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.
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
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
Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture Prevention With Vitamin D Supplementation: A Meta-analysis of Randomized Controlled Trials. JAMA. 2005;293(18):2257–2264. doi:10.1001/jama.293.18.2257
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