Dietary calcium intake and its relation to bone mineral density in patients with inflammatory bowel disease

Objectives. To investigate calcium intake and its association with bone mineral density (BMD) and the type and extent of the disease in patients with inflammatory bowel disease (IBD).
Setting. University hospital clinic.
Subjects. A total of 152 unselected IBD patients and 73 healthy controls.
Measurements. Dietary calcium intake was assessed with a food frequency questionnaire and BMD of the lumbar spina and proximal femur was measured.
Results. The IBD patients had lower dietary calcium intake (1034 [SD 493] mg) than the controls (1334 [514] mg, P <0.001). The difference was significant in the males (1047 [552] mg and 1575 [586] mg, respectively, P <0.001), but not in the females (1020 [422] mg and 1112 [303] mg). The dietary daily calcium intake was below 1000 mg in 53% of the patients and 27% of the controls ( P = 0.0004) and below 400 mg in 9.2% of the patients and none of the controls ( P =0.007). The calcium intake was not associated with the severity or the type of IBD. Seventy-one (47%) patients and eight (11%) controls avoided lactose in their diet ( P < 0.001). In the IBD patients, no association between the calcium intake and BMD was detected, whereas in the controls a positive correlation between the calcium intake and the BMD of the proximal femur was found.
Conclusions. Calcium intakes below the recommendations are seen more often in the IBD patients than in the healthy controls, but in the IBD patients the calcium intake is not associated with BMD in a cross-sectional study. A low-lactose diet is common among IBD patients. To reduce the risk of inadequate calcium intake, unnecessary dietary restrictions concerning, e.g. milk products, should be avoided for these patients.     

Decreased trabecular bone mineral density in newly diagnosed inflammatory bowel disease patients in Korea

BACKGROUND: Decreased bone mineral density (BMD) is common in Western patients with inflammatory bowel disease (IBD). However, BMD has never been studied in Asia where the demographic and socio-economic status are different from the West. The aim of this study was to investigate the prevalence and mechanisms of osteopenia in newly diagnosed Korean patients with IBD. METHODS: We studied 14 patients with Crohn's disease (CD) and 25 patients with ulcerative colitis (UC), all of whom had never been treated with corticosteroids. Bone mineral density was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry. Biochemical parameters including serum osteocalcin, parathyroid hormone, plasma inactive and active vitamin D, and urinary deoxypyridinoline were measured. RESULTS: The BMD Z score at the lumbar spine was lower both in CD and in UC patients, but there was no significant difference between the two groups. There was no significant difference in nutritional status or biochemical parameters of bone metabolism between patients with a normal BMD and those with a decreased BMD. CONCLUSIONS: Low BMD at the lumbar spine is common in newly diagnosed Korean patients with IBD, a result which is similar to Western studies. The mechanism for low bone mass remains undetermined; however, nutritional status and hormonal parameters of bone metabolism, and ethnic differences are not likely to be an important factor in the pathogenesis of this bone loss.     

Low bone mineral density in patients with inflammatory bowel disease

To assess the prevalence and risk factors for low bone mineral density in inflammatory bowel disease, we studied 61 consecutive patients, mean age 36±11 years. Twenty-seven had a Crohn's disease and 34 ulcerative colitis (including 13 with ileoanal anatomosis). Three patients, two women and one man (32, 70, and 45 years old, respectively) had vertebral crush fractures. Bone mineral density measured by dual energy x-ray absorptiometry at spine and femoral level was more than 2sd below normal values in 23% of the patients, all of them having received steroid therapy. Eighteen patients (29%) had never received steroid therapy; their bone mineral density was not different than those who had. Univariate analysis showed a positive correlation between bone mineral density and body weight or oral calcium intakes, and a negative correlation with steroid daily dose. After ileoanal anastomosis, bone mineral density was not different from other groups and showed a positive correlation with time elapsed since coloproctectomy. We concluded that bone mineral density is low in patients with inflammatory bowel disease and exposes them to the risk of bone fracture. Bone mineral density after ileoanal anastomosis may increase with time after surgery.     

Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia

Summary.  Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia. Adults with moderate or severe haemophilia A or B underwent dual-energy X-ray absorptiometry (DXA). BMD was correlated to laboratory values, joint mobility measurements and physical activity questionnaires. Thirty patients completed evaluations. The median age was 41.5 years (range 18–61). Median lowest T-score by DXA was −1.7 (range: −5.8 to +0.6), with the femoral neck being the site of the lowest T-scores. Based on World Health Organization criteria, 70% of patients had decreased BMD. Twenty-seven per cent of the participants ( n  = 8) had osteoporosis and 43% ( n  = 13) had osteopenia. Variables associated with increased bone loss included lower serum 25-hydroxyvitamin D levels ( P  = 0.03), lower body mass index ( P  = 0.047), lower activity scores ( P  = 0.02), decreased joint range of motion ( P  = 0.046), HIV ( P  = 0.03), HCV ( P  = 0.02), history of inhibitor ( P  = 0.01) and age ( P  = 0.03). Adults with haemophilia are at increased risk for developing osteoporosis. A history of HCV and HIV infections, decreased joint range-of-motion, decreased activity levels, history of an inhibitor and low body weight predict bone loss and suggest a population to target for screening. A high prevalence of vitamin D insufficiency was observed. Future studies should investigate interventions, including vitamin D supplementation, to prevent bone loss and fractures for this at-risk population.     

Intravenous pamidronate in combination with calcium and vitamin D: highly effective in the treatment of low bone mineral density in inflammatory bowel disease

Background : The clinical course of patients with ulcerative colitis (UC) is unpredictable, and 17%-38% ultimately require surgery. We hypothesized that mucosal histology may differ between patients requiring surgery and those receiving medication alone. The aim of this study was to elucidate comprehensive criteria consisting of specific histologic features enabling the prediction of failure to medical treatment. Methods : We studied colorectal biopsy specimens from 67 patients ultimately requiring surgery (UC-S) and 90 receiving medication alone for more than 3 years (UC-M), and conducted multiple logistic regression analysis on 70 histologic features together with endoscopic disease extent and patient age. The analysis constructed an equation finding probability of UC-S ( P UC-S ). Based on a receiver-operating characteristic curve, we selected four cut-off values of P UC-S, and determined criteria of five categories: highest-risk, higher-risk, unpredictable, lower-risk and lowest-risk of surgery. Sensitivity and specificity of criteria were evaluated in a 2 × 5 table. Results : Statistically significant features predicting UC-S were deep ulceration (X 1 ), frequent crypt abscesses (X 2 ), focal and segmental mononuclear cell infiltration (X 3 and X 4 ), paucity of eosinophils (X 5 : eosinophil infiltration) and wide extent of the disease (X 6 ). The regression equation was as follows: logit P UC-S =-16.26 + 3.20X 1 + 4.83X 2 + 11.65X 3 + 5.10X 4 - 5.59X 5 + 5.53X 6. Higher-risk and lower-risk showed sensitivity exceeding 91.0% and specificity exceeding 98.5% in predicting the outcome. Conclusions : Our criteria incorporating specific histologic features and endoscopic disease extent reliably predict eventual clinical outcome, and are expected to prove useful in determining the necessity of surgery.     

