title: Tumor necrosis factor-alpha haplotype is strongly associated with bone mineral density in patients with Crohn's disease.
abstract: OBJECTIVE
  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-alpha (TNF-alpha), 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-alpha 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-alpha 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.
authors.affiliation: School of Human Movement Studies, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Naomi
authors.initials: N
authors.lastname: Lee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fowler
authors.forename: Susan
authors.initials: S
authors.lastname: Mason
authors.forename: Douglas
authors.initials: D
authors.lastname: Lincoln
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Taaffe
authors.forename: Graham
authors.initials: G
authors.lastname: Radford-Smith
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000704:Analysis of Variance; D015992:Body Mass Index; D015519:Bone Density; D003424:Crohn Disease / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008297:Male; D010024:Osteoporosis / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D015995:Prevalence; D011793:Queensland / Q000453:epidemiology; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha