甲状旁腺激素（1-34）与唑来膦酸联合预防大鼠废用性骨质减少的相加作用。
Additive effect of PTH (1-34) and zoledronate in the prevention of disuse osteopenia in rats.
作者信息
Vegger Jens Bay, Nielsen Esben Sommer, Brüel Annemarie, Thomsen Jesper Skovhus
机构信息
Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark.
出版信息
Bone. 2014 Sep;66:287-95. doi: 10.1016/j.bone.2014.06.020. Epub 2014 Jun 24.
Immobilization is known to cause a rapid bone loss due to increased osteoclastic bone resorption and decreased osteoblastic bone formation. Zoledronate (Zln) is a potent anti-resorptive pharmaceutical, while intermittent PTH is a potent bone anabolic agent. The aim of the present study was to investigate whether PTH or Zln alone or in combination could prevent immobilization-induced osteopenia. Immobilization was achieved by injecting 4IU Botox (BTX) into the right hind limb musculature. Seventy-two 16-week-old female Wistar rats were randomized into 6 groups; baseline (Base), control (Ctrl), BTX, BTX+PTH, BTX+Zln, and BTX+PTH+Zln. PTH (1-34) (80μg/kg) was given 5days/week and Zln (100μg/kg) was given once at study start. The animals were killed after 4weeks of treatment. The bone properties were evaluated using DEXA, μCT, dynamic bone histomorphometry, and mechanical testing. BTX resulted in lower femoral trabecular bone volume fraction (BV/TV) (-25%, p<0.05), lower tibial trabecular bone formation rate (BFR/BS) (-29%, p<0.05), and lower bone strength (Fmax) at the distal femur (-19%, p<0.001) compared with Ctrl. BTX+PTH resulted in higher femoral BV/TV (+31%, p<0.05), higher tibial trabecular BFR/BS (+297%, p<0.05), and higher Fmax at the distal femur (+11%, p<0.05) compared with BTX. BTX+Zln resulted in higher femoral BV/TV (+36%, p<0.05), lower tibial trabecular BFR/BS (-93%, p<0.05), and higher Fmax at the distal femur (+10%, p<0.05) compared with BTX. BTX+PTH+Zln resulted in higher femoral BV/TV (+70%, p<0.001), higher tibial trabecular BFR/BS (+59%, p<0.05), and higher Fmax at the distal femur (+32%, p<0.001) compared with BTX. In conclusion, BTX-induced immobilization led to lower BV/TV, BFR/BS, and Fmax. In general, PTH or Zln alone prevented the BTX-induced osteopenia, whereas PTH and Zln given in combination not only prevented, but also increased BV/TV and BFR/BS, and maintained Fmax at the distal femoral metaphysis compared with Ctrl.
已知固定不动会因破骨细胞骨吸收增加和成骨细胞骨形成减少而导致快速的骨质流失。唑来膦酸盐（Zln）是一种强效的抗吸收药物，而间歇性甲状旁腺激素（PTH）是一种强效的骨合成代谢剂。本研究的目的是调查单独使用PTH或Zln或联合使用是否可以预防固定不动引起的骨质减少。通过向右侧后肢肌肉注射4IU肉毒杆菌毒素（BTX）来实现固定不动。将72只16周龄的雌性Wistar大鼠随机分为6组；基线组（Base）、对照组（Ctrl）、BTX组、BTX+PTH组、BTX+Zln组和BTX+PTH+Zln组。PTH（1-34）（80μg/kg）每周给药5天，Zln（100μg/kg）在研究开始时给药一次。治疗4周后处死动物。使用双能X线吸收法（DEXA）、显微计算机断层扫描（μCT）、动态骨组织形态计量学和力学测试来评估骨特性。与Ctrl组相比，BTX导致股骨小梁骨体积分数（BV/TV）降低（-25%，p<0.05），胫骨小梁骨形成率（BFR/BS）降低（-29%，p<0.05），股骨远端骨强度（Fmax）降低（-19%，p<0.001）。与BTX组相比，BTX+PTH导致股骨BV/TV升高（+31%，p<0.05），胫骨小梁BFR/BS升高（+297%，p<0.05），股骨远端Fmax升高（+11%，p<0.05）。与BTX组相比，BTX+Zln导致股骨BV/TV升高（+36%，p<0.05），胫骨小梁BFR/BS降低（-93%，p<0.05），股骨远端Fmax升高（+10%，p<0.05）。与BTX组相比，BTX+PTH+Zln导致股骨BV/TV升高（+70%，p<0.001），胫骨小梁BFR/BS升高（+59%，p<0.05），股骨远端Fmax升高（+32%，p<0.001）。总之，BTX诱导的固定不动导致BV/TV、BFR/BS和Fmax降低。一般来说，单独使用PTH或Zln可预防BTX诱导的骨质减少，而联合使用PTH和Zln不仅可预防，还可增加BV/TV和BFR/BS，并与Ctrl组相比维持股骨远端干骺端的Fmax。
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