Article

Prevalence and predictors of abnormal bone mineral metabolism in recently diagnosed adult celiac patients

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Abstract

This study aimed to evaluate the prevalence of low bone mineral density (BMD) in recently diagnosed adult celiac patients and to identify the factors associated with this. We investigated 54 newly diagnosed adult celiac patients between February 2008 and April 2009. BMD was measured in all patients and its correlation with clinical and biochemical parameters was analyzed. Fifty-four (24 male) newly diagnosed celiac patients with a mean±SD age of 30.6 ± 9.3 years (range 18-50) were included. Thirty-nine (72.2 %) presented with intestinal symptoms, and the rest with extraintestinal symptoms. Low vitamin D levels were seen in 11 (20.3 %) patients and elevated iPTH (secondary hyperparathyroidism) in 12 (22.2 %) patients. Twenty-one (39 %) patients had normal BMD, 23 (43 %) had osteopenia (T-score -1 to -2.5), and 10 (18 %) patients had osteoporosis (T-score <-2.5). A statistically significant association was seen between BMD and age of onset, duration of illness, serum tTGA levels, serum vitamin D levels, and histopathological changes. Low BMD is common in newly diagnosed adult celiac patients with approximately one fifth of them having osteoporosis. BMD should be measured in all newly diagnosed celiac patients and calcium and vitamin D supplementation included in the treatment regimen.

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... 3 It has been demonstrated that up to 75% of patients with coeliac disease (CD) suffer from bone mass loss (osteopenia or osteoporosis). [4][5][6][7][8][9][10] Despite the strong association between low BMD and CD, guidelines do not express with certainty whether each patient with a new diagnosis of CD should undergo a DEXA scan. [11][12][13] At present, DEXA investigations are suggested only for patients with CD who are peri-or post-menopausal females or males over 55 years and those with overt malabsorption or a history of fragility fractures. ...
... The observed prevalence of low BMD in this consecutively diagnosed cohort of adult CD patients was approximately 60%, in line with previously reported prevalence data (40%-75%). [4][5][6][7][8][9][10] The gender ratio reflected the usual distribution of CD (females:males ¼ 2:1), making our cohort a suitable representation of the gender distribution in CD. 13,23 Previous studies considered primarily female coeliac patients (both pre-and post-menopausal), patients who had been on a GFD for variable periods of time or also included children in their evaluation, representing important biases in the assessment of the prevalence of BMD alterations in adults with CD. 12,15 In our cohort of newly diagnosed CD patients, males were more frequently affected by osteoporosis than females, with an OR of 4.7, highlighting male gender as a risk factor for osteoporosis in CD. The majority of papers studying the prevalence of osteopenia and/or osteoporosis in coeliac patients did not show a significant difference between genders. ...
... Our data demonstrated that older age (!45 years) at the time of CD diagnosis was a significant risk factor for osteoporosis. This finding, supported by previous studies, 5,8,9,34 is consistent with the known linear relationship between increasing age and the risk of low BMD. 1 Approximately one-third of the examined coeliac patients showed increased PTH values, with a statistically significant prevalence in the patients with osteoporosis in the univariate analysis. In the logistic regression, the results were just below significance, with an OR of 3.9 (CI 95% 0.97 to 15.5; p ¼ 0.055), likely due to the number of lost patients included in the regression. ...
Article
Background: Up to 75% of patients with untreated coeliac disease (CD) present with osteopenia or osteoporosis. Guidelines do not express with certainty whether each patient with newly diagnosed CD should undergo a dual-energy x-ray absorptiometry (DEXA) scan. Aim: The aim of this article is to evaluate the prevalence of bone mineral density (BMD) alterations at diagnosis and risk factors associated with osteoporosis. Methods: A total of 214 adult patients (median age 38 years; female = 71.5%) newly diagnosed with CD underwent DEXA. The patients were divided into three groups: patients with normal BMD, those with osteopenia and those with osteoporosis. Clinical, histological and serological features were assessed and compared among the three groups. Logistic regression including relevant independent variables was performed. Results: DEXA indicated that 39.7%, 42.5% and 17.8% of the CD patients had normal BMD, osteopenia and osteoporosis, respectively. Logistic regression indicated that features significantly associated with osteoporosis were male gender (OR 4.7; 95%CI 1.1 to 20.8), age ≥45 years (OR 6.5; 95% CI 1.3 to 32.2), underweight (OR 7.4; 95% CI 1.3 to 42.5) and greater histological damage (Marsh 3C; OR 5.8; 95% CI 1.4 to 24.1). Conclusions: BMD alterations were found in 60.3% of newly diagnosed adult coeliac patients. Osteoporosis was significantly associated with age ≥45 years, male gender, underweight and Marsh 3C, suggesting that at CD diagnosis, a DEXA scan might be beneficial, particularly in these subgroups of patients.
... 12 However, most of the studies that have assessed the prevalence of osteoporosis in CD or prevalence of CD in patients with osteoporosis have not measured BMD at the distal one-third radius and some only measured the lumbar spine region. 9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] The distal one-third radius is a skeletal site composed predominantly of cortical bone and particularly sensitive to the effects of elevated parathyroid hormone (PTH). 27 While bone loss in CD is likely multifactorial, a major mechanism is thought to be villous atrophy in the small bowel, the main site of calcium and vitamin D absorption. ...
... To our knowledge, this is the largest CD cohort in whom the prevalence of osteoporosis has been evaluated with DXA and one of only a few studies to measure BMD at the one-third radius. 9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] Osteoporosis was present in nearly one-half of our participants 50 years of age or older. Further osteoporosis was as common at the forearm as the spine. ...
... Most studies have not assessed the distal onethird radius and some included the spine only. The spine is subject to artifactually high BMD in older adults due to arthritis and vascular calcification, 9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] leading to potential underestimates of osteoporosis prevalence. Most prior studies have been small and may not accurately reflect prevalence. ...
... [142,143,145] Vitamin D levels were demonstrated to be low in 5%-88% of untreated adult patients, and in 0%-70% of untreated pediatric patients . [146][147][148] Circulating levels of calcium were described to be low in 0%-26% of untreated adults and 0%-41% of pediatric patients. [140,149,150] Magnesium deficiency was reported in 7%-11% of untreated pediatric CD patients. ...
... [182] The GFD has also become particularly popular among athletes. Lis et al. (2015) [147] showed in a survey that out of 910 non-celiac athletes, 40% of those observe a GFD, while over half believe gluten avoidance improves competitive performance and 74% believe it improves "body composition for sport performance". Furthermore, some high-profile athletes have publicly attributed their success to avoiding gluten. ...
... Vitamin D levels were demonstrated to be low in 5%-88% of untreated adult patients, and in 0%-70% of untreated pediatric patients [18,[25][26][27][40][41][42]45]. Circulating levels of calcium were described to be low in 0%-26% of untreated adults and 0%-41% of pediatric patients [17,19,37,40,45,46]. ...
