Tumor necrosis factor-α haplotype is strongly associated with bone mineral density in patients with Crohn's disease

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Journal of Gastroenterology and Hepatology

Volume 22 Issue 6 Page 913Issue 6 - 919 - June 2007

To cite this article: Naomi Lee, Fowler, Mason, Lincoln, Dennis R Taaffe, Graham Radford- (2007) Tumor necrosis factor-α haplotype is strongly associated with bone mineral density in patients with Crohn's disease Journal of Gastroenterology and Hepatology 22 (6), 913–919. doi:10.1111/j.1440-1746.2006.04679.x

GASTROENTEROLOGY

Tumor necrosis factor-α haplotype is strongly associated with bone mineral density in patients with Crohn's disease

Naomi Lee,**School of Human Movement Studies, University of Queensland,

Fowler,Inflammatory Bowel Disease Research Unit, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Center, Queensland Institute of Medical Research,

Mason,Department of Gastroenterology, Royal Brisbane and Women's Hospital and

Lincoln,§§Cancer and Population Studies Group, Queensland Institute of Medical Research, Queensland, Australia Dennis R Taaffe**School of Human Movement Studies, University of Queensland, and Graham Radford-,Inflammatory Bowel Disease Research Unit, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Center, Queensland Institute of Medical Research, Department of Gastroenterology, Royal Brisbane and Women's Hospital and Dr Graham Radford-, Department of Gastroenterology, Level 9A, Ned Hanlon Building, Royal Brisbane and Women's Hospital, PO Herston, Qld 4029, Australia. Email: graham_radford-smith@...

*School of Human Movement Studies, University of Queensland, Inflammatory Bowel Disease Research Unit, Royal Brisbane and Women's Hospital Research Foundation Clinical Research Center, Queensland Institute of Medical Research, Department of Gastroenterology, Royal Brisbane and Women's Hospital and §Cancer and Population Studies Group, Queensland Institute of Medical Research, Queensland, Australia

Dr Graham Radford-, Department of Gastroenterology, Level 9A, Ned Hanlon Building, Royal Brisbane and Women's Hospital, PO Herston, Qld 4029, Australia. Email: graham_radford-smith@...

Abstract

Background and Aim: There is limited consensus on the major variables that determine bone integrity and bone loss in patients with Crohn's disease. Twin and family studies in the general population indicate that up to 85% of variance in bone mineral density is inherited. The aim was to determine the prevalence of bone loss and both molecular and clinical risk factors for bone loss in a large Crohn's disease population.

Methods: This was a cross-sectional study of 304 patients with Crohn's disease attending the Inflammatory Bowel Disease unit at Royal Brisbane and Women's Hospital, Queensland. The results of bone density testing were ascertained directly and by a mailed questionnaire. Bone mineral density data were combined with clinical information and correlated with single nucleotide polymorphisms within the tumor necrosis factor-α (TNF-α), interleukin-10, and NOD2/CARD15 genes.

Results: Of 304 Crohn's disease patients, 101 had undergone previous bone density testing. Forty-five patients (45%) had been diagnosed with osteopenia and 18 (18%) were osteoporotic. After multivariate analysis, both the TNF-α GT haplotype and the −857 CC genotype showed strong associations with bone mineral density overall (P = 0.003 and P = 0.002, respectively). Body mass index (P = 0.01) and previous bowel resection in female patients (P = 0.03) were predictive of a higher spine bone density, while body mass index (P = 0.003) and the effect of years since first bowel resection (P = 0.02) remained independent predictors of proximal femur bone mineral density. There were no other significant associations observed.

Conclusions: This study has identified a novel protective association between a TNF-α haplotype and bone mineral density in Crohn's disease. It confirms the important influence of body mass index and intestinal resection on bone loss in this population.