NSUP: Vitamin D (2008)

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

Assess risk factors associated with vitamin D inadequacy in post-menopausal women with osteoporosis from various latitudes and geographical areas.

Inclusion Criteria:
  • Female
  • Post-menopausal for at least two years (absence of menses, natural or surgical)
  • Prevalent osteoporosis defined as one of the following:
    • Bone mineral density T-score up to -2.5 at any site or written documentation of diagnosed osteoporosis in the medical chart
    • A low-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:

Not stated.

Description of Study Protocol:

Recruitment

Women recruited from northern, central and southern Europe, the Middle East, Latin America, the Pacific Rim and Asia either as they presented for routine medical care to the clinic or from a database of those attending the clinic.

Design

  • Health data were collected at a single cinic visit
  • A survey was used to gather information on factors that can potentially influence serum 25(OH)D levels
  • Single blood sample collected for assessment of serum 25(OH)D and serum intact PTH.

Statistical Analysis

  • For each potential risk factor, univariate logistic regresson models were used to obtain the unadjusted odds ratio (OR) and corresponding 95% confidence interval for the relative risk of vitamin D inadequacy
  • Risk factors with P≤0.10 were included in a multivariate stepwise logistic regression analysis
  • Final logistic regression model included only risk factors with P≤0.05.
Data Collection Summary:

Timing of Measurements

  • Collected at single cinic visit
    • Height
    • Weight
    • Information regarding past medical history
    • Current and prior medication.
  • Survey gathered information on
    • Dietary and supplemental vitamin D intake
    • Weekly sun exposure
    • General health
    • Discussion with the doctor about the importance of vitamin D in bone health
    • Highest level of education.
  • The section of the survey assessing the routine intake of vitamin D-rich foods was customized for each country to include a list of specific vitamin D-rich foods (e.g., fish) that were commonly eaten in that country
  • Single blood sample collected for assessment of serum 25(OH)D and serum intact PTH.

Dependent Variables

Serum 25(OH)D levels.

Independent Variables

Geographic location with various latitudes.

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

Swedish, English, German, Dutch, French, Swiss, Hungarians, Spanish, Turkish, Lebanese, South Korean, Japanese, Thais, Malaysians, Mexicans, Brazilians, Chileans and Australians.

Other Relevant Demographics

Risk Factor N (%)
Age 70 or under
1,740 (67.2)
Over 70
849 (32.8)
Race White
1,579 (61.0)
Asian
558 (21.6)
Other
452 (17.5)
BMI 30kg/m2 or less
2,233 (86.2)
Over 30kg/m2
356 (13.8)
Latitutde Equatorial
550 (21.2)
Non-equatorial
2,039 (78.8)
Vitamin D Supplements 400 IU or more daily
951 (36.7)
Under 400 IU daily
452 (17.5)
No supplement
1,186 (45.8)
Discussed Vitamin D with Doctor Yes
1,403 (54.2)
No

1,180 (45.6)

Sun Exposure Index Groups 0.63 or less
1,160 (44.8)
Over 0.63
1,155 (44.6)
Skin Tone Light
947 (36.6)
Medium
1,317 (50.9)
Dark
289 (11.2)
General Health Excellent or very good
510 (19.7)
Good

1,128 (43.6)

Fair or Poor

950 (36.7)
Education Level High school or less
1,869 (72.2)
University
717 (27.7)
Travel to Sunny Areas Yes
559 (21.6)
No
2,030 (74.4)
Missing
274 (10.6)

 

Anthropometrics and Labs

N (%) or SD

Mean Serum 25(OH)D Level

67nmol/L (+0.08)

BMD T-Score <-2.5 at Any Site   

2,210 (85.4%)

BMI (kg/m2)

1 (4.5)
Mean Serum PTH Level
30.7pg/ml (+17.6)

 