Article
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Nutrient deficiencies are well recognized as secondary consequences of celiac disease (CD) and closely related to the clinical presentation of affected patients. Despite their clinical significance, consensus is lacking on the pattern and frequency of nutrient deficiencies in CD, the usefulness of their assessment at the time of diagnosis and during follow-up. This review aims to provide an overview of nutrient deficiencies among pediatric and adult CD patients at diagnosis and on a gluten-free diet (GFD), and their potential causes in CD. Secondly, we review their impact on CD management strategies including the potential of nutrient supplementation. A search of Medline, Pubmed and Embase until January 2019 was performed. Despite a high variability between the reported deficiencies, we noted that nutrient deficiencies occur frequently in children and adults with CD at diagnosis and during treatment with a GFD. Both inadequate dietary intake and/or diminished uptake due to intestinal dysfunction contribute to nutrient deficiencies. Most deficiencies can be restored with (long-term) treatment with a GFD and/or supplementation. However, some of them persist while others may become even more prominent during GFD. Our results indicate a lack of comprehensive evidence on the clinical efficacy of nutrient supplementation in CD management highlighting the need for further studies.
... An Indian report showed low BMD measurement in earlier age of CD. In this study, all CD patients were also less than 50 years old, 39% of patients had normal BMD, and 61% of newly diagnosed CD cases had low BMD and lumbar and femoral BMD were not separated, but they did not mention to the confounding risk factors for low BMD [33]. Pritcha et al. also showed that 56% of CD patients had normal BMD, 28% osteopenia, and 5% osteoporosis. ...
Article
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Background Celiac disease (CD) is known as a reason of metabolic osteopathy. Progression of non-invasive methods such as bone densitometry has shown that an important ratio of CD cases is faced with impaired bone mass and such cases are prone to bone fractures. Variety of low bone mineral density in CD is probably because of ignored confounding factors such as age, menopause, and drug. The aim of our study was to systematically review the osteoporosis and osteopenia incidences among premenopausal females and males with CD. Methods This systematic review was done based on preferred reporting items for systematic reviews (PRISMA) guidelines. PubMed and Scopus and Cochran databases were searched according to the relevant medical subject headings (MeSH) of CD and bone mineral density until 2018. Prevalence of osteopenia and osteoporosis were used as effect size for meta-analysis. Cochrane Q (p < 0.05) and I² index were presented to reveal the heterogeneity. Results 54 eligible full text reviews were included and nineteen selected for data extraction. Eleven articles didn’t have our inclusion criteria and had ignored confounding factors like age and menopause, and we excluded; data extraction was done in eight studies. A total of 563 premenopausal women and men who were from, UK, Brazil, India, Hungary, and Poland were included. The pooled prevalence of osteoporosis was 14.4% [95%CI: 9–20.5%] (Cochrane Q = 7.889, p = 0.96, I² = 49.29%), and osteopenia was 39.6% [31.1–48.8%] (Cochrane Q = 14.24, p = 0.07, I² = 71.92%), respectively. Conclusion Our findings suggest that bone loss is more prevalent in celiac disease and can be associated with increased risk of fracture. However, but results are pooled prevalence and we need more case –control studies with more sample size and consideration of confounding factors.
... For microscopic mechanical properties [15][16][17] of the bone, mineral content is a critical parameter that vary with disease (e.g. Osteoporosis, changes in subchondral trabecular bone with osteoarthritis), prosthetic implantation, weightlessness, ethnicity, age [18], and diabetes [19]. ...
Article
Bone derives its mechanical strength from the complex arrangement of collagen fibrils (type-I primarily) reinforced with hydroxy-apatite (HAp) mineral crystals in extra- and intra-fibrillar compartments. This study demonstrates a novel approach to obtain organic matrix of bone through its demineralization as well as mechanically characterize it at small length scales using static and dynamic indentation techniques. Sample surface preparation protocol used in the present work maintained the surface integrity of demineralized bone samples which resulted sample surface of roughness (RMS) magnitude of approximately 14 nm (averaged over 1 × 1 μm² area duly verified by atomic force microscope (AFM)). Elemental composition analysis via energy dispersive X-ray spectroscopy (EDX) (for probed depth upto 2 μm) confirmed the complete removal of HAp mineral from bone samples during their demineralization using EDTA leaving collagen molecule assemblies unaffected as represented by Second Harmonic Generation (SHG) imaging. The modulus magnitudes of organic matrix obtained using from quasistatic as well as dynamic indentations (at constant frequency of 30 Hz) as ∼2.6 GPa and 4.5 GPa respectively, demonstrated the influence of loading rate on the estimated mechanical properties. For indentation depth to surface roughness ratio greater than ∼5:1, interestingly, measured material properties of organic matrix were found to depend on increasing magnitude of indentation depth of up to ∼500 nm value which probed from few collagen fibrils to next level of hierarchy i.e. collagen fibers. These findings are very useful to accurately determine the elastic and visco-elastic response of organic matrices of mineralized tissues for various applications including tissue engineering, bio-mimetics, etc.
... A lot of disorders are related to changes in the concentration of vitamin E but it is unclear whether this is the result or the cause of the disease. There have been numerous reports about fat-soluble vitamins insufficiency in adult subjects with gluten enteropathy [29,30]. The plasma or serum concentrations of α-tocopherol more than 16.2 μmol/l are considered as sufficient; less than 11.6 and range between 11.6 and 16.2 indicate a deficiency and low levels of vitamin E, respectively, while lately it has been proposed that the adequate plasma concentration of α-tocopherol to prevent neoplasm and cardiovascular disorders is more than 30 umol/l [31]. ...
Article
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INTRODUCTION Oxidative stress is considered as one of the mechanisms responsible for gluten toxicity, but its role in celiac disease (CD) remains unclear. OBJECTIVES To evaluate oxidative imbalance in the pathomechanism of CD by determining the concentrations of nitric oxide (NO) and selected antioxidant parameters. PATIENTS AND METHODS The study involved 197 adult patients: 53 patients with untreated active CD, 92 celiac patients on gluten-free diet (GFD), and 52 controls. Serum concentrations of antioxidants (uric acid, bilirubin, ferritin, albumin) and serum levels of celiac antibodies, NO, glutathione peroxidase (GPx3) and vitamin E were measured. A histopathological study of duodenal biopsy was performed. RESULTS Celiac patients had higher uric acid concentrations than controls (P<0.001). NO levels were higher in patients with active CD than in controls (P<0.01) and were significantly correlated with the degree of mucosal damage (r2=0.04; P=0.01). Vitamin E levels were decreased in celiac patients (P<0.01) and GPx3 activity was reduced in patients with active CD compared with controls (P<0.001). CONCLUSIONS Oxidative imbalance may be involved in the pathomechanism of CD in adults. GFD only partially reduces oxidative stress. Serum NO levels seem to be a marker of the effectiveness of treatment. Uric acid may act as an antioxidant in CD.
... A recent study Our particular study has revealed the presence of zinc deficiency in two-thirds of the patients with celiac disease at the time of diagnosis and vitamin D deficiency in more than half. Patients with celiac disease experience metabolic bone diseases, including osteoporosis, osteopenia, and bone fractures (10,(17)(18)(19)(20)(21). There are several factors that affect the development of metabolic bone disease in patients with celiac disease. ...
