Short Cyclic Regimen With Parathyroid Hormone (PTH) Results in Prolonged Anabolic Effect Relative to Continuous Treatment Followed by Discontinuation in Ovariectomized Rats

作者全名："Tseng, Wei-Ju; Lee, Wonsae; Zhao, Hongbo; Liu, Yang; Wang, Wenzheng; de Bakker, Chantal Mj; Li, Yihan; Osuna, Carlos; Tong, Wei; Wang, Luqiang; Ma, Xiaoyuan; Qin, Ling; Liu, X. Sherry"

作者地址："[Tseng, Wei-Ju; Lee, Wonsae; Zhao, Hongbo; Liu, Yang; Wang, Wenzheng; de Bakker, Chantal Mj; Li, Yihan; Osuna, Carlos; Tong, Wei; Wang, Luqiang; Ma, Xiaoyuan; Qin, Ling; Liu, X. Sherry] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA; [Liu, Yang] Chongqing Med Univ, Dept Orthodont, Stomatol Hosp, Chongqing, Peoples R China; [Wang, Wenzheng; Tong, Wei] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthopaed, Wuhan, Peoples R China; [de Bakker, Chantal Mj] Univ Calgary, Cumming Sch Med, McCaig Inst Bone & Joint Hlth, Dept Radiol, Calgary, AB, Canada; [Wang, Luqiang] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Orthopaed, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China; [Ma, Xiaoyuan] Shandong Univ, Qilu Hosp, Dept Orthopaed, Jinan, Peoples R China"

通信作者："Liu, ER (通讯作者)，Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, 371 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA."

来源：JOURNAL OF BONE AND MINERAL RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000744759000001

JCR分区：Q1

影响因子：6.2

年份：2022

卷号：37

期号：4

开始页：616

结束页：628

文献类型：Article

关键词：PARATHYROID HORMONE; PTH TREATMENT DISCONTINUATION; BONE MICROARCHITECTURE; BONE MECHANICS; BONE CELL ACTIVITIES; CYCLIC TREATMENT REGIMEN

摘要："Despite the potent effect of intermittent parathyroid hormone (PTH) treatment on promoting new bone formation, bone mineral density (BMD) rapidly decreases upon discontinuation of PTH administration. To uncover the mechanisms behind this adverse phenomenon, we investigated the immediate responses in bone microstructure and bone cell activities to PTH treatment withdrawal and the associated long-term consequences. Unexpectedly, intact female and estrogen-deficient female rats had distinct responses to the discontinuation of PTH treatment. Significant tibial bone loss and bone microarchitecture deterioration occurred in estrogen-deficient rats, with the treatment benefits of PTH completely lost 9 weeks after discontinuation. In contrast, no adverse effect was observed in intact rats, with sustained treatment benefit 9 weeks after discontinuation. Intriguingly, there is an extended anabolic period during the first week of treatment withdrawal in estrogen-deficient rats, during which no significant change occurred in the number of osteoclasts, whereas the number of osteoblasts remained elevated compared with vehicle-treated rats. However, increases in number of osteoclasts and decreases in number of osteoblasts occurred 2 weeks after discontinuation of PTH treatment, leading to significant reduction in bone mass and bone microarchitecture. To leverage the extended anabolic period upon early withdrawal from PTH, a cyclic administration regimen with repeated cycles of on and off PTH treatment was explored. We demonstrated that the cyclic treatment regimen efficiently alleviated the PTH withdrawal-induced bone loss, improved bone mass, bone microarchitecture, and whole-bone mechanical properties, and extended the treatment duration. (c) 2021 American Society for Bone and Mineral Research (ASBMR)."

基金机构："Penn Center for Musculoskeletal Diseases (PCMD) [NIH/NIAMS P30-AR069619, NIH/NIAMS K01-AR066743]; National Science Foundation (NSF) [1661858]"

基金资助正文："Research reported in this publication was supported by the Penn Center for Musculoskeletal Diseases (PCMD) NIH/NIAMS P30-AR069619, NIH/NIAMS K01-AR066743 (to XSL) and National Science Foundation (NSF) Award #1661858 (to XSL)."