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.

项目摘要/摘要 骨折是伯恩（Burnen）的主要公共卫生，其残疾，成本，发病率和死亡率。在 近年来，髋部骨折率高于预期，椎骨骨折的发生似乎是 急剧上升，尤其是在75岁之后。越来越多的研究表明，酸中毒，甚至 当亚临床时，会直接影响骨骼，并可能对骨骼代谢和健康产生不利影响。 酸中毒可以抑制成骨细胞功能和骨骼形成，同时促进骨骼分辨率和分解， 因此，损害了骨骼修复每日磨损并积聚的微型罕见的能力 随着衰老，并有可能导致更高的断裂风险。护士健康研究（NHS）I和II以及 卫生专业人员后续研究（HPFS）正在进行的大规模研究，数十年 后续饮食和饮食和生活方式数据，以及存档的生物样本。整合代谢组学技术 进入基于人群的研究正在成为一种有价值的研究工具，可以为您提供新颖的见解 影响断裂风险的细胞过程。因此，该提议的目标是前瞻性研究 通过饮食酸负荷，血浆碳酸氢盐水平和 血浆代谢产物和发生骨折的风险。我们假设酸碱状态的扰动 通过饮食依赖性和独立的机制，导致酸中毒增加将与 较高的断裂风险。我们可能会检查饮食中酸负荷与发生髋关节的风险的关联 NHS I和II和HPF中的椎骨骨折（AIM 1）。我们将使用髋关节的嵌套病例对照研究 这三个队列中的断裂病例（n = 650）和匹配的对照（n = 650） 在血浆碳酸氢盐水平（AIM 2），血浆代谢产物（AIM 3）和发生髋部骨折的风险之间 女人和男人。将测量收集的已归档血浆样本的诊断前的诊断。 使用最先进的，高通量的液体或气相色谱的代谢产物，然后是质量 光谱法（LC/MS/MS和GC/MS）平台。使用高级计算和生物统计学方法 代谢组学和高维数据分析，我们将使用针对性的代谢组学方法以及 一种不可知的方法，使用所有可用的等离子体代谢物数据来构建不同的代谢物特征 区分髋部骨折病例和对照。最终，我们希望这些研究能够产生新的见解 裂缝的发展可能导致他们的预防和治疗方法。