Article
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Background/aim: To establish the frequency of vitamin and mineral deficiency in children newly diagnosed with celiac disease. Materials and methods: The files of patients diagnosed with celiac disease in our Pediatric Gastroenterology Clinic from June 2008 to June 2013 were reviewed retrospectively. Results: A total of 52 pediatric patients diagnosed with celiac disease via serology and duodenal biopsy and who fulfilled the study criteria were enrolled in the study. The mean diagnosis age of the patients was 8.5 ± 3.9 years and 33 (63.5%) of the patients were female. Vitamin D, vitamin A, vitamin E, zinc, and iron deficiencies were determined in 27 (51.9%), 4 (7.7%), 7 (13.5%), 35 (67.3%), and 18 (34.6%) patients, respectively, at the time of diagnosis. Vitamin D deficiency was observed more frequently in patients with growth retardation at the time of application (P = 0.02). Conclusion: Vitamin D, zinc, and iron deficiency are frequently observed in pediatric patients with celiac disease at the time of diagnosis. Therefore, serum vitamin D, zinc, and iron levels should be checked in all children diagnosed with celiac disease.
... Bone disease in CD is attributed to malabsorption and secondary hyperparathyroidism, which results in reduced bone mass, alteration in bone quality and increased risk of fractures1112. Bisphosphonates are most commonly used for the prevention and treatment of all forms of osteoporosis13. ...
Article
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Background & objectives: The symptoms of celiac disease (CD) are varied and metabolic bone disease (MBD) is less recognized amongst all manifestations in CD patients. Bone disease in CD is attributed to secondary hyperparathyroidism, which in turn is associated with increased bone remodelling. Improvement in bone mineral density (BMD) with gluten free diet (GFD) is known, but the data on efficacy of bisphosphonates in CD patients are limited. Bisphosphonates being a potent inhibitor of bone resorption may be useful in patients with CD having low BMD. The aim of the present investigation was to study the effect of zoledronic acid on BMD in CD patients. Methods: A total of 28 CD patients were randomized to receive GFD, calcium and cholecalciferol (group A), and zoledronic acid (group B). Baseline biochemical tests and T-score by dual energy x-ray absorptiometer were done and repeated after 12 months. Results: The T-score showed improvement in the control arm (group A) from -3.31 ± 1.46 to -2.12 ± 1.44, a gain of 35.9 per cent (P<0.05) and in drug arm (group B) -2.82 ± 1.27 to -1.06 ± 1.84, registering a gain of 62.4 per cent (P<0.001). However, there was no difference in improvement of T-score in zoledronic acid group as compared to the control group. Interpretation & conclusions: Administration of zoledronic acid was not found to be better than GFD alone in increasing BMD in CD patients with low BMD in this pilot study.
... Vitamin D deficiency is frequently seen in patients with CD and between 20 and 55% of patients with CD are vitamin D deficient at diagnosis [23,24]. Calcium is likely malabsorbed in many patients with active CD but serum levels are maintained through PTH. ...
Article
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Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals and represents a major health issue. The immune mediated response results in villous atrophy of the small intestine with subsequent malabsorption. The classic mode of presentation is that of a malabsorption syndrome resulting in deficiencies of macro and micronutrients. The gluten-free diet is the only treatment currently available for this disorder. The aim of this special report is to elucidate and explain the various nutritional deficiencies seen in newly diagnosed patients with celiac disease and while on the gluten-free diet. Though initiation of the gluten-free diet results in improvement of symptoms and most deficiencies, certain nutritional limitations are associated with the gluten-free diet.
Article
Objective To evaluate the vitamin D status of children with a new diagnosis of celiac disease compared with healthy controls. Study design 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 were used for comparisons. Differences in frequencies were evaluated with the χ2 test. Associations between variables were estimated by calculating Pearson correlation coefficients. Results 131 children with celiac disease were 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 control subjects (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 celiac disease children as compared with controls (31% vs 12%; p<0.0001). The concentration of 25-OHD was significantly lower in patients than in controls during summer (p<0.01), and autumn (p<0.0001). Conclusion 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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Celiac disease (CD) is an immune-mediated enteropathy that occurs in genetically susceptible hosts with the ingestion of gluten-containing products. Ongoing gluten consumption leads to intestinal damage, characterized by villous blunting and increased intraepithelial lymphocytes, resulting in malabsorption. Pertinent to the development of bone disease, malabsorption of calcium and vitamin D leads to secondary hyperparathyroidism and metabolic bone disease among individuals with CD. In this article, we review the pathogenesis of CD and the effects of malabsorption on bone health. Imbalances in bone resorption and formation particularly in individuals with CD and persistent disease activity ultimately lead to a state of bone loss and impaired mineralization. Initiation of a gluten-free diet is critical in the management of CD-related metabolic bone disease, demonstrating improvements in bone mineral density within the first year of dietary adherence.
Article
Vitamin D-deficient Saudi adolescent girls were screened for anti-tissue transglutaminase (IgA-tTG) antibodies to determine whether the presence of severe vitamin D deficiency was associated with celiac disease. All 9 participants who were positive for IgA-tTG antibodies had severe vitamin D deficiency (25(OH)D < 12.5 nmol/l), suggesting that this population should be screened for celiac disease. Purpose The current cross-sectional study aimed to see if severe vitamin D deficiency is associated with celiac disease (CD) among Saudi adolescent girls. Methods A total 200 adolescent females aged 13–19 years old with vitamin D deficiency (serum 25(OH)D < 50 nmol/l) were screened for IgA tTG (anti-tissue transglutaminase antibodies). Results Of the 200 girls, 9 (4.5%) were positive for IgA tTG antibodies; all of whom had serum 25(OH)D < 12.5 nmol/l. A strong significant inverse association was observed between tTG antibody levels and serum 25(OH)D (R = − 0.53; p < 0.001) among antibody negative participants. Finally, participants with positive IgA tTG antibodies was 37.2 times higher for participants with 25(OH)D < 12.5 nmol/l than those whose vitamin D status was higher [OR = 37.2 (95% CI 4.6–299.7) (p = 0.0002)]. Conclusion The data suggests that CD maybe a risk factor for severe vitamin D deficiency and that patients presenting with very low levels of 25(OH)D of less than 12.5 nmol/l—in the absence of an obvious cause—may need to be screened for CD.
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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.
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Osteoporosis is a skeletal disease characterized by decreased bone mass and microarchitectural changes in bone tissue that increase the susceptibility to fracture. Secondary osteoporosis is loosely defined as low bone mineral density or increased risk of fragility fracture caused by any factor other than aging or postmenopausal status. The purpose of this review is to discuss the current understanding of the pathophysiology and contribution to fracture risk of many of the more common causes of secondary osteoporosis, as well as diagnostic considerations, outlined by organ system. While not comprehensive, included are a wide array of diseases, conditions, and medications that have been associated with bone loss and susceptibility to fractures. The hope is to highlight the importance to the general clinician of screening for and treating the osteoporosis in these patients, so to limit the resultant increased morbidity associated with fractures.
