INFLAMMATORY BOWEL DISEASE

Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density

M T Abreu¹, V Kantorovich², E A Vasiliauskas¹, U Gruntmanis², R Matuk², K Daigle², S Chen², D Zehnder³, Y-C Lin⁴, H Yang⁴, M Hewison³, J S Adams²

¹ Division of Gastroenterology, Inflammatory Bowel Disease Center, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
² Department of Medicine, Division of Endocrinology, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
³ Division of Medical Sciences, University of Birmingham, Birmingham, UK
⁴ Department of Pediatrics, Division of Medical Genetics, Steven Spielberg Pediatric Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Correspondence to:
Correspondence to:
Dr M T Abreu
Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8631 West 3rd St, Suite 245E, Los Angeles, CA 90048, USA; Maria.Abreu{at}cshs.org

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)₂D). We further hypothesised that this was secondary to increased synthesis of 1,25(OH)₂D by inflammatory cells in the intestine. The aim of this study was to examine the relationship between 1,25(OH)₂D 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 1-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)₂D (>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)₂D 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)₂D levels and lumbar BMD (r = –0.301, p = 0.005) independent of therapeutic glucocorticoid use. 1,25(OH)₂D levels also correlated with CD activity. Lastly, immunohistochemistry and RT-PCR demonstrated increased expression of intestinal 1-hydroxylase in patients with CD.

Conclusions: These data demonstrate that elevated 1,25(OH)₂D 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.

Abbreviations: IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease; BMD, bone mineral density; 25(OH)D, 25-hydroxyvitamin D; 1, 25(OH)₂D, 1,25-dihydroxyvitamin D; PTH, parathyroid hormone; iPTH, immunoreactive parathyroid hormone; DXA, dual energy x ray absorptiometry; PCR, polymerase chain reaction; VDR, vitamin D receptor; mHBS, modified Harvey-Bradshaw

Keywords: vitamin D; inflammatory bowel disease; Crohn’s disease; bone mineral density; osteoporosis

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