CD: Bone Density (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To determine bone mineral density in patients studied in the first year after diagnosis of celiac disease, and to detect changes in bone mineral density over the subsequent year.  In addition, we have performed the iliac crest bone biopsy to elucidate the underlying bone pathology in patients with skeletal symptoms at the time of diagnosis.
Inclusion Criteria:
Diagnosis of celiac disease based on clinical presentation and small intestinal biopsy in all patients prior to treatment with gluten-free diet.
Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

None specified.

Design

Nonrandomized Clinical Trial.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten-free diet for 1 year.  No vitamin, mineral or hormone supplements.

Statistical Analysis

Statistical significance of differences between paired data was calculated using Wilcoxon's signed rank test.  Correlation coefficient was determined using Spearman's rank correlation.  The 95% confidence intervals are based on Student's t distribution.

Data Collection Summary:

Timing of Measurements

Lumbar spine and femoral neck bone mineral density measured within 1 year of diagnosis and after 12 months of gluten-free diet.

Dependent Variables

  • Weight and height, BMI
  • Blood tests included hemoglobin, mean corpuscular volume, serum calcium, phosphate, and alkaline phosphatase
  • Bone mineral density measured with DEXA at lumbar spine and femoral neck  

Independent Variables

  • Gluten-free diet:  compliance monitored by dietitian

Control Variables

 

Description of Actual Data Sample:

Initial N: 21 adults (14 females, 7 males), 21 sex- and age-matched controls.  Female patients were also matched for menopausal status.

Attrition (final N):  See above

Age:  Average age 49.7 years (range 31.0 - 66.1) 

Ethnicity:  Not mentioned. 

Other relevant demographics:  All patients had a clinical and hematological response to gluten-free diet.  12 showed significant improvement on repeat small bowel biopsy, but 2 had persistent subtotal villous atrophy after 6 and 12 months. 

Location:  Royal United Hospital, Bath, UK 

 

Summary of Results:

Other Findings

Bone mineral density was significantly lower in patients than in paired age- and sex-matched controls at lumbar spine (0.819 g/cm2 vs 1.021 g/cm2, p < 0.001) and femoral neck (0.663 g/cm2 vs 0.794 g/cm2, p < 0.001).

There were frequent minor abnormalities of serum calcium, phosphate, and alkaline phosphatase - only 4 (19%) of patients had normal values of all 3 biochemical parameters.

Repeat measurement after 12 months demonstrated that patients had a significant gain in bone mineral density at lumbar spine (0.047 g/cm2/year, 6.6%/year, p < 0.001) and femoral neck (0.033 g/cm2/year, 5.5%/year) (p < 0.002), whereas no significant change in bone mineral density was detected in controls.

In patients there was a strong correlation between rate of change in bone mineral density at lumbar spine and the rate of change at the femoral neck (r = 0.76, P < 0.001).

Despite the improvement of bone mineral density in patients compared with controls, bone mineral density after 12 months was still significantly lower in patients compared to controls at lumbar spine (0.863 g/cm2 vs 1.014 g/cm2, p < 0.001) and at femoral neck (0.693 g/cm2 vs 0.799 g/cm2, p < 0.002).

Patients (n=13) whose initial bone mineral density measurement was less than 6 months after commencing gluten-free diet had significant increase in bone mineral density at lumbar spine and femoral neck after 12 months (p < 0.01), whereas the patients whose first bone mineral density measurement was 6 - 12 months after commencing gluten-free diet showed no significant increase at either site (p > 0.10). 

Author Conclusion:
These results confirm previously reported findings of low bone mineral density in patients at the time of presentation of celiac disease.  The gain of bone mineral density at both lumbar spine and femoral neck was apparent in almost all of the patients in our study, ranging from modest increases in most patients to the dramatic increases seen in patients with osteomalacia.  Treatment of celiac disease with a gluten-free diet is associated with a significant increase in bone mineral density, although patients still had lower bone mineral density than controls.
Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:
Question dietary compliance with 2 subjects having persistent villous atrophy.
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? ???
  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? 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