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.     

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.     

The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseases

Objective: To detect the frequency and the predictive factors of low bone mineral density in inflammatory bowel disease (IBD) patients, so as to optimize bone mineral density (BMD) monitoring and treatment for those at risk. Subjects and methods: Thirty Asian patients were included in this study and were divided into 18 patients with ulcerative colitis (UC), and 12 patients with Crohn’s disease (CD). All patients were diagnosed by colonoscopy and histopathological biopsy and were subjected to routine laboratory investigations in addition to 25 hydroxy vitamin D levels as well as serum calcium, phosphorus and alkaline phosphatise. BMD was measured by using dual‐energy X‐ray absorptiometry (DEXA) scan at lumbar spine and femoral neck; predictive factors for BMD were analyzed by group comparison and step‐wise regression analysis. Results: There was increased frequency of osteoporosis and osteopenia involving the lumbar spine in patients with IBD being more common among CD patients than in the UC group. Positive correlations were found between low BMD measurements and vitamin D levels, body mass index (BMI) (P < 0.001) as well as steroid cumulative dose and duration of therapy (P < 0.001); stepwise regression analysis showed that CD and vitamin D deficiency are predictive factors for both osteoporosis and osteopenia (P = 0.024, P = 0.027, respectively). Conclusion: Low BMD was found to be more frequent among patients with CD than UC; in addition CD and vitamin D deficiency act as predictive factors for low BMD. We recommend that calcium and vitamin D should be given to all IBD patients; in addition, bisphosphonate administration should be put into consideration.     

PMN-elastase in assessment of patients with inflammatory bowel disease

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5±33.2 ng/ml vs 60.1±24.6 ng/ml (means±sd),P=0.0017; ulcerative colitis: 98.2±54.9 ng/ml vs 59.2±16.8 ng/ml,P=0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6±15.3 ng/g vs 13.6±12.5 ng/g,P=0.0021) and active ulcerative colitis (46.5±60.5 ng/g vs 20.2±25.0 ng/g,P=0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma:r=0.72,P<0.001; feces:r=0.423,P<0.001) but not fecal elastase concentrations (r=0.0083,P=0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r=0.431,P<0.01) and in ulcerative colitis (r=0.515,P=0.05). In 28 patients with highly active Crohn's disease [median severity activity index (SAI) 203] and 11 patients with highly active ulcerative colitis [median Rachmilewitz index (RI) 14] studied before and four weeks after steroid therapy, treatment lowered the median SAI to 140 and the median RI to 4.5. Mean plasma elastase concentrations decreased concomitantly from 83±44.9 ng/ml to 61.8±25.8 (P=0.0035) in patients with Crohn's disease and from 110±49.5 to 71.6±28.8 ng/ml (P=0.0069) in patients with ulcerative colitis. In conclusion, there is a release of PMN-elastase in active IBD, which can be detected in plasma as well as in feces. Plasma elastase levels reflect disease activity in patients with IBD. The variation of the data and the large overlap between different groups, however, strongly reduce the clinical value.This research was supported by the SFB 154 of the Deutsche Forschungsgemeinschaft. V. Gross is supported by a Heisenberg-Stipendium of the Deutsche Forschungsgemeinschaft.     

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.     

Updated bone mineral density status in Saudi patients with inflammatory bowel disease

BACKGROUND Little is known about inflammatory bowel disease(IBD) burden and its impact on bone mineral density(BMD) among adult patients in Saudi Arabia. To the best of our knowledge, our study is the only study to give an update about this health problem in adult Saudi patients with IBD. IBD is a great risk factor for reduced BMD due to its associated chronic inflammation, malabsorption, weight loss and medication side effects. Consequently, screening for reduced BMD among patients with IBD is of utmost importance to curb and control anticipated morbidity and mortality among those patients.AIM To assess the relationship between IBD and BMD in a sample of adult Saudi patients with IBD.METHODS Ninety adult patients with IBD-62 Crohn's disease(CD) and 28 ulcerative colitis(UC)-were recruited from King Fahad Specialist Hospital gastroenterology clinics in Buraidah, Al-Qassim. All enrolled patients were interviewed for their demographic information and for IBD-and BMD-related clinical data. All patients had the necessary laboratory markers and dual-energy x-ray absorptiometry scans to evaluate their BMD status. Patients were divided into two groups(CD and UC) to explore their clinical characteristics and possible risk factors for reduced BMD.RESULTS The CD group was significantly more prone to osteopenia and osteoporosis compared to the UC group; 44% of the CD patients had normal BMD, 19% had osteopenia, and 37% had osteoporosis, while 78% of the UC patients had normal BMD, 7% had osteopenia, and 25% had osteoporosis(P value 0.05). In the CD group, the lowest t-score showed a statistically significant correlation with body mass index(BMI)(r = 0.45, P 0.001), lumbar z-score(r = 0.77, P 0.05) and femur z-score(r = 0.85, P 0.05). In the UC group, the lowest t-score showed only statistically significant correlation with the lumbar z-score(r = 0.82, P 0.05) and femur z-score(r = 0.80, P 0.05). The ROC-curve showed that low BMI could predict the lowest t-score in the CD group with the best cut-off value at ≤ 23.43(m/kg2); area under the curve was 0.73(95%CI: 0.59–0.84), with a sensitivity of 77%, and a specificity of 63%.CONCLUSION Saudi patients with IBD still have an increased risk of reduced BMD, more in CD patients. Low BMI is a significant risk factor for reduced BMD in CD patients.     

