Sclerostin Antibody Treatment Enhances Bone Strength but Does Not Prevent Growth Retardation in Young Mice Treated With Dexamethasone
Sclerostin Antibody Treatment Enhances Bone Strength but Does Not Prevent Growth Retardation in Young Mice Treated With Dexamethasone
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DOI：
10.1002/art.30385
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发表时间：
2011-08-01
影响因子：
--
通讯作者：
Robinson, M. K.
中科院分区：
文献类型：
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作者：
Marenzana, M.;Greenslade, K.;Robinson, M. K.
Objective.已知暴露于超生理水平的糖皮质激素药物对骨形成和线性生长具有不利影响。患有骨质疏松症的患者缺乏骨调节蛋白硬化素，具有过度的骨形成，并且通常身高高于平均水平。本研究旨在探讨抗硬化素单克隆抗体（Scl-AbI）对地塞米松（DEX）染毒小鼠的影响。在2项独立研究中，用DEX（或溶剂对照）和Scl-AbI抗体（或同种型匹配的对照抗体[Ctrl-Ab]）同时给药幼龄小鼠。分析线性生长、骨体积和强度以及骨转换标志物水平。在DEX处理的小鼠中，Scl-AbI与对照处理（Ctrl-Ab）相比对线性生长没有显著影响。然而，在用DEX和Scl-ABI处理的小鼠中，注意到股骨干骺端处的骨小梁（骨体积/总体积+117%，与Ctrl-Ab处理的小鼠相比）和股骨骨干处的皮质骨的宽度和体积（分别为+24%和+20%，与Ctrl-Ab处理的小鼠相比）显著增加。Scl-AbI治疗还改善了DEX治疗小鼠股骨骨干处的机械强度（通过4点弯曲研究评估）（与Ctrl-Ab治疗小鼠相比，Scl-AbI治疗小鼠的最大负荷+60%，极限强度+47%）。在接受Scl-AbI的DEX治疗小鼠中未检测到骨钙素水平升高，尽管5 b型抗酒石酸酸性磷酸酶水平显著低于接受DEX和Ctrl-Ab的小鼠。Scl-AbI治疗不能阻止DEX对线性生长的有害影响，但抗体确实增加了皮质骨和小梁骨，并改善了DEX治疗小鼠的骨机械性能。
Objective. Exposure to supraphysiologic levels of glucocorticoid drugs is known to have detrimental effects on bone formation and linear growth. Patients with sclerosteosis lack the bone regulatory protein sclerostin, have excessive bone formation, and are typically above average in height. This study was undertaken to characterize the effects of a monoclonal antibody to sclerostin (Scl-AbI) in mice exposed to dexamethasone (DEX).Methods. Young mice were concomitantly treated with DEX (or vehicle control) and Scl-AbI antibody (or isotype-matched control antibody [Ctrl-Ab]) in 2 independent studies. Linear growth, the volume and strength of the bones, and the levels of bone turnover markers were analyzed.Results. In DEX-treated mice, Scl-AbI had no significant effect on linear growth when compared to control treatment (Ctrl-Ab). However, in mice treated with DEX and Scl-ABI, a significant increase in trabecular bone at the femoral metaphysis (bone volume/total volume +117% versus Ctrl-Ab-treated mice) and in the width and volume of the cortical bone at the femoral diaphysis (+24% and +20%, respectively, versus Ctrl-Ab-treated mice) was noted. Scl-AbI treatment also improved mechanical strength (as assessed by 4-point bending studies) at the femoral diaphysis in DEX-treated mice (maximum load +60% and ultimate strength +47% in Scl-AbI-treated mice versus Ctrl-Ab-treated mice). Elevated osteocalcin levels were not detected in DEX-treated mice that received Scl-AbI, although levels of type 5b tartrate-resistant acid phosphatase were significantly lower than those observed in mice receiving DEX and Ctrl-Ab.Conclusion. Scl-AbI treatment does not prevent the detrimental effects of DEX on linear growth, but the antibody does increase both cortical and trabecular bone and improves bone mechanical properties in DEX-treated mice.