Acid-Base Status as a Novel Risk Factor for Fractures

酸碱状态是骨折的新危险因素

• 批准号: 9906852
• 负责人: Julie Paik
• 金额: $ 76.19万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9906852
• 关键词: Acidosis; Acids; Adult; Affect; Age; Aging; Alkalies; Amino Acids; Anions; Archives; Attention; Automobile Driving; Bicarbonates; Biological Assay; Biostatistical Methods; Bone Density; Bone Regeneration; Bone Resorption; Bone remodeling; Buffers; Cell physiology; Citrates; Clinical; Cohort Studies; Computing Methodologies; Cross-Sectional Studies; Cysteine; Data; Data Analyses; Development; Diagnosis; Diet; Epidemic; Equilibrium; Excretory function; Follow-Up Studies; Fracture; Gas Chromatography; Generations; Glutamine; Goals; Health Professional; Hip Fractures; Impairment; Incidence; Investigation; Kidney; Lead; Liquid Chromatography; Liver; Longitudinal Studies; Malates; Mass Fragmentography; Mass Spectrum Analysis; Measures; Metabolic acidosis; Methionine; Morbidity - disease rate; Nested Case-Control Study; Nurses' Health Study; Osteoblasts; Osteogenesis; Osteoporosis; Plasma; Population Study; Potassium; Prevalence; Prevention; Principal Component Analysis; Production; Prospective Studies; Public Health; Research; Risk; Risk Factors; Salts; Sampling; Sex Differences; Site; Skeleton; Spinal Fractures; Statistical Methods; Sulfur; Sulfuric Acids; Technology; Testing; Time; Urine; Woman; base; biological specimen archives; bone; bone health; bone metabolism; case control; clinically significant; cohort; cost; dietary; disability; extracellular; follow-up; fracture risk; insight; lifestyle data; lifetime risk; liquid chromatography mass spectrometry; men; metabolomics; mortality; multidimensional data; novel; novel strategies; prospective; repaired; secondary analysis; tool; western diet; wrist fracture

Project Summary/Abstract Fractures are a major public health burden with its associated disability, cost, morbidity and mortality. In recent years, hip fracture rates are higher than expected and the incidence of vertebral fracture appears to be rising dramatically, especially after age 75 years. A growing body of research suggests that acidosis, even when subclinical, directly affects bone and can have detrimental effects on bone metabolism and health. Acidosis can inhibit osteoblast function and bone formation while promoting bone resorption and breakdown, thus impairing the bone’s ability to repair microdamage that occurs with daily wear and tear and accumulates with aging, and potentially contributing to higher fracture risk. The Nurses’ Health Studies (NHS) I and II and the Health Professionals Follow-up Study (HPFS) are ongoing large-scale cohort studies with decades of follow-up and rich dietary and lifestyle data, and archived biosamples. Integrating metabolomics technology into population-based studies is emerging as a valuable research tool which could provide novel insights into cellular processes that affect fracture risk. Therefore, this proposal’s goal is to prospectively study the association between acid-base status, assessed through dietary acid load, plasma bicarbonate level and plasma metabolites, and risk of incident fracture. We hypothesize that perturbations in acid-base status through diet-dependent and independent mechanisms resulting in increased acidosis will be associated with higher fracture risk. We will prospectively examine the association of dietary acid load with risk of incident hip and vertebral fracture in NHS I and II and HPFS (Aim 1). We will use a nested case-control study of hip fracture cases (n=650) and matched controls (n=650) within these three cohorts to study the association between plasma bicarbonate level (Aim 2), plasma metabolites (Aim 3) and risk of incident hip fracture in women and men. Archived plasma samples collected pre-hip fracture diagnosis will be measured for metabolites using state-of-the art, high-throughput liquid or gas chromatography followed by mass spectrometry (LC/MS/MS and GC/MS) platforms. Using advanced computational and biostatistical methods in metabolomics and high-dimensional data analyses, we will use a targeted metabolomics approach as well as an agnostic approach to build distinct metabolite signatures using all of the available plasma metabolite data to distinguish hip fracture cases from controls. Ultimately, we expect these studies to produce new insights into the development of fractures that may lead to new approaches to their prevention and treatment.

项目概要/摘要 骨折与相关的残疾、费用、发病率和死亡率是一个主要的公共卫生负担。 近年来，髋部骨折发生率高于预期，椎骨骨折的发生率似乎也有所下降。 酸中毒的发生率急剧上升，尤其是在 75 岁以后。 当处于亚临床状态时，会直接影响骨骼，并对骨骼代谢和健康产生不良影响。 酸中毒会抑制成骨细胞功能和骨形成，同时促进骨吸收和分解， 从而损害骨骼修复因日常磨损而发生并累积的微损伤的能力 随着年龄的增长，可能会导致更高的骨折风险。护士健康研究 (NHS) I 和 II 以及 卫生专业人员随访研究 (HPFS) 是一项持续进行的大规模队列研究，历时数十年 跟踪和丰富的饮食和生活方式数据，并整合代谢组学技术。 基于人群的研究正在成为一种有价值的研究工具，可以提供新的见解 因此，该提案的目标是前瞻性研究影响骨折风险的细胞过程。 酸碱状态之间的关联，通过膳食酸负荷、血浆碳酸氢盐水平和 我们追踪了酸碱状态的扰动。 通过饮食依赖和独立机制导致酸中毒增加将与 我们将前瞻性地研究膳食酸负荷与髋关节事故风险的关系。 NHS I 和 II 以及 HPFS 中的椎体骨折（目标 1）。 在这三个队列中研究骨折病例 (n=650) 和匹配对照 (n=650) 之间的关联 血浆碳酸氢盐水平（目标 2）、血浆代谢物（目标 3）与髋部骨折事件风险之间的关系 将测量髋部骨折诊断前收集的存档血浆样本。 使用最先进的高通量液相或气相色谱分析代谢物，然后进行质谱分析 光谱分析（LC/MS/MS 和 GC/MS）平台使用先进的计算和生物统计方法。 代谢组学和高维数据分析，我们将使用有针对性的代谢组学方法以及 一种不可知的方法，使用所有可用的血浆代谢物数据来构建不同的代谢物特征 最终，我们期望这些研究能够产生新的见解。 骨折的发展可能会导致预防和治疗骨折的新方法。