Chemotactic activity in inflammatory bowel disease

An important histologic feature of inflammatory bowel disease (IBD) is infiltration of the colonic mucosa with neutrophils. To investigate the nature of the chemotactic agents responsible for this infiltration, colonic mucosa from three normals and nine patients with inflammatory bowel disease (seven ulcerative colitis, two Crohn's colitis) was assayed for chemotactic activity for human neutrophilsin vitro in a Boyden chamber. There was more (>10-fold more) chemotactic activity in homogenates of inflammatory bowel disease mucosa than in homogenates of normal colonic mucosa. Analysis of the chemotactic activity in the inflammatory bowel disease mucosa revealed that most was lipid extractable. Moreover, when the lipid extract was fractionated by reverse-phase high-pressure liquid chromatography, the only fraction with significant chemotactic activity was the fraction that coeluted with leukotriene B₄. The chemotactic response to IBD mucosa was blocked by anti-LTB₄ antisera. The amount of chemotactic activity in lipid extracts of different inflammatory bowel disease specimens correlated well with the concentration of leukotriene B₄ measured by UV absorbance (250 ng/g of mucosa). These data suggest that leukotriene B₄ is an important stimulus to neutrophil chemotaxis in inflammatory bowel disease and, thus, may play a major role in the amplification of the inflammatory response in this condition.This work is supported by a grant from the National Foundation for Ileitis and Colitis and grant AM-33165 from the National Institutes of Health.     

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.     

Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

Hospital discharges for inflammatory bowel disease

The present study analyzes time trends of inflammatory bowel disease (IBD) in England-Wales and the United States based on nationwide hospitalization statistics. Because these statistics cover the total population of each country, they may give a more representative picture of the true trends than previous analyses concerning only one region or health center. The Hospital In-patient Enquiry was used to evaluate time trends in England-Wales from 1962 to 1985, data from the National Hospital Discharge Survey and the Commission on Professional Activities were used for trends in the United States from 1970 to 1987. A rise of Crohn's disease persisted unabated in the old age groups throughout the observation period. It was less marked in those aged under 35 and reached a plateau during the most recent decade. In ulcerative colitis, discharge rates increased in the older age groups, but remained constant or declined in the middle or younger age groups, respectively. Similar trends were observed in all three surveys. The hospitalization data confirm similar age-specific trends of mortality. The difference between younger and older age groups suggests that generations born 60–80 years ago have become more likely to be affected by IBD leading to hospitalization and mortality. As these high-risk generations grow older, there is a relative rise of hospitalization and mortality from IBD in these subjects.Supported by grant So 172/1-1 from the Deutsche Forschungsgemeinschaft.     

TWEAK is not elevated in patients with newly diagnosed inflammatory bowel disease

Objective: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) may be involved in the pathogenesis of inflammatory bowel disease. The aim was to investigate if TWEAK may reflect disease activity in inflammatory bowel disease.

Materials and methods: In this cohort study, 139 consecutive patients with newly diagnosed and previously untreated inflammatory bowel disease – 95 with ulcerative colitis (UC) and 44 with Crohn’s disease (CD) – underwent colonoscopy. Disease activity was assessed by the Mayo score and the Mayo endoscopic score (MES) for UC, or the Simple Endoscopic Score (SES) for CD. Serum C-reactive protein (CRP) and fecal calprotectin were measured in IBD patients, as were plasma TWEAK levels in patients and 85 healthy subjects. Associations between TWEAK levels and disease activity markers were explored.

Results: In the total IBD group, the median (interquartile range) TWEAK level was 430?pg/ml (109–6570), in UC 502?pg/ml (109–4547) and in CD patients 352?pg/ml (101–9179), respectively. Healthy subjects had a median (IQR) TWEAK of 307?pg/ml (63–3492). There were no significant differences in TWEAK levels between the total IBD group and healthy control subjects, nor between UC and CD, or between UC/CD and healthy subjects. Furthermore, we found no significant associations between Mayo scores, MES-UC, SES-CD, CRP, and fecal calprotectin with plasma TWEAK levels.