炎症性肠病并发低骨量/骨质疏松的危险因素分析

目的 对炎症性肠病(IBD)患者的骨密度状况进行评估,探讨其下降的危险因素.方法 通过对IBD患者血液学指标、身高、体重及腰椎骨密度进行测量,并与健康志愿者比较,分析IBD患者骨质疏松的危险因素.结果 共收集克罗恩病(CD)77例,溃疡性结肠炎(UC)43例,37例健康志愿者作为对照组.CD组、UC组及对照组的腰椎骨质的T值分别为-1.72±1.20、-1.26±1.12和-0.62±0.87,CD组的T值低于UC组(P=0.045)和对照组(P=0.000),UC组T值低于对照组(P=0.014).CD组、UC组及对照组的腰椎骨质疏松的发生率分别为23.3%、14.0%和0;CD组的腰椎骨质疏松发生率高于对照组,差异有统计学意义(P=0.003);UC组的腰椎骨质疏松发生率有高于对照组的趋势,但差异无统计学意义(P=0.053).多元回归分析显示,低体重(BMI≤18.4kg/m~2)是CD(OR=11.25,95%CI 3.198～39.580,P=0.000)和UC(OR=14.50,95%CI 1.058～88.200,P=0.045)患者骨质疏松的危险因素.年龄、病程、病变部位、CD活动指数(CDAI)、服用糖皮质激素、服用免疫抑制剂、血清25-羟基维生素D浓度等因素与骨质疏松的发生无相关性.结论 骨密度下降的发生在IBD患者中较为普遍,低体重是IBD患者骨质丢失的危险因素.     

Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease

Objectives. To explore the relationships between vitamin D intake, serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (250HD) concentrations, and bone mineral density (BMD) in inflammatory bowel disease (IBD).
Setting. A university hospital clinic in Finland.
Subjects. One hundred and fifty randomly selected patients with IBD from the hospital register and 73 healthy controls.
Measurements. BMD of the lumbar spine and the proximal femur was measured with dual energy X-ray absorptiometry. Vitamin D intake and serum levels of 250HD and PTH were determined.
Results. The IBD patients had a lower serum 250HD concentration (28.4 [SD 12.0] nmol L^-1) than the controls (36.1 [16.7] nmol L^-1; P =0.001), whereas no differences in the vitamin D intake or the serum PTH levels were found. The serum 250HD concentrations and the vitamin D intake of the patients with ulcerative colitis ( n =67) were similar to those of the Crohn's disease patients ( n =76). The patients with Crohn's disease of the small bowel had slightly, but not significantly, lower serum 250HD concentrations (25.6 [11.0] nmol L^-1) than the other Crohn's disease patients (31.4 [14.3] nmol L^-1; P =0.061). In the IBD patients, the vitamin D intake and the serum 250HD and PTH concentrations were not associated with BMD.
Conclusions. Patients with IBD have lower serum levels of 250HD than healthy controls, but similar serum PTH concentrations and vitamin D intake. Vitamin D intake, and the serum levels of 250HD and PTH are not associated with BMD, and malabsorption is unlikely to be a major factor in the aetiology of bone loss in unselected IBD patients.     

Allelic variation at the interleukin 1beta gene is associated with decreased bone mass in patients with inflammatory bowel diseases

BACKGROUND: Interleukin 1beta (IL-1beta) and its natural antagonist have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Both cytokines influence bone formation. IL-1beta stimulates osteoclast activity while interleukin 1 receptor antagonist (IL-1ra) enhances bone formation. AIMS: To determine whether the decreased bone mass in IBD is related to gene polymorphisms coding for IL-1beta and IL-1ra, and thus identify patients with an increased risk. METHODS: Bone mineral densitometry was performed at the femoral neck, lumbar spine, and the distal third of the radius in 75 IBD patients (34 men/41 women; 40.3 (1.6) years) and in 58 healthy controls (HC; 28 men/30 women; 32.4 (1.2) years). Values were correlated with the TaqI and AvaI gene polymorphisms in the IL1B and the variable number of tandem repeats gene polymorphism in the IL1RN gene. RESULTS: In IBD patients, but not in HC, carriers of allele 2 at the AvaI gene polymorphism (IL1B-511*2) had significantly lower Z scores at the lumbar spine (-0.82 (0.13) v -0.29 (0.21) p=0.03) and the femoral neck (-0.59 (0.14) v 0.15 (0.19); p=0.003) than non-carriers. These patients also had a higher risk for osteopenia or osteoporosis at the femoral neck (odds ratio 3.63 (95% confidence interval 0.95-13.93)). No association was found between bone mass and the other gene polymorphisms analysed in IBD patients or in HC. CONCLUSIONS: Our results suggest that genetic variability may be a major determinant of bone loss in IBD. Carriers of IL1B-511*2, who are hypersecretors of IL-1beta, have a higher risk of presenting with low bone mass in IBD. Screening for this allele may contribute to determination of the risk of bone loss at the time of disease onset.     

