Bone and celiac disease

Celiac disease is an intestinal disease due to an abnormal immuno-mediated response to gluten and other peptides from different cereals in genetically susceptible subjects. Several systemic alterations, including bone alterations, may be present in affected subjects. Once considered rare, it is now known to be quite frequent in both Europe and North America, as the recent availability of specific serological markers has drastically changed our perspective on its prevalence. The diagnosis of celiac disease may be very difficult because the clinical picture is highly variable and the characteristic intestinal signs and symptoms may be completely absent. Among the extra-intestinal alterations, bone mass decrease and bone metabolism derangement are frequently present and can be the only signs of an otherwise silent celiac disease. Clinical and epidemiological data are now plentiful but no conclusive data on the pathogenesis of bone involvement in celiac disease are available yet. Bone alterations were once thought to derive from calcium and vitamin D deficiency secondary to simple intestinal malabsorption, but now a more complex interaction between cytokines and local/systemic factors influencing bone formation and reabsorption is envisaged, Also, there is now substantial evidence supporting a lifelong gluten-free diet as the first-choice therapy for celiac disease, and as far as we know, this is the only effective measure to restore bone metabolism to an apparent normality. In the young, an early-started gluten-free diet can even lead to a satisfactory recovery of bone mass. In adults, however, there is no spontaneous recovery, and there are no conclusive data on the efficacy of standard therapies for osteoporosis in reducing the fracture risk. For these reasons, we feel that a review of the clinical findings on bone problems in celiac disease may be useful for both gastroenterologists and osteoporosis specialists.     

Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease.

Celiac disease is an autoimmune disorder characterized by atrophy of the intestine villi triggered by ingestion of gluten in genetically susceptible individuals. The association between celiac disease and low BMD has been recognized, but the mechanisms of disturbance are poorly understood. We show imbalance of cytokines relevant to bone metabolism in celiac patients' sera and the direct effect of these sera on in vitro bone cell activity. INTRODUCTION: Celiac disease is associated with mineral metabolism derangement and low BMD. We investigated whether imbalance of serum factors in celiac patients could affect human bone cell activity in vitro. MATERIALS AND METHODS: We studied two groups of celiac patients--one on a gluten-free diet and another before the diet--both with decreased bone mass. Patients were investigated for bone turnover markers, and their sera were used for culturing bone cells from healthy donors and evaluate changes in cell activity. RESULTS: The N-terminal telopeptide of procollagen type I and interleukin (IL)-6 were higher than normal in patients not on the gluten-free diet. IL-1beta and TNF-alpha/beta were normal in all patients. IL-12 was reduced in all patients, whereas IL-18 was reduced only in patients on the diet. The RANKL/osteoprotegerin (OPG) ratio was increased in patients not on the gluten-free diet. Persistently increased osteoclast numbers were obtained from peripheral blood mononuclear cells of healthy donors on incubation with sera of patients not on the gluten-free diet versus control sera and sera from patients on the diet. In human osteoblasts from healthy individuals, IL-18 was reduced on incubation with sera from all patients, whereas OPG expression was lower when sera from patients not on the diet were used. Proliferation, alkaline phosphatase, and nodule mineralization were increased in osteoblast cultures containing sera from all celiac patients, either on or not on the gluten-free diet.Conclusions: We conclude that bone loss in celiac disease might also be caused by a cytokine imbalance directly affecting osteoclastogenesis and osteoblast activity.     

Celiac Disease and Bone Health in Children and Adolescents: A Systematic Review and Meta-Analysis

