Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.
Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.
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成年 Brtl/+ 成骨不全小鼠模型表现出对硬化素抗体治疗的合成代谢反应，骨量和强度增加。
DOI：
10.1007/s00198-014-2737-y
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发表时间：
2014-08
影响因子：
4
通讯作者：
Kozloff, K. M.
中科院分区：
文献类型：
--
作者：
Sinder, B. P.;White, L. E.;Salemi, J. D.;Ominsky, M. S.;Caird, M. S.;Marini, J. C.;Kozloff, K. M.
成骨不全症（Osteogenesis imperfecta， OI）是一种遗传性的与胶原蛋白相关的骨质发育不良，其特征是骨质脆性，骨折风险增加。尽管成骨不全骨折的风险在青春期前是最大的，成人成骨不全仍然有骨折的风险。抗吸收双膦酸盐通常用于治疗成人成骨不全，但疗效不一。持续改善整个骨骼骨量的新疗法可能会改善患者的预后。硬化蛋白中和抗体（Scl-Ab）是一种新的合成代谢疗法，在临床前研究中通过典型的wnt信号通路刺激骨形成显示出疗效。本研究的目的是评估成年6月龄Brtl/+ OI模型中的Scl-Ab，该模型含有典型的Col1a1上杂合的导致OI的Gly>Cys替换。6月龄WT和Brtl/+小鼠用Scl-Ab （25mg/kg， 2次/周）或Veh治疗5周。进行OCN和TRACP5b血清测定、动态组织形态测定、显微ct和力学测试。成年Brtl/+小鼠对Scl-Ab表现出强烈的合成代谢反应，血清骨钙素和骨形成率增加。这种合成代谢反应可改善股骨小梁和皮质骨量。力学测试显示Scl-Ab增加了Brtl/+股的刚度和强度。Scl-Ab在成骨不全成人Brtl/+模型中成功合成代谢。
Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Anti-resorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 mo old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly>Cys substitution on Col1a1. 6mo old WT and Brtl/+ mice were treated with Scl-Ab (25mg/kg, 2x/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.
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影响因子：
6.2
作者：
Ominsky, Michael S.;Vlasseros, Fay;Paszty, Chris
通讯作者：
Paszty, Chris
影响因子：
6.2
作者：
Chevrel, G;Schott, AM;Meunier, PJ
通讯作者：
Meunier, PJ
影响因子：
4.1
作者：
Meganck, Jeffrey A.;Kozloff, Kenneth M.;Thornton, Michael M.;Broski, Stephen M.;Goldstein, Steven A.
通讯作者：
Goldstein, Steven A.
影响因子：
6.2
作者：
Bivi, Nicoletta;Condon, Keith W.;Allen, Matthew R.;Farlow, Nathan;Passeri, Giovanni;Brun, Lucas R.;Rhee, Yumie;Bellido, Teresita;Plotkin, Lilian I.
通讯作者：
Plotkin, Lilian I.
特立帕肽治疗 I 型成骨不全症成人患者
影响因子：
4.2
作者：
Gatti, Davide;Rossini, Maurizio;Adami, Silvano
通讯作者：
Adami, Silvano