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: 8885952
• 负责人: Jack M Guralnik
• 金额: $ 35.68万
• 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 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8885952
• 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; Dietary intake; Elderly; Endocrine; Exclusion Criteria; Exposure to; Funding; Gait; Genetic; Goals; Health; Heterogeneity; Hormones; 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; Parathyroid gland; Phosphorus; Physical Function; Population; Public Health; Publications; Published Comment; Publishing; Race; Randomized; Recommendation; Research; Research Personnel; Serum; Societies; Solutions; Speed; Statistical Methods; Structural Models; Subgroup; Sun Exposure; Supplementation; United States National Institutes of Health; Vitamin D; Woman; Writing; bone; bone health; calcium intake; cohort; design; dietary supplements; experience; fall risk; falls; fibroblast growth factor 23; flexibility; frailty; functional outcomes; genetic variant; inclusion criteria; indexing; innovation; instrumental activity of daily living; men; muscle strength; novel; osteoporosis with pathological fracture; outcome forecast; prospective; public health relevance; 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分别公开争论 20 ng/mL 或 30 ng/mL 作为骨骼健康的目标，但两个团体都同意需要更有力的证据来确定骨骼外结果（例如跌倒和身体功能）的目标浓度。这个问题很严重：>25% 的老年人身体机能较差，50% 的老年人 25(OH)D 浓度在 20 至 30 ng/mL 之间。通过为维生素 D 补充剂试验的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，目标充当纳入/排除标准或基线亚组以及次要结果。我们的解决方案是使用 NIH 资助的现有数据集，凭经验识别和验证老年人（= 65 岁）中与较低跌倒风险和更好的身体功能相关的特定性别（可能通过其他因素分层；例如种族、遗传变异）25(OH)D 目标。严峻的挑战 25(OH)D 不能随机化；因此，观测数据是解决方案的关键部分。传统的统计方法无法解决这个问题。因此，我们将开发 通过调整和完善结构建模和机器学习方法来采用新颖的统计方法，并将其应用于我们的目标。我们将使用 4 项前瞻性队列研究（包括超过 12,500 名老年人）来实现这些目标：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 25(OH)D 减少跌倒、行动能力、日常生活活动和日常生活工具性活动（功能结果）的目标；以及步态速度、肌肉力量，以及 虚弱（邻近条件）（目标 1）； 2) 描述 25(OH)D 和血清钙磷浓度对功能结果/近端状况的联合影响（目标 2）； 3) 通过内分泌和代谢因素（PTH、血清碱性磷酸酶、aklotho、成纤维细胞生长因子 23）量化 25(OH)D 对功能结果/近端状况的调节（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。