EAL

NSUP: Vitamin D (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study whether supplementing with calcium-vitamin D₃-fortified milk reduced bone loss at clinically relevant skeletal sites in men older than 50 years.

Inclusion Criteria:

Community-living white men older than 50 years
Total hip, femoral neck or lumbar spine BMD Z-score within two standard deviations.

Exclusion Criteria:

Taken calcium and vitamin D supplements in the preceding 12 months
Participated in regular high-intensity resistance training in the previous six months or more than 150 minutes per week of moderate to high-impact weight-bearing exercise
Had a BMI over 35kg/m²
Lactose intolerant
Consumed more than four alcoholic beverages per day
Had a history of osteoporotic fracture
Medical disease
Medication use known to affect bone metabolism.

Description of Study Protocol:

Recruitment: Through advertisements in newspapers and community centers and presentations in the community within residential areas of Melbourne, Australia
Design: 167 men 50 to 87 years old were randomized to either a calcium-vitamin D₃-fortified milk (N=85) or to a control group (N=82)
Blinding used: Computer-generated random number list
Intervention: Two 200ml reduced fat (1%) ultra-high-temperature milk containing 500mg calcium and 400 IU of vitamin D₃.

Statistical Analysis

Baseline characteristics between the groups were compared by independent T-tests for continuous variables and X² tests for categorical variables
Changes in weight and BMD were expressed as the percentage changed from baseline
Between-group differences were calculated by subtracting the within groups changes from baseline for the milk supplementation group from the within group changes for the control group at six, 12, 18 and 12 months
All serum 25(OH)D and PTH data were log-transformed
Percentage change in these traits represents the absolute differences from baseline in the log-transformed data multiplied by 100
Time, group and interaction effects during the 24-month study period were examined using pooled time series regression analysis for longitudinal data with random model effects
This analysis is similar to an intention-to-treat analysis in that it includes all participants who entered the study and had at least one follow-up measurement, however a unique feature of this analysis is that it uses all observed data points to obtain a maximum estimate of within person covariance which is used to appropriately adjust time, group and interaction SF
In comparing changes within groups for BMD, results were analyzed unadjusted and adjusted for baseline, age, height, weight (or change in weight) and BMD
The changes in the calcitrophic hormones were also assessed unadjusted and adjusted for baseline age, PTH or 25(OH)D
The inclusion of smoking status and alcohol intake as covariates did not affect any of the results and were not included in the final analysis
All data are presented as means ±SD for 95% CI unless stated.

Data Collection Summary:

Timing of Measurements

Baseline, six, 12, 18 and 24 months

Weight
PTH
25(OH)D
Femoral neck
Total hip
Lumbar spine
Ultradistal radius
33% radius.

Dependent Variables

BMD at femoral neck, total hip, lumbar spine, ultradistal radius and 33% radius
Serum (OH)D
PTH.

Independent Variables

Amount of calcium and vitamin D3 in the diet.

Description of Actual Data Sample:

Initial N: 167 men
Attrition (final N): 149.

Age

Milk Group: 62.1±7.7
Control Group: 61.7±7.7.

Ethnicity

White.

Anthropometrics

Baseline Characteristics	Milk Group (N=85)	Control Group (N=82)
Weight (kg)	80.6±12.6	81.1±10.7
Height (cm)	174.7±7.3	174.9±7.5
BMI (kg/m²)	26.3±3.2	26.5±3.0
Femoral Neck (g/cm@)	0.948±0.115	0.949 +/-0.102
Total Hip (g/cm²)	3.033±0.119	1.038±1.118
Ultradistal Radius (g/cm²)	0.415±0.053	0.417±0.055
33% Radius (g/cm²)	0.786±0.071	0.378±0.066
PTH (pg/ml)	29.2±12.2	30.6±10.4
25(OH)D (nM)	77.2±22.6	76.1±20.5
Energy Expenditure in Moderate Activities (kJ/week)	8,537±7,474	8,965±8,443
Weight-Bearing Exercise (hours per week)	5.3±4.2	5.8±5.1

Location

Melbourne, Australia.

Summary of Results:

Mean Percentage Change (unadjusted) From Baseline for Weight, Serum PTH, 25(OH)D and BMD in the Milk Supplementation and Control Group, Group and the Mean Net Percentage Difference (95% CI) Between the Groups for the Change Relative to Baseline at 24 Months

Parameters	24 Months		Net Difference (Mean, 95% CI)
Parameters	Milk	Control	Net Difference (Mean, 95% CI)
Weight	0.68	-.011	0.79 (-0.40,1.97)
PTH	-11.31	5.5	-16.8 (-26.7,-6.9)
25(OH)D	7.4	-19.9	27.3 (18.7, 36.0)
Femoral Neck	-0.70	-2.22	1.51 (0.55, 2.48)
Total Hip	0.52	0.38	0.90 (0.04, 1.84)
Lumbar Spine	2.13	1.44	0.69 (0.33, 1.72)
UD Radius	0.71	2.28	1.57 (0.79, 2.35)
33% Radius	0.17	-0.57	0.40 (-0.24, 1.05)

Author Conclusion:

Supplementing the diet with 400ml per day of milk containing 1,000mg of calcium and 800 IU vitamin D₃ was effective for suppressing PTH and stopping or reducing bone loss at a number of skeletal sites at major risk of fracture.

Funding Source:

University/Hospital:

Deakin University

Reviewer Comments:

Please review the numbers I listed in the tables as my study copy was difficult to read
Very few side effects from consumption of fortified milk
High study compliance (over 85%)
Small but non-significant weight-gain (0.5kg) after 24 months
Seven men stopped taking the fortified milk at different time-points throughout the study: Three men stopped taking the milk within the first six months, with the remaining men stopping between 11 and 21 months.

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?	Yes
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?		Yes
	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%.)	Yes
	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?	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?	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?	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?	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)?	Yes
	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