Action And Mechanism Of BSNXD And DHEA In Preventing And Curing Postmenopausal Osteoporosis

Part I Action of BSNXD and DHEA on mice of PMOPObjective To investigate the effect of Bu-shen-ning-xin decoction (BSNXD) and dehydroepiandrosterone (DHEA) on postmenopausal osteoporosis (PMOP).Methods Female BALB/c mice (8-9 months age) were divided randomly into six groups containing ten mice per group. Mice of group 1 were left intact and served as a normal control group (NC group), mice of group 2 were operated without lesion of ovary (Sham operation group). Mice of groups 3~6 were ovariectbmized and, after a 7-day delay to allow for foundation of osteoporosis, were afforded with the same volume of Chinese traditional medicine (BSNXD group), dehydroepiandrosterone (DHEA group), 17p-estradiol (E2 group) and saline (Saline group), respectively. The skeleton, blood and uterus of each group were collected after 12 weeks of treatment. The uteri were weighed and analyzed histomorphometrically for differences. The level of IL-4/IFN-r, DHEA and DHEA-S in serum was detected by ELISA or EIA. The excised vertebra (L3-4) and left femurs were measured for the bone mineral density (BMD) by double energy x ray absorption (DEXA), the right femurs were measured for norphometry, the left tibia were analyzed for osteoblastic apoptosis. The semi-quantitative RT-PCR was performed to compare the mRNA level of osteoprotegerin (OPG) from tibia and ERa/p from uterus. The osteoblasts were isolated from calvaria and cultured for analyzing the cell proliferation. Both bone and uterus from every group were processed for the activity of aromatase.Results The level of BMD and area of bone trabecula of BSNXD group and DHEA group were higher than that of Saline group (P < 0.05 and P < 0.01, respectively). The level of IFN-r, DHEA and DHEA-S in BSNXD group and DHEA group were improved significantly, the IL-4 level was reduced comparing to that of Saline group (P < 0.05 and P < 0.01, respectively). In BSNXD group,moreover, the level of DHEA was positively related to that of IFN-r (P < 0.01), negatively related to that of IL-4 (P < 0.05). The weight of uterus and the ratio of uterus to body of BSNXD group and DHEA group were dominantly lower than that of E2 group (P < 0.01), the same to that of Saline group. More potent viability and less apoptosis of osteoblasts were seen in bone of BSNXD and DHEA group. BSNXD could improve the aromatase activity not of uterus but of bone. The level of OPG mRNA in bone, ERa and ERB mRNA in uterus from BSNXD and DHEA group were all higher than that from Saline group.Conclusions BSNXD could improve the level of DHEA (-s) in blood and enhance the aromatase activity in bone. Both BSNXD and DHEA could prevent and cure the PMOP with little side-effect on uterus. The mechanism of BSNXD for PMOP was related to that enhancing the osteoblastic viability and aromatase activity of bone, regulating the bias of Th1/Th2, improving the expression of OPG which could inhibit the activity of osteoclasts.