NSUP: Vitamin D (2008)

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

To study the effect of a year of treatment of calcium and vitamin D supplements on bone mineral density and bone markers in patients with a recent low energy fracture.

Inclusion Criteria:
  • Women and men aged more than 50 years who were admitted to Roskilde Arnt University Hospital in Koge with a relevant low-energy fracture
  • All women were menopausal (at least two years since last menstruation).
Exclusion Criteria:
  • Dementia or otherwise lacking the ability to sign an informed consent form
  • History of cancer other than superficial skin cancers
  • Excessive alcohol abuse
  • Use of hormone replacement therapy
  • Osteoporosis medication
  • Intake of cholecalciferol of more than 800 IU or using 1,25-dihydroxycholecalciferol
  • Serum creatinine more than 130mcg per L or serum alanine aminotransferase more than 2.5 times the upper limit.
Description of Study Protocol:

Recruitment

277 patients with low energy hip fracture; 141 patients with fracture of the distal forearm and 46 patients with a fracture of the proximal humerus were screened for participation. The hip fracture patients were recruited over an 18-month period and informed of the study during their hospital stay. The upper extremity fracture patients were recruited over a 12-month period and were informed of the study through the mail and invited if they met the inclusion criteria.

Design

122 patients randomly assigned in blocks to receive either:

  • 3,000mg calcium carbonate (corresponding to a dose of 1,200mg elementary calcium) plus 1,200 IU cholecalciferol and 200 IU cholecalciferol given as multi-vitamin (total of 1,400 IU corresponding to 35mcg cholecalciferol)
  • Placebo plus 200 IU cholecalciferol given as a multi-vitamin (five mcg cholecalciferol).

Intervention

Calcium carbonate plus cholecalciferol.

Statistical Analysis

  • T-tests used to compare means
  • Intention-to-treat analysis
  • Pearson's correlation or general linear to analyze relations between variables.
Data Collection Summary:

Timing of Measurements

  • Control visits at one, three and 12 months after inclusion
  • Physical performance evaluated after inclusion and after 12 months.

Dependent Variables

  • Bone mineral density
  • Serum concentrations of intact N-terminal propeptide of type I collagen
  • Serum osteocalcin concentrations
  • Serum concentrations of C-terminal telopeptide of type I collagen
  • Vitamin D status
  • Serum intact PTH.

 Independent Variables

  • Calcium
  • Vitamin D.

 

 

Description of Actual Data Sample:
  • Initial N: 122 (101 women, 21 men)
  • Attrition (final N): 79
  • Age: More than 50 years old
  • Ethnicity: Undisclosed.

Anthropometics

Baseline Hip Fracture Intervention Hip Fracture Placebo Upper Extremity Fracture Intervention Upper Extremity Fracture Placebo P2
Age
77±6
72±10
64±7
66±9
<0.01
BMI (kg/m2)
21.6±4.0
23.3±4.4
27.5±5.1
25.3±5.1
<0.01
PINP (ug/L)
74.6±32.3
94.6±44.6
75.2±31.7
69.1±19.6
NS
OC (ng/mL)
16.9±8.2
21.1±12.9
22.5±11.0
29.2±12.5
<0.001
ICTP (ug/L)
11.7±4.3
13.1±6.3
9.4±5.3
7.3±2.4
<0.01
25(OH)D (nmol/L)
33.1±16.7
39.9±16.8
62.4±17.7
68.5±33.8
<0.01
PTH (pmol/L)
3.4±1.0
4.1±1.6
3.7±1.5
4.7±3.4
NS
BMD L2-L4 (g/cm2)
0.899±0.239
0.809±0.186
0.945±0.153
0.868±0.210
NS
BMD Hip, Total (g/cm2)
0.573±0.080
0.618±0.130
0.824±0.130
0.759±0.151
<0.01
Timed Up & Go Test(s)
33.9±18.3
34.4±14.6
8.1±0.9
8.4±2.4
<0.001

 

Location

Koge, Denmark.

 

Summary of Results:
  Hip Fracture Intervention Group Hip Fracture Placebo Upper Extremity Fracture Group Intervention Upper Extremity Fracture Group Placebo P-value
Vitamin D 82±19nmol/L 53±16nmol/L 90±24nmol/L 77±31nmol/L P<0.001

Hip Fracture Group

  • PINP reached lower level in intervention group after 12 months, compared with baseline (P<0.001)
  • Osteocalcin concentrations were significantly higher in the placebo group than in the intervention group after 12 months (P=0.05)
  • ICTP decreased below baseline after 12 months (P=0.05).

Upper Extremity Group

  • PINP concentrations significantly lower in intervention group compared with placebo group (P<0.05)
  • Osteocalcin concentrations were signficantly higher in the placebo group than intervention group after 12 months (P=0.001)
  • ICP declined in intervention group after 12 months (P=0.05).

Bone Mineral Density

BMD (g/cm2)

Intervention Group (N=35)

Placebo Group (N=44)
Per-Protocol Analysis Change LBMD (g/cm2)
0.006
-0.012 (2)
Change HBMD (g/cm2)
0.006
0.002
Intention to Treat Analysis Change LBMD (g/cm2)
0.004
-0.008 (2)
Change HBMD (g/cm2)
-0.001
-0.001

 

  • Calcium and vitamin D resulted in a significant increase in BMD of the lumbar spine after 12 months compared to baseline for the intervention group, but had decreased in the placebo group
  • There were no significant changes in the BMD of the hip.
Author Conclusion:
  • Hip fracture patients had poorer bone status, vitamin D deficiency and lower physcial performance, compared with the upper extremity fracture patients
  • Calcium and vitamin D supplementation for one year increased vitamin D status and BMD in the lumbar spine region, especially in those less than 70 years old
  • Biochemical markers increased one month after fracture and then declined
  • Supplementation with calcium and vitamin D decreased bone loss in patients with low-energy fractures.
Funding Source:
Government: Danish Research Council
Industry:
Eli Lilly Osteoporosis Research Fund
Pharmaceutical/Dietary Supplement Company:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:
  • Variation in time to inclusion into the study could have had an influence on the concentration of bone markers
  • Drop-out rate was significantly higher for hip-fracture patients
  • Lumbar spine BMD was evaluated without leg elevation, which may have resulted in underestimation of the effect of treatment
  • Poor compliance and participant dropout.
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? Yes
  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? 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? 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