EAL

NSUP: Vitamin D (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the relationship between serum 25-and serum parathyroid hormone (PTH) in calcium-sufficient African-American women in mid-life; to determine if this relationship is predictive of bone loss in this population.

Inclusion Criteria:

Healthy
Post-menopausal
African-American
Female
Mid-life, aged 50 to 75 years old.

Exclusion Criteria:

A total calcium intake of less than 1,200mg per day or greater than 1,500mg per day
Women on hormone replacement therapy.

Description of Study Protocol:

Recruitment: Not described
Design: Randomized, placebo controlled trial of 208 free-living African-American women aged 50 to 75 years old with a total calcium intake between 1,200mg to 1,500mg per day
Blinding used: Yes.

Intervention

Subjects were randomly assigned to receive daily either 20mcg (800 IU) of oral vitamin D₃ or a matched placebo
At the end of the 24-month period, the dose of vitamin D₃was raised to 50 micrograms per day (2,000 IU per day)
Subjects were seen on-site every three months
A food-frequency questionnaire for calcium and vitamin D intakes was completed by participants, with the assistance of a nurse, at each visit to assess the supplemental calcium requirement (total daily intake of 1,200mg to 1,500mg)
In addition, a three-day dietary log was filled out by subjects at baseline and 24 months.

Statistical Analysis

Loess method
Student’s T-test (paired data)
Pearson's correlation
Spearman's correlation coefficient
Fisher's exact test
Chi-squared test.

Data Collection Summary:

Timing of Measurements

The following data was collected at three, six, 12, 18, 24, 27, 30 and 36 months:

Serum 25(OH)D
Serum PTH
Food Frequency Questionnaire.

The Following Data was Collected at Zero and 24 Months

Three-day dietary log.

Dependent Variables

Serum 25(OH)D
Serum PTH.

Independent Variables

Calcium intake.

Description of Actual Data Sample:

Initial N: 208 females
Attrition (final N): Not described
Age: Mean age of 60 years
Ethnicity: African-American
Anthropometrics: Mean BMI, 29.8±4,6
Location: Bone and Mineral Research Center, Winthrop University Hospital, Mineola, New York.

Summary of Results:

The authors noted a significant inverse relation between serum PTH and 25(OH)D
A Loess plot suggested a breakpoint between 40nmol per L and 50nmol per L for serum 25(OH)D
- This threshold estimate is confirmed by noting that the difference between the change in PTH (baseline to one year, -13.4) in patients with less than 42nmol 25(OH)D per L at baseline and the change in PTH (baseline to one year plus, -2.8) in patients with more than 42nmol 25(OH)D per L was greatest when 42nmol 25(OH)D per L was used as the threshold
- There was a highly significant difference in PTH from baseline to one year in patients who started the study with 25(OH)D and less than 42nmol per L (P<0.0001)
- There was no significant change in those who started the study at 25(OH)D and more than 42nmol per L
- Vitamin D [25(OH)D] reduced below threshold and PTH increase much more rapidly (slope of the line below 40nmol to 50nmol per L 25(OH)D is 10 times larger than slope of line above threshold).
A line-line model was fitted to the data and it showed a spline knot at 44nmol per L
There was no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40nmol per L.

Author Conclusion:

The data suggests that a serum concentration of 40nmol to 50nmol 25(OH)D per L is needed to prevent a rise in PTH concentrations in calcium-sufficient African-American women in mid-life
Although a threshold for 25(OH)D can be identified, it is suggested that it should not be used to recommend optimal vitamin D status.

Funding Source:

Government:

NIA, NIH

Reviewer Comments:

Limited description of inclusion and exclusion criteria
Limited presentation of demographic data
No description of randomization scheme.

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?		???
	4.1.	Were follow-up methods described and the same for all groups?	???
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	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.)	Yes
	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?	Yes
	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?	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