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AIM:: The purpose of this study was to identify the frequency of fat-soluble vitamin deficiencies in children with celiac disease (CD) and to determine the value of routine testing for these deficiencies. We conducted a retrospective medical record review of patients with a confirmed diagnosis of CD and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic. Patients' demographics, fat-soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected. Eighty-three patients were included in the final analysis: 51 female and 32 male, with average age at diagnosis of 12.8 years in females and 13.0 years in males. The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of CD was reported in 32 patients. Average vitamin levels for vitamin E, 25-hydroxyvitamin D, and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 mcg/dL, respectively. No patients had vitamin A deficiency, 2 patients had vitamin E deficiency, and 9 patients had mild to moderate vitamin D deficiency (none had severe deficiency). Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy. Thirty-one patients had insufficiency of 25-hydroxyvitamin D, which was less than the reported frequency of vitamin D insufficiency in the general pediatric population in United States in 2004. None of the patients was receiving vitamin supplements at the time of diagnosis. Fat-soluble vitamin deficiencies are uncommon in children with new diagnosis of CD. Routine measuring of fat soluble vitamins levels may not be necessary.
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To investigate whether the serological marker for coeliac disease, tissue transglutaminase autoantibody (tTGAb), is associated with decreased bone mass density (BMD) and increased frequency of fractures in middle-aged women screened for osteoporosis. The study comprised 6480 women (mean age 56 years, range 50-64) who answered a number of questionnaires and who underwent dual X-ray absorptiometry of the wrist bone. Serum samples were analysed for tTGAb using radioligand binding assays. A tTGAb level of >4 U/ml was used to determine a positive value and a level of >17 U/ml was used as an alternative discrimination of high levels. A tTGAb level >4 U/ml was found among 90/6480 (1.4%) women and correlated with lower BMD (multiple linear regression coefficient -382.1; 95% CI = - 673.6-90.7, p=0.011) and with fracture frequency (r=0.18, p=0.023). The 59 women with tTGAb levels >or=17 U/ml had a lower BMD (0.41+/-0.08 g/cm(2) versus 0.44+/-0.08 g/cm(2), p=0.001) and a lower T-score (-1.40+/-1.28 versus -0.90+/-1.40, p=0.003) as well as a higher prevalence of osteoporosis (13.4% versus 6.5%, p=0.008) compared with the remaining 6421 women with tTGAb levels <17 U/ml. Furthermore, fracture frequency was more pronounced in women with tTGAb levels >or=17 U/ml, among whom 19/59 (32.2%) had fractures during the study period compared with 1204/6421 (18.8%) among women with tTGAb levels <17 U/ml (p=0.009). High levels of tTGAb indicating coeliac disease are associated with lower BMD and higher fracture frequency in women between 50 and 64 years of age. Osteometry is therefore warranted in middle-aged women detected with tTGAb.
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This article examines associations between gluten, polymorphisms of the major histocompatibility complex, and mucosal pathology representative of the spectrum of gluten sensitivity. Sequences of wheat, rye, and barley prolamins contain recurring tetrapeptide motifs that are predicted to have beta-reverse-turn secondary structure and that, with in vitro assays, appear active. Structural polymorphisms of major histocompatibility complex subloci identify codon switches within the second exon that control the third hypervariable region in the outer domain of the beta chain. Observations of the intestinal response to gluten reveal five interrelated lesions (preinfiltrative, infiltrative, hyperplastic, destructive, and hypoplastic) that are interpretable as cell-mediated immunologic responses. These responses originate in the lamina propria, where a series of antigen-specific inflammatory processes has now been identified. There is no evidence that celiac sprue is a disease of jejunal enterocytes. Furthermore, the role of intraepithelial space lymphocytes in pathogenesis, if relevant, needs further experimental dissection. Also awaiting further definition are polymorphisms of the celiac lymphocyte antigen receptor and their relationship to gliadin oligopeptide(s) and predisposing genes. The nature and basis of nonresponsive celiac sprue require more thoughtful initiatives to elucidate the immunologic mechanism(s) of unresponsiveness and evaluate possible means of reversal. Finally, a more sensible definition of gluten sensitivity (unhampered by qualitative morphological imagery) is ultimately called for in order to accommodate the biomolecular advances addressed in this review.
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A cross sectional study was undertaken to examine the relationship between coeliac disease and bone mineral density. The 135 female coeliac patients registered on the database of the Department of Gastroenterology at Hull Royal Infirmary were approached by letter, advising them of a potential risk of osteoporosis and inviting them to undergo bone densitometry. A total of 81 registered women (60%) attended the Osteoporosis Laboratory, Princess Royal Hospital and underwent dual energy x ray absorptiometry at the lumbar spine (L2-L4) and femoral neck. Historical data relating to the time of diagnosis and adherence to a gluten free diet were obtained. A control group was selected from the local normal population and was first matched for height, weight, and menopausal status. Postmenopausal patients were then further matched to controls of equivalent menopausal age. In coeliac patients, bone mineral density expressed in g/cm2 as mean (SD) was significantly lower at the lumbar spine (1.076 (0.186)) than in the control group (1.155 (0.143), p < 0.001). This was also the case at the femoral neck (0.887 (0.142) versus 0.965 (0.127), p < 0.001). When the coeliac patients were stratified by menopausal status, it was found that femoral neck bone mineral density was significantly below control values in both premenopausal and postmenopausal women. Spinal bone mineral density exhibited a significant decrement only in the postmenopausal group. The age at diagnosis of coeliac disease and adherence to a gluten free diet did not influence bone mineral density at either hip or spine. These results confirm coeliac patients' higher risk of osteopenia. Coeliac disease should be added to the list of medical conditions which constitute an indication for bone densitometry in order that the individual risk of osteoporosis related fracture may be determined.
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Osteopenia is a common complication of celiac disease. The aims of this study were to evaluate whether treatment produces bone remineralization and whether calcium and vitamin D supplementation are necessary to reduce osteopenia. Bone mineral density and biochemical parameters of bone and mineral metabolism were measured in 14 newly diagnosed adult celiac disease patients. All patients were treated with a gluten-free diet and were randomized to receive diet only (n = 7) or diet plus calcium (1.0 g/day) and vitamin D (32,000 IU/wk) supplementation (n = 7). Bone density was measured at baseline and at 6 and 12 months of follow-up. Tests for biochemical determinations were repeated every 3 months. At diagnosis, 11 patients had evidence of osteopenia (> 1 SD below normality) in the spine and total skeleton. After 12 months of gluten restriction, overall bone mass had increased 5.0% (p < 0.01) in the lumbar spine and 5.0% (p < 0.002) in the total skeleton. When one only considers those 11 patients who strictly followed gluten restriction, bone density increased 8.4% in the lumbar spine and 7.7% in the total skeleton. Remineralization occurred throughout the skeleton but was more pronounced in the axial than in the peripheral skeleton. The increase in bone mass was independent of age or menopause. Remineralization in patients treated with diet only was similar to that of patients treated with diet and supplements. Basal biochemical parameters showed a high bone turnover with secondary hyperparathyroidism. Treatment induced a decrease in bone turnover activity. However, a complete restoration of biochemical parameters was not achieved. Strict gluten avoidance promoted a significant increase in bone mineral density. However, values still remain markedly low after 1 yr in several patients. Although calcium and vitamin D supplementation did not provide additional benefit to that obtained by diet alone in the doses administered, our results do not preclude a possible effect of vitamin D at higher dose.
