Kent V. Haderslev

Short-term Administration of Glucagon-like Peptide-2. Effects on Bone Mineral Density and Markers of Bone Turnover in Short-Bowel Patients with No Colon

Background: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of shortbowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. Methods: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 μg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. Results: Mean ± s x (SEM) percent changes in spinal and hip BMD were 1.1 ± 0.4% ( P < 0.05) and 1.9 ± 0.8% ( P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% ( P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. Conclusion: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection

Background and aims: Vitamin D deficiency is common in patients with small intestinal resection and may lead to secondary hypersecretion of parathyroid hormone (PTH), which in turn may result in increased bone turnover rate and loss of bone mineral. The aims of this study were to investigate the prevalence of vitamin D deficiency, as assessed by low serum concentrations of 25-hydroxyvitamin D (25(OH)D) in patients with small intestinal resection and to explore the relation of 25(OH)D to PTH, markers of bone turnover rate, and bone mineral density (BMD) in these patients. Patients: Forty two patients with small intestinal resection, a faecal energy excretion of more than 2.0 MJ/day, and a mean length of the remaining small intestine of 199 cm were included. Diagnoses were Crohn’s disease (n=35) and other (n=7). Methods: 25(OH)D was analysed by radioimmunoassay and bone turnover rate was assessed by measurement of serum osteocalcin, serum alkaline phosphatase, urine pyridinoline, and urine deoxypyridinoline. BMD was measured by dual energy x ray absorptiometry. Results: Mean 25(OH)D concentration was 13.4 (SD 9.7) ng/ml, which was significantly below the reference mean of 26.4 (SD 13.2) ng/ml (p<0.001). Vitamin D deficiency (25(OH)D concentration ≤8 ng/ml) was found in 38.1% of patients and was accompanied by raised concentrations of PTH and significantly increased markers of bone resorption (p<0.05). Low 25(OH)D concentrations correlated significantly with lower BMD z scores of the spine (r=0.38; p=0.02) and hip (r=0.33; p=0.04). Conclusions: We found reduced 25(OH)D concentrations in patients with small intestinal resection, and showed that a deficient 25(OH)D concentration is associated with significantly increased markers of bone resorption and decreased BMD values.

Assessment of the longitudinal changes in bone mineral density in patients receiving home parenteral nutrition.

BACKGROUND Low bone mineral density (BMD) is commonly reported in patients receiving home parenteral nutrition (HPN), but it remains unclear whether or not an accelerated bone loss occurs during HPN therapy. We evaluated the spinal, hip, and forearm bone mass density longitudinally in a cohort of 75 patients receiving HPN. METHODS A total of 943 regional dual-energy x-ray absorptiometry scans, 335 spinal, 318 hip, and 290 forearm, obtained between 1995 and 2003 in 75 patients receiving HPN, were used for the analysis of the annual changes in BMD. The average (SD) number of scans per patients was 4.4 (2.9), and follow-up time was 4.1 (1.9) years. Diagnoses were Crohns disease (n = 35) and other conditions (non-Crohns diseases; n = 40). Data were analyzed using a linear random coefficient model. RESULTS There was a statistically significant overall decline over time in spinal, hip, and forearm BMD, corresponding roughly to a 1% annual loss (p < .005); however, the loss was not significantly larger than that of age and sex-matched healthy subjects. In Crohns disease patients, model estimates of spinal and hip BMD on the initiation of HPN therapy were significantly reduced compared with normal, whereas values were not significantly reduced in non-Crohns disease patients. CONCLUSIONS With the current protocols for HPN treatment, the annual decline in BMD is moderate and not significantly larger than in age- and sex-matched healthy subjects. A considerable part of the metabolic bone disease in these patients is related to the underlying disease for which the HPN was indicated.

Does paracentesis of ascites influence measurements of bone mineral or body composition by dual-energy x-ray absorptiometry?

Measurements of bone mineral content (BMO) and density (BMD) by dual-energy x-ray absorptiometry (DXA) may be affected by changes in soft tissue overlying bone. Furthermore, the accuracy error for body composition determined by DXA may be high in the trunk region due to the complex bone geometry. Our objective was to evaluate the impact of paracentesis on measurements of bone mineral and body composition by DXA. DXA (Norland XR-36; Norland, Fort Atkinson, WI) scans were performed in six patients with cirrhosis of the liver before and after treatment of ascites by paracentesis. There were no significant differences in the spinal BMC (change [delta] = 0.04%) and BMD (delta = -0.9%) (P > .05), nor in total body BMC ([TBBMC] delta = 1.9%) and BMD ([TBBMD] delta = 0.4%) (P > .05). The median volume of ascites drained (6.8 L; range, 1.6 to 14.7) was not significantly different from the median change in total (5.8 kg; range, 2.0 to 16.1) or trunk lean tissue mass ([LTM] 5.8 kg; range, 1.9 to 11.9) (P > .05). The changes in body weight correlated with the changes in trunk LTM (r = .93, standard error of the estimate [SEE] = 1.8 kg, P = .007). Total and regional fat mass were not changed significantly by the paracentesis. We conclude that measurements of total body and spinal bone mineral by DXA are unaffected by large changes in the soft tissue composition and height of the trunk. Furthermore, the change in body composition induced by ascites drainage was accurately determined as a change in total body and trunk LTM on a group level.

