Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength

Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength
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DOI:
10.1016/j.bone.2010.02.015
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发表时间:
2010-06-01
期刊:
影响因子:
4.1
通讯作者:
Rizzoli, Rene
Rizzoli, Rene
中科院分区:
医学2区
文献类型:
--
作者:
Ammann, Patrick;Brennan, Tara C.;Rizzoli, Rene

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前言:等卡路里蛋白质营养不良与骨量减少、骨强度降低以及ICE-I水平降低有关。目前尚不清楚给予生长激素(GH)是否能纠正这些骨骼代谢的改变。材料和方法:6个月龄的雌性大鼠喂食含2.5%或15%酪蛋白的等卡路里饲料2周。然后用牛生长激素(BGH,0.5或2.5 mg/kg体重)或赋形剂作为皮下注射,每天两次,给任何一种饮食的大鼠注射,持续4周。在胫骨近端进行骨密度、最大载荷和组织形态计量学分析。此外,还检测了尿脱氧吡啶酚、血浆骨钙素和ICE-I浓度。结果:无论饲料中蛋白质含量如何,BGH均引起血浆ICE-I呈剂量依赖性增加。然而,补肾活血方可剂量依赖性地降低低蛋白饮食大鼠的骨密度和骨强度。短期内补肾活血方对正常蛋白饮食大鼠的骨密度无明显影响,但组织形态计量学检测该组大鼠骨形成明显改善,而低蛋白饮食组大鼠骨密度无明显改善。破骨细胞表面仅在低蛋白BGH处理组增加。结论:这些结果强调了膳食蛋白质摄入量在短期应用生长激素对骨骼反应中的重要作用,并强调了生长激素治疗对蛋白质摄入量减少患者的影响需要进一步研究的必要性。(C)2010 Elsevier Inc.保留所有权利。
Introduction: Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower ICE-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism.Materials and methods: Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5 mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and ICE-I concentrations were measured. Weight was monitored weekly.Results: bGH caused a dose-dependent increase in plasma ICE-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets.Conclusion: These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake. (C) 2010 Elsevier Inc. All rights reserved.