Bone mass and metabolism in patients with celiac disease

doi:10.1016/0016-5085(95)90276-7

Gastroenterology

Volume 109, Issue 1, July 1995, Pages 122-128

https://doi.org/10.1016/0016-5085(95)90276-7 Get rights and content

Abstract

$Background & Aims:$ Several aspects of the pathogenesis of osteopenia in celiac disease are still unclear. Therefore, bone mass and metabolism were evaluated in adults with celiac disease in a cross-sectional study. $Methods:$ Bone mineral density (BMD), assessed by total body dual-photon absorptiometry, and serum indices of bone metabolism and remodeling were evaluated in 17 patients with untreated celiac disease, 14 with celiac disease on a gluten-free diet, and 24 healthy volunteers. $Results:$ BMD, expressed as a z score, was significantly lower in patients with untreated celiac disease than in patients with treated celiac disease and volunteers and lower in patients with treated celiac disease than in volunteers. Similar changes were observed in serum calcium level, whereas intact parathyroid hormone level was significantly higher in untreated than in treated patients with celiac disease and volunteers, and no difference was found between the latter two groups. 25-Vitamin D level was significantly lower and 1,25-vitamin D level significantly higher in untreated celiac disease than in treated celiac disease and volunteers. Indices of bone remodeling were significantly higher in untreated than in treated patients and volunteers and significantly and positively correlated with iPTH in untreated patients with celiac disease. $Conclusions:$ BMD is almost invariably low in patients with untreated celiac disease. Results in treated patients suggest that gluten-free diet improves but does not normalize BMD. Untreated celiac disease is characterized by high levels of 1,25-vitamin D and by increased bone turnover, caused by the increase in intact parathyroid hormone level.

References (56)

JG Mann et al.
The subtle and variable clinical expressions of gluten-induced enteropathy (adult celiac disease, nontropical sprue)
RE Barry et al.
Coeliac disease: the clinical presentation
Clin Gastroenterol
(1974)
JE Harrison et al.
Calcium kinetic studies in patients with malabsorption syndrome
Gastroenterology
(1969)
GW Hepner et al.
Osteomalacia and celiac disease
S Mora et al.
Effect of gluten-free diet on bone mineral content in growing patients with celiac disease
Am J Clin Nutr
(1993)
J Fox et al.
Deficiency of vitamin D metabolites directly stimulates renal 25-hydroxyvitamin D₃-1-hydroxylase activity in rats
Metabolism
(1991)
WJ Maierhofer et al.
Bone resorption stimulated by elevated serum of 1,25-(OH)₂-vitamin D concentrations in healthy men
Kidney Int
(1983)
P Crabbè et al.
Urinary hydroxyproline excretion in malabsorption states
Gastroenterology
(1965)
PD Delmas
Biochemical markers of bone turnover I: theoretical considerations and clinical use in osteoporosis
Am J Med
(1993)
TI Bennet et al.
Idiopathic steatorrhea (Gee's disease)

MP Caraceni et al.

Bone and mineral metabolism in adult celiac disease

Am J Gastroenterol

(1988)

S Bodè et al.

Body composition and calcium metabolism in treated coeliac disease

Gut

(1991)

X McFarlane et al.

Osteoporosis: a frequent finding in treated adult coeliac disease

Gut

(1992)

GP Butcher et al.

Reduced bone mineral density in coeliac disease

T Valdimarsson et al.

Bone mineral density in coeliac disease

Scand J Gastroenterol

(1994)

MR Clements et al.

The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency

Clin Endocrinol

(1992)

U Goldbourt et al.

Weight-height indices

Br J Prevent Soc Med

(1974)

E Seeman et al.

Differential effects of endocrine dysfunction on the axial and appendicular skeleton

J Clin Invest

(1982)

SR Nussbaum et al.

Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia

Clin Chem

(1987)

BW Hollis et al.

Determination of vitamin D status by radioimmunoassay with an ¹²⁵I-labelled tracer

Clin Chem

(1993)

TA Reinhardt et al.

