Vitamin D with calcium reduces mortality

patient level pooled analysis of 70,528 patients from eight major vitamin D trials

Lars Rejnmark, Alison Avenell, Tahir Masud, Frazer Anderson, Haakon E. Meyer, Kerrie M. Sanders, Kari Salovaara, Cyrus Cooper, Helen E. Smith, Elizabeth T. Jacobs, David Torgerson, Rebecca D. Jackson, JoAnn E. Manson, Kim Brixen, Leif Mosekilde, John A. Robbins, Roger M. Francis, Bo Abrahamsen

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Abstract

Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies.Results:The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06).Conclusion:Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone.
Original languageEnglish
Pages (from-to)2670-2681
Number of pages12
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number8
Early online date17 May 2012
DOIs
Publication statusPublished - 1 Aug 2012

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Vitamin D
Calcium
Mortality
Confidence Intervals
Meta-Analysis
Hazards
Randomized Controlled Trials
Odds Ratio
Numbers Needed To Treat
Intention to Treat Analysis
Proportional Hazards Models
Research Design
Health

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Vitamin D with calcium reduces mortality : patient level pooled analysis of 70,528 patients from eight major vitamin D trials. / Rejnmark, Lars; Avenell, Alison; Masud, Tahir; Anderson, Frazer; Meyer, Haakon E.; Sanders, Kerrie M.; Salovaara, Kari; Cooper, Cyrus; Smith, Helen E.; Jacobs, Elizabeth T.; Torgerson, David; Jackson, Rebecca D.; Manson, JoAnn E.; Brixen, Kim; Mosekilde, Leif; Robbins, John A.; Francis, Roger M.; Abrahamsen, Bo.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 8, 01.08.2012, p. 2670-2681.

Research output: Contribution to journalArticle

Rejnmark, L, Avenell, A, Masud, T, Anderson, F, Meyer, HE, Sanders, KM, Salovaara, K, Cooper, C, Smith, HE, Jacobs, ET, Torgerson, D, Jackson, RD, Manson, JE, Brixen, K, Mosekilde, L, Robbins, JA, Francis, RM & Abrahamsen, B 2012, 'Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 8, pp. 2670-2681. https://doi.org/10.1210/jc.2011-3328
Rejnmark, Lars ; Avenell, Alison ; Masud, Tahir ; Anderson, Frazer ; Meyer, Haakon E. ; Sanders, Kerrie M. ; Salovaara, Kari ; Cooper, Cyrus ; Smith, Helen E. ; Jacobs, Elizabeth T. ; Torgerson, David ; Jackson, Rebecca D. ; Manson, JoAnn E. ; Brixen, Kim ; Mosekilde, Leif ; Robbins, John A. ; Francis, Roger M. ; Abrahamsen, Bo. / Vitamin D with calcium reduces mortality : patient level pooled analysis of 70,528 patients from eight major vitamin D trials. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 8. pp. 2670-2681.
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abstract = "Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies.Results:The IPD analysis yielded data on 70,528 randomized participants (86.8{\%} females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7{\%} [hazard ratio, 0.93; 95{\%} confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95{\%} CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95{\%} CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95{\%} CI, 0.91-1.06).Conclusion:Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone.",
author = "Lars Rejnmark and Alison Avenell and Tahir Masud and Frazer Anderson and Meyer, {Haakon E.} and Sanders, {Kerrie M.} and Kari Salovaara and Cyrus Cooper and Smith, {Helen E.} and Jacobs, {Elizabeth T.} and David Torgerson and Jackson, {Rebecca D.} and Manson, {JoAnn E.} and Kim Brixen and Leif Mosekilde and Robbins, {John A.} and Francis, {Roger M.} and Bo Abrahamsen",
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TY - JOUR

T1 - Vitamin D with calcium reduces mortality

T2 - patient level pooled analysis of 70,528 patients from eight major vitamin D trials

AU - Rejnmark, Lars

AU - Avenell, Alison

AU - Masud, Tahir

AU - Anderson, Frazer

AU - Meyer, Haakon E.

AU - Sanders, Kerrie M.

AU - Salovaara, Kari

AU - Cooper, Cyrus

AU - Smith, Helen E.

AU - Jacobs, Elizabeth T.

AU - Torgerson, David

AU - Jackson, Rebecca D.

AU - Manson, JoAnn E.

AU - Brixen, Kim

AU - Mosekilde, Leif

AU - Robbins, John A.

AU - Francis, Roger M.

AU - Abrahamsen, Bo

PY - 2012/8/1

Y1 - 2012/8/1

N2 - Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies.Results:The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06).Conclusion:Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone.

AB - Introduction:Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium.Subjects and Methods:Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies.Results:The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84-0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88-0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91-1.06).Conclusion:Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone.

U2 - 10.1210/jc.2011-3328

DO - 10.1210/jc.2011-3328

M3 - Article

VL - 97

SP - 2670

EP - 2681

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 8

ER -