Orthopaedics, Department of Clinical and Experimental Medicine, Linköping University, Linkoping, Sweden.
J Orthop Res. 2014 Mar;32(3):471-6. doi: 10.1002/jor.22525. Epub 2013 Nov 14.
We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25 mg/kg, twice weekly) or PTH (5 µg/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (µCT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p = 0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. µCT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing.
我们比较了硬骨素抗体与甲状旁腺激素（PTH）在用于治疗骺骨愈合的大鼠模型中的临床相关剂量的效果。将钢或聚甲基丙烯酸甲酯（PMMA）螺钉双侧插入年轻雄性大鼠的胫骨近端。在 4 周的时间里，动物接受磷酸盐缓冲盐水（对照）、硬骨素抗体（25mg/kg，每周两次）或 PTH（5µg/kg，每天）注射。然后通过机械测试和 X 射线微断层扫描（µCT）评估螺钉周围的愈合反应。为了区分对愈合的影响和对骨骼的一般影响，还评估了其他未受创伤的骨部位和血清生物标志物。治疗 4 周后，与对照组相比，PTH 使螺钉拔出力增加了 48%（p=0.03），而抗体则没有明显效果。相比之下，抗体增加了股骨皮质和椎体的强度，而 PTH 没有明显效果。µCT 仅显示出统计学上显著的抗体的轻微变化，主要在皮质部位。结果表明，相对低剂量的 PTH 特异性地刺激骺骨修复（螺钉固定），而硬骨素抗体具有广泛的作用，主要影响皮质骨，对骺骨愈合的影响较小。