A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: applications to clinical studies

J Clin Endocrinol Metab

(1984)

BW Hollis

Assay of circulating 1,25-dihydroxyvitamin D involving a novel single-cartridge extraction and purification procedure

Clin Chem

(1986)

PD Delmas et al.

Bone Gla protein (osteocalcin) assay standardization report

J Bone Miner Res

(1990)

J Mellko et al.

Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen

Clin Chem

(1990)

J Risteli et al.

Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation

Clin Chem

(1993)

M Hollander et al.

Non-parametric statistical methods

(1973)

S Siegel

Non-parametric statistics for the behavioral sciences

(1956)

AJ Moss et al.

Gluten-sensitive enteropathy with osteomalacia but without steatorrhea

N Engl J Med

(1965)

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To evaluate the vitamin D status of children with a new diagnosis of celiac disease compared with healthy controls.
This was a case-control study. Cases were consecutive children with newly diagnosed celiac disease. Controls were healthy children matched for age, sex, ethnicity, and month of blood testing. Plasma 25-hydroxyvitamin D (25-OHD) was measured as the index of vitamin D nutritional status. The Student t test was used for comparisons. Differences in frequencies were evaluated with the χ² test. Associations between variables were estimated by calculating Pearson correlation coefficients.
There were 131 children with celiac disease enrolled (62% females; mean age 8.1 ± 1.1 years). The control group included 131 healthy children (62% females; mean age 8.2 ± 1.2). All were of European origin. Plasma 25-OHD levels were significantly lower in patients than in controls (25.3 ± 8.0 and 31.6 ± 13.7 ng/mL; P < .0001). The percentage of children with vitamin D deficiency (<20 ng/mL) was significantly higher in children with celiac diseaseas compared with controls (31% vs 12%; P < .0001). The concentration of 25-OHD was significantly lower in patients than in controls during summer (P < .01) and autumn (P < .0001).
In this case-control study, at diagnosis, children with celiac disease showed lower levels of plasma 25-OHD compared with healthy subjects. Vitamin D status should be checked at diagnosis of celiac disease, particularly during summer and fall months.
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Lemieux et al. report a normal value of PTH on a gluten-free diet [17]. As expected, other papers report a low level of vitamin D at diagnosis associated with a high PTH level [10,14,16,20,21]. Only a few studies exist on the benefit of vitamin D supplementation in CeD patients.
Within the wide spectrum of symptoms and alteration of systems that characterizes CeD, several studies indicate a low-level of vitamin D, therefore recent guidelines suggest its evaluation at the time of diagnosis. This review examines the data from existing studies in which vitamin D has been assessed in CeD patients. Our review indicates that most of the studies on vitamin D in adult CeD report a 25 (OH) vitamin D deficiency at diagnosis that disappears when the patient goes on a gluten-free diet, independently of any supplementation. Instead, when the calcitriol, the active 1,25 (OH) vitamin D form, was evaluated, it resulted in the normal range at the time of CeD diagnosis. A strict and lifelong gluten-free diet can help recover vitamin D level without any supplementation.
Implementation and adherence to osteoporosis screening guidelines among coeliac disease patients
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To investigate implementation of osteoporosis screening guidelines in coeliac disease patients and determine how often bone mineral density (BMD) assessment leads to therapeutic intervention.
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Of 222 adults with coeliac, only 80 (36%) underwent DXA after their diagnosis. Of those, 43 had DXA for osteoporosis screening specifically related to their coeliac diagnosis. Of these 43 patients, 28 (65.1%) had low BMD. A therapeutic intervention was made in the majority of these patients (21/28, 75%). Of 330 pediatric coeliac cases, 52 (15.8%) had DXA specifically in the context of the coeliac disease diagnosis with only 5 being complicated coeliac disease. Of these, 3 (5.8%) had low BMD and only 2 underwent therapeutic intervention.
Osteoporosis screening guidelines are not followed in the majority of patients with coeliac disease but, when followed, frequently lead to therapeutic intervention. Osteoporosis screening guidelines in coeliac disease need to be updated, strengthened and publicized.
Celiac Disease Does Not Influence Fracture Risk in Young Patients with Type 1 Diabetes
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To examine the risk of any fractures in patients with both type 1 diabetes (T1D) and celiac disease (CD) vs patients with T1D only.
We performed a population-based cohort study. We defined T1D as individuals aged ≤30 years who had a diagnosis of diabetes recorded in the Swedish National Patient Register between 1964 and 2009. Individuals with CD were identified through biopsy report data between 1969 and 2008 from any of Sweden's 28 pathology departments. Some 958 individuals had both T1D and CD and were matched for sex, age, and calendar period with 4598 reference individuals with T1D only. We then used a stratified Cox regression analysis, where CD was modeled as a time-dependent covariate, to estimate the risk of any fractures and osteoporotic fractures (hip, distal forearm, thoracic and lumbar spine, and proximal humerus) in patients with both T1D and CD compared with that in patients with T1D only.
During follow-up, 12 patients with T1D and CD had a fracture (1 osteoporotic fracture). CD did not influence the risk of any fracture (adjusted hazard ratio = 0.77; 95% CI = 0.42-1.41) or osteoporotic fractures (adjusted hazard ratio = 0.46; 95% CI = 0.06-3.51) in patients with T1D. Stratification for time since CD diagnosis did not affect risk estimates.
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This observation coincides with microarchitectural findings and it is likely associated with the fact that the distal radius is the site where most fractures occur in the young CD population. Our group and several others had previously shown a lower aBMD in all areas of the skeleton assessed by DXA in CD patients [2–8]. Global bone mineral density assessment, including areal BMD DXA measurements in the radius and total vBMD (D100) measured by HR-pQCT of both radius and distal tibia, showed a comparable deterioration with a similar statistical significance.
Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones—distal radius and tibia—in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18–49) and 22 healthy women of similar age (median age 30 years, range 21–41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm³ (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm³ (118.6 ± 31.5 vs. 161.9 ± 33.6, p < 0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p < 0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm³ 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a—8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had a greater bone microarchitectural deficit than those with subclinical CD. HR-pQCT was used to successfully identify significant deterioration in the microarchitecture of trabecular and cortical compartments of peripheral bones. Impairment was characterized by lower trabecular number and thickness—which increased trabecular network heterogeneity—and lower cortical density and thickness. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture recovers and to what extend after gluten-free diet.

