EAL

CD: Bone Density (2006)

Citation:

Molteni N, Bardella MT, Vezzoli G, Pozzoli E, Bianchi P. Intestinal calcium absorption as shown by stable strontium test in celiac disease before and after gluten-free diet. Am J Gastroenterol 1995; 90: 2025-2028.

PubMed ID: 7485015

Study Design:

Non-Randomized Controlled Trial

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To investigate the effect of 12 months of gluten-free diet on mineral and bone metabolism in women with celiac disease, and to assess intestinal calcium absorption using the strontium test.

Inclusion Criteria:

Celiac disease diagnosed histologically and confirmed by histological response to gluten-free diet.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Women consecutively diagnosed with celiac disease.

Design

Nonrandomized Clinical Trial.

Blinding used (if applicable)

No blinding used.

Intervention (if applicable)

12 months of gluten-free diet.

Statistical Analysis

Data obtained at the 2 observation times were first evaluated separately with the usual descriptive statistics. Data obtained at diagnosis were then compared with the normal distribution using the Kolmogorov-Smirnov method for goodness of fit test. Student's t test for paired data was used to compare bone mineral density values in patients and 36 age-matched healthy women. Pearson's correlation coefficients for all of the variables considered were then computed within each group. Finally, the nonparametric Kruskal-Wallis test was performed to demonstrate any significant difference between the 2 groups.

Data Collection Summary:

Timing of Measurements

BMI, biochemical and bone mineral indices, strontium absorption test, and bone mineral density measured at diagnosis and after 12 months of gluten-free diet.

Dependent Variables

BMI, hemoglobin, serum albumin, potassium, and prothrombin activity measured by standard methods
Serum phosphorus, magnesium, alkaline phosphatase, plasma calcium, and urinary calcium and phosphorus by spectrophotometric method
Vitamin D and 25-OH vitamin D determined by protein binding assay
Mid-molecule parathyroid hormone by radioimmunoassay
Calcium absorption estimated using stable strontium absorption test
Bone mineral density measured at the distal two-thirds of the dominant forearm by 125 I photon absorptiometry and compared with that of 2 age-matched healthy women

Independent Variables

Gluten-free diet not mentioned or monitored

Description of Actual Data Sample:

Initial N: 18 women, 36 age-matched controls

Attrition (final N): 18 women, 36 age-matched controls

Age: Mean age 36.8 years, range 18 - 68 years

Ethnicity: Not mentioned

Anthropometrics Age-matched controls

Location: Italy

Summary of Results:

	Diagnosis	After GFD	K-W P value	Reference Range
BMI (kg/m2)	19.51 +/- 2.82	21.62 +/- 2.76	0.012	20 - 25
Hemoglobin (mmol/l)	1.61 +/- 0.31	2.03 +/- 0.13	0.001	1.86 - 2.48
Albumin (g/l)	40.0 +/- 0.80	46.0 +/- 0.39	0.0095	35 - 55
Potassium (mmol/l)	3.7 +/- 0.50	4.2 +/- 0.23	0.0012	3.5 - 5
Prothrombin Activity (%)	81.61 +/- 14	89.56 +/- 11.82	NS	70 - 100
Calcium (mmol/l)	2.04 +/- 0.31	2.35 +/- 0.10	<0.001	2.25 - 2.75
Phosphorus (mmol/l)	1.05 +/- 0.24	1.19 +/- 0.13	NS	1.0 - 1.5
Magnesium (mmol/l)	0.71 +/- 0.13	0.81 +/- 0.05	0.0194	0.75 - 1.25
25-OH vitamin D (ng/ml)	15.83 +/- 4.73	16.38 +/- 6.72	NS	8.9 - 38.1
1.25 (OH)2 vitamin D (pg/ml)	33.21 +/- 7.77	44.43 +/- 12.99	NS	16 - 42
Alkaline Phosphatase (U/l)	358 (123 - 1252)	195 (72 - 524)	0.0099	94 - 274
MM-PTH (pmol/l)	53.43 (14.1 - 184)	23.72 (11.9 - 102)	0.0102	11.5 - 77.1
Urinary Calcium (mmol/24 h)	1.52 +/- 2.01	2.30 +/- 1.46	0.0094	1.25 - 10
Urinary Phosphorus (mmol/24 h)	15.98 +/- 10.8	25.90 +/- 8.72	0.0459	16.5 - 48.5

Other Findings

Clinically, 6 patients presented an acute malabsorption syndrome, 7 complained of chronic GI symptoms, 5 had no GI symptoms at all. Iron deficiency anemia was present in 4.

Mean strontium absorption at diagnosis was markedly decreased with respect to control values (13.84 +/- 9.03% vs 22.47 +/- 4.21%, p < 0.0001) and 11 of the 18 patients (61%, subgroup A) had low values.

In all patients, mean hemoglobin, serum potassium, magnesium, plasma calcium, urinary calcium, and phosphorus were significantly abnormal at diagnosis, whereas only the subgroup A had significantly reduced BMI, 25-OH vitamin D, and elevated alkaline phosphatase. This subgroup differed in BMI (p < 0.003) and calciuria (p < 0.035) with respect to the other patients.

Mean bone mineral density was significantly decreased compared with controls (573.5 +/- 98.89 vs 664.55 +/- 49.37, p < 0.001), without significant differences between subgroups A and B (581.45 +/- 97.31 vs 561 +/- 107.84).

Strontium absorption correlated significantly with BMI (p < 0.01), plasma calcium (p < 0.05) and 25-OH vitamin D (p < 0.05).

After 12 months of gluten-free diet, all patients showed clinical improvement and BMI rose significantly, although it was still lower than controls (p < 0.001). All biochemical variables and strontium absorption normalized (23.23 +/- 5.54%, r = 0.0287, p = 0.0001). Bone mineral density did not change significantly (573.5 +/- 98.89 vs 589.4 +/- 97.45).

Author Conclusion:

Our results indicate that gluten-free diet without any pharmacological supplements is effective in resolving symptoms and biochemical indices and improving bone mineral metabolism. At diagnosis, the patients frequently had intestinal calcium malabsorption, as demonstrated by strontium test, with an early renal compensatory mechanism. After the gluten-free diet, the normalization of calcium absorption and the decrease of mid-molecule parathyroid hormone suggested a normalization of mineral metabolism, although a positive effect on bone mineral density was not evident at that time. In conclusion, the frequency of chronic, albeit subclinical intestinal calcium malabsorption in our patients with celiac disease and the finding that bone demineralization also occurred in younger patients suggest that a bone mineral metabolism study is mandatory in each newly diagnosed subject.

Funding Source:

University/Hospital:

University of Milan (italy)

Reviewer Comments:

Gluten-free diet not monitored.

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?	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?	Yes
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?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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?	No
	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?		???
	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?	No
	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?	???
	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?	N/A
	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)?	N/A
	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