NSUP: Vitamin D (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To review and synthesize the literature regarding the association of vitamin D2 or D3 on incident fractures. 

Inclusion Criteria:

Research studies that were either parallel design RCT or factorial design that focused on examining the relationship between vitamin D and incident fracture(s).

Exclusion Criteria:
  • Not parallel design RCT or factorial design
  • Research did not examine relationship between vitamin D and fracture incident.

 

Description of Study Protocol:

Recruitment

The following databases were searched:

  • MEDLINE (1996 to the third week of June 2006)
  • Embase (2002 to the 25th week of 2006)
  • CINAHL (1982 to the fourth week of June 2006)
  • AMED (1985 to June 2006)
  • Biological Abstracts (1990 to February 2005)
  • The Cochrane Central Register of Controlled Trials (CENTRAL; second quarter of 2006). 

No language restrictions were applied and studies were restricted to human subjects. 

Design

Studies for inclusion were limited, whenever possible, to randomized, controlled trial (RCTs) to limit bias. Prospective cohorts, case-control and before-after studies were included due to the lack of studies addressing the association between serum 25(OH)D concentrations and bone health outcomes. 

The results of the search were assessed using a three-step process. First, bibliographic records, including title, keywords, and abstract, were screened by one reviewer. Potentially relevant records were then screened independently by two reviewers using the full-text report and strict eligibility criteria. Conflicts were discussed and resolved through consensus or adjudication by a third reviewer. Relevant studies were subsequently assessed for study design and categorized by question. 

Statistical Analysis

  • Meta-analysis of RCTs that assessed interventions, populations and outcomes (e.g., fractures or falls) was concluded using a random effects model, with an assessment of statistical heterogeneity
  • For continuous outcomes [e.g., serum 25(OH)D concentrations and Bone Mineral Density (BMD)], the difference in means between treatment groups was used for the meta-analyses
    • The absolute change in 25(OH)D concentrations was used for quantitative pooling
    • A weighted average was used to calculate the 25(OH)D values for the combined treatment and placebo group. The difference in means was then calculated using the weighted averages for the two combined groups.
  • To avoid differences in the reporting of units for 25(OH)D concentrations, (i.e., nmol per L, ng per ml) all values were converted to nmol per L that was the unit used for data synthesis.
Data Collection Summary:

Timing of Measurements

The results of the search were assessed using a three-step process

  • First, bibliographic records, including title, keywords and abstract, were screened by one reviewer
  • Potentially relevant records were then screened independently by two reviewers using the full-text report and strict eligibility criteria
  • Conflicts were discussed and resolved through consensus or adjudication by a third reviewer
  • Relevant studies were subsequently assessed for study design and categorized by question. 

Dependent Variables

Incident fracture(s).

Independent Variables

Vitamin D2 or D3.

Control Variables

  • Age
  • Gender.
Description of Actual Data Sample:
  • Two trials were classified as secondary prevention trials as all participants had a history of fractures
  • Four other trials reported a baseline fracture prevalence that ranged from 10.7% to 26%
  • Seven trials reported only post-menopausal females
  • Eight trials included both older males and post-menopausal females: Of these eight trials, the percentage of females ranged from 25% to 95%
  • There were no trials in women of reproductive age
  • Nine trials included community dwelling participants
  • One trial included community dwelling participants living independently in apartments
  • Four trials included cohorts of participants living in residential homes
  • One trial was conducted with hospitalized participants who had been community-dwelling prior to admission.
Summary of Results:

Findings

  • Compliance with vitamin D was reported in 11 trials and was greater than 80% in five trials
  • Compliance was less than 80% in six trials
  • In the three largest trials, the compliance ranged from 55% to 63%
  • Combining the results from 13 randomized trials of vitamin D2 or D3±calcium resulted in a non-significant reduction in total fractures that persisted when only trials of higher quality were combined
  • When combining seven trials of vitamin D3(400 IU to 800 IU) plus calcium, there was a reduction in the risk of total and hip fractures
  • However, in a subgroup analysis, this benefit was only evident when combining trials of institutionalized elderly subjects
  • One possible explanation is that the mean serum 25(OH)D level achieved in trials of institutionalized participants was higher than in the trials on community dwellers and provided greater levels of vitamin D repletion
  • The combined estimate from trials with higher end-of-study serum 25(OH)D concentrations (greater than or equal to 74nmol per L) was consistent with a significant reduction in fractures
  • This needs to be interpreted with caution, given the variability in the 25(OH)D assays and incomplete assessment of vitamin D status in the fracture trials
  • The evidence for vitamin D3 plus calcium supplementation in community-dwelling individuals is less strong, although one trial found a significant fracture reduction in community dwelling older men and women
  • In a sub-group from the WHI trial, there was a reduction in hip fractures in women over age 60 years 
  • Vitamin D3 combined with calcium is effective in reducing fractures in institutionalized populations.
Author Conclusion:

Vitamin D3 combined with calcium is effective in reducing fractures in institutionalized populations.

Funding Source:
Government: Agency for Healthcare Research and Quality
Reviewer Comments:

An evaluation of publication bias suggested the possibility of bias, with a lack of smaller trials that failed to find an effect of vitamin D on fracture reduction. 

 

Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
 
Validity Questions
  1. Was the question for the review clearly focused and appropriate? Yes
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? Yes
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? Yes
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? Yes
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? Yes
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? Yes
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? Yes
  10. Was bias due to the review's funding or sponsorship unlikely? Yes