Allelic variation at the interleukin 1 beta gene is associated with decreased bone mass in patients with inflammatory bowel diseases

Background-Interleukin 1 beta (IL-1 beta) and its natural antagonist have b een implicated in the pathogenesis of inflammatory bowel disease (IBD). Bot h cytokines influence bone formation. IL-1 beta stimulates osteoclast activ ity while interleukin I receptor antagonist (IL-1ra) enhances bone formatio n. Aims-To determine whether the decreased bone mass in IBD is related to gene polymorphisms coding for IL-1 beta and IL-1ra, and thus identify patients with an increased risk. Methods-Bone mineral densitometry was performed at the femoral neck, lumbar spine, and the distal third of the radius in 75 IBD patients (34 men/41 wo men; 40.3 (1.6) years) and in 58 healthy controls (HC; 28 men/30 women; 32. 4 (1.2) years). Values were correlated with the TaqI and Aval gene polymorp hisms in the IL1B and the variable number of tandem repeats gene polymorphi sm in the IL1RN gene. Results-In IBD patients, but not in HC, carriers of allele 2 at the Aval ge ne polymorphism (IL1B-511*2) had significantly lower Z scores at the lumbar spine (-0.82 (0.13) v -0.29 (0.21) p = 0.03) and the femoral neck (-0.59 ( 0.14) v 0.15 (0.19); p = 0.003) than non-carriers.. These patients also had a higher risk for osteopenia or osteoporosis at the femoral neck (odds rat io 3.63 (95% confidence interval 0.95-13.93)). No association was found bet ween bone mass and the other gene polymorphisms analysed in IBD patients or in HC. Conclusions-Our results suggest that genetic variability may be a major det erminant of bone loss in IBD. Carriers of IL1B-511*2, who are hypersecretor s of IL-1 beta, have a higher risk of presenting with low bone mass in IBD. Screening for this allele may contribute to determination of the risk of b one loss at the time of disease onset.