CD: Bone Density (2006)
Clinical pattern was considered "classical" if patient underwent intestinal biopsy due to presence of malabsorption, or was considered "subclinical" if patient presented with minimal, transient, or apparently unrelated symptoms, or underwent intestinal biopsy as part of prospective screening program. Diagnosis of celiac disease was based upon the finding of subtotal villous atrophy at jejunal biopsy which subsequently improved after gluten-free diet.
Recruitment
Healthy controls recruited from medical staff.
Design
Cross-Sectional Study and Nonrandomized Clinical Trial based on 8 subjects in each group.
Blinding used (if applicable)
Not applicable.
Intervention (if applicable)
Gluten-free diet.
Statistical Analysis
Bone mineral density values (Z scores) were expressed as mean +/- SD. Parametric one-way ANOVA was computed for the comparison of the means between groups. Bone mineral density values before and after gluten-free diet of the 16 patients followed longitudinally were compared by the Student's paired t-test. All other variables were expressed as medians and total ranges, and the comparisons between the groups were performed by the nonparametric analysis of the variance (Kruskal-Wallis test). The Spearman's correlation coefficient was computed for the nonparametric estimates of the level of association between 2 variables. A two-tailed p value <0.05 was considered significant.
Timing of Measurements
Measurements taken at study entry. Bone mineral density remeasured in 16 patients (8 classical and 8 subclinical) after a period of gluten-free diet.
Dependent Variables
- Bone mineral density at lumbar spine by X-ray dual photon absorptiometry
- Serum calcium, corrected for albumin where appropriate, and serum alkaline phosphatase measured by standard methods
- Serum intact parathyroid hormone measured by 2-site immunoradiometric assay
- Serum 25-OH-D3 measured by radioimmunoassay
- Serum 1,25-OH2-D3 was measured by radioreceptor assay
- Serum osteocalcin was measured by radioimmunoassay
- Serum carboxy-terminal pyridinoline-cross-linked telopeptide of type I collagen measured by radioimmunoassay
Independent Variables
- Gluten-free diet. Compliance judged as being good by an experienced dietitian. Post-treatment biopsy was improved in all patients and none of them showed continuing evidence of active celiac disease, i.e. subtotal villous atrophy.
Control Variables
Initial N: 14 untreated subclinical or silent patients (11 females, 3 males), 10 untreated classical patients (9 female, 1 male), and 15 healthy volunteers (13 females, 2 males) on a gluten-containing diet
Attrition (final N): See above
Age: Classical patients: median age 26.5 years (18 - 58 years), subclinical patients: median age 28.5 years (18 - 66 years), healthy volunteers: median age 28 years (19 - 65 years)
Ethnicity: Italian
Other relevant demographics: Gluten-free diet duration: median 10.5 months, range 9 - 24 months.
Anthropometrics: BMI was significantly lower (p < 0.005) in the classical patients (median 18.15, range 16.4 - 21.1) compared with the subclinical patients (median 21.29, range 18.25 - 27.05) and the healthy volunteers (median 22.31, range 20.94 - 26.78), while there was no difference between the subclinical patients and healthy volunteers.
Location: Bologna, Italy
Subclinical | Classical | Volunteers | |
Calcium | 2.19 (1.97 - 2.44) | 2.09 (1.26-2.23) | 2.37 (2.24-2.49) |
iPTH |
46.5 (22-177) |
73 (27-244) |
28 (10-55) |
25(OH)D3 | 15.2 (5-27) | 15 (5-30) | 27 (14-33) |
1,25(OH)2D3 | 51 (35-70) | 65 (27-115) | 25 (17-39) |
Alkaline Phosphatase | 165 (87-350) | 230 (110-635) | 155 (85-270) |
Osteocalcin | 3.6 (0.6 - 5.9) | 4.1 (1.2 - 9.4) | 2.1 (0.5 - 3.5) |
ICTP |
4.35 (2.4 - 9.5) |
7.6 (4.2 - 20) |
2.5 (1.3 - 5.9) |
Other Findings
In the subclinical group, bone mineral density at the lumbar spine was significantly higher than in the classical group (-1.3 +/- 0.8, 73% vs -2.6 +/- 0.6, 88%, respectively; p < 0.001), but significantly lower than in volunteers (+0.4 +/- 1.1, 104%, p < 0.001).
Bone mineral density was not significantly correlated with age at diagnosis either in classical (r = 0.08) or in subclinical (r = 0.38) patients.
Significant differences were observed in serum calcium, whereas, with regard to parathyroid hormone, no significant difference was found between subclinical and classical patients.
25-vitamin D was significantly lower, and 1,25-vitamin D was significantly higher in subclinical and classical patients than in healthy volunteers.
Indices of bone remodeling were higher in the subclinical and classical groups than in the volunteers, but lower in the subclinical than in classical patients.
8 subclinical and 8 classical patients were reexamined after a period of gluten-free diet, and in both groups, bone mineral density had significantly improved (subclinical: from -1.3 +/- 1.1, 87% to -0.4 +/- 1.3, 95.5%; classical: from -2.7 +/- 0.9, 72% to -2.0 +/- 1.2, 80%). Mean improvement in Z score was similar in subclinical (+0.8 +/- 0.3, 8.5%) and in classical (+0.7 +/- 0.8, 8.4%) and did not correlate with duration of gluten-free diet.
After gluten-free diet, bone mineral density values of the classical group (-2.0 +/- 1.2, 80.5%) were still significantly lower than those of volunteers (+0.4 +/- 1.1, 104%, p < 0.001) whereas no significant difference was found between the subclinical group (-0.4 +/- 1.3, 95%) and volunteers.
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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? | ??? | |
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? | ??? | |
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? | ??? | |
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.) | ??? | |
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? | N/A | |
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? | 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? | 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)? | 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? | N/A | |
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 | |