溃疡性结肠炎患者骨密度变化及其相关因素的研究

目的探讨溃疡性结肠炎（UC）患者骨密度（BMD）变化及其与血清中钙、磷、镁、碱性磷酸酶（ALP）、白蛋白（ALB）、肿瘤坏死因子-α（TNF-α）、血管内皮生长因子（VEGF）、白细胞介素-6（IL-6）的相关性。方法用定量CT（QCT）对入选的96例UC患者和100名健康人（对照组）进行BMD测定和相关实验室指标的检测。结果UC组50岁以上者BMD明显低于相应年龄对照组（P〈0.05）;重度UC患者血钙、磷、镁较对照组明显下降（P〈0.05）;BMD与VEGF（r=-0.425,P〈0.05）、TNF-α（r=-0.642,P〈0.05）、IL-6（r=-0.465,P〈0.05）呈负相关。结论UC患者可引起BMD降低而发生骨质疏松,与血钙、磷、镁、白蛋白等营养物质代谢紊乱、年龄、炎性细胞因子等密切有关。     

Effect of venesection on bone mineral density in an eugonadal woman with haemochromatosis

BACKGROUND: A 41-year-old premenopausal woman with newly diagnosed haemochromatosis was found to have osteopenia on screening bone mineral densitometry. METHODS AND RESULTS: Liver biopsy showed grade 3 haemochromatosis with an hepatic iron index of 4. Investigation for secondary factors for osteopenia revealed no cause. The patient was clinically and biochemically eugonadal. Following venesection of 8 L blood (4 g iron) over 17 months and calcium supplementation, her bone density rose significantly. Neck of femur bone density increased by 6.0% over 13 months and lumbar vertebral bone density increased by 7.2%. There are no previous reports of response of bone density to venesection in eugonadal patients or in women with haemochromatosis.     

Longitudinal study of bone mineral density in patients with Crohn's disease

Osteoporosis is frequent in Crohn's disease. The aim of the study was to assess the rate of bone loss over time retrospectively and the influence of disease-related factors on bone loss. Twenty-nine patients (8 male), admitted for repeated bone mineral density assessments (BMD) were enrolled. BMD measured by dual energy x-ray absoptiometry was expressed in grams per square centimeter, and as sex- and age-matched Z score. The mean interval between BMD assessments was 41 months, during which period 27 patients used corticosteroids (mean dose 8.6 g) and 21 patients some form of bone protective medication. Initial Z scores at a mean age of 41 years were significantly below zero (spine –1.6 ± 1.4; femur –1.4 ± 1.4). Over time, no change in absolute BMD was observed accompanied by an improvement in Z scores. At the same time, an increase in body weight and a decrease in erythrocyte sedimentation rate (ESR) was observed. Multilinear regression analysis demonstrated change in ESR as independent predictor for change in femoral Z score. In conclusion, low BMD is frequent in Crohn's disease, but decline of BMD over time was not found, despite ongoing use of corticosteroids.     

