Ma Y F, Lin B Y, Jee W S, Lin C H, Chen Y Y, Ke H Z, Li X J
Division of Radiobiology, University of Utah School of Medicine, Salt Lake City, USA.
J Bone Miner Res. 1997 Feb;12(2):267-75. doi: 10.1359/jbmr.1997.12.2.267.
The objects of this study were (1) to determine the effects of risedronate (Ris) and prostaglandin E2 (PGE2) alone and in combination, on tibial diaphyses of older intact female rats; and (2) to observe the fate of any extra bone if formed after withdrawal of the treatment. Nine-month-old female Sprague-Dawley rats were treated with 6 mg of PGE2/kg/day, 1 or 5 micrograms of Ris/kg twice a week, or 6 mg of PGE2/kg/day plus 1 or 5 micrograms of Ris/kg twice a week for the first 60 days and followed by vehicle injections for another 60 days. Cross-sections of double fluorescent labeled, undecalcified tibial diaphyses proximal to the tibiofibular junction were processed for histomorphometry. We found that: (1) neither the 1 microgram nor the 5 micrograms of Ris treatment in the 60-day on/60-day off group showed any histomorphometric differences from age-related controls; (2) while the 60 days of PGE2 treatment added extra cortical bone (6%) on the tibial shaft (due to stimulation of periosteal, endocortical, and marrow trabecular bone formation), the new endocortical and most of the new marrow trabecular bone were lost when treatment was withdrawn; however, the new periosteal bone remained; (3) PGE2 with Ris added the same amount of new bone to tibial diaphysis as did PGE2 alone and upon withdrawal, new marrow trabecular bone was lost but new periosteal and endocortical bones were preserved in PGE2 + 1 microgram of Ris on/off group. In contrast, all the new bone was maintained in the PGE2 + 5 micrograms of Ris on/off group; (4) PGE2 + Ris cotreatment failed to block the increase in cortical bone porosity induced by PGE2; and (5) in the PGE2 alone and PGE2 + 1 microgram of Ris on/off groups bone turnover was higher than that in the PGE2 + 5 micrograms of Ris on/off group. These results indicate that on/off treatment with PGE2 and Ris is superior to PGE2 alone in that it forms the same amount of new bone during treatment, but preserves more cortical bone during withdrawal. Depression of bone resorption and turnover were the tissue mechanisms responsible for this protection.
(1)确定雷奈酸锶(Ris)和前列腺素E2(PGE2)单独及联合应用对老龄未切除卵巢雌性大鼠胫骨干的影响;(2)观察治疗停止后若形成额外骨组织的转归情况。对9月龄雌性斯普拉格-道利大鼠,在最初60天给予6 mg PGE2/kg/天、1或5 μg Ris/kg每周两次,或6 mg PGE2/kg/天加1或5 μg Ris/kg每周两次,随后60天注射赋形剂。对胫腓关节近端双荧光标记的未脱钙胫骨干横断面进行组织形态计量学分析。我们发现:(1)60天用药/60天停药组中,1 μg和5 μg Ris治疗组与年龄相关对照组相比,组织形态计量学上均无差异;(2)60天PGE2治疗增加了胫骨干皮质骨(6%)(由于刺激了骨膜、皮质内和骨髓小梁骨形成),治疗停止后,新的皮质内骨和大部分新的骨髓小梁骨丢失,但新的骨膜骨保留;(3)PGE2与Ris联合应用时,胫骨干新增骨量与单独应用PGE2时相同,停药后,PGE2 + 1 μg Ris用药/停药组新的骨髓小梁骨丢失,但新的骨膜骨和皮质内骨保留。相比之下,PGE2 + 5 μg Ris用药/停药组所有新骨均得以维持;(4)PGE2与Ris联合治疗未能阻止PGE2诱导的皮质骨孔隙率增加;(5)单独应用PGE2组和PGE2 + 1 μg Ris用药/停药组的骨转换高于PGE2 + 5 μg Ris用药/停药组。这些结果表明,PGE2与Ris序贯治疗优于单独应用PGE2,因为在治疗期间形成相同量的新骨,但在停药期间保留更多皮质骨。骨吸收和转换的抑制是这种保护作用的组织学机制。