Intermittent treatment with human parathyroid hormone (hPTH[1‐34]) increased trabecular bone volume but not connectivity in osteopenic rats
Intermittent treatment with human parathyroid hormone (hPTH[1‐34]) increased trabecular bone volume but not connectivity in osteopenic rats
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人甲状旁腺激素（hPTH[1-34]）的间歇治疗增加了骨质减少大鼠的骨小梁体积，但没有增加连接性
DOI：
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发表时间：
1995
影响因子：
6.2
通讯作者：
J. Kinney
中科院分区：
文献类型：
--
作者：
N. Lane;J. Thompson;G. Strewler;J. Kinney
先前的研究已经确定，间歇性甲状旁腺激素（PTH）治疗增加骨量和改善骨质疏松动物模型的生物力学强度。本研究的目的是通过X射线断层扫描方法（XTM），使用三维（3D）离体原位形态测量法，确定间歇性人甲状旁腺激素（hPTH[1-34]）治疗是否增加了已建立的骨质减少大鼠模型中的骨小梁体积和连接性。使用6个月龄退休Sprague道利种鼠。30只动物进行卵巢切除术（OVX），6只进行假手术。在OVX后第56天，处死PTH治疗前OVX组。将剩余OVX动物随机分为4组，每组6只动物，每7天注射5次溶剂或hPTH（1 - 34），剂量为4、40或400 μg/kg体重（BW）/天，持续28天，并在OVX后第84天处死。处死时，采集左侧近端胫骨进行XTM扫描。与用载体治疗的卵巢切除动物相比，中剂量和高剂量的hPTH（1 - 34）显著增加骨小梁体积和骨小梁厚度（p < 0.05）。在hPTH（1-34）40和400 μg/kg BW给药组中，骨小梁体积等于或大于假手术动物。OVX后第84天，与假手术组相比，小梁骨连接性降低近50%，并且任何hPTH（1 - 34）治疗均未增加。在骨质减少OVX大鼠中间歇性hPTH（1 - 34）治疗通过增厚现有骨小梁使骨小梁体积增加至对照水平或更高。在小梁连接丧失50%后开始治疗时，人PTH（1-34）未重建连接。我们假设，为了重建小梁连接，必须在小梁之间形成显著距离之前进行治疗干预。需要进一步的研究来反驳或证实我们的假设。
Previous studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1–34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three‐dimensional (3D) ex vivo in situ morphometry by X‐ray tomographic methods (XTM). Six‐month‐old retired Sprague‐Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post‐OVX, a prePTH‐treatment OVX group was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1‐34) at 4, 40, or 400 μg/kg of body weight (BW)/day and were sacrificed on day 84 post‐OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1‐34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p < 0.05). The trabecular bone volume was equal to or greater than the Sham‐operated animals in both hPTH(1–34) 40 and 400 μg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the Sham‐operated group at day 84 post‐OVX and did not increase with any of the hPTH(1‐34) treatments. Intermittent hPTH(1‐34) treatment in osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabecule. Human PTH(1–34) did not re‐establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re‐establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis.
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DOI：
10.1172/jci116483
发表时间：
1993-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
V. Shen;D. Dempster;R. Birchman;R. Xu;R. Lindsay
通讯作者：
V. Shen;D. Dempster;R. Birchman;R. Xu;R. Lindsay
影响因子：
4.8
作者：
T. Wronski;C. Yen;H. Qi;L. Dann
通讯作者：
T. Wronski;C. Yen;H. Qi;L. Dann
影响因子：
4.8
作者：
WRONSKI, TJ;CINTRON, M;DANN, LM
通讯作者：
DANN, LM
影响因子：
4.1
作者：
WRONSKI, TJ;DANN, LM;HORNER, SL
通讯作者：
HORNER, SL