Context: Celiac disease is characterized by deficits in bone mineral accrual and longitudinal growth. Objective: The purpose of this study was to determine the differences in bone health and stature among children and adolescents with celiac disease versus healthy controls. Data Sources: Articles published before February 27, 2018 were located using searches of the Physical Education Index (n = 186), PubMed (n = 180), Scopus (n = 3), SPORTDiscus (n = 3), and Web of Science (n = 4). Study Selection: Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed via dual-energy X-ray absorptiometry, and height was measured using a stadiometer. Data Extraction: Effect sizes (ES) were calculated as follows: the mean difference of the celiac disease group and healthy control group, divided by the pooled standard deviation. The inverse variance weight was used to calculate the overall mean ES. Random-effects models were used to aggregate a mean ES, 95% confidence intervals (CIs) and to identify potential moderators. Results: The results of 30 effects gathered from 12 studies published between 1996 and 2017 indicated BMC (ES = −0.54, 95% CI: −0.69 to −0.40; p < 0.0001) and aBMD (ES = 0.72, 95% CI: −0.96 to −0.47; p < 0.0001) were lower in youth with celiac disease. Limitations: These results were limited to only cross-sectional and baseline data from longitudinal studies reporting BMC and BMD, however did not assess changes in bone health over time. Conclusion: Children and adolescents with celiac disease have suboptimal bone health and shorter stature.     

THE PREVALENCE OF HLA DQ2 AND DQ8 IN PATIENTS WITH CELIAC DISEASE,IN FAMILY AND IN GENERAL POPULATION

Background:

Celiac disease is an enteropathy characterized by gluten sensitivity and broad clinical aspect. Has a multifactorial cause and depends on genetic, immunological and environmental factors for its development. The genetic influence is given mostly by the human leukocyte antigens HLA DQ2 and DQ8.

Aim:

To evaluate the prevalence of human leukocyte antigens DQ2 and DQ8 in three different groups: patients with celiac disease, first-degree relatives and the general population.

Method:

Retrospective analysis that evaluated serologic and endoscopic data of 74 patients with celiac disease and 109 non-celiac, which were subdivided into two subgroups: non-celiac who had first-degree relatives with celiac and non-celiac who did not. All patients underwent laboratory examination for screening genetic sensitivity given by HLA DQ2 and HLA DQ8 by.

Results:

The presence of HLA DQ2 and DQ8 was identified in 98,4% of 74 celiac patients, of which 79,7% had only HLA DQ2; 8,1% had only HLA DQ8 and 10,8% had both antigens histocompatibility. In the group of relatives of celiac patients, were included 29 patients; among them, 89,6% had HLA DQ2 and/or DQ8; 76% only the HLA DQ2, 10,3% only HLA DQ8 and 3,4% presented both human leukocyte antigens (HLA).

Conclusion:

HLA DQ2/DQ8 was present in 98,4% of celiac patients; 89,6% relatives of celiac family and in 55,4% of people from the general population without family celiac.     

Unexplained polyarthralgia and celiac disease

Celiac disease is an immunological disorder whose best-known manifestations are gastrointestinal symptoms. However, early joint manifestations are common and frequently overlooked features of celiac disease. We report a case in which unexplained inflammatory polyarthralgia and iron-deficiency anemia led to the diagnosis of celiac disease. Autoimmune thyroiditis was also a feature. Early diagnosis and treatment of celiac disease protect patients against complications such as digestive neoplasis. A simple and rapid tool for achieving the early diagnosis is the measurement of the serum of anti-gliadin, anti-endomysial and anti-tissue transglutaminase antibodies. However, a duodenal biopsy remains the only means of making the definitive diagnosis of celiac disease.     

Practical Approach to the Flattened Duodenal Biopsy

Celiac disease features duodenal intraepithelial lymphocytosis with or without villous atrophy. Lymphocytosis without villous atrophy will be proven to represent celiac disease in 10% to 20% of cases. The differential diagnosis is broad: Helicobacter pylori gastritis, NSAID injury and bacterial overgrowth are considerations. Lymphocytosis with villous atrophy is very likely to be celiac disease, but there are mimics to consider, including collagenous sprue, tropical sprue, drug injury, and common variable immunodeficiency. Histologic clues to a diagnosis other than celiac disease include paucity of plasma cells, excess of neutrophils, granulomas, and relative paucity of intraepithelial lymphocytes.     

