Iwamoto Jun, Takeda Tsuyoshi, Sato Yoshihiro, Shen Chwan-Li, Yeh James K
Department of Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
J Nutr Sci Vitaminol (Tokyo). 2006 Oct;52(5):307-15. doi: 10.3177/jnsv.52.307.
The purpose of the present study was to examine the effect of pretreatment with risedronate and/or vitamin K2 and treatment continuation with reduced dosing frequency of the drugs on the early cancellous bone loss induced by ovariectomy (OVX) in rats. Eighty female Sprague-Dawley rats, 4 mo of age, were randomized by the stratified weight method into eight groups (n= 10 in each group); rats subjected to OVX, but not sham-operated rats, were treated with vehicle, risedronate, vitamin K2 (menatetrenone), or risedronate+vitamin K2 for 4 wk before the surgery, and the treatment was either discontinued (pretreatment groups) or continued after the surgery (treatment continuation groups) for 2 wk. Sham-operated rats (controls) were treated with the vehicle throughout the experimental period. During the 4 wk prior to the surgery (pretreatment), risedronate and vitamin K2 were administered five times a week either subcutaneously at a dose of 2.5 microg/kg body weight (risedronate) or orally at the dose of 30 mg/kg body weight (vitamin K2). During the 2 wk after the surgery (treatment continuation), the dosing frequency of the drugs was reduced to twice a week. Risedronate and vitamin K2 had an anti-resorptive effect on the bone. Pretreatment with risedronate alone, but not vitamin K2 alone, prevented the loss of the cancellous bone volume/total volume (BV/TV) of the proximal tibial metaphysis after OVX. Treatment continuation with vitamin K2 alone prevented the loss of the cancellous BV/TV after OVX, while treatment continuation with risedronate alone increased the cancellous BV/TV to beyond the values in controls. Pretreatment with risedronate+vitamin K2 had a more beneficial effect in increasing the cancellous bone mass than pretreatment with risedronate alone. Treatment continuation with risedronate and/or vitamin K_ appeared to have a more beneficial effect in increasing the cancellous bone mass than the respective pretreatment. Neither the total tissue area nor the cortical area of the tibial diaphysis was affected by any treatment. The present study demonstrated that pretreatment with risedronate had a beneficial effect on the early cancellous bone loss after OVX in rats, with a more beneficial effect when combined with vitamin K2. Moreover, even though the dosing frequency of the drugs was reduced after OVX, treatment continuation appeared to be more beneficial than pretreatment for increasing the cancellous bone mass.
本研究的目的是检测用利塞膦酸盐和/或维生素K2预处理以及降低药物给药频率持续治疗对大鼠卵巢切除（OVX）诱导的早期松质骨丢失的影响。80只4月龄雌性斯普拉格-道利大鼠通过分层体重法随机分为八组（每组n = 10）；接受OVX的大鼠，而非假手术大鼠，在手术前用赋形剂、利塞膦酸盐、维生素K2（甲萘醌）或利塞膦酸盐+维生素K2治疗4周，治疗在手术后要么停止（预处理组）要么继续（持续治疗组）2周。假手术大鼠（对照组）在整个实验期间用赋形剂治疗。在手术前的4周（预处理期），利塞膦酸盐以2.5μg/kg体重的剂量每周皮下注射5次（利塞膦酸盐），维生素K2以30mg/kg体重的剂量口服。在手术后的2周（持续治疗期），药物给药频率降至每周2次。利塞膦酸盐和维生素K2对骨有抗吸收作用。单独用利塞膦酸盐预处理可防止OVX后胫骨近端干骺端松质骨体积/总体积（BV/TV）的丢失，但单独用维生素K2预处理则不能。单独用维生素K2持续治疗可防止OVX后松质骨BV/TV的丢失，而单独用利塞膦酸盐持续治疗则使松质骨BV/TV增加至超过对照组的值。用利塞膦酸盐+维生素K2预处理在增加松质骨量方面比单独用利塞膦酸盐预处理有更有益的效果。用利塞膦酸盐和/或维生素K2持续治疗在增加松质骨量方面似乎比各自的预处理有更有益的效果。胫骨骨干的总组织面积和皮质面积均未受任何治疗的影响。本研究表明，用利塞膦酸盐预处理对大鼠OVX后的早期松质骨丢失有有益作用，与维生素K2联合使用时效果更有益。此外，尽管OVX后药物给药频率降低，但持续治疗在增加松质骨量方面似乎比预处理更有益。
