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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis

C Jackson, S Gaugris, SS Sen, and D Hosking.

Review published: 2007.

CRD summary

This review found that there is a trend towards a reduced risk of falls associated with vitamin D treatment. Evidence relating to fracture risk was inconclusive. The conclusion about risk of falls is not well supported by the evidence presented, as no benefit was found for postmenopausal women and the review was not designed to apply to any other population group.

Authors' objectives

To determine the effect of vitamin D supplementation on the risk of fall and fracture, primarily in postmenopausal women.


MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Database of Systematic Reviews were searched from 1985 to June 2005. The reference lists of relevant guidelines, systematic reviews and meta-analyses were reviewed. The search was restricted to articles published in English.

Study selection

Studies of any design were eligible for inclusion, provided they compared vitamin D versus placebo, or vitamin D plus calcium versus calcium alone (with or without concomitant non-osteoporosis medications). Studies of postmenopausal women were eligible; those that also included men aged over 65 years were eligible too, but the data for men were only included in the analysis if the results for women could not be extracted separately. The primary outcomes of the review were spontaneous fall and vertebral or nonvertebral fractures. The secondary outcomes were serum level of the following biochemical markers: serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase and urinary cross-linked N-telopeptides of type I collagen.

The intervention in the included studies was oral cholecalciferol (vitamin D3) at doses ranging (in most cases) from 300 to 800 international units daily, administered with or without calcium. Some participants were also taking other medications (e.g. corticosteroids or thyroid medications). The participants were aged from 45 to over 80 years and lived in a variety of settings, such as the community, nursing homes and apartments for the elderly (where stated). The inclusion criteria of the primary studies varied with respect to the fracture or osteoporosis history of the participants. In all studies the mean baseline serum 25-hydroxyvitamin D indicated that participants were vitamin D-inadequate. Nearly half of the studies in the review included both men and women, without separate analysis. The duration of follow-up varied from 18 weeks to over 5 years.

The authors did not state how many reviewers selected articles for the review, or how any disagreements were resolved.

Assessment of study quality

The quality of the included studies was assessed using the Jadad scoring method. The authors did not state how the assessment was performed.

Data extraction

Relative risks were calculated from the numbers of events in the control and intervention groups of each study, along with 95% confidence intervals (CIs). For continuous outcomes (biochemical markers), differences from baseline were extracted for both groups.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction

Methods of synthesis

Pooled risk ratios (RRs) with 95% CIs were calculated using fixed-effect models for falls, vertebral fractures and nonvertebral fractures. Heterogeneity between the studies was assessed using the χ2 test. Subgroup analyses were conducted to determine whether effects differed among postmenopausal women.

Results of the review

Nine studies were included: 8 randomised controlled trials (RCTs; n=7,798 eligible for the review) and one prospective controlled study (n=368).

All the included RCTs were of high quality.

Vitamin D versus controls: when studies including only postmenopausal women were pooled, no statistically significant difference between the groups was found for falls (3 RCTs), nonvertebral fractures (2 RCTs) or vertebral fractures (2 RCTs). When all of the included studies were pooled, no statistically significant difference between the groups was found for falls or fractures, although there was a non significant trend for less falls in the vitamin D group (RR 0.88, 95% CI: 0.78, 1.00; 5 studies). There was no significant heterogeneity for any of these analyses.

The data were scanty and inconclusive for secondary outcomes.

Authors' conclusions

There is a trend towards a reduction in the risk of falls associated with vitamin D treatment, but no clear evidence about the association between vitamin D and risk of fractures.

CRD commentary

The review objective and inclusion criteria were unclear with respect to the participant group of interest. Consequently, nearly half of the primary studies included both men and women and were thus of unknown applicability to postmenopausal women. Relevant sources were searched for studies, but the search terms were not reported. No attempt was made to locate unpublished data and the search was restricted by language, so some studies might have been missed. Publication bias was not assessed. It is unclear whether steps were taken to minimise bias and error in the study selection, validity assessment and data extraction processes by having more than one reviewer make decisions independently. Although study validity was assessed, there were no details about the validity of individual RCTs (e.g. drop-out rates) and the validity assessment tool used was not designed for non-RCTs. Appropriate methods were used to pool studies and test for statistical heterogeneity, and potential sources of clinical and methodological heterogeneity were well addressed in the text. The poor reporting of review methods and lack of detail about study quality make it difficult to assess the reliability of the findings. Moreover, the authors’ conclusions are not supported by the evidence presented: no significant benefit from vitamin D was found for postmenopausal women and the review was not designed to apply to any other population group..

Implications of the review for practice and research

Practice: The authors stated that vitamin D3 should be considered as part of routine clinical management of osteoporosis. This proposal is not well supported by the evidence presented in the review.

Research: The authors did not state any implications for further research.


Merck and Co. Inc.

Bibliographic details

Jackson C, Gaugris S, Sen S S, Hosking D. The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis QJM: an International Journal of Medicine 2007; 100(4): 185-192. [PubMed: 17308327]

Indexing Status

Subject indexing assigned by NLM


Accidental Falls; Aged; Aged, 80 and over; Bone Density Conservation Agents /therapeutic use; Cholecalciferol /administration & dosage /deficiency; Dietary Supplements; Hip Fractures /prevention & control; Middle Aged; Osteoporosis /prevention & control; Postmenopause /metabolism; Risk Factors; Spinal Fractures /prevention & control; Treatment Outcome; Vitamin D Deficiency /complications /diet therapy



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 17308327