title: Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Vitamin D deficiency has been associated with poor physical performance.
  
  
  OBJECTIVE
  To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline.
  
  
  METHODS
  One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall.
  
  
  METHODS
  Three study groups with monthly treatments, including a low-dose control group receiving 24,000 IU of vitamin D3 (24,000 IU group), a group receiving 60,000 IU of vitamin D3 (60,000 IU group), and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol (24,000 IU plus calcifediol group).
  
  
  METHODS
  The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index.
  
  
  RESULTS
  The study cohort comprised 200 participants (men and women ≥ 70 years with a prior fall). Their mean age was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Intent-to-treat analyses showed that, while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60,000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24,000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24,000 IU group (47.9%; 95% CI, 35.8%-60.3%) (P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60,000 IU group (mean, 1.47) and the 24,000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24,000 IU group (mean, 0.94) (P = .09).
  
  
  CONCLUSIONS
  Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01017354.
authors.affiliation: Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland2Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland.
authors.forename: Heike A
authors.initials: HA
authors.lastname: Bischoff-Ferrari
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.
authors.forename: Bess
authors.initials: B
authors.lastname: Dawson-Hughes
authors.affiliation: Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: E John
authors.initials: EJ
authors.lastname: Orav
authors.affiliation: Department of Geriatrics, University of Basel, Basel, Switzerland.
authors.forename: Hannes B
authors.initials: HB
authors.lastname: Staehelin
authors.affiliation: Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland2Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland.
authors.forename: Otto W
authors.initials: OW
authors.lastname: Meyer
authors.affiliation: Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Theiler
authors.affiliation: Department of Orthopedic Surgery, University of Basel, Basel, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Dick
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: Department of Geriatrics and Aging Research, University Hospital Zurich, Zurich, Switzerland2Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Egli
mesh_terms: D000058:Accidental Falls / Q000517:prevention & control*; D000368:Aged; D000369:Aged, 80 and over; D002112:Calcifediol / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000502:physiology; D008297:Male; D051346:Mobility Limitation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000517:prevention & control*
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002112:Calcifediol