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1) The aim of the study was to identify the atypical celiac disease (CD) in a cohort of symptomatic osteoporotic patients, younger than 55 years of age and 2) To study associated clinical and laboratory features and outcome with gluten-free diet. We studied 33 patients (F:M = 28:5), mean age 29 years (range 15-52 years) with osteoporosis (WHO diagnostic criteria, T-score less than -2.5 on DEXA scan) from January 2000 - June 2002. Serological screening for CD was done by detecting circulating IgA antibodies to tissue transglutaminase by ELISA. Patients with presence of antibodies to transglutaminase were subjected to biopsy from the 2nd part of the duodenum by upper GI endoscopy. The biopsies were reported independently by two pathologists who were blinded for the serology report. Measurement of mucosal thickness, crypts and villi were done with an ocular micrometer. Other parameters like complete hemogram, serum iron, total iron binding capacity (TIBC), calcium profile, 25-OH-D, parathyroid hormone (PTH) were evaluated. Assessment of clinical and laboratory parameters was performed within 4-12 weeks of starting gluten-free diet (GFD). Thirteen patients had circulating IgA antibodies to transglutaminase. Intestinal biopsies were performed on 11 patients and were consistent with the diagnosis of CD (total villous atrophy--two, subtotal villous atrophy with crypt hyperplasia--nine). Patients with CD had significant anaemia when compared with non-CD osteoporotic patients. Other important observations in these 11 patients were low serum calcium and phosphorus, low 25-OH-D, high PTH. Significant improvement in clinical and laboratory parameters was noted in all patients within 6-12 weeks of starting GFD. Symptomatic osteoporotic patients (younger than 55 years of age) especially with associated anaemia should be investigated for CD. Simple measures like omission of wheat from diet (GFD) lead to significant improvement in symptoms within weeks.
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There is an increased prevalence of osteoporosis among patients with celiac disease. However, the relative prevalence of celiac disease among osteoporotic and nonosteoporotic populations is not known, and the benefit of screening the osteoporotic population for celiac disease remains controversial. We evaluated 840 individuals, 266 with and 574 without osteoporosis, from the Washington University Bone Clinic by serologic screening for celiac disease. Individuals with positive serologic test results for antitissue transglutaminase or antiendomysial antibody were offered endoscopic intestinal biopsy to confirm the diagnosis of celiac disease. Individuals with biopsy-proven celiac disease were treated with a gluten-free diet and followed up for improvement in bone mineral density. Twelve (4.5%) of 266 patients with osteoporosis and 6 (1.0%) of 574 patients without osteoporosis tested positive by serologic screening for celiac disease. All but 2 serologically positive individuals underwent in-testinalbiopsy. Nine osteoporotic patients and 1 nonosteoporotic patient had positive biopsy results. The prevalence of biopsy-proven celiac disease was 3.4% among the osteoporotic population and 0.2% among the nonosteoporotic population. All biopsy-positive individuals tested positive by antitissue transglutaminase and antiendomysial antibody. The antitissue transglutaminase levels correlated with the severity of osteoporosis as measured by T score, demonstrating that the more severe the celiac disease the more severe the resulting osteoporosis. Treatment of the patients with celiac disease with a gluten-free diet resulted in marked improvement in T scores. The prevalence of celiac disease among osteoporotic individuals (3.4%) is much higher than that among nonosteoporotic individuals (0.2%). The prevalence of celiac disease in osteoporosis is high enough to justify a recommendation for serologic screening of all patients with osteoporosis for celiac disease.
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In recent years there has been increasing recognition that the pattern of presentation of coeliac disease may be changing. The classic sprue syndrome with diarrhoea and weight loss may be less common than the more subtle presentations of coeliac disease such as an isolated iron deficiency anaemia. As a result, the diagnosis of this treatable condition is often delayed or missed. Recent serologic screening tests allow non-invasive screening to identify most patients with the disease and can be applied in patients with even subtle symptoms indicative of coeliac disease. Both benign and malignant complications of coeliac disease can be avoided by early diagnosis and a strict compliance with a gluten free diet. The aim of this study is to evaluate the trends in clinical presentation of patients diagnosed with adult coeliac disease. In addition, we studied the biochemical and serological features and the prevalence of associated conditions in patients with adult coeliac disease. This is an observational, retrospective, cross-sectional review of the medical notes of 32 adult patients attending the specialist coeliac clinic in a district general hospital. Anaemia was the most common mode of presentation accounting for 66% of patients. Less than half of the patients had any of the classical symptoms of coeliac disease and 25% had none of the classical symptoms at presentation. Anti-gliadin antibodies, anti-endomysial antibody and anti-tissue transglutaminase showed 75%, 68% and 90% sensitivity respectively. In combination, serology results were 100% sensitive as screening tests for adult coeliac disease. Fifty nine percent patients had either osteoporosis or osteopenia. There were no malignant complications observed during the follow up of our patients. Most adults with coeliac disease have a sub clinical form of the disease and iron deficiency anaemia may be its sole presenting symptom. Only a minority of adult coeliac disease patients present with classical mal-absorption symptoms of diarrhoea and weight loss. Patients with atypical form of disease often present initially to hospital specialists other than a gastro-enterologist. An awareness of the broad spectrum of presentations of adult coeliac disease, among doctors both in primary care and by the various hospital specialists in secondary care, is necessary to avoid delays in diagnosis. It is important to include serological screening tests for coeliac disease systematically in the evaluation of adult patients with unexplained iron deficiency anaemia or unexplained gastro-intestinal symptoms and in those who are considered to be at increased risk for coeliac disease.
Article
Background: Serum antibodies to tissue transglutaminase (tTGA) are reported to have high sensitivity and specificity for coeliac disease and to correlate closely with endomysial antibodies (EmA). We assessed their performance in a coeliac population with a high proportion of EmA-negative patients, who have been under-represented in previous studies. Methods: We used a commercial ELISA kit to test for IgA class tTGA in sera from a population of 73 untreated coeliac patients with normal serum IgA and a high percentage (19%) EmA-negative, taking 58 patients with normal duodenal biopsies as controls. EmA was measured using indirect immunofluorescence. Results: Forty-six (63%) patients with villous atrophy (VA) had both tTGA and EmA. However, when considered separately, sensitivities of tTGA and EmA for VA were similar (75% versus 81%) and both had high specificity (98% versus 97%). As 9 patients were tTGA-positive only and 13 had EmA only, selection of patients for biopsy on the presence of either antibody wo...
