Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Bone. 2013 Mar;53(1):51-8. doi: 10.1016/j.bone.2012.11.037. Epub 2012 Dec 11.
PTH and strontium ranelate (SrR) have both been shown to reduce bone loss induced by immobilization. PTH is a potent bone anabolic agent, whereas SrR has been suggested to be an antiresorptive as well as a bone anabolic agent. The aim of the study was to investigate whether PTH, SrR, and PTH and SrR in combination could counteract immobilization-induced bone loss in a rat model. Immobilization was induced by injecting 4IU Botox (BTX) into the muscles of the right hind limb. Seventy-two female Wistar rats, 3-months-old, were divided into the following groups: Baseline, Controls, BTX, BTX+PTH, BTX+SrR, and BTX+PTH+SrR (n=12 in each group). PTH was given as injections (SC) at a dosage of 60μg/kg/d, and SrR as 900mg/kg/d in the diet. The experiment lasted for 4weeks. BTX resulted in lower trabecular bone formation rate (-68%) and periosteal bone formation rate (-91%), and a higher fraction of osteoclast-covered surfaces (+53%) compared with controls. This was accompanied by significantly lower trabecular bone volume fraction (-24%), trabecular thickness (-16%), and bone strength (-14% to -32% depending on site). PTH alone counteracted immobilization-induced losses in trabecular (4-fold increase vs. BTX) and periosteal (5-fold increase vs. BTX) bone formation rate, trabecular thickness (+25% vs. BTX) and femoral neck strength (+24% vs. BTX). In contrast, SrR did not influence BTX-induced loss of bone formation rate, trabecular bone volume fraction, trabecular thickness, or bone strength. Finally, no additive effect was found when PTH and SrR treatments were combined. In conclusion, PTH counteracted loss in bone architecture and bone strength in immobilized rats, whereas as no effect of SrR was found. Moreover, no additional effect was found by combining PTH with SrR.
甲状旁腺激素和锶雷奈酸（SrR）均已被证明可减少固定引起的骨质流失。甲状旁腺激素是一种有效的骨合成代谢药物，而 SrR 则被认为是一种抗吸收剂和骨合成代谢药物。本研究旨在探讨甲状旁腺激素、SrR 以及两者联合应用是否能在大鼠模型中对抗固定引起的骨丢失。通过向右侧后肢肌肉注射 4IU 肉毒杆菌毒素（BTX）来诱导固定。将 72 只 3 月龄雌性 Wistar 大鼠分为以下几组：基线组、对照组、BTX 组、BTX+PTH 组、BTX+SrR 组和 BTX+PTH+SrR 组（每组 12 只）。甲状旁腺激素以 60μg/kg/d 的剂量皮下注射给药，SrR 以 900mg/kg/d 的剂量添加至饮食中。实验持续 4 周。BTX 导致骨小梁形成率降低（-68%）和骨膜骨形成率降低（-91%），破骨细胞覆盖表面增加（+53%），与对照组相比。这伴随着骨小梁体积分数显著降低（-24%）、骨小梁厚度降低（-16%）和骨强度降低（取决于部位，降低 14%至 32%）。单独使用甲状旁腺激素可逆转固定引起的骨小梁（增加 4 倍，与 BTX 相比）和骨膜（增加 5 倍，与 BTX 相比）骨形成率、骨小梁厚度（增加 25%，与 BTX 相比）和股骨颈强度（增加 24%，与 BTX 相比）的丢失。相比之下，SrR 对 BTX 引起的骨形成率、骨小梁体积分数、骨小梁厚度或骨强度降低没有影响。最后，当联合使用甲状旁腺激素和 SrR 时，没有发现相加作用。总之，甲状旁腺激素逆转了固定大鼠的骨结构和骨强度丢失，而 SrR 则没有效果。此外，联合使用甲状旁腺激素和 SrR 没有额外的效果。
