Skeletal microstructure and bone fragility in young patients with inflammatory bowel disease and their relation to inflammatory cytokines and chemokines
and aims: Inflammatory bowel diseases (IBD) appearing during childhood and adolescence may compromise peak bone mass acquisition because of the deleterious effects on the skeleton caused mainly by inflammation and malabsorption. The aim of the study was to determine if there was a correlation between the skeletal microstructure, inflammatory markers and bone fragility in IBD.
102 young subjects from the Swiss IBD cohort were studied. Areal bone mineral density (aBMD) at distal radius, hip and spine as well as morphometric vertebral fractures were assessed by DXA. Volumetric (v)BMD, trabecular and cortical bone microstructure at distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, volumetric BMD and microstructure were compared between IBD and healthy controls (n=389) matching (2:1) for age, sex, height and fracture history, and between fractured and nonfractured patients accounting for multiple confounders. In IBD patients we measured 16 cytokines (IL-1b, IL- 1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, TNFα, IFN γ) and 7 chemokines (MIP-1a, MIP-1b, IP-10, MIG/CXCL9, Eotaxin, MCP-1 and RANTES).
clinical fractures were reported by 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. Adjusted for age, sex and height, tibia trabecular (Tb)vBMD, thickness and distribution were significantly associated with fractures, while aBMD was not. After adjustment for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness remained associated with fractures. Compared to healthy controls, IBD subjects had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at distal radius and tibia, and these alterations were correlated with disease severity.
IBD patients with fracture had significantly lower levels of IP10 and MIP-1b compared with IBD patients without fractures. Conclusions These results indicate that patients with IBD have alterations in bone mass and microstructure related to fractures from a young age, which is associated with the level of distinct inflammatory markers.