Inhibition of Sclerostin by Monoclonal Antibody Increases Bone Formation, Bone Mass, and Bone Strength in Aged Male Rats
Inhibition of Sclerostin by Monoclonal Antibody Increases Bone Formation, Bone Mass, and Bone Strength in Aged Male Rats
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DOI：
10.1002/jbmr.182
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发表时间：
2010-12-01
影响因子：
6.2
通讯作者：
Ke, Hua Zhu
中科院分区：
文献类型：
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作者：
Li, Xiaodong;Warmington, Kelly S.;Ke, Hua Zhu
本研究的目的是评估通过用sclerostin抗体处理的sclerostin抑制作用（Scl-Abll）对老年人骨形成、骨量和骨强度的影响，性腺完整的雄性大鼠模型16个月大的雄性Sprague-Dawley大鼠每周两次皮下注射赋形剂或5或25 mg/kg的Scl-Abll，持续5周（9-10只/组）体内双能X线骨密度仪（DXA）分析显示腰椎骨密度明显增加（L-1至L-5）和长骨在治疗后3周和5周，与基线或载体对照相比，5和25 mg/kg Scl-Abll治疗组中的股骨和胫骨（股骨和胫骨）分析表明，与载体对照相比，在两个Scl-Abll剂量组中，在第五腰椎椎体（L-5）、股骨骨干（FD）和股骨颈（FN）处的骨小梁和皮质结构得到改善。增加的皮质和骨小梁骨量与L5、FD、高剂量组的FN和骨形成参数（即，矿化表面、矿物质沉积率和骨形成率）在胫骨近端干骺端和胫骨干的骨小梁、骨膜，和皮质内表面。这些结果表明，通过用硬化蛋白抗体处理的硬化蛋白抑制增加了骨形成，骨质量，和骨强度，此外，表明硬化素的药理学抑制可能代表老年男性低骨量的有希望的合成代谢疗法（C）2010年美国骨与矿物质研究学会
The purpose of this study was to evaluate the effects of sclerostin inhibition by treatment with a sclerostin antibody (Scl-Abll) on bone formation, bone mass, and bone strength in an aged, gonad-intact male rat model Sixteen-month-old male Sprague-Dawley rats were injected subcutaneously with vehicle or Scl-Abll at 5 or 25 mg/kg twice per week for 5 weeks (9-10/group) In vivo dual-energy X-ray absorptiometry (DXA) analysis showed that there was a marked increase in areal bone mineral density of the lumbar vertebrae (L-1 to L-5) and long bones (femur and tibia) in both the 5 and 25 mg/kg Scl-Abll-treated groups compared with baseline or vehicle controls at 3 and 5 weeks after treatment Ex vivo micro-computed tomographic (mu CT) analysis demonstrated improved trabecular and cortical architecture at the fifth lumbar vertebral body (L-5), femoral diaphysis (FD), and femoral neck (FN) in both Scl-Abll dose groups compared with vehicle controls The increased cortical and trabecular bone mass was associated with a significantly higher maximal load of L5, FD, and FN in the high-dose group Bone-formation parameters (le, mineralizing surface, mineral apposition rate, and bone-formation rate) at the proximal tibial metaphysis and tibial shaft were markedly greater on trabecular, periosteal, and endocortical surfaces in both Scl-Abll dose groups compared with controls These results indicate that sclerostin inhibition by treatment with a sclerostin antibody increased bone formation, bone mass, and bone strength in aged male rats and, furthermore, suggest that pharmacologic inhibition of sclerostin may represent a promising anabolic therapy for low bone mass in aged men (C) 2010 American Society for Bone and Mineral Research