Genetic factors determine extent of bone loss in inflammatory bowel disease.
OBJECTIVE
Although bone loss and osteoporosis are well-known long-term sequelae of inflammatory bowel disease (IBD), the risk factors for increased bone loss have not been identified. Balances of pro- and anti-inflammatory cytokines influence mechanisms of both chronic inflammation and bone resorption. The aim of this study was to identify genetic risk factors for rapid bone loss in IBD patients as a model of disease- and inflammation-associated bone loss.


METHODS
Multiple clinical parameters, biochemical markers of bone metabolism (vitamin D, parathyroid hormone, N-terminal telopeptide of type-I collagen, desoxypyridinoline, bone alkaline phosphatase), and bone mineral density were prospectively assessed in 83 IBD patients over 1.6+/-0.3 years. Eighty-six healthy bone marrow donors served as controls for allelotyping. The allele status of the interleukin 1 receptor antagonist (IL-1ra), IL-6, heat shock protein 70-2 (hsp 70-2), and heat shock protein 70-hom (hsp hom) genes was typed and correlated with clinical course of IBD and extent of bone loss.


RESULTS
The extent of bone loss was not correlated to clinical severity of disease or application of corticosteroids. Noncarriage of the 240-base pair allele of the IL-1ra gene and carriage of the 130-base pair allele of IL-6 were independently associated with increased bone loss. Genetic variations of the hsp genes were not associated with degree of bone loss. The combined presence of the named risk factors was significantly associated with increasing bone loss.


CONCLUSIONS
Genetic variations in the IL-6 and IL-1ra gene identify IBD patients at risk for increased bone loss.
Schulte
C M
CM
Division of Endocrinology, Department of Internal Medicine, University of Essen, Germany. claudia.schulte@uni-essen.de
Dignass
A U
AU
Goebell
H
H
Röher
H D
HD
Schulte
K M
KM
D015502:Absorptiometry, Photon; D000469:Alkaline Phosphatase / Q000097:blood; D000483:Alleles; D000596:Amino Acids / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D001862:Bone Resorption / Q000209:etiology / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000503:physiopathology; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D003424:Crohn Disease / Q000235:genetics / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000235:genetics; D018895:Microsatellite Repeats; D010024:Osteoporosis / Q000209:etiology / Q000235:genetics*; D010455:Peptides / Q000097:blood; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012795:Sialoglycoproteins / Q000235:genetics*
D000596:Amino Acids; D015415:Biomarkers; D024042:Collagen Type I; D018840:HSP70 Heat-Shock Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D010455:Peptides; D012795:Sialoglycoproteins; C052929:collagen type I trimeric cross-linked peptide; C036020:deoxypyridinoline; D003094:Collagen; D004247:DNA; D000469:Alkaline Phosphatase