[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.161.216.242. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Review
May 11, 2005

Fracture Prevention With Vitamin D SupplementationA Meta-analysis of Randomized Controlled Trials

Author Affiliations
 

Author Affiliations: Department of Nutrition, Harvard School of Public Health (Drs Bischoff-Ferrari, Willett, and Giovannucci); Division of Rheumatology, Immunology, and Allergy, The Robert B. Brigham Arthritis and Musculoskeletal Diseases Clinical Research Center, and Division of Aging, Brigham and Women’s Hospital (Dr Bischoff-Ferrari); Department of Epidemiology and Channing Laboratory, Brigham and Women’s Hospital (Drs Willett and Giovannucci); Department of Medicine, Tufts-New England Medical Center (Dr Wong); Department of Health Policy and Health Services Research, Boston University Goldman School of Dental Medicine (Mr Dietrich); and Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University (Dr Dawson-Hughes), Boston, Mass.

JAMA. 2005;293(18):2257-2264. doi:10.1001/jama.293.18.2257
Context

Context 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.

Data Sources 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.

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

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

Data Synthesis 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.

×