CD: Bone Density (2006)
Kemppainen T, Kroger H, Janatuinen E, Arnala I, Lamberg-Allardt C, Karkkainen M, Kosma VM, Julkunen R, Jurvelin J, Alhava E, Uusitupa M. Bone recovery after a gluten-free diet: a 5-year follow-up study. Bone 1999; 25: 355-360.
PubMed ID: 10495140
NEUTRAL:None specifically mentioned.
Recruitment
Study group consisted of 28 newly diagnosed celiac patients recruited between 1990 and 1991.
Design
Nonrandomized Clinical Trial.
Blinding used (if applicable)
No blinding used.
Intervention (if applicable)
Gluten free diet for 5 years.
Statistical Analysis
The results for continuous variables are given as mean +/- SD with range. The results for noncontinuous variables are given as frequency and percentage. Distributions of variables were checked using the Kolmogorov-Smirnov test. One-way ANOVA as used to check the equality of variance. The Chi square test and Fisher test were used to analyze the differences between the groups in the frequency and proportion of categorized variables. The McNemar test and the Cochran Q-test were used to analyze the differences between time points. The Friedman and Wilcoxon tests were applied in the comparisons of continuous variables between time points. The Mann-Whitney U-test was performed for comparisons between groups. Spearman correlations were used to analyze the association between the change of weight, change of BMI, change of biochemical measurements, and bone mineral density response.
Timing of Measurements
Bone mineral density, duodenal biopsies, blood samples, questionnaire and 4 day food records completed at baseline, at 1 year and at 5 years.
Dependent Variables
- Bone mineral density measured at the lumbar spine, femoral neck, trochanter and Ward's area using dual energy x-ray absorptiometry
- Questionnaire regarding medication, use of calcium supplements, general symptoms, fractures and menopausal status
- Body weight determined witih digital scale, height with stadiometer
- Esophagogastroduodenoscopy performed in all subjects and duodenal biopsy specimens obtained to verify diagnosis of celiac disease and its severity. Specimens obtained at the duodenal bulb at 5 cm intervals as far as possible and graded as normal, partial, subtotal and total villous atrophy
- Blood samples taken after overnight fast. Serum calcium and alkaline phosphatase measured using routine clinical laboratory methods. Serum intact parathyroid hormone measured using immunoradiometric assay. Serum 25-hydroxy vitamin D measured by commercial radio immunoassay. Serum cross-linked carboxyl-terminal telopeptide of type I collagen measured using an equilibrium radio immunoassay. Serum C-terminal extensition peptide of type I procollagen measured with radio immunoassay.
Independent Variables
- Gluten-free diet compliance recorded using a specific questionnaire. Four day food records were checked by a nutritionist and calcium intake calculated with a software program.
Initial N: 28 patients originally recruited for study (9 men, 19 women). 6 patients withdrew from 5 year follow-up. Baseline characteristics of withdrawals were not different from those who remained in study.
Attrition (final N): At year 1, 27 subjects remained. At 5 years, 22 subjects remained.
Age: At baseline: women = 44.1 +/- 13.6 years (23 - 66 years), men = 48.6 +/- 12.3 years (24 - 65 years)
Ethnicity: Not mentioned.
Other relevant demographics: 12 premenopausal at baseline, 7 postmenopausal, with 2 of the 7 using estrogen preparations and average age at menopause of 45.0 +/- 6.8 years (30 - 50 years).
