Effects of Copper on Bone Component in the Femoral Tissues of Rats: Anabolic Effect of Zinc Is Weakened by Copper

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The effects of copper on biochemical components in the femoral-diaphyseal (cortical bone) and -metaphyseal (trabecullar bone) tissues of rats in vivo and in vitro were investigated. Rats were orally administered copper sulfate (50, 100, or 200 μg Cu/100 g body weight) once daily for 7 d. Calcium content in the diaphyseal and metaphyseal tissues was significantly decreased with the administration of copper (200 μg/100 g), while alkaline phosphatase activity in these tissues was not significantly changed by copper administration. The diaphyseal DNA content was significantly decreased with the administration of copper (50, 100, or 200 μg/100 g). Moreover, the femoral-diaphyseal and -metaphyseal tissues were cultured for 48 h in serum-free medium containing either vehicle or copper (10⁻⁷—10⁻⁴ M). Culture with copper (10⁻⁷—10⁻⁴ M) caused a significant decrease in alkaline phosphatase activity in the diaphyseal and metaphyseal tissues, while calcium and DNA contents in these tissues were not significantly changed. Culture with parathyroid hormone [PTH (1-34); 10⁻⁷ M], a bone-resorbing factor, caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. This decrease was completely inhibited in the presence of copper (10⁻⁶ or 10⁻⁵ M). Culture with zinc sulfate (10⁻⁴ M) caused a significant increase in calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. The effects of zinc (10⁻⁴ M) in increasing femoral calcium content and alkaline phosphatase activity were not seen in the presence of cycloheximide (10⁻⁶ M), an inhibitor of protein synthesis, suggesting that the effects of zinc are involved in newly synthesized protein components. The effects of zinc in increasing calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues were significantly weakened in the presence of copper (10⁻⁴ M). The inhibitory effects of copper were further enhanced in the presence of cycloheximide. This study demonstrates that supplementation with copper in adequate copper nutrition does not have anabolic effects on bone components in vivo and in vitro and that copper weakens the anabolic effects of zinc in vitro.