Article
Background. Caeliac disease is an immune-mediated enteropathy induced by gluten in genetically predisposed individuals. Malabsorption of vitamins and minerals is a common finding in untreated patients and disturbance in bone metabolism is therefore a suspected complication. We wanted to assess vitamin D status, parathyroid hormone (PTH) and bone mineral density (BMD) in patients with newly diagnosed caeliac disease. Material and methods. Altogether 118 patients (93 females) were investigated. Median age was 42.5 years (range 20 - 87 years). Vitamin D metabolites, PTH and biochemical markers of bone metabolism were measured in blood. Lumbar spine, femoral neck and total body BMD were measured by dual x-ray absorptiometry (DXA); Z scores were obtained by comparison with locally derived age- and sex matched reference values. Results. Vitamin D deficiency (25-hydroxyvitamin D < 30 nmol/l) was present in 20 % of the patients; 30 % of the patients had secondary hyperparathyroidism (PTH ≥7.0 pmol/l). BMD was significantly reduced (p < 0.001) at all skeletal sites measured. There was no relationship between vitamin D status and BMD, but PTH was negatively correlated to BMD at all skeletal sites (p < 0.005). Body mass index (BMI) was positively correlated to BMD in these patients (p < 0.001). Conclusion. Hypovitaminosis D and secondary hyperparathyroidism are common in patients with newly diagnosed caeliac disease in addition to low BMD.
Article
Background: The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible signific ...
Article
Since no information is available on bone derangements in subclinical coeliac disease (CD), we evaluated bone mineral density (BMD, expressed as z score) at lumbar spine, by X-ray dual-photon absorptiometry, and serum indices of bone metabolism and remodeling in 14 subclinical or silent patients, 10 classical patients, and 15 healthy volunteers all on a gluten-containing diet. In the subclinical group, BMD at lumbar spine was significantly higher than in the classical group (-1.3 ± 0.8, 73% vs. -2.6 ± 0.6, 88%, respectively ; p < 0.001), but significantly lower than in volunteers (+0.4 ± 1.1, 104% ; p < 0.001). Similar changes were observed in serum calcium, whereas, as regards parathyroid hormone, no significant difference was found between subclinical and classical patients. 25-vitamin D was significantly lower, and 1,25-vitamin D was significantly higher in subclinical and classical patients than in healthy volunteers. Indices of bone remodeling were higher in the subclinical and classical groups than in the volunteers, but lower in the subclinical than in classical patients. Eight subclinical and 8 classical patients were re-examined after a period of gluten-free diet (GFD), and in both groups BMD had significantly improved. Our results show that osteopenia is a frequent feature also in subclinical CD, although the extent of bone and mineral metabolism derangements is lower than in classical CD. GFD is able to normalize BMD in subclinical and to significantly improve it in classical patients.
Article
The detection of auto antibodies directed against tissue transglutaminase (anti-tTG antibodies) has a well-established role in the diagnosis of coeliac disease, but the value of these antibodies in long-term follow-up is controversial. To determine if serial anti-tTG antibody measurements could confirm adherence to a gluten-free diet (GFD) and identify patients at risk of disease complications. In a 54-month cohort follow-up study, 182 adult patients were assessed. Data recorded included self-assessment of GFD adherence; anti-tTG antibody concentration and serum ferritin, vitamin B12 and folate. Where available, bone mineral density (BMD) and duodenal histology data were retrieved. Persistently elevated anti-tTG antibody levels were significantly associated with abnormal duodenal histology (P < 0.001), low ferritin (P < 0.01) and poor adherence to the GFD (P < 0.001). The specificity was >85% while the sensitivity was 39-60%. Anti-tTG antibody concentrations fell rapidly following successful initiation of a GFD, and maintenance of normalization identified those who continued to be adherent to the diet. This study supports a strategy of using anti-tTG antibody concentrations to monitor newly diagnosed and established patients with coeliac disease, and to target dietetic intervention to reduce the risk of complication.
Article
A diagnosis of coeliac disease was confirmed in 57 patients referred to a gastroenterology clinic over a 5 1/2-year period. Although diarrhoea was present in two-thirds of the patients, this was the major symptom leading to referral in less than half of them. When present, diarrhoea was usually intermittent and frequently not typical of steatorrhoea. Symptoms were of less than six months' duration in half the patients, but a review of the past and family history strongly indicated the possibility of coeliac disease in 39 of the 57 patients. A high spontaneous abortion rate during pregnancy was noted. The frequent absence of the classical features of malabsorption, diarrhoea with typical steatorrhoea and chronic debility was noted. All screening tests for malabsorption were found to be unreliable and their routine use was rarely justified. A random serum folate and carotene assay proved as valuable as more expensive and troublesome tests. It is stressed that in any case in which there is a clinical suspicion of this diagnosis, a small intestinal biopsy should be undertaken.
Article
Intestinal disease might contribute to osteopenia. Measurements of IgA antibodies to gliadin have been established as an accepted screening procedure for detection of coeliac disease. When we applied these measurements to 92 patients with verified osteoporosis, 11 subjects (12%) were found to have elevated levels. This is markedly higher than the incidence in healthy subjects (3%). However, the patients with raised levels of IgA antibodies displayed no clinical symptoms and no laboratory evidence of calcium malabsorption. Thus their values for serum calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and osteocalcin, as well as the fasting urinary excretion of hydroxyproline and calcium, were similar to those found in other patients with osteoporosis. Intestinal biopsy verified coeliac disease in three patients and was normal in another three. This gives an incidence of verified coeliac disease in this patient group that is approximately tenfold higher than that in the healthy population. Subclinical coeliac disease appears to be unusually over-represented among patients with idiopathic osteoporosis, and screening for gliadin antibodies might therefore be a valuable addition to the routine assessment of the osteopenic patient. The mechanisms underlying the relationship are not clear, but calcium malabsorption is not evident.
Article
Peripheral single photon absorptiometry was used to measure forearm bone mineral density in 22 celiacs on gluten-free diet from childhood (male 14, female 8, age 13-20) and 29 untreated adult celiacs at diagnosis (male 5, female 24, age 18-56, 14 with subclinical disease), compared with healthy sex- and age-matched controls. Bone mineral density was similar in patients treated from childhood and their controls [(668.4 +/- 65.3 vs. 654.9 +/- 69.6 mg/cm2, (mean +/- SD)], but significantly lower in untreated patients than in their controls (598.3 +/- 83.1 vs 673.2 +/- 42.7 mg/cm2, p less than 0.001). It was also significantly lower in the 12 younger untreated celiacs (18-28 yr) versus controls (619.4 +/- 68.5 vs 669.1 +/- 39.3 mg/cm2, p less than 0.01). In the untreated women, but not their controls, a negative correlation (p less than 0.05) was observed between bone mineral density and age. Bone mineral density did not correlate with severity of clinical or biochemical abnormalities. These results suggest that bone derangements are common in celiacs diagnosed in adulthood, even if they never presented evident malabsorption symptoms, and emphasize the importance of early diagnosis and treatment.
Article
We report the clinical, laboratory, and pathological findings in a series of 52 consecutive patients with adult celiac sprue observed over a 20-year period. The frequency of that diagnosis increased from an average of 0.7 case/year during the period 1966-1975 to 5.8 cases/year during the period 1981-1985. Apart from two patients with dermatitis herpetiformis, nonclassical clinical presentations were observed in 16 of 50 (32%) patients overall and in 13 of 28 (46%) patients diagnosed since 1981. Diarrhea was the most common complaint leading to the diagnosis; since 1981, hematologic abnormalities warranted investigation in 38% of the patients. Decreased iron stores (88%), decreased red cell folate (82%), or both (74%), and abnormal radiographic studies of the small bowel (83%) were the most sensitive tests in the diagnostic investigation. We conclude that atypical or nonclassical presentations of adult celiac sprue, mostly with hematologic abnormalities, are not uncommon.