Location: Kuopio University Hospital, Finland
|
|
Baseline (n=28) |
At 1 Year (n=27) |
At 5 Years (n=22) |
|
Lumbar Spine - Women |
1.077 +/- 0.167 |
1.115 +/- 0.116 (p<0.001) |
1.105 +/- 0.175 |
|
Femoral Neck - Women |
0.879+/- 0.126 |
0.909 +/- 0.116 |
0.887 +/- 0.128 |
|
Femoral Trochanter - Women |
0.745 +/- 0.103 |
0.798 +/- 0.102 (p<0.05) |
0.804 +/- 0.091 (p<0.05) |
|
Femoral Ward's - Women |
0.780 +/- 0.149 |
0.813 +/- 0.160 (p<0.001) |
0.794 +/- 0.167 |
|
BMI - Women |
22.2 +/- 2.9 |
23.2 +/- 3.1 (p<0.05) |
24.5 +/- 3.0 (p<0.05) |
|
Lumbar Spine - Men |
1.034 +/- 0.276 |
1.033 +/- 0.259 |
1.057 +/- 0.261 |
|
Femoral Neck - Men |
0.872 +/- 0.156 |
0.897 +/- 0.146 |
0.893 +/- 0.155 |
|
Femoral Trochanter - Men |
0.799 +/- 0.165 |
0.838 +/- 0.153 |
0.849 +/- 0.200 (p<0.05) |
|
Femoral Ward's - Men |
0.739 +/- 0.216 |
0.758 +/- 0.200 (p<0.05) |
0.758 +/- 0.192 |
|
BMI - Men |
22.8 +/- 1.9 |
23.9 +/ 1.9 |
23.9 +/- 2.8 (p<0.05) |
|
ICTP - All |
2.8 +/- 0.7 |
2.7 +/- 0.7 |
3.3 +/- 0.8 (p<0.01) |
|
PICP - All |
128 +/- 38 |
99 +/- 32 (p<0.001) |
125 +/- 46 |
|
Parathormone - All |
41 +/- 19 |
33 +/- 9 (p<0.05) |
43 +/- 16 (p<0.05) |
|
25-OH-vitamin D - All |
22 +/- 8 |
25 +/- 11 |
45 +/- 19 (p<0.01) |
|
Calcium -All |
2.27 +/- 0.10 |
2.37 +/- 0.08 (p<0.001) |
2.38 +/- 0.11 (p<0.01) |
|
Phosphorus - All |
1.09 +/- 0.20 |
0.98 +/- 0.13 (p<0.05) |
1.02 +/- 0.14 |
|
Alkaline Phosphatase - All |
154 +/- 45 |
133 +/- 49 (p<0.05) |
183 +/- 92 |
Other Findings
Compliance with the gluten-free diet was good: 96% at 1 year and 82% at 5 years. Calcium intake was 940 (330 - 1900) mg/day at baseline and 1424 (660 - 2700) mg/day at 5 years.
At the 5 year follow-up, 7 patients had partial and 1 had subtotal villous atrophy, although the others had totally recovered. Adherence to the diet was inversely associated with the grade of villous atrophy at 5 years (p = 0.03).
During the follow-up period, BMI increased significantly (8%, p = 0.007).
Both in men and women, bone mineral density increased at the lumbar spine (2%), the femoral neck (1%), the trochanter (6%), and the Ward's area (3%) during the follow up. The increase in bone mineral density was found already during the first year of follow up.
After 1 year, bone mineral density increased or remained the same in 69% of patients at the lumbar spine, 67% of patients at the femoral neck, 89% of patients at the trochanter, and 67% of patients at the Ward's area.
During the 5-year follow-up, bone mineral density increased or remained the same in 52% of patients at the lumbar spine, 46% of patients at the femoral neck, 68% of patients at the trochanter, and 59% of patients at the Ward's area.
In general, measured values of biochemical measurements shifted to normal after 1 year except 25-OH vitamin D and parathormone. At baseline, 19 out of 28 patients, after 1 year, 14 out of 26 patients, and after 5 years, 2 out of 26 patients had low serum 25-OH vitamin D values (p = 0.0001). A high serum parathormone value was noticed in 6 out of 25 patients at baseline, but after 1 year, 5 of them showed normalized values (p = 0.03).
In conclusion, our results indicate that bone disease in celiac patients can recover during the long-term gluten-free diet. The improvement in bone mineral density occurs mostly within the first year, partly along with weight gain. Different degrees of villous atrophy, occurrence of secondary hyperparathyroidism, variability of nutritional status, and variable recovery of them may explain the great interindividual variability in the bone mineral density changes observed. In women, this is partly explained by different menopausal status during follow-up. Some patients diagnosed in adulthood run the risk of maintaining a low bone mineral density. Although the strict gluten-free diet is crucial for healthy bones in celiac patients, some patients may need additional osteoporosis therapy to prevent further loss of bone.
| University/Hospital: | Kuopio University Hospital (Finland), University of Helsinki (Finland) |
|
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? | No | |
| 2.2. | Were criteria applied equally to all study groups? | N/A | |
| 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? | N/A | |
| 3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | N/A | |
| 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.) | N/A | |
| 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? | ??? | |
| 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? | N/A | |
| 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 | |