Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice
Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice
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DOI：
10.1016/j.bone.2010.04.587
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发表时间：
2010-08-01
期刊：
影响因子：
4.1
通讯作者：
Boyd, Steven K.
中科院分区：
文献类型：
--
作者：
Kristensen, Erika;Hallgrimsson, Benedikt;Boyd, Steven K.
生长激素(GH)在骨量的发育过程中是必不可少的，儿童时期的生长激素缺乏症(GHD)经常通过每日注射GH来治疗。目前还不清楚GHD及其治疗对骨骼有什么影响。生长激素缺乏纯合子(LIT/LIT)小鼠，雌雄各半，每日注射生长激素，从早期(21天龄)或晚期(35天龄，相当于青春期结束)开始。一组生长激素水平正常的杂合子小鼠作为对照。在21-60日龄的5个时间点进行第四腰椎的微CT扫描，分析骨小梁形态和体积骨密度，以确定GH对骨微结构的影响。早期GH治疗导致研究终点(60天)的骨体积比(p=0.006)、组织密度(p=0.005)和结构模型指数(p=0.004)显著改善，而骨小梁厚度没有检测到变化。与杂合子小鼠相比，GHD小鼠的骨小梁数量增加，小梁间隔减少，无论治疗方式如何。这表明GHD和GH处理组小鼠的骨小梁结构存在根本差异，与杂合子对照组相比，这些小鼠的骨小梁较薄的数量增加。除连接密度外，晚期治疗组与GHD组小鼠之间无显著差异。综上所述，这些结果表明，骨骼对青春期前开始的GH治疗有反应，但对青春期后开始的治疗没有反应，GH治疗并没有将骨小梁结构挽救到杂合子对照组的水平。(C)2010 Elsevier Inc.保留所有权利。
Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset.Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture.Early GH treatment led to significant improvements in bone volume ratio (p = 0.006), tissue mineral density (p = 0.005), and structure model index (p = 0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. (C) 2010 Elsevier Inc. All rights reserved.