The effect of genistein on the bone components in the femoral-metaphyseal and diaphyseal tissues of elderly female rats was investigated. 2. The oral administration of genistein (100 and 200 microg/kg body weight) for 3 days to rats caused a significant increase in alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the femoral-metaphyseal and diaphyseal tissues. A dose of 50 microg genistein/kg appreciably increased alkaline phosphatase activity and DNA content in the metaphyseal but not the diaphyseal tissues. 3. Alkaline phosphatase activity, DNA and calcium contents in the femoral-metaphyseal and diaphyseal tissues were significantly elevated by the oral administration of zinc sulfate (5.5 mg Zn/kg) for 3 days. The effect of zinc on increasing bone DNA and calcium contents was synergistically enhanced by the simultaneous administration of genistein (100 microg/kg). 4. The stimulatory effect of zinc sulfate (10(-5) M) or genistein (10(-5) M) on bone calcium content was also seen in a culture system using the femoral-metaphyseal and diaphyseal tissues in vitro. This effect was completely prevented by the presence of cycloheximide (10(-6) M). 5. The present findings suggest that genistein has an anabolic effect on bone components and that the effect is enhanced by zinc, owing to its stimulating effect on bone protein synthesis.
