NSUP: Vitamin D (2008)
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.
- 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).
- 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.
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.
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.
- 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.
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.
- 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.
Government: | Danish Research Council | ||
Industry: |
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Not-for-profit |
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- 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
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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 | |