Sost缺乏导致更大的骨血管孔隙度，但随着年龄的增长，骨细胞腔隙特性相似
{"_":" deficiency leads to greater bone vascular porosity, but similar osteocyte lacunar properties with increasing age.","i":["Sost"]}
摘要(中文译文)
硬化蛋白中和抗体是一种已获批的合成代谢药物，用于增加骨量。大量临床前研究考察了接受硬化蛋白中和抗体治疗的小鼠或缺乏硬化蛋白的小鼠（如基因敲除小鼠）的骨量和微结构变化。令人惊讶的是，尽管该治疗主要应用于老年个体，尚无临床前研究考察硬化蛋白缺乏随衰老变化的影响。因此，我们的主要目的是考察长期缺乏硬化蛋白对骨微结构的影响，包括不同年龄段骨细胞陷窝和骨血管孔隙特性的变化。我们的结果表明，硬化蛋白基因缺失导致小鼠整个生命周期中持续的骨形成，而野生型对照小鼠则经历骨成熟，随后出现与年龄相关的骨量下降。陷窝参数也因硬化蛋白缺失而受到影响，年轻小鼠的陷窝密度和体积发生改变，但这些差异在老年小鼠中不存在。我们的次要目的是考察短期硬化蛋白缺乏对成年雌性C57BL6J小鼠截骨术后编织骨和皮质骨骨微孔隙的影响。短期硬化蛋白抗体治疗未改变板层骨或新形成编织骨内的血管孔隙或陷窝孔隙，提示治疗时机和持续时间对疗效至关重要。总之，硬化蛋白敲除小鼠表现出持续的皮质骨增厚和显著的骨血管孔隙，尤其随着小鼠衰老而更为明显。随着硬化蛋白中和抗体在老龄人群中更广泛地长期使用，本研究有助于我们理解长期抑制硬化蛋白的效果。
Abstract
Sclerostin neutralizing antibody is an approved anabolic drug used to increase bone mass. Numerous preclinical studies examined bone mass and microstructural changes in mice receiving sclerostin neutralizing antibodies or mice lacking sclerostin, such as knock out mice. Surprisingly no preclinical studies examined the effect of sclerostin deficiency with aging, despite the treatment being used primarily in older individuals. Thus, our primary aim was to examine the effect of long-term deficiency on bone microstructure, including osteocyte lacunar and bone vascular porosity properties across ages. Our results show that deletion led to sustained bone formation across the mouse's lifespan, whereas wild-type control mice experienced bone maturation followed by age-related declines in bone volume. Lacunar parameters were also affected due to deletion, with altered lacunar density and volume in young mice, but these differences were not present in old mice. Our secondary aim was to examine the effect of short-term sclerostin deficiency on bone microporosity in woven and cortical bone after an osteotomy in adult female C57BL6J mice. Short term sclerostin antibody treatment did not alter vascular or lacunar porosity within lamellar or newly formed woven bone, suggesting that timing and duration are critical for therapeutic efficacy. In summary, KO mice exhibit sustained cortical thickening and pronounced bone vascular porosity, particularly as the mice aged. As sclerostin neutralizing antibody becomes more widely used in an aging population, for extended periods of time, this work helps us understand the effects of long-term inhibition.
如何引用
AMA
Taylor deVet, Anthony Helou, Sara Checa, Alexander Rack, Ina Kramer, Fabian Wilde, et al. {"_":" deficiency leads to greater bone vascular porosity, but similar osteocyte lacunar properties with increasing age.","i":["Sost"]}. Bone reports. 2026; doi:10.1016/j.bonr.2026.101937.
APA
Taylor deVet, Anthony Helou, Sara Checa, Alexander Rack, Ina Kramer, Fabian Wilde, et al (2026). {"_":" deficiency leads to greater bone vascular porosity, but similar osteocyte lacunar properties with increasing age.","i":["Sost"]}. Bone reports. https://doi.org/10.1016/j.bonr.2026.101937
GB/T 7714
Taylor deVet, Anthony Helou, Sara Checa, Alexander Rack, Ina Kramer, Fabian Wilde, et al. {"_":" deficiency leads to greater bone vascular porosity, but similar osteocyte lacunar properties with increasing age.","i":["Sost"]}[J]. Bone reports, 2026 doi:10.1016/j.bonr.2026.101937.
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