PDF(Pubmed)
Abstract：
Abaloparatide is a peptide analog of parathyroid hormone-related protein (PTHrP 1-34) and was approved in 2017 as the second osteoanabolic peptide for treating osteoporosis. We previously showed that intermittent abaloparatide is equally as effective as PTH (1-34). This study was designed to compare the catabolic effects of PTH (1-34) and abaloparatide on bone in young female wild-type mice. Two-month-old C57Bl/6J female mice were continuously infused with human PTH (1-34) or abaloparatide at 80 μg/kg BW/day or vehicle for 2 weeks. At euthanasia, DEXA-PIXImus was performed to assess bone mineral density (BMD) in the whole body, femurs, tibiae, and vertebrae. Bone turnover marker levels were measured in sera, femurs were harvested for micro-computer tomography (μCT) analyses and histomorphometry, and tibiae were separated into cortical and trabecular fractions for gene expression analyses. Our results demonstrated that the infusion of abaloparatide resulted in a similar decrease in BMD as infused PTH (1-34) at all sites. μCT and histomorphometry analyses showed similar decreases in cortical bone thickness and BMD associated with an increase in bone turnover from the increased bone formation rate found by in vivo double labeling and serum P1NP and increased bone resorption as shown by osteoclast numbers and serum cross-linked C-telopeptide. Trabecular bone did not show major changes with either treatment. Osteoblastic gene expression analyses of trabecular and cortical bone revealed that infusion of PTH (1-34) or abaloparatide led to similar and different actions in genes of osteoblast differentiation and activity. As with intermittent and in vitro treatment, both infused PTH (1-34) and abaloparatide similarly regulated downstream genes of the PTHR1/SIK/HDAC4 pathway such as Sost and Mmp13 but differed for those of the PTHR1/SIK/CRTC pathway. Taken together, at the same dose, infused abaloparatide causes the same high bone turnover as infused PTH (1-34) with a net resorption in female wild-type mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
摘要：
Abaloparide是甲状旁腺激素相关蛋白（PTHrP1-34）的肽类似物，并于2017年被批准为治疗骨质疏松症的第二种骨合成代谢肽。我们先前表明间歇性阿巴罗帕拉肽与PTH同样有效(1-34)。本研究旨在比较PTH（1-34）和阿巴罗帕拉肽对年轻雌性野生型小鼠骨骼的分解代谢作用。两个月大的C57Bl/6J雌性小鼠连续输注人PTH(1-34)或80μg/kgBW/天的阿巴罗帕拉肽或载体2周。安乐死时，进行DEXA-PIXImus以评估全身的骨矿物质密度（BMD），股骨,胫骨,和椎骨。在血清中测量骨转换标志物水平，采集股骨进行微计算机断层扫描（μCT）分析和组织形态计量学，将胫骨和胫骨分离为皮质和小梁部分进行基因表达分析。我们的结果表明，在所有部位，输注阿帕拉肽导致BMD的降低与输注PTH（1-34）相似。μCT和组织形态计量学分析显示，皮质骨厚度和BMD的降低相似，与体内双重标记和血清P1NP发现的骨形成速率增加引起的骨转换增加有关，如破骨细胞数量和血清交联的C-端肽所示，骨吸收增加。骨小梁在两种治疗中均未显示出重大变化。小梁和皮质骨的成骨细胞基因表达分析表明，输注PTH（1-34）或abaloparatide导致成骨细胞分化和活性基因的相似和不同作用。与间歇和体外治疗一样，输注的PTH(1-34)和阿巴罗帕拉肽对PTHR1/SIK/HDAC4通路的下游基因如Sost和Mmp13的调节相似,但对PTHR1/SIK/CRTC通路的调节不同.一起来看,在相同的剂量下，输注的阿帕拉肽与输注的PTH（1-34）引起相同的高骨转换，在雌性野生型小鼠中具有净吸收。©2023作者。JBMRPlus由WileyPeriodicalsLLC代表美国骨骼和矿物研究学会出版。