New strategies for diagnosis and management of celiac disease

Celiac disease is a gastrointestinal disorder characterized by inflammation, leading to injury to the mucosal lining of the small intestine. The inflammation occurs when gliadin, a protein found in such gluten-containing foods as wheat, rye, and barley, is ingested by genetically susceptible individuals. The mucosal damage and subsequent malabsorption of nutrients leads to various complications. Researchers estimate that more than 2 million people in the United States have celiac disease-a prevalence that is greater than was previously believed. Approximately 60,000 Americans are diagnosed annually with celiac disease. Until recently, diagnosis has been complicated by the fact that the indicators of celiac disease are nonspecific. However, because of the development of new, easy-to-administer serology tests, diagnosis has become much less complicated. After conducting a review of the literature, the authors recommend a serologic testing sequence for diagnosis of celiac disease and urge that adults and children with an assortment of symptoms be tested for this disease. Common signs and symptoms of celiac disease include anemia, arthralgia, fatigue, infertility, neuropathy, and weight loss, in addition to such gastrointestinal symptomatology as abdominal pain, anorexia, bloating, constipation, and diarrhea. The only treatment for patients with celiac disease remains a gluten-free diet.     

腹腔干结扎可行性临床研究进展

目的探讨腹腔干结扎的可行性。方法收集和回顾有关腹腔干结扎的相关文献。结果腹腔干分为肝总动脉、脾动脉及胃左动脉3支，腹腔干分支的变异较多而且与肠系膜上动脉之间通过胃十二指肠动脉和胰十二指肠动脉形成广泛的侧支吻合。腹腔干损伤、腹腔干动脉瘤、上消化道出血、腹腔干周围肿瘤切除和门静脉高压症的病例中，腹腔干结扎后不会有明显的并发症。但是，腹腔干结扎亦可能导致胆囊坏死、穿孔，肝脏的局限性梗死，甚至比较高的死亡率。结论腹腔干结扎还不是常规的治疗手段，但是在特定的情况下，腹腔干结扎可能是一种可行和有效的挽救生命的治疗手段。     

Bone loss in celiac disease is related to secondary hyperparathyroidism.

Celiac disease is a major cause of intestinal malabsorption. Previous studies have demonstrated that celiac disease is associated with significant osteoporotic bone loss. These studies have suggested that successful treatment of the malabsorption is associated with amelioration of the bone loss. Such studies have failed to examine bone mass at peripheral skeletal sites which is more likely to be responsive to changes in parathyroid hormone (PTH) in response to calcium malabsorption. We have examined bone density in the lumbar spine, femoral neck, and distal forearm in 35 patients with celiac disease who had been established on gluten-free diet. In addition, the concentrations of PTH and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Bone density was below that expected for the subject's age and gender at all sites. This was most marked in the distal forearm where the bone density was 1.40 SD below expected (p < 0.0001). In the forearm, there was a negative relationship between bone density and PTH concentration (r = -0.49, p = 0.009). In the forearm and lumbar spine, there was a negative relationship between 1,25(OH)2D concentration and bone density. Bone mass was not related to the concentration of 25-hydroxyvitamin D at any of the skeletal sites measured. Bone density is reduced in the peripheral skeleton in celiac disease and this deficit persists despite treatment with apparent normalization at axial skeletal sites. This reduction in bone mass is related to the presence of secondary hyperparathyroidism which should be sought in all patients with treated celiac disease.     

Celiac Disease and Its Role in the Development of Metabolic Bone Disease

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.     

Surgical treatment of celiac artery aneurysm associated with median arcuate ligament

Celiac artery aneurysms are rare but potentially fatal because of the risk of rupture. Atherosclerosis and fibrous dysplasia are the two most common etiologies. Median arcuate ligament compression of the celiac artery is common but usually asymptomatic. We report three cases of post-stenotic celiac artery aneurysm with median arcuate ligament compression admitted to our hospital over the past two years. Although the incidence is rare with only 8 cases reported in the literature, a median arcuate ligament may have a role in the development of celiac artery aneurysms and its presence can influence the surgical strategy.     

