低骨质疏松症的风险。此外，该拟议的R03的发现有可能导致老年人的未来干预试验。