Effects of cyclic vs. daily treatment with human parathyroid hormone (1-34) on murine bone structure and cellular activity
Effects of cyclic vs. daily treatment with human parathyroid hormone (1-34) on murine bone structure and cellular activity
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DOI：
10.1016/j.bone.2006.09.010
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发表时间：
2007-02-01
期刊：
影响因子：
4.1
通讯作者：
Dempster, David W.
中科院分区：
文献类型：
--
作者：
Iida-Klein, Akiko;Lu, Shi Shou;Dempster, David W.
之前..我们通过比较 hPTH(1-34) 的周期给药与每日给药，证明人甲状旁腺激素 (1-34) 片段 (hPTH(1-34)) 增加的骨强度与其对小鼠股骨 BMD 和皮质骨结构的影响成比例。第 7 周时，循环疗法和每日疗法均类似地增加了椎骨 BMD。在这里，我们通过静态和动态组织形态计量学检查了每日和循环 PTH 方案对骨结构和细胞活性的影响。20 周龄的完整雌性 C57BL/J6 小鼠接受以下方案治疗（每组 n = 7）：每天注射载体，持续 7 周[对照]；每日注射 hPTH(1-34)（40 μg/kg/天），持续 7 周[每日 PTH]；每天注射 hPTH(1-34)（40 μg/kg/天）和媒介物，每周交替注射，持续 7 周[循环 PTH]。在安乐死前第9天和第10天以及第2天和第3天，皮下注射钙黄绿素（10 mg/kg）。研究结束时，将腰椎 1-3 和左侧股骨切除、清洁并进行组织形态测定。在腰椎中，每日和循环 PTH 方案显着增加了松质骨体积（BV/TV）、小梁数量、小梁破骨细胞和成骨细胞周长、小梁矿物质沉积率（MAR）和 与对照组相比，骨形成率 (BFR) 以及骨膜 MAR 和 BFR，两个 PTH 治疗组之间没有显着差异。在两个 PTH 治疗组中都观察到小梁隧道增加。两种方案都倾向于增加椎体皮质骨形成参数，骨膜部位的影响比骨内膜部位的影响更明显，导致皮质宽度显着增加。在股骨中，周期性 PTH 对 BV/TV、小梁宽度和数量、小梁和皮质内成骨细胞和破骨细胞周长、皮质宽度以及小梁和骨膜 BFR 的影响不如每日 PTH 显着。在改善小鼠椎骨的松质骨和皮质骨微结构以及细胞活性方面，循环 PTH 方案与每日方案一样有效。 (c) 2006 Elsevier Inc. 保留所有权利。
Previously.. we demonstrated that the human parathyroid hormone (1-34) fragment (hPTH(1-34)) increased bone strength in proportion to its effects on BMD and cortical bone structure in the murine femur by comparing cyclic vs. daily administration of hPTH(1-34). Both cyclic and daily regimens increased vertebral BMD similarly at 7 weeks. Here, we have examined the effects of daily and cyclic PTH regimens on bone structure and cellular activity by static and dynamic histomorphometry.Twenty-week-old, intact female C57BL/J6 mice were treated with the following regimens (n=7 for each group): daily injection with vehicle for 7 weeks [control]; daily injection with hPTH(1-34) (40 mu g/kg/day) for 7 weeks [daily PTH]; and daily injection with hPTH(1-34) (40 mu g/kg/day) and vehicle alternating weekly for 7 weeks [cyclic PTH]. At days 9 and 10, and 2 and 3 prior to euthanasia, calcein (10 mg/kg) was injected subcutaneously. At the end of study, the lumbar vertebrae 1-3 and the left femora were excised, cleaned, and processed for histomorphometry.In the lumbar vertebrae, daily and cyclic PTH regimens significantly increased cancellous bone volume (BV/TV), trabecular number, trabecular osteoclast and osteoblast perimeters, trabecular mineral apposition rate (MAR) and bone formation rate (BFR), and periosteal MAR and BFR compared to control, with no significant difference between the two PTH-treated groups. Increased trabecular tunneling was observed in both PTH-treated groups. Both regimens tended to increase vertebral cortical bone formation parameters with the effects at the periosteum site being more marked than those at the endosteum site, resulting in a significant increase in cortical width. In the femur, the effects of cyclic PTH on BV/TV, trabecular width and number, trabecular and endocortical osteoblast and osteoclast perimeters, cortical width, and trabecular and periosteal BFR were less marked than those of daily PTH. A cyclic PTH regimen was as effective as a daily regimen in improving cancellous and cortical bone microarchitecture and cellular activity in the murine vertebra. (c) 2006 Elsevier Inc. All rights reserved.