Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial.
BACKGROUND
Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.


OBJECTIVE
To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.


METHODS
A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.


METHODS
500,000 IU of cholecalciferol or placebo.


METHODS
Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.


RESULTS
Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.


CONCLUSIONS
Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.


BACKGROUND
anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.
Sanders
Kerrie M
KM
Department of Clinical and Biomedical Sciences, Barwon Health, University of Melbourne, Geelong, Victoria, Australia 3220. kerrie@barwonhealth.org.au
Stuart
Amanda L
AL
Williamson
Elizabeth J
EJ
Simpson
Julie A
JA
Kotowicz
Mark A
MA
Young
Doris
D
Nicholson
Geoffrey C
GC
D000058:Accidental Falls / Q000517:prevention & control*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D008297:Male; D012307:Risk Factors; D012621:Seasons; D017211:Treatment Failure
D050071:Bone Density Conservation Agents; D002762:Cholecalciferol