Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.
BACKGROUND
The role and dose of oral vitamin D supplementation in nonvertebral fracture prevention have not been well established.


OBJECTIVE
To estimate the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons.


METHODS
A systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-2005). Additional studies were identified by contacting clinical experts and searching bibliographies and abstracts presented at the American Society for Bone and Mineral Research (1995-2004). Search terms included randomized controlled trial (RCT), controlled clinical trial, random allocation, double-blind method, cholecalciferol, ergocalciferol, 25-hydroxyvitamin D, fractures, humans, elderly, falls, and bone density.


METHODS
Only double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (> or =60 years) that examined hip or nonvertebral fractures were included.


METHODS
Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators.


RESULTS
All pooled analyses were based on random-effects models. Five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met our inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both hip and nonvertebral fracture prevention was observed, which disappeared after pooling RCTs with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebral fracture, 1.03; 95% CI, 0.86-1.24).


CONCLUSIONS
Oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.
Bischoff-Ferrari
Heike A
HA
Department of Nutrition, Harvard School of Public Health, Boston, Mass 02115, USA. hbischof@hsph.harvard.edu
Willett
Walter C
WC
Wong
John B
JB
Giovannucci
Edward
E
Dietrich
Thomas
T
Dawson-Hughes
Bess
B
D000368:Aged; D002762:Cholecalciferol / Q000627:therapeutic use; D019587:Dietary Supplements; D004872:Ergocalciferols / Q000627:therapeutic use; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000008:administration & dosage / Q000627:therapeutic use*
D004872:Ergocalciferols; D014807:Vitamin D; D002762:Cholecalciferol