Effect of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) on endochondral ossification lesions induced by a lethal oral dose of uranyl nitrate

A 350 mg/kg body weight (b.w.) oral dose of uranyl nitrate (UN) caused 100% mortality in mice three days after administration, due to resulting kidney lesions. Mortality decreased 50% after an oral (o) or subcutaneous (sc) dose of bisodic etidronate (EHBP). Given that bone is also a target organ for uranium (U) in acute intoxication, the aim of this work was to study the effect of exposure to a lethal oral dose of UN on endochondral ossification, and the latter's response to EHBP treatment. One hundred male Balb/c mice weighing 25 g were assigned to one of ten groups. Group I served as control. Group II received a lethal 350 mg/kg b.w. oral dose of UN by gavage. Groups III, IV, VII, and VIII received an equal dose of UN immediately followed by a single 500 mg/kg oral dose of EHBP in groups III and VII and a single 50 mg/kg subcutaneous dose of EHBP in groups IV and VIII. Groups V and IX only received a single 500 mg/kg oral dose of EHBP, and groups VI and X received a single 50 mg/kg subcutaneous dose of EHBP. The animals in groups II, III, IV, V, and VI were sacrificed 48 h after the onset of the experiment, whereas those in groups VII, VIII, IX, and X were killed at 14 days. Histologic and histomorphometric studies were performed on the femurs to determine growth cartilage width, bone volume, and metaphyseal bone activity. Our results showed that all growth cartilage and metaphyseal bone histomorphometric parameters were significantly lower in animals exposed to UN at 48 h than in controls. EHPB administration was found to prevent this condition at 48 h reaching similar values to those of controls. Although histomorphometric values did not reach control values at 14 days, they were higher than those of animals exposed to UN at 48 h not treated with EHBP. It is noteworthy that these values also decreased in animals only receiving EHBP at 14 days. Our results show that EHBP effectively ameliorates the adverse effects of a lethal dose of UN on endochondral ossification.