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每周特立帕肽治疗可通过改善去卵巢食蟹猴的皮质壳结构来增加椎体强度。

Weekly teriparatide treatment increases vertebral body strength by improving cortical shell architecture in ovariectomized cynomolgus monkeys.

机构信息

Department of Orthopedic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

Department of Orthopedic Surgery, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

出版信息

Bone. 2019 Apr;121:80-88. doi: 10.1016/j.bone.2019.01.006. Epub 2019 Jan 8.

Abstract

Weekly teriparatide treatment is reported to reduce the incidence of osteoporotic vertebral fractures. However, the effect of weekly teriparatide on cortical bone has not been clarified. This study aimed to examine the effects of weekly teriparatide treatment on bone mass, intracortical structure, and remodeling of the lumbar vertebral cortical shell and its relation to mechanical properties in ovariectomized cynomolgus monkeys. Female monkeys, aged 9 to 15 years, were divided into four groups: (1) SHAM group, (2) ovariectomized group (OVX group), (3) OVX with 1.2 μg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 μg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double-labeled with calcein, and lumbar vertebrae were analyzed with histomorphometry and compressive mechanical tests. Following ovariectomy, we found reductions in the anterior cortical shell area of the vertebrae and reductions in nearly all of the tested vertebral mechanical properties. Weekly teriparatide significantly preserved the anterior cortical shell area and the energy absorption capacity of the lumbar vertebrae in a dose-dependent manner. Multiple regression analyses indicated that improved mechanical properties were more associated with the increased anterior cortical shell area rather than the cancellous bone volume. The intracortical structure of the Haversian canals was also preserved following teriparatide treatment after ovariectomy. These findings suggest the importance of the cortical shell as a therapeutic target in the treatment of osteoporosis. Weekly teriparatide treatment increases the compressive mechanical strength of the lumbar vertebrae by thickening the anterior cortical shell.

摘要

每周特立帕肽治疗据报道可降低骨质疏松性椎体骨折的发生率。然而,每周特立帕肽对皮质骨的影响尚未阐明。本研究旨在研究每周特立帕肽治疗对去卵巢食蟹猴腰椎皮质壳骨量、皮质内结构和重塑的影响及其与机械性能的关系。9 至 15 岁的雌性猴子分为四组:(1)SHAM 组,(2)去卵巢组(OVX 组),(3)每周 1.2μg/kg 特立帕肽组(LOW 组),(4)每周 6.0μg/kg 特立帕肽组(HIGH 组)。18 个月后,所有动物均用 calcein 双标记,并用组织形态计量学和压缩力学试验分析腰椎。去卵巢后,我们发现椎体前皮质壳面积减少,几乎所有测试的椎体机械性能都降低。每周特立帕肽以剂量依赖性方式显著保留了腰椎前皮质壳面积和能量吸收能力。多元回归分析表明,机械性能的改善与前皮质壳面积的增加更相关,而不是松质骨体积的增加。去卵巢后特立帕肽治疗还保留了 Haversian 管的皮质内结构。这些发现表明皮质壳作为骨质疏松症治疗的治疗靶点的重要性。每周特立帕肽治疗通过增加前皮质壳的厚度来增加腰椎的压缩力学强度。

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