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NSUP: Vitamin D (2008)

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

To determine if the intake of fortified (1,000mg per day calcium plus 800 IU per day vitamin D3) milk has an effect on bone geometry, vBMD and strength in men aged 50 to 87 years of age.

Inclusion Criteria:

All participants previously enrolled in a two-year randomized controlled trial.

Exclusion Criteria:
  1. Those who had taken calcium or vitamin D supplements in the preceding 12 months
  2. Participated in regular intensity resistance training in the previous six months or greater than 150 minutes per week of moderate to high impact weight bearing exercise
  3. Had a BMI greater than 35kg/m2
  4. Lactose intolerant
  5. Consumed more than four alcoholic beverages per day
  6. History of osteoporotic fracture
  7. Medical disease or taking medication that affects bone metabolism.
Description of Study Protocol:
  • Recruitment: Ambulatory community living Caucasian men aged 50 to 87 years from residential areas in Melbourne, Australia
  • Design: 110 men divided into groups according to age (less than 65 years or 65 years and above) and dietary calcium intake (less than 800mg per day or 800mg per day and above). All participants then randomized into the fortified milk group or control group. 
  • Intervention: Milk fortified group consumed 400ml per day of reduced fat milk (1%) fortified with approximately 1,000mg calcium plus 800 IU vitamin D3 above typical intake. Control group continued with usual diet.
     

 Statistical Analysis

  1. SPSS version 12.0.1 for Windows
  2. Independent T-tests used to compare baseline characteristics between groups for continuous variables
  3. Chi-square tests used to compare baseline characteristics between groups for categorical variables
  4. Paired T-tests and ANCOVA used to assess the significance of within and between group changes, respectively
  5. Post-hoc analysis used to examine the influence of age on skeletal responses to fortified milk.
Data Collection Summary:

Timing of Measurements

  • At baseline
    • Height (cm)
    • Weight (kg)
    • BMI (kg per m2)
    • Weight-bearing activities (hours per week).
  • At baseline, 12 and 24 months
    • 25(OH)D (nmol per L)
    • PTH (pg per ml).
  • At baseline and 24 months: QCT measurements used to record changes in cortical and trabecular vBMD and bone geometry at the lumbar spine and mid-femur
  • At baseline and six month intervals
    • Height (cm)
    • Weight (kg)
    • BMI (kg/m2)
    • Weight-bearing activities (hours per week)
    • Total energy intake (kJ per day)
    • Dietary calcium intake (mg per day)
    • 25(OH)D (nmol per L)
    • PTH (pg per ml)
    • CHAMPS physical activity survey and medication, smoking and alcohol use determined via questionnaire.

Dependent Variables

  • Variable One: Mid-femur measured by QCT including total area, cortical area and trabecular vBMD bone geometry, cortical vBMD, calculated maximum (Imax) and minimum (Imin) moments of inertia and Ipolar (polar moment of inertia)
  • Variable Two: Lumbar spine measured by QCT including total vBMD, trabecular vBMD, vCSI (veterbral compression strength index), cortical and trabecular vBMD bone geometry after QCT before vCSI was calculated, etc.

Independent Variables

Calcium plus vitamin D3 fortified milk.

Description of Actual Data Sample:

Initial N

  • 110
  • Milk Supplementation Group: 61
  • Control Group: 50.

Attrition (Final N)

110.

Age

  • Milk Supplementation Group: 62.9±7.6
  • Control Group: 62.8±7.2.

Ethnicity

Caucasian.

