Chronic exposure to natural uranium via drinking water affects bone in growing rats

Abstract

BackgroundBone is the main site of uranium accumulation after long term contamination. Several studies describe that at high dose of exposure, uranium impairs bone growth. Nevertheless little is known about the effects of chronic exposure at low doses of this radionuclide on bone, especially when ingested via drinking water, which is considered as the main exposure pathway for the public. MethodsIn this study, male rats were exposed to natural uranium in drinking water for a 9month period, either at 40mgl−1 starting just after birth (post-natal model) or starting at 3months of age (adult model). ResultsIn the post-natal model at 40mgl−1, three-dimensional microtomography analysis showed that NU decreased significantly the cortical bone diameter in NU-contaminated rats. Bone histomorphometry analysis also showed a significant increase of the osteoid thickness in trabecular bone of the femur of NU-contaminated rats. In addition, mRNA expression in trabecular bone of genes involved in osteoblast differentiation (OSX, BMP2, RUNX2), bone remodeling (TRAP, OCN), bone mineralization (BSP, OPN, DMP1), calcium transport (TRPV5) as well as vitamin D receptor (VDR) was significantly decreased in this model. In contrast, in the adult model, no morphometric, cellular and molecular changes were observed in bone. General significanceThis study showed for the first time that NU at this concentration has no detectable effect in adult bone while it significantly affects growing bone, which thus appears more sensitive to low dose contamination by this radionuclide.