Article
To determine the prevalence of hypovitaminosis D and secondary hyperparathyroidism (SHPT) and to assess bone turnover by using markers of bone formation and resorption in celiac disease (CD). Forty-three patients with CD were investigated: group 1, newly diagnosed celiacs (n = 19); group 2, treated celiacs responding histologically to a gluten-free diet (n = 16); group 3, refractory celiacs, unresponsive to a gluten-free diet and immunosuppressive therapy (n = 8). Serum was drawn for intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], ionized calcium (Cai), total alkaline phosphatase (AP), and biochemical markers of bone formation: procollagen I carboxyterminal propeptide (PICP) and osteocalcin (Oc). Urinary indices of bone resorption, deoxypyridinoline (DPD), pyridinoline (PyD), and hydroxyproline (OHP), were measured in a 2-h fasting urine. In 22 patients, computerized tomographic scan for bone mineral density (BMD) was performed. The prevalence in groups 1, 2, and 3, respectively, of hypovitaminosis D (< 50 nmol/L) was 58%, 25%, and 88%, and the prevalence of SHPT (> 5.4 pmol/L) was 25%, 19%, and 25%. Bone resorption markers were significantly elevated in all groups, and bone formation indices were elevated in the newly diagnosed celiacs compared with a group of healthy adults. Low BMD (T-score greater than -1 SD unit) was found in 68% of patients assessed; 36% of patients had a T-score greater than -2.5 SD units. Hypovitaminosis D and SHPT are common in newly diagnosed and refractory celiacs but are less common in those who respond to a gluten-free diet. Newly diagnosed patients have a high bone turnover state with elevation of both bone formation and resorption indices. Those with refractory disease demonstrate a remodeling imbalance with high bone resorption.
Article
Since no information is available on bone derangements in subclinical coeliac disease (CD), we evaluated bone mineral density (BMD, expressed as z score) at lumbar spine, by X-ray dual-photon absorptiometry, and serum indices of bone metabolism and remodeling in 14 subclinical or silent patients, 10 classical patients, and 15 healthy volunteers all on a gluten-containing diet. In the subclinical group, BMD at lumbar spine was significantly higher than in the classical group (-1.3 +/- 0.8, 73% vs. -2.6 +/- 0.6, 88%, respectively; p < 0.001), but significantly lower than in volunteers (+0.4 +/- 1.1, 104%; p < 0.001). Similar changes were observed in serum calcium, whereas, as regards parathyroid hormone, no significant difference was found between subclinical and classical patients. 25-vitamin D was significantly lower, and 1,25-vitamin D was significantly higher in subclinical and classical patients than in healthy volunteers. Indices of bone remodeling were higher in the subclinical and classical groups than in the volunteers, but lower in the subclinical than in classical patients. Eight subclinical and 8 classical patients were reexamined after a period of gluten-free diet (GFD), and in both groups BMD had significantly improved. Our results show that osteopenia is a frequent feature also in subclinical CD, although the extent of bone and mineral metabolism derangements is lower than in classical CD. GFD is able to normalize BMD in subclinical and to significantly improve it in classical patients.
Article
We investigated the bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in adult celiac patients with varying disease states. In this cross-sectional study the data on the severity of celiac disease and BMD were collected from 77 celiac patients (28 newly diagnosed and 49 previously diagnosed celiac patients), and BMD results were compared with those of 157 control subjects matched for age, gender, and menopausal status. The celiac patients had significantly lower BMD than the control subjects at the lumbar spine (-6%) and femoral neck (-5%). The mean BMD did not differ significantly among celiac patients classified by severity of disease. Based on Z scores, 35% of the celiac patients and 17% of the control subjects had low BMDs for age at the lumbar spine (p = 0.005), whereas 31% of celiac patients and 16% of control subjects had Z scores of < or =-1 at the femoral neck (p = 0.01). Altogether, 26% of all celiac patients, but only 5% of control subjects, were classified as having osteoporosis (T score < or =-2.5 SD) at the lumbar spine (p = 0.03), whereas osteoporosis was rare at the femoral neck in both groups (3% vs. 1%, p = 1.00). Prevalence of osteopenia and osteoporosis was highest in newly diagnosed celiac patients and in patients with disease not in remission. A low 25-(OH)D vitamin concentration was a typical biochemical abnormality in our patients (64% of men and 71% of women). The main associated variables of low BMD were age (men), low serum vitamin D level, low body weight, and postmenopausal status (women). The present study suggests that celiac disease constitutes a risk factor for osteoporosis. This finding applies particularly to untreated and poorly treated patients.
Article
In this paper, we review the histological features of coeliac disease and propose a standardized report scheme based on the Marsh classification. Furthermore, terms used by pathologists are defined. The most important histological differential diagnoses are given, as well as a definition of the different clinical forms of coeliac disease such as symptomatic, silent, latent, potential, treated and refractory coeliac disease, Eur J Gastroenterol Hepatol 11:1185-1194 (C) 1999 Lippincott Williams & Wilkins.
Article
To evaluate the impact of a 1-year gluten-free diet on bone metabolism and nutritional status in coeliac disease. Bone mineral density, serum indices of bone remodelling, clinical and biochemical nutritional assessment were evaluated in 86 consecutive newly-diagnosed, biopsy proven, coeliac disease patients (untreated). A complete reevaluation, including intestinal biopsy, was repeated within 1 year of dietary treatment (treated). Untreated: according to WHO criteria, 34% of patients had a normal bone mineral density, 40% had osteopenia and 26% osteoporosis. Between males and females there were no statistical differences in bone metabolism or in most of the nutritional indices, while, between fertile and postmenopausal women, bone mineral density and several bone metabolism markers were significantly different. Compared to subjects with a normal bone mineral density, osteopenics had higher bone specific alkaline phosphatase (BAP) and Bone-Gla-protein (BGP) values. In patients with a concomitant BAP increase and 25OH vitamin D serum level reduction, bone mineral density and several bone turnover markers were statistically different compared to patients without such a serological pattern. Treated: notwithstanding intestinal biopsy which showed a mucosal recovery in only 57%, gluten-free diet led, even in postmenopausal women, to a significant improvement in bone mineral density, bone metabolism and nutrition, except for folic acid, albumin and pre-albumin serum levels which persisted as abnormal in patients with obdurate mucosal impairment. Coeliac disease patients are at high risk for developing a low bone mineral density and bone turnover impairment. A gluten-free diet can improve this situation even in postmenopausal women and in patients with incomplete mucosal recovery.
Article
The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease.
Article
Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States. Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21-83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr). Osteoporosis (T score < -2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between -1.0 and -2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 +/- 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation. Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease.
