BACKGROUND: Bone 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. METHODS: In this study, male rats were exposed to natural uranium in drinking water for a 9 month period, either at 40 mg l(-1) starting just after birth (post-natal model) or starting at 3 months of age (adult model). RESULTS: In the post-natal model at 40 mg l(-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 SIGNIFICANCE: This 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.
BACKGROUND: Bone 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. METHODS: In this study, male rats were exposed to natural uranium in drinking water for a 9 month period, either at 40 mg l(-1) starting just after birth (post-natal model) or starting at 3 months of age (adult model). RESULTS: In the post-natal model at 40 mg l(-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 SIGNIFICANCE: This 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.