Yao Wei, Cheng Zhiqiang, Koester Kurt J, Ager Joel W, Balooch Mehdi, Pham Aaron, Chefo Solomon, Busse Cheryl, Ritchie Robert O, Lane Nancy E
Department of Medicine, Aging Center, UC Davis Medical Center, Sacramento, CA 95817, USA.
Bone. 2007 Nov;41(5):804-12. doi: 10.1016/j.bone.2007.06.021. Epub 2007 Jul 10.
The treatment of osteoporotic women with bisphosphonates significantly reduces the incidence of bone fractures to a degree greater than can be explained by an increase in bone mineral density. In this study, 18-month Fischer 344 rats were ovariectomized and treated with a single dose of risedronate (intravenous, iv, 500 microg), zoledronic acid (iv, 100 microg) or continuous raloxifene (2 mg/kg, po, 3x/week). High resolution microCT was used to measure lumbar vertebral bone microarchitecture, the degree of bone mineralization (DBM) and the distribution of mineral. Small angle X-ray scattering was used to investigate mineral crystallinity. We found prolonged estrogen deficiency, reduced trabecular bone volume, and increased micro architecture bone compression strength lowered the degree of mineralization. Treatment with resorptive agents (bisphosphonates>raloxifene) prevented the loss of mineralization, trabecular bone volume and bone compression strength. Crystal size was not changed with OVX or with anti-resorptive treatments. In conclusion, in the aged estrogen-deficient rat model, single intravenous doses of two bisphosphonates were effective in maintaining the compressive bone strength for 180 days by reducing bone turnover, and maintaining the DBM to a greater degree than with raloxifene.
用双膦酸盐治疗骨质疏松症女性可显著降低骨折发生率,其降低程度大于骨矿物质密度增加所能解释的范围。在本研究中,对18月龄的Fischer 344大鼠进行卵巢切除,并给予单剂量的利塞膦酸盐(静脉注射,500微克)、唑来膦酸(静脉注射,100微克)或连续给予雷洛昔芬(2毫克/千克,口服,每周3次)。使用高分辨率显微CT测量腰椎骨微结构、骨矿化程度(DBM)和矿物质分布。使用小角X射线散射研究矿物质结晶度。我们发现,长期雌激素缺乏、小梁骨体积减少以及微结构骨抗压强度增加会降低矿化程度。用吸收剂(双膦酸盐>雷洛昔芬)治疗可防止矿化、小梁骨体积和骨抗压强度的丧失。晶体大小在卵巢切除或抗吸收治疗后未发生变化。总之,在老龄雌激素缺乏大鼠模型中,单次静脉注射两种双膦酸盐可通过减少骨转换有效维持180天的骨抗压强度,并比雷洛昔芬更大程度地维持DBM。