Article
The disease mechanisms of complex inflammatory disorders are difficult to define because of extensive interactions between genetic and environmental factors. Coeliac disease is a typical complex inflammatory disorder, but this disease is unusual in that crucial genetic and environmental factors have been identified. This knowledge has allowed functional studies of the predisposing HLA molecules, the identification of antigenic epitopes and detailed studies of disease-relevant T cells in coeliac disease. This dissection of the pathogenic mechanisms of coeliac disease has uncovered principles that are relevant to other chronic inflammatory diseases.
Article
Osteoporosis is increasingly recognized as a source of significant disability, an awareness that has prompted clinicians to actively pursue the diagnosis among high-risk patients. Fractures have an obvious associated morbidity, negative impact on quality of life, and both direct and indirect costs. Hip fractures have long been associated with an increased mortality rate, but only recently has excessive mortality also been shown to accompany non–hip fractures and low bone mass.1-3 The excessive mortality associated with fractures is largely confined to elderly males and postmenopausal females. Many patients with gastrointestinal (GI) disorders at risk for osteoporosis are young, and these data may not apply to them. Much of the available clinical information regarding osteoporosis screening, outcomes, and therapeutic interventions is derived from the postmenopausal osteoporosis literature. It is recognized, however, that osteoporosis may accompany many other medical conditions, occurring as a sequela to disease or even to its treatment.
Article
Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten. Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners. Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people. The disease is associated with an increased rate of osteoporosis, infertility, autoimmune diseases, and malignant disease, especially lymphomas. The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium. An important component of the disease is the intraepithelial lymphocyte that might become clonally expanded in refractory sprue and enteropathy-associated T-cell lymphoma. Study of the mechanism of the immune response in coeliac disease could provide insight into the mechanism of inflammatory and autoimmune responses and lead to innovations in treatment.
Article
The major modes of presentation of patients with celiac disease are the classic diarrhea-predominant form and silent celiac disease. Those with silent celiac disease lack diarrhea, although they may present with manifestations of celiac disease that include an irritable bowel syndrome, anemia, osteoporosis, neurologic diseases, or malignancy. A significant proportion of patients are diagnosed through screening at-risk groups including relatives of patients and insulin-dependant diabetics. Nondiarrheal presentations now are seen more commonly than those with diarrhea. Patients with celiac disease have a greater burden of disease than the general population because of autoimmune diseases and malignancies. There is a need for screening studies of patients with conditions associated with celiac disease to determine whether the large numbers of people with undiagnosed celiac disease currently are seeking health care.
Article
To assess the degree of osteopenia in children with celiac disease (CD) at the time of diagnosis and the effect of a gluten-free diet (GFD). Longitudinal and prospective study. In total, 24 children (18 girls, six boys) diagnosed with CD by means of an intestinal biopsy were included in the study. Mean+/-s.d. age was 4.9+/-4.3 years. In all, 16 patients were under (2.20+/-0.82 year) and eight were over the age of 4 years (10.30+/-2.90 year). The time between the first symptoms and diagnosis was 17.30+/-24.70 months (range: 2-109 months). Spine bone mineral content (BMC), area and bone mineral density (BMD) were measured by DXA at baseline and 1.17+/-0.93 years after GFD. Before treatment, mean+/-s.d. BMD was 0.46+/-0.13 g/cm(2), the BMD Z-score was -1.36+/-1.20, and was below -1 s.d. in 14 patients (58%). BMC, area and BMD increased significantly on GFD. BMD increased from 0.46+/-0.13 to 0.55+/-0.13 g/cm(2) (P<0.001). BMD Z-score improved from -1.36+/-1.20 to -0.23+/-1.20 after GFD. However, BMD increased more than 1 s.d. in 15 of the 16 children under the age of 4 years, a similar increase was only observed in four of the eight children aged more than 4 years, some of whom did not follow GFD strictly. Height and weight increased significantly with GFD (P<0.001) and the increase correlated positively with the increase in BMD. Axial BMD below -1 s.d. was found in 58% of children with celiac disease. Axial bone mass reverted to normal values in most children under the age of 4, who had low bone mass, all of whom followed GFD strictly.
Article
While severe villous atrophy (SVA) is the most typical histological feature in adult celiac disease (ACD), partial villous atrophy (PVA) is now also frequently found. So far, the impact of the severity of villous atrophy on the clinical presentation of ACD has been scarcely investigated. We aimed to compare the clinical, biological and immune features and outcomes in ACD patients presenting with PVA at diagnosis versus patients with SVA. Medical files of 48 patients with ACD diagnosed between 1992 and 2003 were retrospectively studied. The diagnosis was based on the presence of intestinal villous atrophy, with increases in intraepithelial lymphocytes and circulating celiac specific antibodies. Villous atrophy was classified as severe (subtotal and total) or partial. Symptoms, biological signs of malabsorption, immune markers, bone mineral density at diagnosis and response to gluten-free diet were recorded. At diagnosis, ten patients (four M/six F) had PVA and 38 patients (five M/33 F) had SVA, with a median age of 54 and 33 years, respectively (p<0.05). Positivity for specific antibodies, HLA typing and frequency of autoimmune disease at diagnosis were similar in both PVA and SVA patients, as was their response to gluten-free diet. Diarrhea, malabsorption syndrome and osteopenia were independent of the degree of villous atrophy. PVA was observed in 21% of patients with ACD. Except for their older age at diagnosis, patients with PVA presented with similar clinical, biological and immune characteristics and outcomes as did patients with SVA.
Article
Celiac disease is considered rare in North America. However, an increasing incidence and widening clinical spectrum have been reported in many countries, and serologic screening suggests a higher prevalence of minimally symptomatic disease. This study reports temporal trends in the incidence of celiac disease in Olmsted County, Minnesota. All county residents diagnosed with celiac disease between 1950 and 2001 were identified through the Rochester Epidemiology Project. Incidence rates were calculated assuming a Poisson distribution, and changes in incidence by calendar year, age, and gender were assessed by using Poisson regression. Altogether, 82 new cases of celiac disease were identified during the 50-year period. There was a marked female predominance (P < 0.005), and the incidence rates increased with age (P < 0.001) and calendar period (P < 0.001). The overall annual incidence of celiac disease was 2.1 per 100,000 (95% confidence interval [CI], 1.7-2.6) but increased from 0.9 per 100,000 (CI, 0.5-1.2) in 1950-1989 to 3.3 per 100,000 (95% CI, 2.2-4.4) in the 1990s. The incidence was 9.1 per 100,000 (95% CI, 5.2-13.0) in the final 2 years of the study. Serology prompted biopsy in a substantial proportion of recent diagnoses. Clinical features also changed over time, with less diarrhea and weight loss at presentation. Celiac disease has increased recently in this well-characterized population. Milder clinical features and use of serology suggest an increased detection rate, although a true increase in incidence may have also occurred. Celiac disease is not rare in North America.
Celiac disease in osteoporotic Indians
  • Y A Gokhale
  • P D Sawant
  • C M Chodankar
  • YA Gokhale
Bone remodeling indices and secondary hyperparathyroidism in celiac disease
  • A P Keaveny
  • R Freaney
  • Mc Kenna
  • AP Keaveny
Bone metabolism in patients with newly diagnosed caeliac disease. Beinmetabolisme hos nydiagnostiserte cøliakipasienter
  • M O Vitenskap
  • MO Vitenskap