Bone mineral density directly correlates with duodenal Marsh stage in newly diagnosed adult celiac patients

Abstract

Objectives. To estimate the prevalence of low bone mineral density (BMD) in a prospective series of adult celiac patients and to identify nutritional and metabolic factors associated with osteoporosis and osteopenia. Methods. Patients over 18 years of age who were consecutively and newly diagnosed with celiac disease (CD) were recruited. A bone density scan with dual-energy X-ray absorptiometry was carried out on the left hip and lumbar spine; nutritional parameters were analyzed and a hormone study conducted in order to exclude secondary low BMD. Results. 40 patients (36 females/4 males) between the ages of 18 and 68 (mean 44.25 years) were recruited. Overall, at the moment of diagnosis 45% of patients exhibited low BMD at both demarcations. Risk of hip fracture was generally low, but ascended to mild in patients with villous atrophy (p = 0.011). Differences in major fracture risk were also observed depending on Marsh stage (p = 0.015). Significant differences were observed in nutritional status between patients with and without duodenal villous atrophy, with body mass index and blood levels of prealbumin, iron, vitamin D and folic acid significantly lower in Marsh III stage patients. No differences were found in blood hormone levels between Marsh stages or BMDs. The degree of bone mass loss in the lumbar spine directly correlated to Marsh stage. In the hip, a parallel association between BMD and Marsh stage was also observed, but did not reach statistical significance. Conclusion. Duodenal villous atrophy, through malabsorption, was the main determinant factor for low BMD in adult-onset CD patients.     

The pancreas and inflammatory bowel diseases

Summary This article reviews the literature and gives an overview on prevalence and possible explanations for pancreatic involvement in inflammatory bowel diseases (IBD). IBD patients have a markedly elevated risk for developing acute pancreatitis as well as pancreatic insuffiency. Multiple potential causes for pancreatitis in IBD patients exist. In the majority of cases acute pancreatitis appears to be related to drug side effects or local structural complications rather than a true extraintestinal manifestation of IBD. Nevertheless, some cases of acute pancreatitis remain unexplained. Prevalence of chronic pancreatitis in IBD patients also seems to be relatively high. However, etiology of pancreatic duct changes and/or the occurrence of exocrine insufficiency remain unclear. In most cases chronic pancreatitis is clinically unapparent, although in some patients it may be accompanied by clinically relevant exocrine insufficiency.     

High prevalence and correlates of low bone mineral density in young adults with sickle cell disease

Sickle cell disease (SCD) is a prevalent genetic disorder in which sickle hemoglobin leads to tissue hypoxia and adverse effects on bone. Published studies suggest that children with SCD often have undiagnosed osteopenia or osteoporosis. Minimal data exist on the prevalence of low bone mineral density (BMD) in adults. Our objective was to describe the prevalence of osteopenia and osteoporosis in adults with SCD and to identify patient or disease characteristics associated with low BMD. We conducted a cross-sectional study of adults with SCD. Through questionnaires, we collected data about disease course and osteoporosis risk factors. Patients underwent dual X-ray absorptiometry (DXA) measurement of BMD at the hip, spine, and forearm and sampling of blood and urine for markers of bone turnover, sickle cell disease severity, and secondary causes of osteoporosis. Our main outcome measure was prevalence of osteopenia and osteoporosis as defined by WHO criteria. Of 32 adults with SCD (14 men and 18 women) with a mean age of 34 years, 72% (95% confidence interval 53-86%) had low BMD at one or more anatomic sites. Thirteen patients were classified as osteoporotic and 10 as osteopenic. The prevalence of low BMD was greatest in the lumbar spine (66% of patients). Significant correlates of decreased BMD included low BMI (P < 0.01), male sex (P = 0.02), and low serum zinc concentrations (P < 0.01). The prevalence of osteopenia and osteoporosis in young adults with SCD is extremely high. Further research is needed to address fracture risk and therapeutic interventions.     

