Supplementing Vitamin D in Unselected Elderly People through a Yearly Bolus to Reduce the Risk of Fractures: Is this Practice Effective?

Mini Review

J Endocr Disord. 2015; 2(1): 1017.

Supplementing Vitamin D in Unselected Elderly People through a Yearly Bolus to Reduce the Risk of Fractures: Is this Practice Effective?

Messori A*, Trippoli S and Marinai C

Department of HTAESTAR Toscana, University of Firenze, Italy

*Corresponding author: Messori A, Department of HTAESTAR Toscana, University of Firenze, Via San Salvi 12, 50100 Firenze, Italy

Received: October 26, 2015; Accepted: November 18, 2015; Published: November 27, 2015


A number of studies have investigated the effectiveness of vitamin D given as an annual dose to unselected elderly people to reduce the risk of fractures, but the results are conflicting. Since new clinical studies have recently been made available, we carried out an updated analysis on this issue.

Our study was aimed at evaluating the effectiveness of this annual dose of vitamin D. Patients were unselected elderly people. Fractures were the endpoint of our analysis. The clinical material was represented by observational and randomized studies that included a patient group given the vitamin D annual bolus and a control group given no such supplementation. Our meta-analysis was based on the random-effect model of Der Simonian and Laird. Relative Risk (RR) was our outcome measure.

After a standard PubMed search, we identified 5 clinical studies that met the criteria of our analysis (total number of patients: 115,220). The fracture rates were pooled across the studies. The meta-analytical RR was estimated to be 0.81 (95% confidence interval, 0.59 to 1.13). There was a high degree of heterogeneity in this clinical material.

Our results indicate that the supplementation of vitamin D based on an annual mega-dose does not reduce the incidence of fractures in unselected elderly people.

Keywords: Osteoporosis; Fractures; Vitamin D; Annual bolus; Elderly people


The effectiveness of vitamin D supplementation in unselected elderly people has been evaluated by numerous clinical studies [1- 7] aimed at improving the clinical outcomes of bone health (e.g. fractures and falls). One important practical criterion to distinguish these supplementation studies from one another is the schedule adopted for the administration of vitamin D.

The great majority of these clinical studies employed a daily administration of vitamin D (or, anyhow, a regular schedule of repeated administrations). According to the systematic review of Newberry et al., [2] and the DIPART pooled analysis of 7 randomized studies [6], the effectiveness of the daily supplementation appears to be controversial. For example, the DIPART analysis [6] indicated that vitamin D given alone in doses of 10-20 microg was not effective in preventing fractures; by contrast, calcium and vitamin D given together were shown to reduce hip fractures and total fractures, and probably vertebral fractures. Conflicting results were shown by other clinical studies as well [2]. So, on the one hand, no firm conclusion can currently be made on the effectiveness of this intervention. More importantly, since the results reported thus far in the literature for the regular regimen of repeated doses are conflicting [1-7], it seems very unlikely that this therapeutic controversy will be settled in the near future on the basis of new analyses of published data and/or new data from original studies.

A quite small subset of the clinical studies focused on vitamin D supplementation employed a single mega-dose of vitamin D (single annual bolus scheme) that has generally been administered to unselected elderly patients in conjunction with the influenza vaccination [2,6]. Also the effectiveness of the annual winter schedule is controversial, but one important advantage in exploring if this dosing schedule works is that the available studies are fewer than in the case of daily administration; therefore this permits an attempt to clarify this question through a new analysis.

The present study was carried out as an original meta-analysis aimed at evaluating if the annual bolus scheme can reduce the incidence of fractures in unselected elderly people in comparison with patients not given any form of vitamin D supplementation.


Study design. The design of our meta-analysis can be summarized as follows. We firstly conducted a literature search aimed at identifying all clinical studies evaluating the effectiveness of the annual mega-dose in unselected elderly people. The clinical end-point for our analysis was the incidence of fractures. Then, we carried out a standard pair wise meta-analysis to determine the effectiveness of the mega-dose in comparison with no vitamin D supplementation.

Literature search

Our literature search was conducted in PubMed (www.pubmed. org) and covered the period from inception (1966) to present time (last query on 30 September 2015). A single search term (namely “vitamin D supplementation AND fracture*”) was employed. The PRISMA schematic [8] was adopted to describe the flow leading to the identification of pertinent studies. Although the number of citations retrieved through the first search based on the above keyword was high (more than 1,400), we analyzed all of these articles individually by examining the abstract or, when necessary, their full text. In this way, despite the operational complexity of this approach, we successfully identified the clinical studies that met our inclusion criteria. We thought that there was no simple method of literature analysis that could (more automatically) distinguish the studies employing the mega-dose from the remaining studies employing other dosing schedules.

The inclusion criteria for our analysis were as follows: (i) administration of vitamin D to unselected elderly people (aged = 65 years); (ii) dosing schedule based on a single annual mega-dose of at least 150,000 IU; (iii) information on the incidence of fractures in treated patients and in controls; (iv) randomised and non-randomised design. For each clinical study, we extracted the basic information needed for our analysis as well as the information on the above endpoint, expressed as a crude rate.

Meta-analytic methodology

As regards the assessment of methodological quality, two reviewers (AM and ST) applied the Cochrane Collaboration’s tool [9] to evaluate the risk of bias in the included studies. This tool assesses six domains (namely: random sequence generation, concealment of allocation, blinding of participants and personnel, incomplete data, selective outcome reporting of outcomes, and other sources of bias). Studies with adequate procedures in all domains were considered to have a low risk of bias.

For our statistical analysis, we employed a standard model of traditional pair-wise meta-analysis [3]. Although two versions of this model (i.e., fixed-effect and random-effect) are available, we chose the random-effect model because we anticipated the presence of heterogeneity in our clinical material. The outcome measure adopted for our analysis was Relative Risk (RR), which was estimated along with its 95% Confidence Interval (CI).

All of our analyses were conducted by using the software package Open Meta-Analyst (version 4.16.12, Tufts University, URL: https://


Our literature search, conducted according to the PRISMA approach (Figure 1), identified 5 studies [10-13] that met the inclusion criteria of our analysis (Table 1). The total number of patients was 115,220. The study by Rossini et al. [10], in which the patients treated in the year 2000 were separately assessed from those treated in 2001, was handled as two separate studies. The analysis of the methodological quality of studies (data not shown) did not provide any important clue to improve the interpretation of our results; of course, the quality scores were much better for randomised studies than for the remaining ones. There were some differences across the studies in the amount of vitamin D contained in the bolus dose (from 150,000 to 500,000 IU), age range, and type of fractures.