Metabolites of Dietary Intake and Risk of Knee Osteoarthritis

项目摘要/摘要 骨性关节炎(OA)是最常见的关节炎形式，也是活动受限和 老年人的身体残疾。在缺乏疾病修正疗法的情况下，迫切需要 有效的、广泛可用的方法，以帮助预防和管理这一常见情况。 与炎症、肥胖和其他代谢危险因素相关的饮食因素似乎在 骨性关节炎发病机制。然而，很少有人体研究研究饮食因素之间的联系。 以及未来膝关节骨性关节炎发展的风险。我们有来自骨关节炎倡议(OAI)的初步数据，一个 反复测量骨性关节炎症状和放射学结果的大群组，表明 西式饮食模式，特点是大量摄入红肉/加工肉、精制谷物、甜点/ 甜食与膝骨性关节炎的风险增加有关。相比之下，谨慎的饮食模式 以水果/蔬菜、豆类、全谷类、家禽和鱼类的高摄入量为特征的 降低了膝骨性关节炎的风险。因此，坚持健康饮食可能会为老年人提供一种潜在的策略 预防膝骨性关节炎。然而，自我报告饮食评估方法，如食物频率 问卷(FFQ)和饮食记录可能会受到回忆偏差和测量误差的影响。生物标记物 考虑到营养的生物可利用性和新陈代谢的饮食摄入量可能更好地代表了一种长期的 营养状况。最近，代谢组学通过测量大量的下游成分或 代谢产物(代谢物)，提供了反映生物状态的最完整的概况 环境、饮食和遗传的相互作用，因此可能更准确地定义饮食暴露 并在流行病学研究中提供更好的疾病风险估计。到目前为止，干预研究已经 确定了与主要食物的饮食摄入量有关的各种代谢物。其中50多人已经被 多项研究证实了这一点。到目前为止，还没有研究评估代谢物之间的联系。 饮食摄入量和膝骨性关节炎的未来风险。我们建议在OAI队列中进行嵌套式病例对照研究 包括261例膝关节骨性关节炎患者和261例匹配对照，以检查个体代谢物 饮食摄入量的代谢特征预测随后发生膝骨性关节炎的风险，以及 饮食相关的代谢物和代谢组谱影响膝骨性关节炎的影像生物标志物。最后，我们会 检查膝骨性关节炎的影像生物标记物是否中介与饮食相关的代谢组谱的关联 有患膝骨性关节炎的风险。这项研究将有助于确定饮食因素与膝骨性关节炎的发展相关，以及 提供了有效的OA预防策略的潜力；因此，它可能会对公共卫生和临床产生巨大的影响 这意味着什么。

PROJECT SUMMARY / ABSTRACT Osteoarthritis (OA) is the most common form of arthritis and the major cause of activity limitation and physical disability in older people. In the absence of disease modifying therapy, there is an urgent need for effective, widely available approaches to aid in the prevention and management of this common condition. Dietary factors associated with inflammation, obesity and other metabolic risk factors appear to play a role in OA pathogenesis. However, few human studies have studied the association between dietary factors and risk of future knee OA development. We have preliminary data from the Osteoarthritis Initiative (OAI), a large cohort with repeated measures of OA symptoms and radiographic outcomes, demonstrating that the Western dietary pattern, characterized by high intakes of red/ processed meats, refined grains, desserts / sweets, was associated with increased risk of radiographic knee OA. In contrast, the Prudent dietary pattern characterized by high intakes of fruits/ vegetables, legumes, whole grains, poultry, and fish was associated with reduced risk of knee OA. Hence, adherence to a healthy diet may provide a potential strategy for the prevention of knee OA. However, self-report dietary assessment methods, such as food-frequency questionnaires (FFQs) and diet records, may be subject to recall bias and measurement error. Biomarkers of dietary intake taking into account the nutrient bioavailability and metabolism may better represent a long-term nutritional status. Recently, metabolomics, by measuring a large number of downstream components or metabolic products (metabolites), provides the most integrated profile of biological status reflecting environmental, dietary and genetic interactions, and therefore may more precisely define dietary exposures and provide better estimates of disease risk in epidemiologic studies. To date, intervention studies have identified a variety of metabolites related to the dietary intake of major foods. More than 50 of them have been validated by multiple studies. To date, no study has ever assessed the association between metabolites of dietary intake and future risk of knee OA. We propose a nested case-control study in OAI cohort including 261 incident knee OA cases and 261 matched controls to examine whether individual metabolites and metabolomic profiles of dietary intake predict subsequent risk of development of knee OA, and whether diet-related metabolites and metabolomic profiles influence imaging biomarkers of knee OA. Finally, we will examine whether imaging biomarkers of knee OA mediate the associations of diet-related metabolomic profiles with risk of knee OA. This study will help to identify dietary factors associated with knee OA development, and offer the potential for effective OA prevention strategies; therefore, it may have large public health and clinical implications.