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

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，尤其是在老龄化人口中。尿酸会影响骨骼健康。最近的证据表明，尿酸在正常生理范围内（3-7 mg/dL）可作为内源性抗氧化剂，并且在一项大型男性横断面研究中，尿酸与较高的骨矿物质密度、较低的骨转换和较低的骨折患病率相关。然而，在升高的水平（高尿酸血症），尿酸可能作为促氧化剂，并有助于炎症。氧化应激和炎症是骨丢失的病因学途径之一。然而，尿酸水平升高与骨的关系尚未研究。维生素C的摄入具有促尿酸排泄作用。因此，维生素C可能有助于维持尿酸浓度在正常生理范围内，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，对维生素C和尿酸与骨质疏松症的相互关系知之甚少。尿酸可能提供了一种独特的尚未探索的机制，维生素C可能通过这种机制影响骨骼健康。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之间的关系，以及高水平尿酸的潜在有害影响，这是以前没有研究过的。因此，具体目标是 研究血清尿酸和骨骼健康的关系，并确定维生素C是否可能代表尿酸和骨骼的潜在生物途径的重要组成部分。来自Fragrance Original队列和第三代（Gen 3）队列的参与者将构成拟议补助金的研究样本。在队列成员中，收集了3，003名男性和女性的血清尿酸样本，并对髋部骨折进行了随访。在Gen 3队列中，1，781名男性和女性在同一次检查中摄入维生素C，血清尿酸和QCT骨测量。我们将使用中介/抑制分析来检查血清尿酸是否介导Gen 3队列中维生素C摄入与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通过药物和饮食调整来治疗。这可能为降低骨质疏松症的风险提供新的治疗策略。此外，R 03的研究结果有可能导致未来在老年人中进行干预试验。

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.