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利塞膦酸盐和骨化三醇对糖皮质激素诱导的骨质疏松大鼠松质骨的比较作用。

Comparative effects of risedronate and calcitriol on cancellous bone in rats with glucocorticoid-induced osteopenia.

作者信息

Iwamoto Jun, Seki Azusa, Takeda Tsuyoshi, Sato Yoshihiro, Yamada Harumoto, Shen Chwan-Li, Yeh James K

机构信息

Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan.

出版信息

J Nutr Sci Vitaminol (Tokyo). 2006 Feb;52(1):21-7. doi: 10.3177/jnsv.52.21.

DOI:10.3177/jnsv.52.21
PMID:16637226
Abstract

OBJECTIVES

To compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous bone in rats with glucocorticoid (GC)-induced osteopenia.

MATERIALS AND METHODS

Thirty female Sprague-Dawley rats, 4 mo of age, were randomly divided by the stratified weight method into three groups of 10 rats each according to the following treatment schedule: 8-wk GC administration with 4-wk vehicle (control), Ris, and Cal as therapeutic treatment initiated after 4-wk GC administration. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg. p.o.) were administered 3 times a week. At the end of the 8-wk treatment period, two-dimensional (2D) bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis, 3D micro-computed tomographic analysis was performed for the distal femoral metaphysis, and the mechanical strength of the distal femoral metaphysis was evaluated by a compression test.

RESULTS

Ris and Cal treatment increased both 2D and 3D cancellous bone mass. However, Ris treatment exhibited more pronounced effects on 2D and 3D cancellous bone mass than Cal treatment, and the effects of both Ris and Cal treatment were greater on 3D cancellous bone mass than on 2D cancellous bone mass. The response of 2D and 3D cancellous bone mass to Ris treatment was characterized by its effect on trabecular number and thickness, which was associated with markedly suppressed bone resorption and bone formation in terms of suppressed bone turnover. On the other hand, the response of 2D cancellous bone mass to Cal treatment was attributed to the effect of Cal on 2D trabecular thickness, and the response of 3D cancellous bone mass to Cal treatment might be characterized by the effect of Cal on 3D trabecular number and thickness, with a more marked effect of trabecular thickness. These effects were primarily due to mildly suppressed bone resorption and maintained or even increased bone formation. Despite the differential effect of Ris and Cal treatment on the cancellous bone structure and bone metabolism, both treatment increased the maximum load and braking energy of the distal femoral metaphysis to a similar extent, suggesting different mechanisms for improving bone strength.

CONCLUSIONS

This study showed the differential effects of Ris and Cal on cancellous bone in rats with GC-induced osteopenia.

摘要

目的

比较利塞膦酸盐(Ris)和骨化三醇(Cal)对糖皮质激素(GC)诱导的骨质疏松大鼠松质骨的影响。

材料与方法

30只4月龄雌性Sprague-Dawley大鼠,按分层体重法随机分为三组,每组10只,按照以下治疗方案进行:8周给予GC,同时4周给予赋形剂(对照组),4周给予GC后开始给予Ris和Cal进行治疗。GC(甲泼尼龙琥珀酸钠,5.0 mg/kg,皮下注射)、Ris(10 μg/kg,皮下注射)和Cal(0.1 μg/kg,口服)每周给药3次。在8周治疗期结束时,对胫骨近端干骺端松质骨进行二维(2D)骨组织形态计量学分析,对股骨远端干骺端进行三维微计算机断层扫描分析,并通过压缩试验评估股骨远端干骺端的力学强度。

结果

Ris和Cal治疗均增加了2D和3D松质骨量。然而,Ris治疗对2D和3D松质骨量的影响比Cal治疗更显著,且Ris和Cal治疗对3D松质骨量的影响大于对2D松质骨量的影响。2D和3D松质骨量对Ris治疗的反应表现为对骨小梁数量和厚度的影响,这与骨转换受抑制导致骨吸收和骨形成明显受抑制有关。另一方面,2D松质骨量对Cal治疗的反应归因于Cal对2D骨小梁厚度的影响,3D松质骨量对Cal治疗的反应可能表现为Cal对3D骨小梁数量和厚度的影响,其中对骨小梁厚度的影响更显著。这些影响主要是由于骨吸收轻度受抑制,骨形成维持甚至增加。尽管Ris和Cal治疗对松质骨结构和骨代谢有不同影响,但两种治疗均使股骨远端干骺端的最大负荷和制动能量增加到相似程度,提示改善骨强度的机制不同。

结论

本研究显示了Ris和Cal对GC诱导的骨质疏松大鼠松质骨的不同影响。

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