title: A pooled analysis of vitamin D dose requirements for fracture prevention.
abstract: 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.).
authors: Center on Aging and Mobility, University of Zurich and Waid City Hospital, Zurich, Switzerland.
authors: Heike A
authors: HA
authors: Bischoff-Ferrari
authors: Walter C
authors: WC
authors: Willett
authors: Endel J
authors: EJ
authors: Orav
authors: Endel J
authors: EJ
authors: Oray
authors: Paul
authors: P
authors: Lips
authors: Pierre J
authors: PJ
authors: Meunier
authors: Ronan A
authors: RA
authors: Lyons
authors: Leon
authors: L
authors: Flicker
authors: John
authors: J
authors: Wark
authors: Rebecca D
authors: RD
authors: Jackson
authors: Jane A
authors: JA
authors: Cauley
authors: Haakon E
authors: HE
authors: Meyer
authors: Michael
authors: M
authors: Pfeifer
authors: Kerrie M
authors: KM
authors: Sanders
authors: Hannes B
authors: HB
authors: Stähelin
authors: Robert
authors: R
authors: Theiler
authors: Bess
authors: B
authors: Dawson-Hughes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000627:therapeutic use; D002136:Calcium, Dietary / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006620:Hip Fractures / Q000517:prevention & control*; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D002136:Calcium, Dietary; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002118:Calcium