Iwamoto Jun, Seki Azusa, Takeda Tsuyoshi, Yamada Harumoto, Sato Yoshihiro, Yeh James K
Department of Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
J Nutr Sci Vitaminol (Tokyo). 2007 Jun;53(3):191-7. doi: 10.3177/jnsv.53.191.
The beneficial effects of alfacalcidol (ALF) on bone mass, bone formation, and bone resorption have been established in ovariectomized rats. Our previous studies showed that high-dose glucocorticoid (GC) administration (methylprednisolone sodium succinate, 5.0 mg/kg, s.c., 3 times a week) for 4 wk induced cancellous osteopenia without significantly affecting cortical bone mass in Sprague-Dawley rats, and that high-dose GC administration for 8 wk also resulted in cortical osteopenia. The purpose of the present study was to examine the effects of ALF on cancellous and cortical bone mass in GC-treated rats. Forty female Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into four groups of 10 rats each, as follows: age-matched control group (CON); 8-wk GC administration with administration of vehicle during the latter 4 wk of treatment (GC group); 8-wk GC administration with administration of a low dose of ALF (0.08 Ag/kg) during the latter 4 wk of treatment (low-dose ALF group); 8-wk administration of GC with administration of a high dose ofALF (0.16 microg/kg) during the latter 4 wk of treatment (high-dose ALF group). The GC (methylprednisolone sodium succinate, 5.0 mg/kg) was administered subcutaneously 3 times a week, and ALF 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. Eight-week GC administration resulted in loss of the cancellous bone volume/total tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular bone formation, increased trabecular and endocortical bone resorption, and decreased periosteal bone formation. Low-dose ALF restored the cancellous BV/TV by mildly suppressing bone resorption and restoring bone formation, whereas high-dose ALF increased it beyond the value observed in the age-matched controls by strongly suppressing bone resorption and markedly increasing bone formation. Both low- and high-dose ALF prevented the GC-induced reduction of the percent Ct Ar by increasing periosteal bone formation and suppressing endocortical bone resorption. The effects of ALF on cancellous bone mass, bone formation, and bone resorption were all dose-dependent. The present study showed the beneficial effects of ALF on cancellous and cortical bone mass in GC-treated rats.
阿法骨化醇（ALF）对去卵巢大鼠的骨量、骨形成和骨吸收具有有益作用。我们之前的研究表明，对Sprague-Dawley大鼠皮下注射高剂量糖皮质激素（GC）（甲泼尼龙琥珀酸钠，5.0 mg/kg，每周3次），持续4周，会导致松质骨减少，但对皮质骨量无显著影响；而高剂量GC给药8周也会导致皮质骨减少。本研究的目的是探讨ALF对GC处理大鼠松质骨和皮质骨量的影响。40只3月龄雌性Sprague-Dawley大鼠，通过分层体重法随机分为4组，每组10只，如下：年龄匹配对照组（CON）；GC给药8周，治疗后4周给予赋形剂（GC组）；GC给药8周，治疗后4周给予低剂量ALF（0.08μg/kg）（低剂量ALF组）；GC给药8周，治疗后4周给予高剂量ALF（0.16μg/kg）（高剂量ALF组）。GC（甲泼尼龙琥珀酸钠，5.0 mg/kg）每周皮下注射3次，ALF每周口服5次。实验结束时，对胫骨近端干骺端的松质骨和胫骨干皮质骨进行静态和动态骨组织形态计量学分析。GC给药8周导致松质骨体积/总体积（BV/TV）和皮质面积百分比（Ct Ar）降低，原因是小梁骨形成减少、小梁和内皮质骨吸收增加以及骨膜骨形成减少。低剂量ALF通过轻度抑制骨吸收和恢复骨形成来恢复松质骨BV/TV，而高剂量ALF通过强烈抑制骨吸收和显著增加骨形成使其超过年龄匹配对照组的观察值。低剂量和高剂量ALF均通过增加骨膜骨形成和抑制内皮质骨吸收来防止GC诱导的Ct Ar百分比降低。ALF对松质骨量、骨形成和骨吸收的影响均呈剂量依赖性。本研究显示了ALF对GC处理大鼠松质骨和皮质骨量的有益作用。
