CD: Bone Density (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To establish whether body composition in patients with celiac disease is normal and influenced by the age at diagnosis or by the duration of the gluten-free diet.
Inclusion Criteria:
All celiac patients were diagnosed by jejunal biopsy and showed clinical and serological response to dietary treatment.
Exclusion Criteria:
Children younger than 2 years were excluded due to lack of collaboration, essential to perform DEXA.  None presented any form of disease or was receiving any therapy that could affect bone metabolism.
Description of Study Protocol:

Recruitment

Children were consecutively recruited.

Design

Cross-Sectional Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten-free diet.  None of the subjects were receiving estrogens, steroids, anticonvulsive drugs or vitamin D or calcium supplements.

Statistical Analysis

Statistical analysis was performed with Stat-view and SuperANOVA software using one-factor ANCOVA; covariates were selected by multiple regression analysis.  BMC, BMD, Spine BMD and BMI and fat mass means in ANCOVA analysis were adjusted using bone area or BMI as covariate.  Student's t test was used for comparison of continuous variables.

Data Collection Summary:

Timing of Measurements

In all children, weight, height, fat mass, fat free mass, bone mineral density, bone mineral content, and spine bone mineral density were measured. 

Dependent Variables

  • Body composition and bone mineral measurements assessed by DEXA

Independent Variables

  • Gluten free diet duration (less than 12 months, 12 - 24 months, or more than 24 months).  Compliance mentioned but methodology not specified. 
  • Age at diagnosis (diagnosed in the first 24 months or diagnosed later)

Control Variables

 

Description of Actual Data Sample:

Initial N: 66 children with celiac disease (33 females, 33 males), 76 healthy controls (36 males, 40 females) matched for age, sex, ethnic origin and calcium intake (calculated by 3 day diet recall).

Attrition (final N):  Same as above

Age:  Celiac children:  mean age 117 months, range 28 - 227 months 

Ethnicity:  Not specfically mentioned, but controls were ethnic-origin-matched. 

Other relevant demographics:  28 were diagnosed in the first 24 months and 38 were diagnosed later.  16 had been on the gluten-free diet for less than 12 months, 11 for 12 - 24 months, and 39 for more than 24 months. 

Location:  Italy 

 

Summary of Results:

 

Parameter Covariate r2 Controls Celiacs t/p
BMC (g) bone area (cm2) 0.96 1130 +/- 118 1134 +/- 118 0.21/0.83
BMD (g/cm2) bone area (cm2) 0.84 0.843 +/- 0.050 0.838 +/- 0.050 0.55/0.58
spine BMD (g/cm2) bone area (cm2) 0.82 0.725 +/- 0.073 0.729 +/- 0.073 0.32/0.75
fat mass (%) BMI 0.52 20.6 +/- 5.6 19.6 +/- 5.6 0.99/0.33
BMI bone area (cm2) 0.45

16.7 +/- 2.0

17.2 +/- 2.0

1.3/0.2

Other Findings

Overall we did not find any significant difference in body composition between overall celiac patients and controls.

However, the fat mass, BMI and spine bone mineral density values in late diagnosed celiac patients were significantly lower than in early diagnosed patients (fat mass:  17.7 +/- 5.7% vs 21.7 +/- 6.1%, p < 0.01, BMI:  18.0 +/- 2.0 vs 16.5 +/- 2.0, p < 0.002, spine BMD: 0.704 +/- 0.071 vs 0.761 +/- 0.071, p < 0.002).  The BMI of early diagnosed patients was significantly higher than the control group (18.0 +/- 2.0 vs 16.7 +/- 2.0, p < 0.005). 

Patients on the diet for less than 12 months (all of them were late diagnosed) showed significantly lower bone mineral content and density than those on diet for more than 24 months (BMC:  1046 +/- 132 vs 1144 +/- 107, p < 0.02, BMD: 0.811 +/- 0.058 vs 0.850 +/- 0.047, p < 0.05, spine BMD: 0.676 +/- 0.096 vs 0.751 +/- 0.078, p < 0.01).

Patients in short-term gluten-free diet group showed lower bone mineral content (995 +/- 138 g vs 1073 +/- 115 g, p < 0.05) and spine BMD (0.662 +/- 0.080 g/cm2 vs 0.710 +/- 0.067 g/cm2, p < 0.05).

No significant difference appeared between celiac patients on medium and long-term gluten-free diets.

Spine mineral density was the only parameter significantly influenced both by age at diagnosis (p < 0.03) and duration of gluten-free diet (p < 0.008).   

Author Conclusion:
Our data confirm the reduction of bone mineral content, bone mineral density and spine BMD in celiac patients on gluten-free diets for less than 12 months as previously reported in a smaller group of pediatric patients.  However, in pediatric age, not only the dietetic treatment but also the timing of the diagnosis seems to play an important role for body composition as shown by the decreased fat mass, BMI and spine BMD in our late diagnosed patients.  In addition, we pointed out that spine BMD is the bone parameter most affected by metabolic changes, and in our experience it has been helpful in showing that only an early diagnosis of celiac disease in childhood and a strict gluten-free diet, lasting more than 12 months, allow celiac patients to reach a normal mineralization without any pharmacological supplementation.
Funding Source:
University/Hospital: University of Pavio
Reviewer Comments:

All short term gluten-free diet subjects were also late diagnosed subjects.  Compliance methodology not described.

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? 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? N/A
  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? ???
  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? ???
  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? 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