Other Relevant Demographics

Characteristic (Baseline) Milk Control
N
61
50
Age (years)
62.9±7.6
62.8±7.2
Height (cm)
174.9±7.2
175.0±7.5
Weight (kg)
80.8±11.7
82.6±9.0
BMI (kg/m2)
26.3±3.1
26.9±2.4
Weight-bearing activities (hours per week)
5.1±3.8
5.8±6.0
Total energy intake (kJ per day)
8,909±6,808
8,675±2,281
Dietary calcium intake (mg per day)
981±406
914±344
25(OH)D (nmol per L)
78.5±23.7
79.2±22.9
PTH (pg per ml)
28.0±10.8
30.1±10.7

Anthropometrics

QCT Mid-Femur (Baseline) Milk Supplementation Group Control Group
Total area (mm2)
671±81
657±75
Medullary area (mm2)
179±53
168±42
Cortical area (mm2)
492±60
489±57
Cortical vBMD (mg/cm3)
1,148±31
1,144±43
Ipolar (mg/cm)
8,041±1,900
7,745±1,652

 

QCT L1-L3 (baseline) Milk Supplementation Group Control Group
Total vBMD (mg/cm3)
161±31
163±26
Trabecular vBMD (mg/cm3)
104±32
107±23
vCSI (g2/cm4)
0.363±0.130
0.368±0.122

Location

Melbourne, Australia.

Summary of Results:

Variables

Treatment Group
(Measures and Confidence Intervals)

Control Group
(Measures and Confidence Intervals)

Statistical Significance of Group Difference

Percentage Change (95% CI)

Percentage Change (95% CI)

Net Percentage Difference (95% CI)
QCT Mid-Femur     Total area
-0.01 (-0.23, 0.21)
-0.05 (-0.22, 0.12)
0.04 (-0.24, 0.32)
Medullary area
-0.06 (-0.83, 0.70)
0.76 (-0.18, 1.70)
-0.82 (-2.00, 0.36)
Cortical area 
-0.03 (-0.37, 0.29)
-0.31 (-0.69, 0.08)
0.28 (-0.23, 0.77)
Cortical vBMD 
-1.52 (-2.35, -0.69)
-2.39 (-3.36, -1.53)
0.87 (-0.31, 2.06)
Ipolar
-1.55 (-2.45, -0.65)
-2.41 (-3.41,-1.41)
0.86 (-0.46, 2.19)
QCT L1-L3  

Total vBMD

 0.36 (-0.99, 1.72)

 -0.60 (-0.24, 1.27)

 0.96 (-1.32, 3.24)
Trabecular vBMD
-2.36 (-3.95, -0.76)
-2.86 (-5.29, -0.43)
0.50 (-2.37,3.38)
vCSI
2.68 (0.21, 5.16)
1.44 (-2.05, 4.93)
1.24 (-2.98, 5.46)

Other Findings

An age split of 62 years or less vs. more than 62 years was the most significant for discriminating the skeletal changes between the Milk Supplementation Group and the Control Group.

Author Conclusion:

Supplementing with reduced fat milk fortified with 1,000mg calcium and 800IU vitamin D3 per day prevented endocortical bone loss and slowed the decline in cortical vBMD at the appendicular skeleton in healthy community-living men over the age of 50 years.

Funding Source:
Government: NHMRC
Industry:
Murray Goulburn Co-op Co Ltd
Food Company:
University/Hospital: Deakin University (Australia)
Not-for-profit
1
Foundation associated with industry:
In-Kind support reported by Industry: Yes
Reviewer Comments:
  • Author-noted limitations
    • Only a portion (110) of the initial 167 randomized to the milk supplementation and control group were examined, which might have skewed results
    • CT scan results may be influenced by age-related changes in the fat content of the marrow
    • Small geometric changes at the mid-femur may be in part due to changes in cortical vBMD as a result of partial volume effects
    • Mid-femur is not a common fracture site.
  • In addition, not listed under limitations by author, seven of the men in the initial trial group stopped taking the fortified milk at different time points throughout the intervention. It is unclear whether that included any of the 61 men in this study.
  • Reading study was a little confusing as the participants for this study were from a larger initial study
  • Not able to differentiate whether the addition of calcium or Vitamin D3 or combination contributed to the benefits to endocortical effects.
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? No
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? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  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? No
  4.1. Were follow-up methods described and the same for all groups? No
  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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  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.) No
  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? No
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  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? ???
  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? No
  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? No
  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? No
  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)? No
  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