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^☆: Supported in part by a grant from the Associazione Ricerca in Medicina.

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Bone mass and metabolism in patients with celiac disease☆

Abstract

Clin Gastroenterol

Gastroenterology

Am J Clin Nutr

Metabolism

Kidney Int

Gastroenterology

Am J Med

Idiopathic steatorrhea (Gee's disease)

Bone and mineral metabolism in adult celiac disease

Am J Gastroenterol

Body composition and calcium metabolism in treated coeliac disease

Gut

Osteoporosis: a frequent finding in treated adult coeliac disease

Gut

Reduced bone mineral density in coeliac disease

Bone mineral density in coeliac disease

Scand J Gastroenterol

The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency

Clin Endocrinol

Weight-height indices

Br J Prevent Soc Med

Differential effects of endocrine dysfunction on the axial and appendicular skeleton

J Clin Invest

Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia

Clin Chem

Determination of vitamin D status by radioimmunoassay with an 125I-labelled tracer

Clin Chem

A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: applications to clinical studies

J Clin Endocrinol Metab

Assay of circulating 1,25-dihydroxyvitamin D involving a novel single-cartridge extraction and purification procedure

Clin Chem

Bone Gla protein (osteocalcin) assay standardization report

J Bone Miner Res

Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen

Clin Chem

Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation

Clin Chem

Non-parametric statistical methods

Non-parametric statistics for the behavioral sciences

Gluten-sensitive enteropathy with osteomalacia but without steatorrhea

N Engl J Med

Determination of vitamin D status by radioimmunoassay with an ¹²⁵I-labelled tracer