老年炎症性肠病患者的骨代谢和骨密度分析

目的 探讨老年炎症性肠病（inflammatory bowel disease,IBD）患者的骨代谢和骨密度情况与健康对照者的差异,为临床防治IBD引起的骨质疏松提供依据.方法 纳入复旦大学附属华东医院IBD患者20例为IBD组,同期健康体检者20例为对照组.记录并比较两组的年龄、病程、病变部位、糖皮质激素（Glucocorticoids,GCs）应用、骨代谢相关血清学指标检查结果以及髋关节和股骨颈骨密度T值.结果 溃疡性结肠炎组髋关节骨量减少的发生率高于对照组,差异有统计学意义（64.3％ vs 30.0％,P=0.048）.UC组的血清25-羟维生素D[25-hydroxyvitamin D,25-（OH） D]浓度低于对照组（t=0.036,P=-2.100）,IBD组的血清β-CTX浓度高于对照组（UC：=0.003,P=2.975; CD：t=0.024,P=2.253）.结论 老年UC患者髋关节骨量减少的发生率增加,25-（OH）D浓度降低;IBD患者血清β-CTX浓度升高.     

类风湿关节炎患者骨密度及骨矿物质含量的变化及意义

目的探讨类风湿关节炎(RA)患者骨密度(BMD)及骨矿物质(BMC)含量的变化及意义。方法选择71例RA患者(RA组)及20例正常人(对照组),采用双能X线骨密度仪检测各组前臂BMD、BMC含量,魏氏法检测血沉(ESR),免疫比浊法检测血清C反应蛋白(CRP),速率散射比浊法检测类风湿因子(RF),ELISA法检测抗环瓜氨酸肽抗体(ACCP);同时进行X线分期,计算患者疾病活动分数(DAS28)。结果 RA组前臂BMD、BMC均低于对照组(P均<0.01),ESR、CRP、RF、ACCP均高于对照组(P均<0.01)。Pearson’s相关分析显示,前臂BMD与DAS28、ESR、RF呈负相关(r分别为-0.357、-0.390、-0.255,P<0.05或<0.01),前臂BMC与DAS28、ESR呈负相关(r分别为-0.344、-0.401,P均<0.01)。多元线性回归分析显示,前臂BMD与RF、年龄呈负相关(T分别为-7.544、-3.254,P均<0.01);前臂BMC与DAS28呈负相关(T=-4.44,P<0.01)。RA组中X线分期为Ⅰ期的有15例,其中BMD示骨质疏松6例、骨量减少2例。结论 RA患者BMD、BMC含量明显减少,其含量减少与RA活动密切相关;RF可能是导致RA骨量丢失的危险因素;BMD检测能更早反映RA患者的骨量丢失情况。     

Keratin 8 Y54H and G62C mutations are not associated with inflammatory bowel disease

BACKGROUND: Keratin 8 is a major component of intermediate filaments in single-layered epithelia of the gastrointestinal tract. Keratin 8 deficient mice display signs of colitis and diarrhoea characteristic for inflammatory bowel disease. Very recently, two keratin 8 mutations, Y54H and G62C, were identified. AIMS: We investigated if these keratin 8 missense mutations were associated with inflammatory bowel disease. PATIENTS: In total, 217 German patients with Crohn' s disease, 131 German patients with ulcerative colitis, and 560 German control subjects were enrolled in this study. METHODS: Samples were analysed by PCR amplification and subsequent melting curve analysis using fluorescence resonance energy transfer probes. RESULTS: The G62C mutation was detected in five (2.3%) patients presenting with Crohn's disease and in three (2.3%) with ulcerative colitis. In comparison, 9 (1.6%) out of 560 controls were heterozygous for this mutation. No patient or control was homozygous for this mutation. Patients carrying one mutant allele did not show any noticeable characteristics in their corresponding phenotype. In contrast, the Y54H mutation was observed in neither any of the 348 patients with inflammatory bowel disease nor in any control subject. CONCLUSIONS: Our data indicate that both keratin 8 mutations, G62C and Y54H, do not play a relevant pathogenic role in inflammatory bowel disease.