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A pooled analysis of vitamin D dose requirements for fracture prevention

Bischoff-Ferrari, HA and Willett, WC and Orav, EJ and Lips, P and Meunier, PJ and Lyons, RA and Flicker, L and Wark, J and Jackson, RD and Cauley, JA and Meyer, HE and Pfeifer, M and Sanders, KM and Stähelin, HB and Theiler, R and Dawson-Hughes, B (2012) A pooled analysis of vitamin D dose requirements for fracture prevention. New England Journal of Medicine, 367 (1). 40 - 49. ISSN 0028-4793

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BACKGROUND: The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent. METHODS: We pooled participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every 4 months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Primary end points were the incidence of hip and any nonvertebral fractures according to Cox regression analyses, with adjustment for age group, sex, type of dwelling, and study. Our primary aim was to compare data from quartiles of actual intake of vitamin D (including each individual participant's adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups. RESULTS: We included 31,022 persons (mean age, 76 years; 91% women) with 1111 incident hip fractures and 3770 nonvertebral fractures. Participants who were randomly assigned to receive vitamin D, as compared with those assigned to control groups, had a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio, 0.90; 95% confidence interval [CI], 0.80 to 1.01) and a 7% reduction in the risk of nonvertebral fracture (hazard ratio, 0.93; 95% CI, 0.87 to 0.99). By quartiles of actual intake, reduction in the risk of fracture was shown only at the highest intake level (median, 800 IU daily; range, 792 to 2000), with a 30% reduction in the risk of hip fracture (hazard ratio, 0.70; 95% CI, 0.58 to 0.86) and a 14% reduction in the risk of any nonvertebral fracture (hazard ratio, 0.86; 95% CI, 0.76 to 0.96). Benefits at the highest level of vitamin D intake were fairly consistent across subgroups defined by age group, type of dwelling, baseline 25-hydroxyvitamin D level, and additional calcium intake. CONCLUSIONS: High-dose vitamin D supplementation (≥800 IU daily) was somewhat favorable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older. (Funded by the Swiss National Foundations and others.) Copyright © 2012 Massachusetts Medical Society.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bischoff-Ferrari, HA
Willett, WC
Orav, EJ
Lips, P
Meunier, PJ
Lyons, RA
Flicker, L
Wark, J
Jackson, RD
Cauley, JAJCauley@edc.pitt.eduJCAULEY
Meyer, HE
Pfeifer, M
Sanders, KM
Stähelin, HB
Theiler, R
Dawson-Hughes, B
Date: 5 July 2012
Date Type: Publication
Journal or Publication Title: New England Journal of Medicine
Volume: 367
Number: 1
Page Range: 40 - 49
DOI or Unique Handle: 10.1056/nejmoa1109617
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0028-4793
Date Deposited: 03 Apr 2015 01:27
Last Modified: 27 Jan 2019 03:55


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