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.

Public Health Relevance

The aging of the population is expected to lead to an increased burden of poor physical function and loss of independence. Low concentrations of 25-hydroxyvitamin D [25(OH)D] are common in older adults and may be one reason for deficits in physical function. Since 25(OH)D can easily be increased by sunlight exposure, diet, and supplements; identifying and validating a target 25(OH)D for functional outcomes in older adults can have a significant impact on public health.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Joseph, Lyndon
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University of Maryland Baltimore
Public Health & Prev Medicine
Schools of Medicine
United States
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Salimi, Shabnam; Shardell, Michelle D; Seliger, Stephen L et al. (2018) Inflammation and Trajectory of Renal Function in Community-Dwelling Older Adults. J Am Geriatr Soc 66:804-811
Shardell, Michelle; Ferrucci, Luigi (2018) Joint mixed-effects models for causal inference with longitudinal data. Stat Med 37:829-846
Salimi, Shabnam; Shardell, Michelle; Miller, Ram et al. (2018) Soluble Tumor Necrosis Factor Alpha Receptor 1, Bone Resorption, and Bone Mineral Density in the Year Following Hip Fractures: The Baltimore Hip Studies. J Bone Miner Res 33:1649-1656
Buta, Brian; Choudhury, Parichoy Pal; Xue, Qian-Li et al. (2017) The Association of Vitamin D Deficiency and Incident Frailty in Older Women: The Role of Cardiometabolic Diseases. J Am Geriatr Soc 65:619-624
Shardell, Michelle; Semba, Richard D; Kalyani, Rita R et al. (2017) Plasma klotho and frailty in older adults: Findings from the InCHIANTI Study. J Gerontol A Biol Sci Med Sci :
Rathbun, Alan M; Shardell, Michelle; Orwig, Denise et al. (2016) Effects of Prefracture Depressive Illness and Postfracture Depressive Symptoms on Physical Performance After Hip Fracture. J Am Geriatr Soc 64:e171-e176
Sanses, Tatiana V D; Schiltz, Nicholas K; Couri, Bruna M et al. (2016) Functional status in older women diagnosed with pelvic organ prolapse. Am J Obstet Gynecol 214:613.e1-7
Shardell, Michelle; Ferrucci, Luigi (2016) Instrumental variable analysis of multiplicative models with potentially invalid instruments. Stat Med 35:5430-5447