Iwamoto Jun, Seki Azusa, Takeda Tsuyoshi, Yamada Harumoto, Sato Yoshihiro, Yeh James K
Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan.
Chin J Physiol. 2008 Jun 30;51(3):121-8.
The purpose of the present study was to examine the effects of combined administration of alfacalcidol (ALF) and risedronate (RIS) on cancellous and cortical bone mass of the tibia in glucocorticoid (GC)-treated young rats. One hundred and nine female Sprague-Dawley rats, 3 months of age, were randomly divided by the stratified weight method into eleven groups according to the following treatment schedule: baseline control, a 4-week age-matched control, and a 4-week GC administration with a 4-week concomitant administration of vehicle, ALF, RIS, or ALF+RIS, and an 8-week age-matched control and 8-week GC administration with a 4-week administration of vehicle, ALF, RIS, or ALF+RIS that was initiated after a 4-week administration of GC. The GC (methylprednisolone sodium succinate, 5.0 mg/kg) and RIS (10 microg/kg) were administered subcutaneously 3 times a week. ALF (0.08 microg/kg) was administered orally 5 times a week. At the end of the experiment, static and dynamic bone histomorphometric analyses were performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial diaphysis. A 4-week GC administration induced a loss of cancellous bone volume/total tissue volume (BV/TV) compared with the age-matched control as a result of decreased bone formation and increased bone erosion, while an 8-week GC administration induced both losses of cancellous BV/TV and of percent cortical area (Ct Ar) compared with the age-matched control as a result of decreased trabecular bone formation and increased trabecular and endocortical bone erosion. ALF prevented the loss of cancellous BV/TV at the 4th week by mildly suppressing bone erosion without reducing bone formation, and it restored cancellous BV/TV and increased percentage of Ct Ar at the 8th week by preventing a reduction in trabecular bone formation and mildly suppressing trabecular bone erosion and by strongly suppressing endocortical bone erosion, respectively. RIS restored only cancellous BV/TV at 8 weeks by strongly suppressing bone formation and bone erosion. Combined administration of ALF and RIS increased total tissue area of cortical bone at the 4th and 8th weeks by markedly increasing periosteal bone formation. The present study showed the efficacy of combined administration of ALF and RIS for the geometry of cortical bone in GC-treated rats.
本研究的目的是检测联合应用阿法骨化醇（ALF）和利塞膦酸盐（RIS）对糖皮质激素（GC）处理的年轻大鼠胫骨松质骨和皮质骨质量的影响。109只3月龄雌性Sprague-Dawley大鼠，根据分层体重法按以下处理方案随机分为11组：基线对照、4周龄匹配对照、4周GC给药并同时4周给予赋形剂、ALF、RIS或ALF+RIS，以及8周龄匹配对照和8周GC给药并在4周GC给药后4周给予赋形剂、ALF、RIS或ALF+RIS。GC（琥珀酸甲泼尼龙，5.0 mg/kg）和RIS（10μg/kg）每周皮下注射3次。ALF（0.08μg/kg）每周口服5次。实验结束时，对胫骨近端干骺端松质骨和胫骨骨干皮质骨进行静态和动态骨组织形态计量学分析。与年龄匹配对照相比，4周GC给药由于骨形成减少和骨侵蚀增加导致松质骨体积/总体积（BV/TV）丢失，而8周GC给药与年龄匹配对照相比，由于小梁骨形成减少和小梁及骨内膜骨侵蚀增加，导致松质骨BV/TV和皮质面积百分比（Ct Ar）均丢失。ALF在第4周通过轻度抑制骨侵蚀而不减少骨形成来防止松质骨BV/TV丢失，并且在第8周通过防止小梁骨形成减少和轻度抑制小梁骨侵蚀以及分别强烈抑制骨内膜骨侵蚀来恢复松质骨BV/TV并增加Ct Ar百分比。RIS仅在8周时通过强烈抑制骨形成和骨侵蚀来恢复松质骨BV/TV。ALF和RIS联合给药在第4周和第8周通过显著增加骨膜骨形成而增加皮质骨的总组织面积。本研究显示了ALF和RIS联合给药对GC处理大鼠皮质骨几何形态的疗效。
