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NSUP: Vitamin D (2008)

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

To compare vitamin D levels of post-menopausal osteoporotic women from different geographic areas at various latitudes.

Inclusion Criteria:
  • Female
  • Post-menopausal for at least two years (natural or surgical absence of menses)
  • Prevalent osteoporosis as defined by one of the following:
    • Bone mineral density T-score up to -2.5 at any site
    • Written documentation of diagnosed osteoporosis in the the medical chart
    • Alow trauma, non-pathological fragility fracture of the hip, spine, wrist, humerus or clavicle after age 45
    • Current or previous treatment for osteoporosis with any approved osteoporosis medication.
Exclusion Criteria:

None described.

Description of Study Protocol:

Recruitment

Participants were recruited from 55 sites in 18 countries, either as they presented for routine medical care to the clinic or from a database of those attending the clinic. Half of the participants were recruited in the first enrollment period (May 2004 to October 2004) and half in the second enrollment period (November 2004 to March 2005).

Design

Data collection for the study took place at a single clinic visit, including

  • Fasting serum 25(OH)D levels and serum intact PTH
  • Baseline height, weight
  • Past medical history and current supplements and medication
  • Health survey including self-reported intake, sun exposure and supplemental vitamin D exposure. 

Statistical Analysis

  • Quadratic fit model with plateau was used to evelaute the associaton between serum 25(OH)D and PTH levels
  • PTH levels, means, SD, SE, median range and percentiles were calculated for 25(OH)D and PTH
  • Vitamin D inadequate defined as serum 25(OH)D less than 30ng per ml.
Data Collection Summary:
  • Timing of measurements: At single clinic visit
  • Dependent variable: Serum 25(OH)D
  • Independent variable: Geographic location at variable latitudes (range, 64N to 38S).
Description of Actual Data Sample:
  • Initial N: 2,606
  • Attrition (final N): 2,589
  • Age: 41 to 96 years; mean, 67.1±7.7
  • Ethnicity: Study participants were from Sweden, UK, Germany, The Netherlands, France, Switzerland, Hungary, Spain, Turkey, Lebanon, South Korea, Japan, Thailand, Malaysia, Mexico, Brazil, Chile and Australia.
  • Demographics: 32 black (1.2%); 1,579 white (61.0%).

Anthropometrics N (%)
Age in Years <55
40 (1.5%)
55-60
555 (21.4%)
61-70
1,145 (44.2%)
71-80
731 (28.2%)
81-90
115 (4.4%)
>90
3 (0.1%)
Sun Exposure Index ≥0.63
1,160 (44.8%)
<0.63
1,155 (44.6%)
Vitamin D Supplementation Active analogue (alfacalcidol and calcitriol)
216 (13.6%)
Vitamin D2/D3
208 (13.1%)
Body Mass Index BMI(kg/m2)
25.1 (4.5)
Range (mean, SD)
13.2, 49.6
>30
356 (13.8%)
BMD T-Score < -2.5 at Any Site
2,210 (85.4%)
Vitamin D-Rich Foods (Based on Median Split) <5 per month
919 (35.5)
≥5 per month
1,126 (43.5)
Vitamin D Supplementation Active analogue (alfacalcidol and calcitriol)
216 (13.6%)
Vitamin D2/D3
208 (13.1%)
Vitamin D Dose ≥400 IU
951 (36.7%)
<400 IU
452 (17.5%)
None
1,186 (45.8%)

Location

Sweden, UK, Germany, The Netherlands, France, Switzerland, Hungary, Spain, Turkey, Lebanon, South Korea, Japan, Thailand, Malaysia, Mexico, Brazil, Chile, Australia.

Summary of Results:

 

Region Serum 25(OH)D (ng/ml-1) Serum PTH (pg/ml-1)
Mean SE Mean SE
Europe (1,020)
29.3
0.5
29.1
0.4
Middle East (401)
20.4
0.5
38.4
1.3
Asia (549)
24.4
0.4
25.8
0.5
Latin America (415)
29.6
0.6
33.7
0.9
Australia (204)
28.0
0.8
31.0
1.2
All countries (2,589)
26.8
0.3
30.7
0.3
  • Overall, 63.9% of women had serum 25(OH)D less than 30ng per ml
  • No region had average more than 30ng per ml
  • Low 25(OH)D was independent of receiving osteoporosis prescription or older age (over 70 years)
  • Low 25(OH)D was associated with winter for non-equator countries and higher serum levels of PTH
  • Post-menopausal women receiving treatment may not be compliant with supplement regimen.

Other Findings

Among post-menopausal women with osteoporosis, even in countries with ample sunlight, vitamin D inadequacy is common.

Author Conclusion:

Post-menopausal women with osteoporosis need to seek ways of increasing their vitamin D intake.

Funding Source:
Industry:
Merck Research Laboratories
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
  • Study is not population-based and therefore findings may not be generalizable to the entire population of women with osteoporosis
  • Commercial assays used to measure 25(OH)D in this study have been shown to overestimate serum levels, as compared with gold standard (HPLC), therefore vitamin D inadequacy could be over-reported here
  • Study included the largest international population that had used single lab site to assay samples, which permits more reliable comparisons among groups.
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) N/A
  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) N/A
 
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? N/A
  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? No
  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? No
  2.2. Were criteria applied equally to all study groups? N/A
  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? N/A
  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? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? No
  4.1. Were follow-up methods described and the same for all groups? N/A
  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? No
  4.4. Were reasons for withdrawals similar across groups? ???
  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? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  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? N/A
  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? No
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  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? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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