NSUP: Vitamin D (2008)

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

To examine the relationship between renal function and falls in elderly women.

Inclusion Criteria:
  • Female
  • 65 years old or older
  • Enrolled in STOP IT, a double-blind randomized, placebo-controlled trial.
Exclusion Criteria:
  • Severe chronic illness
  • Chronic liver disease
  • Chronic kidney disease
  • Severe COPD
  • Severe rheumatoid arthritis
  • Serious heart failure
  • Primary hyperparathyriodism
  • Active renal stone disease
  • Taking certain medications (biphosphonates, anticonvulsants, estrogen, fluoride, thiazide diuretics) in the past six months.
Description of Study Protocol:

Recruitment

Enrolled in STOP IT, a double-blind randomized, placebo-controlled trial.

Design 

  • Three-year prospective cohort of 489 elderly women, aged 65 to 77 years old
  • All participants were enrolled in STOP IT, a double-blind randomized, placebo-controlled trial to test the efficacy of conjugated equine estrogens and calcitriol given individually or in combination on bone loss.

Intervention

All of the women in the STOP IT trial were randomized to one of four groups

  1. Conjugated equine estrogens 0.625mg daily (Premarin); medroxyprogesterone acetate 2.5mg daily (Provera) was added if the woman had a uterus
  2. Calcitriol 0.25mcg twice daily
  3. Combination of both
  4. Placebo.

Falls data was collected prospectively by an interview-administered questionnaire in the incidence of the falls every six months for the entire study period of 36 months.

Statistical Analysis

  • ANOVA (univariate comparisons)
  • T-test
  • Poisson regression
  • ITT analysis.
Data Collection Summary:

Timing of Measurements

  • Data collected at zero, six, 12, 24 and 36 months: Falls data, collected prospectively by an interview-administered questionnaire on the incidence of falls
  • Data collected at zero and 36 months: Fasting blood and 24-hour urine samples.

Dependent Variables

  • Estimated Creatinine Clearance (CrCl)
  • Serum 25-hydroxyvitamin D
  • Serum 1,25(OH)2 D
  • Serum intact parathyroid hormone (PTH).

Independent Variables

 Frequency of falls.

Description of Actual Data Sample:
  • Initial N: 489 females; 414 completed the study 
  • Attrition: Described
  • Age: 65 to 77 years
  • Ethnicity: Not described 
  • Anthropometrics: Not described
  • Location: Creighton University, University Nebraska Medical Center; Omaha, NE.
Summary of Results:
  • CrCl and falls in placebo and treatment groups:
    • No effect of treatment on the number of fallers
    • From the Poisson regression model, urine CrCl, whether measured or estimated from the CG and MDRD formula, was a significant predictor of mean cumulative number of falls in the placebo group (P=0.012), but not in the treatment groups
    • CrCl was not a significant predictor of fallers in any of the treatment groups.
  • Fall incidence using the CrCl classification estimated from the formula of Cockcroft Gault and MDRD: 
    • Results were similar with only the under 60ml per minute group having a significant increase in falls
    • In women with CrCl under 60ml per minute, whether measured or using the formula, calcitriol treatment significantly reduced the cumulative number of falls by 50% (P<0.01), calcitriol plus estrogen reduced falls by 40% (P<0.01), whereas estrogen was not effective
    • The effect of calcitriol treatment was evident by 12 months of treatment and statistically significant at 36 months of treatment.
  • Fall incidence at different levels of CrCl: Under 60ml, 60ml to 70ml, 70ml to 80ml, 80ml to 90ml and over 90ml per minute: Only in the under 60ml per minute group was there a significant increase in falls
  • For groups with CrCl under 60ml vs. over 60ml per minute, the mean cumulative number of falls on placebo was significantly higher in the group with CrCl under 60ml per minute (OR, 1.6,; 95% CI, 1.1 to 2.2; P=0.012).
Author Conclusion:
  • Falls are associated with decreased renal function and insufficient calcitriol production by the kidney 
  • In women with decreased CrCl, calcitriol and calcitriol plus estrogen treatment reduced the number of falls.
Funding Source:
University/Hospital: Creighton University, University Nebraska Medical Center
Reviewer Comments:

  • Statistical differences at baseline of serum 1,25(OH)2D levels, calcium absorption, age and weight
  • Limited presentation of demographic data
  • No power calculation presented
  • No description of diet composition
  • 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) 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? ???
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  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? ???
  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%.) 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? Yes
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? 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? Yes
  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? 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? N/A
  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? 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)? 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? 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