Accuracy of body composition measurements by dual energy x-ray absorptiometry in underweight patients with chronic intestinal disease and in lean subjects

BackgroundTo assess the accuracy of Dual-energy X-ray absorptiometry (DXA) in underweight patients with chronic gastrointestinal disease, we investigated the ability of DXA to detect variations in body composition induced by infusion of parenteral nutrition (PN). Furthermore, the influence of a low body weight per se on the accuracy of DXA was studied by placing packets of lard on lean healthy subjects.MethodsThe hydration study included 11 patients with short bowel syndrome on long-term home parenteral nutrition (9 women and 2 men), and (mean ± SD) 49.5 ± 17.1 yr., 19.3 ± 3.1 kg/m2. The lard study, where packets of lard were placed either over the thighs or the trunk region, was performed in 8 healthy lean male volunteers, 26.4 ± 7.4 yr., and 21.0 + 0.9 kg/m2. Body composition, including measures of the total mass (TM), soft tissue mass (STM), lean tissue mass (LTM), fat mass (FM), and total body mineral content (TBBMC), was assessed by DXA. The fat fraction of the lard packets (3.49 kg), measured in triplicate by chemical fat extraction, was 52.2%.ResultsHydration study; The increase in scale weight (BW) of approximately 0.90 kg due to infusion of PN correlated significantly to the increase in TM (R-square = 0.72, SEE 0.36 kg, p < 0.01), and the increase in STM (R-square = 0.69, SEE 0.38 kg, p < 0.01), however not with the increase LTM (R-square = 0.30, SEE 1.06 kg, p = 0.08). Mean changes in TM (0.88 kg), STM (0.88 kg), and LTM (0.81 kg) were not significantly different from changes in BW (p > 0.05). Lard study; Regardless of position, measurements of FM and LTM of the added lard were not significantly different from expected values. However, the composition of the lard packets into FM and LTM was more accurately detected when the packets were placed over the thighs than over the trunk region. The accuracy of DXA in individual subjects, expressed as the SD of the difference between expected and measured values, was 1.03 kg and 1.06 kg for the detection of changes in LTM and FM, respectively, and 0.18 kg for the detection of changes in STM and TM.ConclusionsOn a group level, DXA provided sufficient accuracy to detect small changes in body composition in underweight patients with chronic gastrointestinal disease. However, the accuracy errors were higher than reported in normal weight subjects. The accuracy was not influenced by a low body weight per se.

Comparison of Dual-Energy X-Ray Absorptiometry to Four Other Methods to Determine Body Composition in Underweight Patients With Chronic Gastrointestinal Disease

Assessment of body composition may provide important information about the nutritional status. The applicability of two safe and convenient methods for body composition analysis, bioelectrical impedance analysis (BIA) and dual-energy x-ray absorptiometry (DXA), in underweight patients with chronic gastrointestinal disease has been sparsely elucidated. Our objective was to compare measurements by DXA with four other methods. Furthermore, we compared total body water (TBW) by BIA using three different BIA equations with measurement of TBW by tritium dilution (TBW-3H2O). Nineteen clinically stable underweight patients with chronic gastrointestinal disease were included in the study (body mass index [BMI], 19.3 +/- 1.2 kg/m2). Body composition was assessed using total body potassium (TBK), isotope dilution of tritium (3H2O), anthropometry (skinfold thickness [SF]), BIA, and DXA. Fat-free mass (FFM) by DXA was in reasonable agreement with body composition measurements by TBK (mean difference(TBK-DXA) = -1.61 kg, r = .88, standard error of the estimate [SEE] = 4.66 kg) and 3H2O (mean difference(3H2O-DXA) = 0.98 kg, r = .93, SEE = 3.34 kg). Although mean values for FFM by DXA differed significantly versus BIA and SF, we found highly significant correlations between the measurements (r = .97 and r = .97, respectively). The mean TBW by BIA was overestimated by 1.9 and 3.1 L compared with TBW-3H2O when prediction equations for normal-weight subjects were used. We conclude that the DXA method is a valuable addition to the list of methods available for body composition studies in clinically stable underweight patients. Our data show that BIA equations for normal-weight subjects overestimated TBW in the patients studied.

Absorption of calcium and magnesium in patients with intestinal resections treated with medium chain fatty acids

BACKGROUND Steatorrhoea is associated with increased faecal loss of calcium and magnesium. Medium chain C8-C10 triglycerides (MCTs) improve fat absorption in patients with small bowel resections but the effects on intestinal absorption of divalent cations are not clear. AIM To assess the effect of dietary replacement of long chain triglycerides (LCTs) with MCTs on calcium and magnesium absorption in patients with small bowel resections. PATIENTS Nineteen adult patients with a remaining small intestine averaging 171 cm (range 50–300). METHODS In a crossover design, patients were randomised to two high fat diets (10 MJ/day, 50% as fat) for four days each separated by one day of washout. Diets were prepared in duplicate and were based on either LCT (LCT period) or equal quantities of LCT and MCT (L/MCT period). Metabolic balances were calculated during the last three days of each period. RESULTS Mean stool volume increased significantly with the L/MCT diet and was 336 ml more than that with the LCT diet (95% confidence interval of mean difference, 26–649 ml). There was no significant change in the net absorption of calcium and magnesium between the two diets. On average, percentage calcium absorption was 8.6% with the LCT diet and 12.5% with the L/MCT diet. Mean percentage magnesium absorption was 5.4% with the LCT diet and 2.9% with the L/MCT diet. CONCLUSIONS Dietary replacement of 50% long chain triglycerides with medium chain triglycerides in small bowel resected patients increased faecal volume significantly. No changes in the intestinal net absorption of calcium and magnesium were demonstrated.

Management of intestinal failure in Europe. A questionnaire based study on the incidence and management.

BackgroundIntestinal failure is the outcome of a number of gastrointestinal diseases and characterized by significant reduction in functional gut mass. If not resolved patients often face long-term nutritional support. This study gathered information about how patients referred with intestinal failure are managed in specialised European centres.MethodsA questionnaire was circulated in 7 European countries via representatives of the ESPEN-HAN working group to seek information about experience in treating patients with intestinal failure. We asked about clinical outcome, information about structure and organisation of the department, referral criteria, treatment procedures and guidelines.Results17 centres in 6 European countries completed the questionnaire: UK, n = 6, France, n = 4, Spain, n = 3, Denmark, n = 2, Italy, n = 1, Poland, n = 1. The experience of the centres in treating patients was in the range 12–30 years. The total number of patients on HPN in all centres was 590. The number of patients referred to centres with intestinal failure during the period January to December 2000 was n = 882: UK, n = 375 (range 2–175), France, n = 308 (range 24–182), Italy and Spain, n = 43 (range 9–52), Denmark n = 51 (range 14–37), the centre in Poland included 53 patients. Comparing all centres the following distribution among patients (median % (range%)) with regard to the endpoints were reported: Oral nutrition 32% (23–50%), enteral/tube feeding 11% (4–23%), HPN 36% (15–57%), lost to follow up 10% (0–35%), dead 9% (5–18%). No patients had an intestinal transplant.ConclusionThe study provides information about how patients with intestinal failure are managed across Europe and the data indicates that treatment practice varies between countries.

Su2095 Survival and Cause-Specific Mortality in an Intestinal Failure Cohort Depending on Home Parenteral Nutrition (HPN) in a Referral Centre From 1970 to 2010

G A A b st ra ct s enhanced microbial fermentation of dietary fiber and dysregulation of choline metabolism. The OPLS-DA model constructed based on samples collected post DI (R2X=30.7%, Q2Y= 0.37) showed higher concentrations of glutamate and 6-aminosalicylic acid in AA compared with AF. Microbial data acquired using HITChip was integrated with fecal profiles using OPLS. At the phylum level, 2 out of 22 identified phyla were significantly correlated with fecal profiles, which are Cyanobacteria and uncultured Mollicutes significantly correlating with fecal glutamate and valerate. By statistically integrating the fecal metabonome and the 130 microbial genus, Bacteroides vulgates et rel. and Bacteroides plebeius et rel. were observed to be correlated with choline, whereas Uncultured Clostridiales II was correlated with pyroglutamate. Uncultured Mollicutes, Eubacterium siraeum et rel and Aneurinibacillus demonstrated similar metabolic activity. Conclusions: These findings indicate that after only two-weeks of a dietary exchange diet, the fecal metabolic profile is significantly altered and that these metabolic changes are closely associated with alterations in the structure and function of the gut microbial network.

Effect of Cyclical Intravenous Clodronate Therapy on Bone Mineral Density and Markers of Bone Turnover in Patients Receiving Home Parenteral Nutrition

Background: Patients receiving home parenteral nutrition (HPN) because of intestinal failure are at high risk of developing osteoporosis. Objective: We studied the effect of the bisphosphonate clodronate on bone mineral density (BMD) and markers of bone turnover in HPN patients. Design: A 12-mo, double-blind, randomized, placebo-controlled trial was conducted to study the effect of 1500 mg clodronate, given intravenously every 3 mo for 1 y, in 20 HPN patients with a bone mass T score of the hip or lumbar spine of less than –1. The main outcome measure was the difference in the mean percentage change in the BMD of the lumbar spine measured by dual-energy X-ray absorptiometry. Secondary outcome measures included changes in the BMD of the hip, forearm, and total body and biochemical markers of bone turnover, ie, serum osteocalcin, urinary pyridinoline, and urinary deoxypyridinoline. Results: The mean (±SEM) BMD of the lumbar spine increased by 0.8 ± 2.0% in the clodronate group and decreased by 1.6 ± 2.0% in...