Resection of the head of the pancreas in three patients with anomalous arrangement or occlusive diseases of the major abdominal visceral arteries

We resected the head of the pancreas in three patients with occlusive diseases or anomalous arrangement of the abdominal visceral arteries. The first patient who was diagnosed with cancer of the head of the pancreas; pancreatoduodenectomy (PD) was performed. Preoperative celiac angiography showed no significant occlusion of the celiac axis, while superior mesenteric arteriography visualized the common hepatic artery, with delayed retrograde filling. At the completion of the PD, an unsuspected atherosclerotic celiac occlusion was identified. Celiac reconstruction was performed. The second patient was diagnosed with cystadenoma of the head of the pancreas and had congenital ostial occlusion of the superior mesenteric artery (SMA), with dilated pancreaticoduodenal (PD) arcades as a celiacomesenteric collateral pathway. Duodenum-preserving resection of the head of the pancreas was performed, with preservation of the PD arcades. The third patient was diagnosed with cancer of the common bile duct, and exhibited a replaced common hepatic artery that arose from the SMA and formed PD arcades. PD was performed, with revascularization of the common hepatic artery. Following surgery, the three patients have done well for 18, 27, and 9 months, respectively. Careful preoperative investigation to identify abnormalities of the visceral arteries is necessary before resection of the head of the pancreas is performed.     

Excess non-spine fractures in women over 50 years with celiac disease: A cross-sectional, questionnaire-based study

The association of celiac disease with fracture is controversial. Recent studies may have underestimated the impact by studying patients with low fracture risk. Since postmenopausal women are at greatest risk of fracture, we have investigated non-spine fracture occurrence in women 50 years with celiac disease. Patients were recruited from hospital and general practice as well as from volunteers, controls from general practice. All completed a questionnaire detailing fracture occurrence. Three hundred and eighty-three female celiac patients and 445 female controls aged 50 years at time of study were compared. Mean age was 61.4±7.8 years in celiac patients and 62.7±9.9 years in controls. Celiac patients were lighter but not shorter. Celiac patients displayed greater all fracture prevalence (odds ratio [OR], 1.51; confidence interval [CI], 1.13:2.02) and fracture after 50 years (OR, 2.20; CI, 1.49:3.25). Wrist fracture was more frequent (OR, 1.65; CI, 1.12:2.41), but significance was lost once height and weight were taken into account. Celiac patients had more multiple fractures (OR, 2.96; CI, 1.81:4.83). To investigate the association of fracture with time from diagnosis, 324 celiac patients were paired with a control by age. No excess fracture risk was found more than 10 years before diagnosis amongst celiac patients diagnosed after age 50 years, but risk increased in the period from 10 years before diagnosis to 5 years after and remained high more than 5 years after diagnosis ( p<0.05). Wrist fracture only increased in the period more than 5 years after diagnosis ( p<0.05). In women diagnosed before 50 years, no excess fracture risk existed. Fracture risk in female celiac patients >50 years is increased overall but is related largely to the peri-diagnostic period. Wrist fracture risk is partly accounted for by height and weight, but is more common more than 5 years after diagnosis. Celiac testing may be indicated in thin women over 50 years with multiple fractures, and after diagnosis adequate calcium and vitamin D intake should be ensured.     

Development of clinical celiac disease after pancreatoduodenectomy: a potential complication of major upper abdominal surgery

Background Celiac disease is a gluten-induced disease of global malabsorption. There is a subset of patients with celiac disease who are free of major symptoms but who have typical damage to the intestinal mucosa (silent disease). We present the case of a 50-year-old white woman with no clinical symptoms of celiac disease who developed diarrhea and weight loss 12 weeks after a pancreatoduodenectomy for ampullary cancer.Methods Microbiological and biochemical examination of the feces did not provide clues useful to diagnosis, and diarrhea was not affected by pancreatic enzyme replacement or administration of antiperistaltic drugs.Results Review of the pathologic specimen and blood tests were compatible with celiac disease.Conclusion This clinical scenario illustrates that subclinical celiac disease may be an underdiagnosed cause of malabsorption after major upper gastrointestinal surgery and should be considered in the differential diagnosis of diarrhea after pancreatoduodenectomy.     

Bone and Celiac Disease

More than 50 % of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.     

