Crohn Disease: Steinhart H

Panaccione R, Fedorak RN, Aumais G, Bernstein CN, Bitton A, Croitoru K, Enns R, Feagan B, Fishman M, Greenberg G, Griffiths A, Marshall JK, Rasul I, Sadowski D, Seidman E, Steinhart H, Sutherland L, Walli E, Wild G, Williams CN, Zachos M, Anonymous00234. · University of Calgary, Calgary, Canada. · Can J Gastroenterol. · Pubmed #15372114 links to  free full text

This publication has no abstract.

Steinhart H. · Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Can J Gastroenterol. · Pubmed #11023557 No free full text.

Abstract: Symptoms of active Crohn's disease may respond to one or more of a number of classes of drug therapies. These include systemic glucocorticoids, budesonide, sulphasalazine, mesalazine (5-aminosalicylates), immunosuppressive agents and antibiotics. More recently, a chimeric mouse-human antibody to tumour necrosis factor (infliximab) has been shown to induce clinical remission and endoscopic improvement in patients with moderately active Crohn's disease refractory to other therapies. Despite this wide range of existing therapies and the potential of emerging biological therapies, recurrent Crohn's disease continues to be a major impediment to the fulfilment of a normal lifestyle and optimal quality of life for patients with Crohn's disease. Many drugs known to be effective for the treatment of active disease have been tried as maintenance therapy to prevent disease relapse or recurrence following medical or surgical therapy. The available evidence suggests that most of these drugs are not as useful in maintaining remission as they are in inducing it. Systemic glucocorticoids, budesonide, mesalazine (5-aminosalicylates), sulphasalazine and antibiotics are all associated with either marginal therapeutic gain in the setting of maintenance therapy or unacceptable long term toxicity. The immunosuppressive agents azathioprine, 6-mercaptopurine and methotrexate have been shown to have a beneficial effect in maintaining remission and may be helpful as steroid-sparing agents. Repeated infusions of antitumour necrosis factor antibody maintain the improvements observed after one or two initial infusions. The relative long term safety, efficacy and cost effectiveness of the various choices of maintenance therapy remain to be determined.

Siffledeen JS, Fedorak RN, Siminoski K, Jen H, Vaudan E, Abraham N, Steinhart H, Greenberg G. · Division of Gastroenterology, University of Alberta, Edmonton, Canada. · Clin Gastroenterol Hepatol. · Pubmed #15704046 No free full text.

Abstract: BACKGROUND & AIMS: Crohn's disease causes an increase in osteopenia and osteoporosis. This study assessed the efficacy of adding etidronate to calcium and vitamin D supplementation for treatment of low bone mineral density in Crohn's disease. METHODS: One hundred fifty-four patients with Crohn's disease with decreased bone mineral density, determined by using dual-energy x-ray absorptiometry, were randomly assigned to receive etidronate (400 mg orally) or not for 14 days; both groups were then given daily calcium (500 mg) and vitamin D (400 IU) supplementation for 76 days. This cycle was repeated 8 times during a period of 24 months. Biochemical characteristics and bone mineral densities were assessed at 6, 12, and 24 months. RESULTS: After 24 months bone mineral density significantly increased from baseline in both the etidronate- and the non-etidronate-treated groups (both groups receiving calcium and vitamin D supplementation) at the lumbar spine (P < .001), ultradistal radius (P < .001), and trochanter (P = .004) sites, but not at the total hip. The increase in bone mineral density was similar in each treatment group. No bone mineral density differences were found when groups were analyzed according to gender, corticosteroid use, bone mineral density at baseline, or age. CONCLUSIONS: Low bone mineral density is frequently associated with Crohn's disease. Supplementation with daily calcium and vitamin D is associated with increases in bone mineral density. The addition of oral etidronate does not further enhance bone mineral density.

Siffledeen JS, Siminoski K, Steinhart H, Greenberg G, Fedorak RN. · Department of Medicine, University of Alberta, Edmonton. · Can J Gastroenterol. · Pubmed #12945007 links to  free full text

Abstract: BACKGROUND: Vitamin D deficiency is a putative, pathogenic cofactor in the increase in osteopenia and osteoporosis seen in patients with Crohn's disease. OBJECTIVE: To determine the frequency of low serum 25-hydroxy-vitamin D3 (25-OHD) levels and the associated alterations in bone mineral density in a cohort of adults with Crohn's disease. METHODS: 25-OHD levels were determined in 242 consecutive patients with Crohn's disease seen in two tertiary inflammatory bowel disease referral centres. Bone mineral density was assessed by dual energy x-ray absorptiometry. RESULTS: Nineteen (8%) patients exhibited vitamin D deficiency (25-OHD less than 25 nmol/L) and 52 (22%) patients exhibited vitamin D insufficiency (25-OHD less than 40 nmol/L). Mean T-scores at the lumbar spine, femoral neck, total hip and ultradistal radius in the group with low 25-OHD did not differ from those of the normal 25-OHD group. Serum alkaline phosphatase and parathyroid hormone levels were higher in the low 25-OHD group than in the normal group. Decreased red blood cell (RBC) folate predicted low 25-OHD in male patients, while smoking, RBC folate and serum iron predicted low 25-OHD in female patients. The rate of low 25-OHD deficiency in the winter was significantly higher than that in the summer (11.9% versus 2.8%, respectively). CONCLUSION: Vitamin D-deficient Crohn's disease patients exhibit biochemical evidence of metabolic bone disease, without detectable differences in bone mineral density. Sunlight exposure, nutrition and smoking status were predictors of vitamin D deficiency in this patient cohort.

Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, Delmonte T, Kocher K, Miller K, Guschwan S, Kulbokas EJ, O'Leary S, Winchester E, Dewar K, Green T, Stone V, Chow C, Cohen A, Langelier D, Lapointe G, Gaudet D, Faith J, Branco N, Bull SB, McLeod RS, Griffiths AM, Bitton A, Greenberg GR, Lander ES, Siminovitch KA, Hudson TJ. · Whitehead Institute/Massachusetts Institute of Technology, Center for Genome Research, Cambridge, Massachusetts, USA. · Nat Genet. · Pubmed #11586304 No free full text.

Abstract: Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.