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肿瘤坏死因子-α单倍型与克罗恩病患者的骨矿物质密度密切相关。

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

作者信息

Lee Naomi, Fowler Elizabeth, Mason Susan, Lincoln Douglas, Taaffe Dennis R, Radford-Smith Graham

机构信息

School of Human Movement Studies, University of Queensland, Brisbane, Queensland, Australia.

出版信息

J Gastroenterol Hepatol. 2007 Jun;22(6):913-9. doi: 10.1111/j.1440-1746.2006.04679.x.

DOI:10.1111/j.1440-1746.2006.04679.x
PMID:17565648
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-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.

摘要

背景与目的

关于决定克罗恩病患者骨完整性和骨质流失的主要变量,目前尚未达成广泛共识。普通人群的双胞胎和家族研究表明,骨矿物质密度高达85%的变异是可遗传的。本研究旨在确定一大群克罗恩病患者中骨质流失的患病率以及骨质流失的分子和临床风险因素。

方法

这是一项横断面研究,研究对象为304名就诊于昆士兰州皇家布里斯班妇女医院炎症性肠病科的克罗恩病患者。骨密度检测结果通过直接测量和邮寄问卷来确定。骨矿物质密度数据与临床信息相结合,并与肿瘤坏死因子-α(TNF-α)、白细胞介素-10和NOD2/CARD15基因内的单核苷酸多态性进行关联分析。

结果

在304名克罗恩病患者中,101人曾接受过骨密度检测。45名患者(45%)被诊断为骨质减少,18名患者(18%)患有骨质疏松症。多因素分析后,TNF-α GT单倍型和-857 CC基因型均与总体骨矿物质密度密切相关(P值分别为0.003和0.002)。体重指数(P = 0.01)和女性患者既往肠道切除术(P = 0.03)可预测较高的脊柱骨密度,而体重指数(P = 0.003)和首次肠道切除术后的年限影响(P = 0.02)仍是股骨近端骨矿物质密度的独立预测因素。未观察到其他显著关联。

结论

本研究发现了TNF-α单倍型与克罗恩病患者骨矿物质密度之间新的保护关联。证实了体重指数和肠道切除术对该人群骨质流失的重要影响。

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