Li J, Mori S, Mashiba T, Kaji Y, Taki M, Komatsubara S, Kawanishi J, Norimatsu H
Department of Orthopedic Surgery, Kagawa Medical University, Japan.
Bone. 1998 Nov;23(5):459-63. doi: 10.1016/s8756-3282(98)00123-9.
The purpose of this study is to determine whether short-term preadministration of bisphosphonates prevents bone loss in rat proximal tibial metaphysis when induced by hindlimb immobilization by bandage. Six-month-old female Sprague Dawley rats were injected with incadronate disodium (YM-175, 10 micrograms/kg) or vehicle, three times per week for 2 weeks (YM or V groups). Then, the left hindlimb was fixed to the abdomen with a bandage (V-B, YM-B groups), or only the abdomen was bandaged as control (V-SHM, YM-SHM groups), for 4 weeks. The animals were subsequently killed and left proximal tibiae were processed undecalcified for quantitative histomorphometric evaluation. Immobilization-induced cancellous bone loss resulted not only from increased percent eroded surface area but also from decreased percent labeling surface and bone formation rate in V-B compared with V-SHM animals. In contrast, preadministration of YM-175 decreased percent eroded surface significantly and prevented the loss of cancellous bone mass in YM-B compared with V-B animals. Cancellous bone mass was neither increased nor decreased by preadministration of YM-175 in YM-SHM animals. Our results suggest that preadministration of bisphosphonates is effective in prevention of bone loss at the tibial metaphysis when induced by hindlimb immobilization in rats.
本研究的目的是确定短期预先给予双膦酸盐是否能预防大鼠因绷带固定后肢而导致的胫骨近端干骺端骨质流失。6个月大的雌性Sprague Dawley大鼠每周注射三次伊班膦酸钠(YM - 175,10微克/千克)或赋形剂,共2周(YM组或V组)。然后,用绷带将左后肢固定于腹部(V - B、YM - B组),或仅包扎腹部作为对照(V - SHM、YM - SHM组),持续4周。随后处死动物,对左侧近端胫骨进行不脱钙处理,以进行定量组织形态计量学评估。与V - SHM组动物相比,固定诱导的松质骨流失不仅源于侵蚀表面积百分比增加,还源于V - B组标记表面积百分比和骨形成率降低。相比之下,与V - B组动物相比,预先给予YM - 175显著降低了侵蚀表面积百分比,并预防了YM - B组松质骨量的流失。在YM - SHM组动物中,预先给予YM - 175既未增加也未减少松质骨量。我们的结果表明,在大鼠中,预先给予双膦酸盐对预防后肢固定诱导的胫骨干骺端骨质流失有效。