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在接受两剂量特立帕肽治疗18个月或治疗12个月后停药6个月的去卵巢猴动物模型中的骨质量。

Bone quality in an ovariectomized monkey animal model treated with two doses of teriparatide for either 18 months, or 12 months followed by withdrawal for 6 months.

作者信息

Paschalis E P, Gamsjaeger S, Burr D B

机构信息

Ludwig Boltzmann Institute for Osteology, at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.

Ludwig Boltzmann Institute for Osteology, at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.

出版信息

Bone. 2022 May;158:116366. doi: 10.1016/j.bone.2022.116366. Epub 2022 Feb 12.

Abstract

Previous studies of ovariectomized (OVX) monkeys, treated with recombinant human parathyroid hormone (PTH) (1-34) at 1 or 5 μg/kg/day for 18 months or for 12 months followed by 6 months withdrawal from treatment, displayed significant changes in geometry, histomorphometry, and bone quality, but without strict tissue age criteria, of the midshaft humerus. Since bone quality significantly depends on tissue age among other factors, the aim of the present study was to establish the bone-turnover independent effects of two doses of PTH, as well as the effects of treatment withdrawal on bone quality by measuring bone material composition at precisely known tissue ages ranging from osteoid, to mineralized tissue older than 373 days. Raman microspectroscopic analysis of bone tissue from the mid-shaft humerus of OVX monkeys demonstrated that the clinically relevant dose of PTH administered for 18 months reverses the effects of ovariectomy on bone quality when compared against SHAM. Both doses investigated in this study restore the mineralization regulation mechanisms to SHAM levels. The study also showed that the beneficial effects induced by 12 months of clinically relevant PTH therapy were sustained after six months of therapy withdrawal.

摘要

先前对去卵巢(OVX)猴子的研究中,给予重组人甲状旁腺激素(PTH)(1-34),剂量为1或5μg/kg/天,持续18个月,或持续12个月后停药6个月,结果显示,肱骨中段在几何形状、组织形态计量学和骨质量方面有显著变化,但缺乏严格的组织年龄标准。由于骨质量在其他因素中很大程度上取决于组织年龄,本研究的目的是通过在从类骨质到超过373天的矿化组织等精确已知的组织年龄下测量骨材料成分,来确定两种剂量的PTH对骨转换的独立影响,以及停药对骨质量的影响。对OVX猴子肱骨中段的骨组织进行拉曼光谱分析表明,与假手术组相比,给予临床相关剂量的PTH 18个月可逆转去卵巢对骨质量的影响。本研究中研究的两种剂量均将矿化调节机制恢复到假手术组水平。该研究还表明,临床相关的PTH治疗12个月所诱导的有益效果在停药6个月后仍持续存在。

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