Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)

Michelle Shardell; Anne R. Cappola; Jack M. Guralnik; Gregory E. Hicks; Stephen B. Kritchevsky; Eleanor M. Simonsick; Luigi Ferrucci; Richard D. Semba; Nancy Chiles Shaffer; Tamara Harris; Gudny Eiriksdottir; Vilmundur Gudnason; Mary Frances Cotch; Eric Orwoll; Kristine E. Ensrud; Peggy M. Cawthon

doi:10.1093/ajcn/nqab025

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)

Michelle Shardell
, Anne R. Cappola
, Jack M. Guralnik
, Gregory E. Hicks
, Stephen B. Kritchevsky
, Eleanor M. Simonsick
, Luigi Ferrucci
, Richard D. Semba
, Nancy Chiles Shaffer
, Tamara Harris
, Gudny Eiriksdottir
, Vilmundur Gudnason
, Mary Frances Cotch
, Eric Orwoll
, Kristine E. Ensrud
, Peggy M. Cawthon

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health.

OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function.

METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes.

RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets.

CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

Original language	English (US)
Pages (from-to)	16-28
Number of pages	13
Journal	American Journal of Clinical Nutrition
Volume	114
Issue number	1
DOIs	https://doi.org/10.1093/ajcn/nqab025
State	Published - Jul 1 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Keywords

extraskeletal health
gait speed
older adults
physical function
vitamin D
Body Composition
United States
Humans
Vitamin D Deficiency
Independent Living
Male
Sex Factors
Aged, 80 and over
Female
Italy
Aged
Physical Functional Performance
Vitamin D/analogs & derivatives

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Meta-Analysis
Research Support, N.I.H., Intramural
Journal Article
Research Support, N.I.H., Extramural

Publisher link

10.1093/ajcn/nqab025

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Shardell, M., Cappola, A. R., Guralnik, J. M., Hicks, G. E., Kritchevsky, S. B., Simonsick, E. M., Ferrucci, L., Semba, R. D., Shaffer, N. C., Harris, T., Eiriksdottir, G., Gudnason, V., Cotch, M. F., Orwoll, E., Ensrud, K. E., & Cawthon, P. M. (2021). Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO). American Journal of Clinical Nutrition, 114(1), 16-28. https://doi.org/10.1093/ajcn/nqab025

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO). / Shardell, Michelle; Cappola, Anne R.; Guralnik, Jack M. et al.
In: American Journal of Clinical Nutrition, Vol. 114, No. 1, 01.07.2021, p. 16-28.

Research output: Contribution to journal › Article › peer-review

Shardell, M, Cappola, AR, Guralnik, JM, Hicks, GE, Kritchevsky, SB, Simonsick, EM, Ferrucci, L, Semba, RD, Shaffer, NC, Harris, T, Eiriksdottir, G, Gudnason, V, Cotch, MF, Orwoll, E, Ensrud, KE & Cawthon, PM 2021, 'Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)', American Journal of Clinical Nutrition, vol. 114, no. 1, pp. 16-28. https://doi.org/10.1093/ajcn/nqab025

@article{d93837f6aa2f44e8a29fcc7fa4579dbd,

title = "Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)",

abstract = "BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health.OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function.METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes.RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2\%) and 494/3937 men (12.5\%) experienced incident slow gait, 1098/7011 women (15.7\%) and 474/3962 men (12.0\%) experienced incident mobility impairment, and 1044/6941 women (15.0\%) and 432/3993 men (10.8\%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95\% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95\% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets.CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.",

keywords = "extraskeletal health, gait speed, older adults, physical function, vitamin D, Body Composition, United States, Humans, Vitamin D Deficiency, Independent Living, Male, Sex Factors, Aged, 80 and over, Female, Italy, Aged, Physical Functional Performance, Vitamin D/analogs \& derivatives",

author = "Michelle Shardell and Cappola, \{Anne R.\} and Guralnik, \{Jack M.\} and Hicks, \{Gregory E.\} and Kritchevsky, \{Stephen B.\} and Simonsick, \{Eleanor M.\} and Luigi Ferrucci and Semba, \{Richard D.\} and Shaffer, \{Nancy Chiles\} and Tamara Harris and Gudny Eiriksdottir and Vilmundur Gudnason and Cotch, \{Mary Frances\} and Eric Orwoll and Ensrud, \{Kristine E.\} and Cawthon, \{Peggy M.\}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.",

year = "2021",

month = jul,

day = "1",

doi = "10.1093/ajcn/nqab025",

language = "English (US)",

volume = "114",

pages = "16--28",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "Elsevier B.V.",

number = "1",

}

TY - JOUR

T1 - Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults

T2 - PRoject on Optimal VItamin D in Older adults (PROVIDO)

AU - Shardell, Michelle

AU - Cappola, Anne R.

AU - Guralnik, Jack M.

AU - Hicks, Gregory E.

AU - Kritchevsky, Stephen B.

AU - Simonsick, Eleanor M.

AU - Ferrucci, Luigi

AU - Semba, Richard D.

AU - Shaffer, Nancy Chiles

AU - Harris, Tamara

AU - Eiriksdottir, Gudny

AU - Gudnason, Vilmundur

AU - Cotch, Mary Frances

AU - Orwoll, Eric

AU - Ensrud, Kristine E.

AU - Cawthon, Peggy M.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health.OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function.METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes.RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets.CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

AB - BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health.OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function.METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes.RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets.CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

KW - extraskeletal health

KW - gait speed

KW - older adults

KW - physical function

KW - vitamin D

KW - Body Composition

KW - United States

KW - Humans

KW - Vitamin D Deficiency

KW - Independent Living

KW - Male

KW - Sex Factors

KW - Aged, 80 and over

KW - Female

KW - Italy

KW - Aged

KW - Physical Functional Performance

KW - Vitamin D/analogs & derivatives

UR - https://www.scopus.com/pages/publications/85110716300

UR - https://www.scopus.com/pages/publications/85110716300#tab=citedBy

U2 - 10.1093/ajcn/nqab025

DO - 10.1093/ajcn/nqab025

M3 - Article

C2 - 33826696

AN - SCOPUS:85110716300

SN - 0002-9165

VL - 114

SP - 16

EP - 28

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 1

ER -

Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

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