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CD: Bone Density (2006)

Citation:

Mora S, Barera G, Ricotti A, Weber G, Bianchi C, Chiumello G.  Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease.  Am J Clin Nutr 1998; 67: 477-481.

PubMed ID: 9497193
 
Study Design:
Non-Randomized Controlled Trial
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To measure the bone mineral density in children and adolescents at diagnosis of celiac disease and after 1 year of a gluten-free diet, as well as study the influence of the coexistence of type 1 diabetes and celiac disease on bone density by comparing the bone mineral density values of diabetic patients with celiac disease and those of patients with celiac disease alone.
Inclusion Criteria:
All children and adolescents newly diagnosed with celiac disease according to recommendations of the European Society of Pediatric Gastroenterology and Nutrition.
Exclusion Criteria:

Subjects who had been immobilized or hospitalized in the preceding 6 months, were taking medications known to affect bone metabolism, had any chronic illness other than type 1 diabetes, or had 1 or more nontraumatic fractures.

Controls were not involved in competitive sports and were excluded if they had a history of chronic illness, one or more fractures, and if they had regularly taken any medication, hormone, vitamin preparation, or calcium supplement.

Description of Study Protocol:

Recruitment

Newly diagnosed children and adolescents eligible.  Controls had volunteered.

Design

Nonrandomized Clinical Trial.

Blinding used (if applicable)

No blinding used.

Intervention (if applicable)

Gluten-free diet for 1.4 +/- 0.04 years.  No vitamin or mineral supplements.

Statistical Analysis

Multiple regression analyses were used to compare the bone mineral density and bone mineral apparent density values of celiac disease and control subjects after confounding variables controlled for.  Annualized increments of bone mineral density were calculated for the 25 patients followed prospectively.  The bone density data obtained from controls and celiac disease patients at diagnosis were plotted against age; simple regression analyses were performed and annual increments of bone mineral density obtained.  One-group t tests were used to test whether the annualized changes of bone density values calculated for celiac patients consuming a gluten-free diet were different from those obtained from control subjects and celiac disease patients at diagnosis.  All significance tests were conducted at the alpha = 0.05 level.

Data Collection Summary:

Timing of Measurements

Bone mineral density measured at diagnosis and after 1.4 +/- 0.04 years of gluten-free diet.

Dependent Variables

  • Bone mineral density measured at the lumbar spine and in the whole skeleton by dual-energy X-ray absorptiometry
  • Bone mineral apparent density calculated using consideration of bone size

Independent Variables

  • Gluten free diet.  Compliance with the diet was ascertained by measurements of antigliadin and antiendomysium antibodies during follow-up period.  Intestinal biopsies performed at the end of the study also showed normal histology.

 

Description of Actual Data Sample:

Initial N: 44 celiac disease patients eligible and measured at diagnosis.  177 healthy controls.

Attrition (final N):  25 patient subset measured after gluten-free diet.

Age:  Aged 2.58 - 20.42 years at diagnosis.  Controls aged 1.52 - 20.99 years. 

Ethnicity:  White 

Other relevant demographics:  20 patients had type 1 diabetes. 

Location:  Italy 

 

Summary of Results:

Other Findings

Mean lumbar spine bone mineral density of all celiac disease patients at diagnosis was 0.708 +/- 0.034 g/cm2, and mean bone mineral apparent density was 0.145 +/- 0.004 g/cm3, significantly lower in celiac disease patients than in controls after age and anthropometric variables were controlled for (difference in bone mineral density of 0.041 +/- 0.017 g/cm2, P = 0.015, and difference in bone mineral apparent density of 0.008 +/- 0.003 g/cm3, P = 0.0088).

Lumbar spine bone mineral density and bone mineral apparent density of patients with celiac disease alone were 0.655 +/- 0.036 g/cm2 and 0.138 +/- 0.004 g/cm3, respectively.  The differences of bone mineral density (-0.027 +/- 0.036 g/cm2) and bone mineral apparent density (-0.0005 +/- 0.0007 g/cm3) between patients with celiac disease alone and patients with celiac disease and diabetes were not significant.

The mean whole-body bone mineral density value of all celiac disease patients at diagnosis was 0.875 +/- 0.020 g/cm2, significantly lower than controls (-0.055 +/- 0.013 g/cm2, P = 0.0001).  Whole-body bone mineral apparent density at diagnosis was 0.094 +/- 0.002 g/cm3, also significantly lower than controls (-0.004 +/- 0.0001 g/cm3, P = 0.04).

Patients with celiac disease alone had a mean whole-body bone mineral density value of 0.843 +/- 0.023 g/cm2 and mean bone mineral apparent density of 0.096 +/- 0.002 g/cm3.  After confounding variables were controlled for, the difference in whole-body bone mineral density between patients with celiac disease alone and patients with celiac disease and diabetes was -0.037 +/- 0.029 g/cm2 (not significant) and bone mineral apparent density was 0.0004 +/- 0.0003 g/cm3 (not significant).

The subjects studied after the gluten-free diet had bone mineral density values not significantly different from those of control subjects.  Multiple regression analysis showed that after the confounding variables were controlled for, the differences in lumbar spine bone mineral density and bone mineral apparent density values between celiac disease patients following gluten-free diets and controls was 0.008 g/cm2 and 0.0002 g/cm3, respectively (not significant).

Whole-body bone mineral density after gluten-free diet was 0.921 +/- 0.021 g/cm2 and bone mineral apparent density was 0.094 +/- 0.002 g/cm3.  The differences in whole-body bone mineral density (0.024 g/cm2) and bone mineral apparent density (0.001 g/cm3) between celiac disease patients and controls were not significant.

Author Conclusion:
In conclusion, children and adolescents with celiac disease have remarkably reduced lumbar spine and whole body bone density.  In our study, we showed that a gluten-free diet promotes a rapid increase of bone mineral density that leads to a complete recovery of bone mineralization.  Our findings emphasize the need for an early diagnosis and treatment in patients with celiac disease, even in asymptomatic patients, to reverse osteopenia, achieve normal mineralization and obtain an adequate peak bone mass at the end of puberty.
Funding Source:
University/Hospital: University of Milan (italy)
Reviewer Comments:
Diet compliance checked with antigliadin and antiendomysial antibodies as well as bowel biopsy.
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? ???
  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? ???
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? N/A
  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? No
  4.1. Were follow-up methods described and the same for all groups? No
  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? No
  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? 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? 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