Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats
Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats
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DOI：
10.1016/j.bone.2010.05.032
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发表时间：
2010-09-01
期刊：
影响因子：
4.1
通讯作者：
Jee, Webster S. S.
中科院分区：
文献类型：
--
作者：
Tian, XiaoYan;Setterberg, Rebecca B.;Jee, Webster S. S.
目前的报告描述了硬化素单抗(scl-AbIII)对成年雌性大鼠黄色(脂肪)骨髓骨骼部位的骨骼影响。10月龄雌性SD大鼠皮下注射赋形剂或Scl-AbIII，剂量分别为5 mg/kg和25 mg/kg，每周2次。注射4周。取黄(脂)髓部位的第5尾侧椎体(CVB)的松质骨进行不脱钙处理，进行定量骨组织形态计量学分析。与赋形剂对照组相比，两种剂量的Scl-AbIII均能显著增加CVB的骨形成参数、骨小梁体积和厚度，降低骨吸收参数。作为参考，我们还发现，两种剂量的scl-AbIII显著减少了骨吸收，增加了红(造血)骨髓部位的骨形成和骨体积，即第四腰椎(LVB)。结果显示，经Scl-AbIII处理后，LVB组的骨小梁体积增加的百分比略大于CVB组。综上所述，这些临床前研究结果表明，抗体介导的硬化素抑制在红色和黄色骨髓骨骼部位都具有显著的骨合成代谢作用。(C)2010 Elsevier Inc.保留所有权利。
The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague-Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites. (C) 2010 Elsevier Inc. All rights reserved.