Multigenerational exposure to genistein does not increase bone mineral density in rats

Genistein has been shown to prevent bone loss in ovariectomized adult rats. However, the effects of genistein on bone in developing and reproductively-intact rats have not been examined. A large multigenerational experiment involved feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) were collected from these animals at necropsy at 2 years of age and subjected to dual-energy x-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. Femurs were collected, and length, cross-sectional area, and cortical bone area were measured directly. Serum was collected for measurement of pyridinoline (PYD) and alkaline phosphatase (ALP). BMD was not affected by genistein in any phase of the experiment. In female rats treated continuously with genistein, BMC and bone area were reduced in the 500 ppm group compared to the 5 ppm group in the lumbar vertebrae, and in all treatment groups compared to control in the caudal vertebrae. In both males and females treated continuously, the cross-sectional area of the femur was reduced in rats treated with 500 ppm compared to those treated with 5 ppm. In female rats treated continuously, PYD was higher in the 100 and 500 ppm groups than in the 0 and 5 ppm groups. In conclusion, the effects of genistein on reproductively-intact rats were not dramatic. High dose of genistein throughout the lifespan resulted in decreased bone size, which may reduce the force required to break the bone.