Statistical methods for vitamin D targets for functional outcomes in older adults

老年人功能结果维生素 D 目标的统计方法

• 批准号: 9147536
• 负责人: Jack M Guralnik
• 金额: $ 32.2万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9147536
• 关键词: 25-hydroxyvitamin D; Activities of Daily Living; Address; Affect; Age; Aging; Alkaline Phosphatase; Award; Biological Markers; Body Composition; Body mass index; Calcium; Clinical; Clinical Research; Clinical Trials; Code; Cohort Studies; Communities; Computer software; Data; Data Set; Diet; Dietary intake; Elderly; Endocrine; Exclusion Criteria; Exposure to; Funding; Gait speed; Genetic; Goals; Health; Heterogeneity; Independent Living; Institute of Medicine (U.S.); Intake; Joints; Language; Lead; Machine Learning; Measures; Mediating; Mediation; Meta-Analysis; Metabolic; Methods; Minerals; Modeling; Observational Study; Outcome; PTH gene; Phosphorus; Physical Function; Public Health; Publications; Published Comment; Publishing; Race; Randomized; Recommendation; Research; Research Personnel; Serum; Societies; Statistical Methods; Structural Models; Subgroup; Sun Exposure; United States National Institutes of Health; Vitamin D; Vitamin D supplementation; Woman; Writing; aging population; bone; bone health; calcium intake; cohort; design; experience; fall risk; falls; fibroblast growth factor 23; flexibility; frailty; functional outcomes; genetic variant; inclusion criteria; indexing; innovation; instrumental activity of daily living; learning strategy; men; muscle strength; novel; osteoporosis with pathological fracture; outcome forecast; prospective; sarcopenia; secondary outcome; sex; skeletal; ultraviolet

 DESCRIPTION (provided by applicant): The concentration of 25-hydroxyvitamin D [25(OH)D] needed for older adults to maintain optimal physical function is unknown. Institute of Medicine and Endocrine Society have publicly debated on 20 ng/mL or 30 ng/mL, respectively, as targets for skeletal health, but both groups agree that stronger evidence is needed to identify target concentrations for extra-skeletal outcomes, e.g., falls and physical function. The problem is significant: >25% of older adults have poor physical function, 50% have 25(OH)D concentrations between 20 and 30 ng/mL. Identifying 25(OH)D targets for older adults will have immediate impact by informing design and analysis of vitamin D supplementation trials. Namely, targets serve as inclusion/exclusion criteria or baseline subgroups and as secondary outcomes. Our solution is to empirically identify and validate sex-specific (possibly stratified by other factors; e.g., race, genetic variants) 25(OH)D targets in older adults (= 65 years) related to lowe risk of falls and better physical function using existing NIH-funded datasets. A critical challenge is that 25(OH)D cannot be randomized; therefore observational data are a crucial part of the solution. Conventional statistical methods are ill-equipped for this problem; thus, we will develop novel statistical methods by adapting and refining structural modeling and machine-learning methods, and apply them to our aims. We will carry out the aims using 4 prospective cohort studies comprising >12,500 older adults: Health, Aging, and Body Composition, Invecchiare in Chianti, Osteoporotic Fractures in Men, and Study of Osteoporotic Fractures. We will: 1) identify and validate 25(OH)D targets for falls reduction, mobility, activities of daily living, and instrumental activities of daily living (functional outcomes); and gait speed, muscle strength, and frailty (proximal conditions) (aim 1); 2) characterize the joint impact of 25(OH)D and serum calcium and phosphorus concentrations on functional outcomes/proximal conditions (aim 2); and 3) quantify mediation of 25(OH)D on functional outcomes/proximal conditions by endocrine and metabolic factors (PTH, serum alkaline phosphatase, aklotho, fibroblast growth factor 23) (aim 3). We will write code in SAS and R statistical languages and disseminate it to the scientific community for use in additional research.

 描述（由申请人提供）：老年人维持最佳身体机能所需的 25-羟基维生素 D [25(OH)D] 浓度尚不清楚，医学研究所和内分泌学会已公开争论过 20 ng/mL 或 30 ng。 /mL 分别作为骨骼健康的目标，但两组都同意需要更有力的证据来确定骨骼外结果的目标浓度，例如跌倒和身体功能问题。意义重大：>25% 的老年人身体功能较差，50% 的老年人 25(OH)D 浓度在 20 至 30 ng/mL 之间。通过为设计和分析提供信息，确定老年人的 25(OH)D 目标将产生立竿见影的影响。也就是说，目标作为纳入/排除标准或基线亚组以及次要结果，我们的解决方案是根据经验确定和验证特定性别（可能按其他因素分层；例如，种族、遗传变异）使用 NIH 资助的现有数据集确定老年人（= 65 岁）的 25(OH)D 目标与降低跌倒风险和改善身体功能相关。 25(OH)D 不能随机化；因此，传统的统计方法不足以解决这个问题； 我们将通过调整和完善结构模型和机器学习方法来实现新的统计方法，并将其应用于我们的目标，其中包括超过 12,500 名老年人的 4 项前瞻性队列研究：健康、衰老和身体成分，基安蒂的 Invecchiare。 、男性骨质疏松性骨折和骨质疏松性骨折研究 我们将： 1) 确定并验证减少跌倒、活动能力和日常活动的 25(OH)D 目标。生活和日常生活的工具性活动（功能结果）；以及步态速度、肌肉力量和 虚弱（近端状况）（目标 1）；2）描述 25(OH)D 和血清钙和磷浓度对功能结果/近端状况的联合影响（目标 2）；以及量化 25(OH)D 的调节作用；内分泌和代谢因素（PTH、血清碱性磷酸酶、aklotho、成纤维细胞生长因子 23）对功能结果/近端状况的影响（目标3).我们将用SAS和R统计语言编写代码并将其传播给科学界 社区用于其他研究。