Association of adult celiac disease with surgical abdominal pain: a case-control study in patients referred to secondary care

BACKGROUND: Acute abdominal pain is the most common indication for surgical admission. Nonspecific abdominal pain (NSAP) may account for up to 40% of cases. There has been no published prospective study in which adult patients presenting with acute abdominal pain are investigated for celiac disease. AIMS: We aimed to assess the association of celiac disease with surgical abdominal pain. PATIENTS AND METHODS: A case-control study was undertaken involving 300 consecutive new unselected patients presenting with acute abdominal pain (in a university hospital) and healthy controls (age and sex matched) without abdominal pain (n = 300). Initial investigations for celiac disease were immunoglobulins, IgA/IgG anti-gliadin (AGA), and endomysial antibodies (EMA). Any patient with a positive IgA AGA, EMA, or only IgG AGA in the presence of IgA deficiency was offered a small bowel biopsy to confirm the diagnosis. RESULTS:: There were 33 patients with abdominal pain who had positive antibodies, of whom 9 had histologically confirmed celiac disease (6 EMA positive; 3 EMA negative). One antibody positive patient (EMA in isolation) declined duodenal biopsy and the remaining 23 had normal duodenal mucosa. Within the control group, there were 2 cases of celiac disease. Compared with matched controls the association of acute abdominal pain with celiac disease gave an odds ratio 4.6. (P = 0.068, 95% confidence interval, 1.11-19.05). When only considering NSAP the prevalence of celiac disease was highly significant at 10.5% (9 of 86, P = 0.006). Patients' symptoms improved on a gluten-free diet at 12- to 18-month follow-up. CONCLUSION: Celiac disease was diagnosed in 3% of patients who presented with unselected acute abdominal pain to secondary care. Targeting patients who have NSAP or celiac associated symptoms/diseases may improve the diagnostic yield.     

Pancreaticoduodenectomy with unusual artery reconstruction in a patient with celiac axis occlusion: report of a case

Celiac axis stenosis is a relatively common finding that may require major revascularization during pancreaticoduodenectomy. We present a patient that underwent pancreaticoduodenectomy for intraductal papillary mucinous neoplasm of the pancreatic head associated with celiac axis obstruction. To secure arterial blood flow to the upper abdominal organs, the superior posterior pancreaticoduodenal artery and the posterior-inferior pancreatic-duodenal artery were carefully preserved, and anastomosed. The postoperative course was complicated by a pseudoaneurysm of the splenic artery that was successfully treated with angiographic embolization through the vascular bypass. This may be a valid alternative procedure for revascularization of the common hepatic artery during pancreaticoduodenectomy in a patient with celiac axis stenosis.     

Giant celiac artery aneurysm with associated visceral occlusive disease

Celiac artery aneurysms are rarely seen in clinical practice. We report an unusual case of a large celiac artery aneurysm in a patient with associated visceral occlusive disease who presented with vague abdominal pain and underwent uneventful open surgical repair.     

Computed Tomographic presentation of obstructive jejunal adenocarcinoma associated with celiac disease and incomplete intestinal malrotation

IntroductionSmall bowel adenocarcinoma is a rare entity most frequently observed with celiac disease. This is the first case report on the association of celiac disease, small bowel adenocarcinoma and intestinal malrotation.Case reportA 40 year-old male patient diagnosed with celiac disease since the age of 5 years complained of epigastric pain and vomiting for three days. Computed tomography (CT) showed a significant gastroduodenal dilatation with thickened intestinal wall proximal to the duodenojejunal flexure. The lumen contained a food bezoar in the center. The duodenojejunal angle was abnormally on the right side of the abdomen and the superior mesenteric vein was anterior to the superior mesenteric artery. Endoscopy after aspiration found a hemi-circumferential and irregular mass which bled at the contact of fibroscope. Biopsies showed an adenocarcinoma and small bowel resection was performed.DiscussionCeliac disease is associated with a high risk of small bowel cancer. The association of incomplete intestinal malrotation, duodenojejunal flexure tumor and celiac disease made the surgery challenging.ConclusionPatients with celiac disease should be carefully monitored and endoscopic or radiologic investigations should be carried out in patients with any doubtful symptoms.