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Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men.

The Cochrane database of systematic reviews
January 1, 1970
Alison Avenell et al. (3 authors)
Journal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tReviewSystematic ReviewHuman Study
Study Details

Study Goal

The researchers aimed to determine whether vitamin D or related compounds, with or without calcium, could prevent fractures in post-menopausal women and older men.

Results Summary

The study found that vitamin D alone was ineffective in preventing fractures, but vitamin D plus calcium resulted in a small reduction in hip fracture risk and a statistically significant reduction in non-vertebral fractures. However, there was a small increase in gastrointestinal symptoms and renal disease associated with calcium and vitamin D supplementation.

Population

Post-menopausal women and older men, including community-dwelling individuals and institutionalized populations.

Effective Dosage

Not specified in the abstract.

Duration

Not specified in the abstract.

Interactions

None mentioned.

Extracted Claims (18)
InterventionDirectionEndpointPopulationDosageImpactClaim #
vitamin D alone
no change
hip fracture
older people
risk ratio (RR) 1.12, 95% confidence intervals (CI) 0.98 to 1.29
unlikely to be effective in preventing
#1
vitamin D alone
no change
any new fracture
older people
RR 1.03, 95% CI 0.96 to 1.11
unlikely to be effective in preventing
#2
vitamin D plus calcium
decrease
hip fracture risk
older adults
RR 0.84, 95% confidence interval (CI) 0.74 to 0.96
results in a small reduction in
#3
vitamin D plus calcium
decrease
new non-vertebral fractures
-
-
associated with a statistically significant reduction in incidence of
#4
vitamin D plus calcium
no change
clinical vertebral fractures
-
-
absence of a statistically significant preventive effect on
#5
vitamin D plus calcium
decrease
any type of fracture
-
RR 0.95, 95% CI 0.90 to 0.99
reduces the risk of
#6
vitamin D
no change
mortality
-
RR 0.97, 95% CI 0.93 to 1.01
was not adversely affected
#7
vitamin D plus calcium supplementation
no change
mortality
-
RR 0.97, 95% CI 0.93 to 1.01
was not adversely affected
#8
vitamin D or an analogue, with or without calcium
increase
hypercalcaemia
-
RR 2.28, 95% CI 1.57 to 3.31
was more common in people receiving
#9
calcitriol
increase
hypercalcaemia
-
RR 4.41, 95% CI 2.14 to 9.09
was more common in people receiving
#10
vitamin D or an analogue, with or without calcium
increase
gastrointestinal symptoms
-
RR 1.04, 95% CI 1.00 to 1.08
small increased risk of
#11
calcium plus vitamin D
increase
gastrointestinal symptoms
-
RR 1.05, 95% CI 1.01 to 1.09
small increased risk of
#12
vitamin D or an analogue, with or without calcium
increase
renal disease
-
RR 1.16, 95% CI 1.02 to 1.33
significant increase in
#13
supplemental calcium
increase
myocardial infarction
-
-
increased association of
#14
supplemental calcium plus vitamin D
increase
myocardial infarction
-
-
increased association of
#15
supplemental calcium plus vitamin D
increase
stroke
-
-
increased association of
#16
supplemental calcium plus vitamin D
decrease
cancer
-
-
decreased association of
#17
calcium and vitamin D
no change
death
-
-
no increased risk of
#18
Abstract

