Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing
Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing
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DOI：
10.1002/jor.22525
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发表时间：
2014-03-01
影响因子：
2.8
通讯作者：
Aspenberg, Per
中科院分区：
文献类型：
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作者：
Agholme, Fredrik;Macias, Brandon;Aspenberg, Per
我们比较了硬化素抗体和临床相关剂量的甲状旁腺激素(PTH)在大鼠干骺端骨愈合模型中的效果。将钢质或聚甲基丙烯酸甲酯(PMMA)螺钉植入幼年雄性大鼠双侧胫骨近端。在4周内，动物接受磷酸盐缓冲盐水(对照组)、硬化素抗体(25 mg/kg，每周两次)或甲状旁腺素(5微克/公斤，每天)注射。然后通过力学测试和X射线显微断层扫描(MU CT)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，还对其他未受创伤的骨骼部位和血清生物标志物进行了评估。治疗4周后，甲状旁腺激素组的螺钉拔出力较对照组增加48%(p=0.03)，而抗体的作用不明显。相反，在PTH没有显著影响的情况下，抗体增加了股骨皮质和椎体的强度。MU CT显示抗体仅有轻微变化，且主要位于皮质部位，具有统计学意义。结果提示，较低剂量的甲状旁腺素可特异性地刺激干骺端修复(螺钉固定)，而硬化素抗体具有广泛的作用，主要作用于皮质骨，对干骺端愈合的影响较小。(C)2013年骨科研究会。由Wiley期刊公司出版，J Orthop Res 32：471-476,2014。
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 (25mg/kg, twice weekly) or PTH (5 mu g/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mu CT). 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. mu CT 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. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:471-476, 2014.