Die therapeutischen Effekte von Estradiol, Dihydrotestosteron, Genistein und Equol auf den osteoporotischen Knochen der orchidektomierten männlichen Sprague-Dawley-Ratte

Abstract

The importance of osteoporosis in men has long been underestimated, and studies of male osteoporosis were rarely performed. In the present study we used 150 orchidectomized Sprague Dawley rats to analyze the therapeutic effects of estradiol, dihydrotestosterone, and the isoflavones genistein and equol on the osteoporotic bone. Following a therapeutic strategy we started dietary administration of the substances after manifestation of osteoporosis 4 weeks after orchidectomy. The orchidectomized control group received soy-free chow only. To quantify osteoporosis and the therapeutic effects of the administrated substances we evaluated bone density of the proximal metaphysis of the tibia by quantitative computer tomography before orchidectomy and after 2, 3, and 8 weeks of treatment, respectively. Additionally, the biochemical markers for bone metabolism, i.e. CrossLaps and osteocalcin were determined in the serum. We found evidence for a significant reduction of bone density in all animals after orchidectomy and biochemical markers of bone metabolism were increased. The parameters of bone metabolism Osteocalcin and the CrossLaps were decreased by estradiol and the supply of estradiol had best effect on bone mineral density compared to the other substances. After 8 weeks of administration of estradiol cancellous density was significantly increased compared to the control group. Similarly, the cortical bone parameters were significantly higher compared to the control. There was less effect of dihydrotestosterone on the osteoporotic bone compared to estradiol. Parameters of bone metabolism were less inhibited by dihydrotestosterone than estradiol and no significant improvement in bone density by dihydrotestosterone could be identified compared to the control. Isoflavones genistein and equol inhibited increased bone metabolism after orchidectomy less than gonadal steroids and there was no significant difference to the control. Concerning bone density, there was no significant effect of genistein or equol. As a conclusion we could find estradiol to reduce increased bone metabolism and further loss of bone density after orchidectomy significantly. However neither treatment was able to restore lost bone density and there was no evidence for a therapeutic effect on bone structure of osteoporotic bone of the orchidectomized Sprague Dawley rat found. Thus, this result supports the importance of prevention of osteoporosis.