BACKGROUND: Vitamin D and related compounds have been used to prevent osteoporotic fractures in older people. This is the third update of a Cochrane review first published in 1996. OBJECTIVES: To determine the effects of vitamin D or related compounds, with or without calcium, for preventing fractures in post-menopausal women and older men. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to December 2012), the Cochrane Central Register of Controlled Trials (2012, Issue 12), MEDLINE (1966 to November Week 3 2012), EMBASE (1980 to 2012 Week 50), CINAHL (1982 to December 2012), BIOSIS (1985 to 3 January 2013), Current Controlled Trials (December 2012) and reference lists of articles. SELECTION CRITERIA: Randomised or quasi-randomised trials that compared vitamin D or related compounds, alone or with calcium, against placebo, no intervention or calcium alone, and that reported fracture outcomes in older people. The primary outcome was hip fracture. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial risk of selection bias and aspects of methodological quality, and extracted data. Data were pooled, where possible, using the fixed-effect model, or the random-effects model when heterogeneity between studies appeared substantial. MAIN RESULTS: We included 53 trials with a total of 91,791 participants. Thirty-one trials, with sample sizes ranging from 70 to 36,282 participants, examined vitamin D (including 25-hydroxy vitamin D) with or without calcium in the prevention of fractures in community, nursing home or hospital inpatient populations. Twelve of these 31 trials had participants with a mean or median age of 80 years or over.Another group of 22 smaller trials examined calcitriol or alfacalcidol (1-alphahydroxyvitamin D3), mostly with participants who had established osteoporosis. These trials were carried out in the setting of institutional referral clinics or hospitals.In the assessment of risk of bias for random sequence generation, 21 trials (40%) were deemed to be at low risk, 28 trials (53%) at unclear risk and four trials at high risk (8%). For allocation concealment, 22 trials were at low risk (42%), 29 trials were at unclear risk (55%) and two trials were at high risk (4%).There is high quality evidence that vitamin D alone, in the formats and doses tested, is unlikely to be effective in preventing hip fracture (11 trials, 27,693 participants; risk ratio (RR) 1.12, 95% confidence intervals (CI) 0.98 to 1.29) or any new fracture (15 trials, 28,271 participants; RR 1.03, 95% CI 0.96 to 1.11).There is high quality evidence that vitamin D plus calcium results in a small reduction in hip fracture risk (nine trials, 49,853 participants; RR 0.84, 95% confidence interval (CI) 0.74 to 0.96; P value 0.01). In low-risk populations (residents in the community: with an estimated eight hip fractures per 1000 per year), this equates to one fewer hip fracture per 1000 older adults per year (95% CI 0 to 2). In high risk populations (residents in institutions: with an estimated 54 hip fractures per 1000 per year), this equates to nine fewer hip fractures per 1000 older adults per year (95% CI 2 to 14). There is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures. However, there is only moderate quality evidence of an absence of a statistically significant preventive effect on clinical vertebral fractures. There is high quality evidence that vitamin D plus calcium reduces the risk of any type of fracture (10 trials, 49,976 participants; RR 0.95, 95% CI 0.90 to 0.99).In terms of the results for adverse effects: mortality was not adversely affected by either vitamin D or vitamin D plus calcium supplementation (29 trials, 71,032 participants, RR 0.97, 95% CI 0.93 to 1.01). Hypercalcaemia, which was usually mild (2.6 to 2.8 mmol/L), was more common in people receiving vitamin D or an analogue, with or without calcium (21 trials, 17,124 participants, RR 2.28, 95% CI 1.57 to 3.31), especially for calcitriol (four trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09), than in people receiving placebo or control. There was also a small increased risk of gastrointestinal symptoms (15 trials, 47,761 participants, RR 1.04, 95% CI 1.00 to 1.08), especially for calcium plus vitamin D (four trials, 40,524 participants, RR 1.05, 95% CI 1.01 to 1.09), and a significant increase in renal disease (11 trials, 46,548 participants, RR 1.16, 95% CI 1.02 to 1.33). Other systematic reviews have found an increased association of myocardial infarction with supplemental calcium; and evidence of increased myocardial infarction and stroke, but decreased cancer, with supplemental calcium plus vitamin D, without an overall effect on mortality. AUTHORS' CONCLUSIONS: Vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people. Supplements of vitamin D and calcium may prevent hip or any type of fracture. There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium. This review found that there was no increased risk of death from taking calcium and vitamin D.

Medical Subject Headings (MeSH)
AgedAged, 80 and overBone Density Conservation AgentsCalcitriolDietary SupplementsFemaleFractures, SpontaneousFrail ElderlyHumansHydroxycholecalciferolsMaleOsteoporosisOsteoporosis, PostmenopausalRandomized Controlled Trials as TopicVitamin DVitamins
Study Links
Quality Scores
Safety70
Efficacy80/10
Quality90/10
Citation Metrics
Total Citations344
Citations/Year31.3
Relative Citation Ratio14.88
NIH Percentile99%
Research Impact Scores
APT Score0.95
Weight Score2.28
Normalized Score0.78
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