Objectives: Many patients with Crohn's disease (CD) have low bone mineral density (BMD) that may not be solely attributable to glucocorticoid use. We hypothesised that low BMD in patients with CD is associated with elevated circulating levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH) 2 D). We further hypothesised that this was secondary to increased synthesis of 1,25(OH) 2 D by inflammatory cells in the intestine. The aim of this study was to examine the relationship between 1,25(OH) 2 D levels and BMD in patients with CD. Methods: An IRB approved retrospective review of medical records from patients with CD (n = 138) or ulcerative colitis (UC, n = 29). Measurements of vitamin D metabolites and immunoreactive parathyroid hormone (iPTH) were carried out. BMD results were available for 88 CD and 20 UC patients. Immunohistochemistry or real time reverse transcription-polymerase chain reaction (RT-PCR) for the enzyme 1a-hydroxylase was performed on colonic biopsies from patients with CD (14) or UC (12) and normal colons (4). Results: Inappropriately high levels of serum 1,25(OH) 2 D (.60 pg/ml) were observed in 42% of patients with CD compared with only 7% in UC, despite no differences in mean iPTH. Serum 1,25(OH) 2 D levels were higher in CD (57 pg/ml) versus UC (41 pg/ml) (p = 0.0001). In patients with CD, there was a negative correlation between 1,25(OH) 2 D levels and lumbar BMD (r = 20.301, p = 0.005) independent of therapeutic glucocorticoid use. 1,25(OH) 2 D levels also correlated with CD activity. Lastly, immunohistochemistry and RT-PCR demonstrated increased expression of intestinal 1a-hydroxylase in patients with CD.Conclusions: These data demonstrate that elevated 1,25(OH) 2 D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.A serious and silent complication of inflammatory bowel disease (IBD) is the development of osteoporosis. [1][2][3][4] Estimates of osteopenia in IBD range from 31% to 59% 5 6 and osteoporosis from 5% to 41%. 1 7-10 Some studies have found that osteoporosis is more prevalent in patients with Crohn's disease (CD) than in those with ulcerative colitis (UC).1 4 11-13 Other studies however, have found similar degrees of bone loss in CD and UC.14 15 Lower bone mineral density (BMD) may be present at diagnosis, 13 16 suggesting factors other than medication may contribute to bone loss. The consequences of low BMD in patients with IBD include an increased risk of vertebral or hip fractures and their associated morbidity. [17][18][19][20] Indeed, recent data suggest that the risk of fractures in patients with CD may be underestimated. In a prospective study of CD patients, asymptomatic fractures were found in 14% of steroid free patients (including steroid naïve patients) and 15% of steroid dependent patients. 21Similar results were repor...

The safety and toxicity associated with the use of selective cyclooxygenase-2 (COX-2) inhibitors in patients with inflammatory bowel disease (IBD) has not been extensively studied. Thirty-three patients with IBD who were prescribed celecoxib or rofecoxib were identified from questionnaire during their clinic visit at the Cedars-Sinai IBD Center between 1999 and 2002. Twenty-six had Crohn's disease (CD), 6 had ulcerative colitis (UC), and 1 had indeterminate colitis (IC). Twenty-one received rofecoxib, 10 celecoxib, and 2 received both medications at different time points. Overall, 13 (39%) patients experienced disease exacerbation, 7 of which had received celecoxib and six rofecoxib. IBD exacerbation associated with COX-2 treatment did not correlate with age, disease activity, or use of immunosuppressive medications. All patients experienced flare-up of their underlying IBD within 6 weeks of initiating COX-2 therapy. Five of 13 (38%) patients had resolution of their symptoms after discontinuing the COX-2 inhibitor, but the remaining patients required additional medical therapy to control their disease. Six other patients (18%) experienced GI side effects not associated with their underlying IBD. Five developed abdominal pain, and one developed a duodenal ulcer and a circumferential ileo-colonic ulceration with GI bleeding. Treatment with COX-2 inhibitors is associated with a high incidence of exacerbation of the underlying IBD and GI-related complications.

SummaryBackgroundMeal tolerance tests are frequently used to study dynamic incretin and insulin responses in the postprandial state; however, the optimal meal that is best tolerated and suited for hormonal response following surgical and medical weight loss has yet to be determined.ObjectiveTo evaluate the tolerability and effectiveness of different test meals in inducing detectable changes in markers of glucose metabolism in individuals who have undergone a weight loss intervention.MethodsSix individuals who underwent surgical or medical weight loss (two Roux‐en‐Y gastric bypass, two sleeve gastrectomy and two medical weight loss) each completed three meal tolerance tests using liquid‐mixed, solid‐mixed and high‐fat test meals. The tolerability of each test meal, as determined by the total amount consumed and palatability, as well as fasting and meal‐stimulated glucagon‐like peptide, glucose‐dependent insulinotropic polypeptide, insulin and glucose were measured.ResultsAmong the six individuals, the liquid‐mixed meal was better and more uniformly tolerated with a median meal completion rate of 99%. Among the four bariatric surgical patients, liquid‐mixed meal stimulated on average a higher glucagon‐like peptide (percent difference: 83.7, 89), insulin secretion (percent difference: 155.1, 158.7) and glucose‐dependent insulinotropic polypeptide (percent difference: 113.5, 34.3) compared with solid‐mixed and high‐fat meals.ConclusionsThe liquid‐mixed meal was better tolerated with higher incretin and insulin response compared with the high‐fat and solid‐mixed meals and is best suited for the evaluation of stimulated glucose homeostasis.

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