Summary of Results:
Region (N) Country (N) Latitude Serum 25(OH)D nmol/L (ng/ml)
Mean SE
Europe (1,020)    
73.3 (29.3)
1.3 (0.5)
Sweden (150) 64 to 58 degrees N
86.5 (34.6)
2.8 (1.1)
United Kingdom (98) 53 to 52 degrees N
58.5 (23.4)
3.3 (1.3)
Germany (100) 53 to 48 degrees N
66.8 (26.7)
3.5 (1.4)
The Netherlands (50) 51 degrees N
77.0 (30.8)
4.8 (1.9)
France (199) 50 to 46 degrees N
70.5 (28.2)
3.8 (1.5)
Switzerland (173) 47 to 46 degrees N
77.3 (30.9)
2.3 (0.9)
Hungary (100) 47 degrees N
78.3 (31.3)
3.8 (1.5)
Spain (150) 43 to 38 degrees N
68.0 (27.2)
2.8 (1.1)
Middle East (401)    
51.0 (20.4)
1.3 (0.5)
Turkey (150) 41 to 38 degrees N
54.5 (21.8)
2.5 (1.0)
Lebanon (251) 34 degrees N
48.8 (19.5)
1.5 (0.6)
Asia (549)    
61.0 (24.4)
1.0 (0.4)
South Korea (101) 38 degrees N
44.0 (17.6)
1.8 (0.7)
Japan (198) 36 to 35 degrees N
51.5 (20.6)
1.0 (0.4)
Thailand (100) 13 degrees N
75.8 (30.3)
2.5 (1.0)
Malaysia (150) 5 to 3 degrees N
7.5.5 (30.2)
2.0 (0.8)
Latin America (415)    
74.0 (29.6)
1.5 (0.6)
Mexico (149) 19 degrees N
65.5 (26.2)
2.3 (0.9)
Brazil (151) 13 to 25 degrees S
81.5 (32.6)
2.5 (1.0)
Chile (115) 34 degrees S
75.5 (30.2)

3.0 (1.2)

Pacific Rim (204)    
70.0 (28.0)
2.0 (0.8)
Australia (204) 31 to 37 degrees  S
70.0 (28.0)
2.0 (0.8)
All Countries (2,589)    
67.0 (26.8)
0.8 (0.3)

Other Findings

  • Potential risk factors include:
    • Race
    • High BMI
    • Living in non-equatorial regions
    • Vitamin D supplementation under 400 IU daily
    • Poor general health
    • Absence of discussion with a doctor regarding the importance of vitamin D to bone health
    • Low education level
    • Low sun exposure
    • Skin reactivity
    • Absence of travel to sunny areas in the past month.
  • Season itself was not a sigificant predictor of vitamin D inadequacy
  • Factors found to have a significant (P<0.05) association with vitamin D inadequacy were:
    • Race (Asian and other)
    • Higher BMI (under 30kg per m2)
    • Latitude of enrolment country (non-equatorial)
    • Vitamin D supplementation (under 400 IU daily and none)
    • Poor general health
    • Absence of discussion with a doctor regarding the importance of vitamin D to bone health
    • Lower education level
    • Less sun exposure
    • Darker skin tones
    • Tanning with difficulty and absence of travel to sunny area in the past month.
Author Conclusion:
  • Among post-menopausal women with osteoporosis (even in countries with ample sunlight), vitamin D inadequacy is common with 64% of post-menopausal women in this 18-country study having vitamin D inadequacy
  • The potential adverse effects of vitamin D inadequacy (particularly on bone health) and its high prevalence suggest that modifable risk factors such as high BMI, inadequate vitamin supplementation, limited education about the importance of vitamin D and low sun exposure, could reasonably be targeted as part of a comprehensive strategy to improve bone health in post-menopausal women.
Funding Source:
Industry:
Merck Research Laboratories
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:

Study sample cannot be considered population-based and therefore results may not be generalizable to all post-menopausal women with or without osteoporosis.

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? 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? ???
  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? 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? 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? ???
  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? ???
  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? 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? 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? ???
  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? 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? N/A
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)? N/A
  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? No
  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