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Normalization of Plasma 25-Hydroxy Vitamin D Is Associated with Reduced Risk of Surgery in Crohn’s Disease

Ananthakrishnan, Ashwin N. MD, MPH*,†; Cagan, Andrew; Gainer, Vivian S. MS; Cai, Tianxi PhD§; Cheng, Su-Chun ScD§; Savova, Guergana PhD||; Chen, Pei||; Szolovits, Peter PhD; Xia, Zongqi MD, PhD†,**; De Jager, Philip L. MD, PhD†,**; Shaw, Stanley Y. MD, PhD†,††; Churchill, Susanne PhD‡‡; Karlson, Elizabeth W. MD†,§§; Kohane, Isaac MD, PhD†,||,‡‡; Plenge, Robert M. MD, PhD†,§§; Murphy, Shawn N. MD, PhD†,‡,||||; Liao, Katherine P. MD, MPH†,§§

doi: 10.1097/MIB.0b013e3182902ad9
Original Clinical Articles

Background: Vitamin D may have an immunologic role in Crohn’s disease (CD) and ulcerative colitis (UC). Retrospective studies suggested a weak association between vitamin D status and disease activity but have significant limitations.

Methods: Using a multi-institution inflammatory bowel disease cohort, we identified all patients with CD and UC who had at least one measured plasma 25-hydroxy vitamin D (25(OH)D). Plasma 25(OH)D was considered sufficient at levels ≥30 ng/mL. Logistic regression models adjusting for potential confounders were used to identify impact of measured plasma 25(OH)D on subsequent risk of inflammatory bowel disease–related surgery or hospitalization. In a subset of patients where multiple measures of 25(OH)D were available, we examined impact of normalization of vitamin D status on study outcomes.

Results: Our study included 3217 patients (55% CD; mean age, 49 yr). The median lowest plasma 25(OH)D was 26 ng/mL (interquartile range, 17–35 ng/mL). In CD, on multivariable analysis, plasma 25(OH)D <20 ng/mL was associated with an increased risk of surgery (odds ratio, 1.76; 95% confidence interval, 1.24–2.51) and inflammatory bowel disease–related hospitalization (odds ratio, 2.07; 95% confidence interval, 1.59–2.68) compared with those with 25(OH)D ≥30 ng/mL. Similar estimates were also seen for UC. Furthermore, patients with CD who had initial levels <30 ng/mL but subsequently normalized their 25(OH)D had a reduced likelihood of surgery (odds ratio, 0.56; 95% confidence interval, 0.32–0.98) compared with those who remained deficient.

Conclusion: Low plasma 25(OH)D is associated with increased risk of surgery and hospitalizations in both CD and UC, and normalization of 25(OH)D status is associated with a reduction in the risk of CD-related surgery.

Article first published online 7 June 2013Supplemental Digital Content is Available in the Text.

*Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts;

Harvard Medical School, Boston, Massachusetts;

Research Computing, Partners HealthCare, Charlestown, Massachusetts;

§Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts;

||Children’s Hospital Boston, Boston, Massachusetts;

Massachusetts Institute of Technology, Cambridge, Massachusetts;

**Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts;

††Center for Systems Biology, Massachusetts General Hospital, Boston, Massachusetts;

‡‡i2b2 National Center for Biomedical Computing, Brigham and Women’s Hospital, Boston, Massachusetts;

§§Division of Rheumatology, Brigham and Women’s Hospital, Boston, Massachusetts; and

||||Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.

Reprints: Ashwin N. Ananthakrishnan, MD, MPH, Crohn’s and Colitis Center, Massachusetts General Hospital, 165 Cambridge Street, 9th Floor, Boston, MA 02114 (e-mail:

Supported by the National Institutes of Health (NIH, U54-LM008748). A. N. Ananthakrishnan is supported by funding from the US NIH (K23 DK097142). K. P. Liao is supported by the NIH (K08 AR060257) and the Katherine Swan Ginsburg Fund. R. M. Plenge is supported by grants from the US NIH (R01-AR056768, U01-GM092691, and R01-AR059648) and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. E. W. Karlson is supported by grants from the NIH (K24 AR052403, P60 AR047782, and R01 AR049880).

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received January 24, 2013

Accepted March 03, 2013

© Crohn's & Colitis Foundation of America, Inc.
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