Conclusions: Plasma TWEAK levels do not reflect disease activity or the grade of inflammation in patients with newly diagnosed inflammatory bowel disease. NCT01551563.     

Metabolic features of inflammatory bowel disease in a remission phase of the disease activity

Capristo E, Mingrone G, Addolorato G, Greco AV, Gasbarrini G (Sacred Heart Catholic University, Rome, Italy). Metabolic features of inflammatory bowel disease in a remission phase of the disease activity. J Intern Med 1998; 243 : 339–47.

Objectives

To evaluate the anthropometric and metabolic characteristics of patients with Crohn's disease (CD) and ulcerative colitis (UC), comparing both groups with healthy volunteers.

Design

A cross-sectional study.

Setting

The Department of Internal Medicine, Catholic University Hospital, Rome, Italy.

Subjects

Thirty-four patients with biopsy-proven inflammatory bowel disease (18 CD; 16 UC) in clinical remission (SCDAI <3 and Powell–Tuck index <4) not receiving steroid therapy.

Interventions

All patients had a clinical examination.

Main outcome measures

Blood indicators of inflammation and nutritional status. Body composition was assessed by both anthropometry and bioimpedance and metabolic variables were measured by indirect calorimetry over a 60–90 min period.

Results

CD had a lower body weight than both controls (58.1 kg, range 41.5–71.0 vs. 66.4 kg, range 57.0–76.0; P < 0.001) and UC) 58.1 kg, range 41.5–71.0 vs. 69.6 kg, range 50.5–94.0; P < 0.001). Fat-free mass (FFM) did not differ between the groups, whilst fat mass was significantly lower in CD than in UC (P < 0.05) and controls (P < 0.001). Normalizing the basal metabolic rate by FFM, a higher value was found in CD compared with UC (143 kJ kg^?1 d–^?1, range 97.5–179 vs. 133 kJ kg^?1 d^?1, range 123–148; P < 0.05) and control subject 143 kJ kg^?1 d^?1, range 97.5–179 vs. 134 kJ kg^?1 d^?1, range 122–162; P < 0.05). The nonprotein respiratory quotient was significantly lower in CD compared to UC 0.80, range 0.73–0.84 vs. 0.84, range 0.79–0.91; P < 0.01) and controls (0.80, range 0.73–0.84 vs. 0.83, range 0.81–0.87; P < 0.001), with a consequently higher lipid oxidation rate in CD.

Conclusions

CD subjects showed a decreased fat mass and enhanced utilization of lipids compared with UC and controls. These data could be explained by the larger intestinal involvement and considered as a contribution to lipid tissue wasting in CD.

     

Bone mineral density in Iranian patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn’s disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1–L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1–L4, L2–L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.     

Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature

BACKGROUND: Inflammatory bowel disease mainly affects the bowel but also has extraintestinal manifestations. AIMS: To report the frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece. PATIENTS; The data files of 256 inflammatory bowel disease patients (diagnosis between 1983-19971 were analysed. METHODS: Retrospective investigation of patient files. RESULTS: In patients with ulcerative colitis: 13.9% (30/215) had developed skin manifestations, 6% (13/215) had kidney stones, 1.39% (3/215) had iridocyclitis, 1.86% (4/215) had primary sclerosing cholangitis, 4.18% (9/215) had sacroiliitis, 8.31% (18/215) had peripheral arthalgias, 2.3% (5/215) had colitic arthritis and finally 1.39% (3/215) had deep vein thrombosis). In patients with Crohn's disease: 24.3% (9/37) had developed skin manifestations, 5.4% (2/37) had kidney stones, 2.7% (1/37) had iridocyclitis, 16.2% (6/37) had sacroiliitis, 8.1% (3/37) had peripheral arthralgias, 5.4% (2/37) had colitic arthritis and, finally, 8.1% (3/37) had deep vein thrombosis. Sacroiliitis (p = 0.01), deep vein thrombosis (p = 0.04) and erythmema nodosum (p = 0.01) were more common in patients with Crohn's disease. CONCLUSIONS: Extraintestinal manifestations are not rare in patients with inflammatory bowel disease, especially in Crohn's disease patients, in our area, but have, generally, a mild profile.     

Inflammatory bowel disease: dogmas and heresies

Perception of a disease state by the practising physician is based on how easily the diagnosis can be made and how predictable the outcome of the chosen therapy is. The academic investigator perceives the same disease based on how well its cause and mechanism are understood, and how rational pathophysiology-based treatments are. Because of incomplete knowledge, neither the practising physician nor the academic investigator are comfortable in dealing with inflammatory bowel disease, and both seek help in the dogmas and heresies inevitably associated with chronic disease of unknown aetiology.     

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.