EAL

NSUP: Vitamin D (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To measure variability in both plasma 25 hydroxyvitamin D levels and vitamin D binding protein (Gc) in peri- and post-menopausal women with and without hormone-replacement therapy.

Inclusion Criteria:

Three to 24 months past the last menstrual bleeding or have experienced peri-menopausal symptoms (including menstrual irregularities) in combination with elevated FSH levels.

Exclusion Criteria:

Metabolic bone disease
Osteoporosis, defined as non-traumatic vertebral fractures
Current oestrogen use
Treatment with glucocorticoids for more than six months
Current or past malignancy
Chronic disease if newly diagnosed or out of control
Hospitalization because of alcohol or drug addiction.

Description of Study Protocol:

Recruitment

The present study was performed as part of the Danish Osteoporosis Prevention Study (DOPS), which is a 20-year prospective, open-label multi-center study (four centers) on the effect of HRT on calcium homeostasis, bone mineral density (BMD) and fracture risk
DOPS is a population-based cohort study in 2,016 women who were peri- or post-menopausal at the time of inclusion
Direct mailing to a random subsample of Danish Caucasian females aged 45 to 58 years.

Design

Women were selected to be in either the randomized or non-randomized group

Randomized group women were randomly allocated to either HRT or no treatment (no placebo) in blocks of 10, using the envelope method
HRT group received oral sequential therapy as first choice
- Oestradiol, one mg per day, Days One to Six, two mg per day on Days Seven to 28
- Norethisteron, one mg per day on Days 19 to 28.
Hysterectomized women received continuous treatment with two mg oestradiol daily.

Blinding Used

Envelope method.

Intervention

HRT

Statistical Analysis

Chi-square test used to assess differences between groups for categorical variables
Two-sample T-test or the Mann-Whitney U-test for continuous variables
ANOVA used for longitudinal changes
Assumptions for repeated-measures ANOVA were checked using Mauchly's test of sphericity and adjustment in the degrees of freedom was made (Huynh-Feldt epsilon)
Post-hoc comparisons were performed with a two-sample test if significant changes were found by repeated-measures ANOVA
The intra-individual total coefficient of variation of measured indices was calculated as the median of the individual CVs (percentage) for the measurements
The Mantel-Haenszel chi-square test to determine potential predictors of interquartile ranges.

Data Collection Summary:

Timing of measurements: Baseline, 1, 2, 5 years
Dependent variables: Plasma 25OH levels
Independent variables: HRT.

Description of Actual Data Sample:

Initial N: 187
Attrition (final N): 187
Age: 45 to 58 years
Ethnicity: Danish Caucasians
Anthropometrics: Differences in plasma 25OH, dietary vitamin D intake, current smokers and sunbathing habits
Location: Denmark.

Summary of Results:

Coefficient of Variation (Percentage) Total All Subjects			CV (Percentage) HRT Group	CV (Percentage) Non-HRT Group	P-Value
25 Hydroxyvitamin D	Years 1-2	13 (5.7-26)	15 (5.5-26)	12 (5.7-19)	0.24
	Years 2-5	17 (6.9-30)	19 (6.8-32)	16 (7.0-27)	0.25
	Years 1-5	16 (7.1-29)	17 (7.5-32)	16 (6.5-28)	0.46
	Years 1, 2, 5	19 (12-27)	21 (13-30)	18 (12-25)	0.15
Vitamin D Binding Protein, Gc	Years 1-2	3.6 (1.5-6.4)	3.5 (1.5-7.5)	3.7 (1.6-6.4)	0.87
	Years 2-5	4.5 (2.2-7.6)	3.7 (1.4-8.1)	5.0 (2.7-7.2)	0.31
	Years 1-5	4.6 (1.9-6.9)	4.6 (1.9-7.1)	4.5 (2.0-6.7)	0.60
	Years 1, 2, 5	4.8 (3.2-7.4)	4.9 (3.1-7.7)	4.8 (3.4-6.7)	0.96

Author Conclusion:

In groups of patients, 25OH measurement can be used to determine the vitamin D status of the population and represents a means of improving vitamin D status at the population level
Baseline plasma 25OHD levels were positively associated with the use of vitamin D supplements and sunbathing, whereas 25OHD levels were inversely associated with smoking.
Note the author's conclusion in the abstract, which is not quite the same as that noted at the end of the sample paper and in the worksheet: In healthy post-menopausal women, HRT increases Gc levels. Owing to the high intra-individual variation in plasma 25OHD, it seems questionable to use a single estimate as a predictor of individual vitamin D status.

Funding Source:

University/Hospital:

University of Aarhus, Aarhus University (all Denmark)

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Assessed 25OHD levels at baseline using a different assay from that used for measurement of the sample obtained at the one-, two- and five-year follow-ups
A limitation of our study is that we assessed 25OHD levels at baseline using a different assay from that used for measurement of samples obtained at the one-, two- and five-year follow-up visits.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes