Iwamoto Jun, Takeda Tsuyoshi, Sato Yoshihiro, Yeh James K
Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan.
Exp Anim. 2007 Apr;56(2):103-10. doi: 10.1538/expanim.56.103.
Hypophysectomy (HX) arrests bone growth and induces osteopenia in the long bones of rats. The present study investigated the combined effect of vitamin K(2) and risedronate on long bone mass in HX rats, in order to determine whether treatment with these two agents had an additive effect. Forty female Sprague-Dawley rats were hypophysectomized at 6 weeks of age by the supplier, and were shipped to our laboratory at three days after surgery along with ten intact rats that served as age-matched controls. The study was started on the day when the rats were received. Three HX rats were excluded from the study because of the failure of HX. Forty-seven rats (6 weeks old) were assigned to the following 5 groups by the stratified weight randomization method: intact controls, HX alone, HX + vitamin K(2) (30 mg/kg, p.o., daily), HX + risedronate (2.5 microg/kg, s.c., 5 days a week), and HX + vitamin K(2) + risedronate. The dosing period was 4 weeks. HX resulted in a decrease of the femoral bone area, bone mineral content (BMC) and bone mineral density (BMD), as well as a decrease in the cancellous bone mass of the proximal tibial metaphysis and the total tissue and cortical areas of the tibial diaphysis. These changes were associated with a marked reduction in the serum level of insulin like growth factor (IGF)-I and with elevation of serum alkaline phosphatase (ALP) and pyridinoline. Administration of vitamin K(2) increased the serum ALP level in HX rats, but did not affect any of the other parameters. On the other hand, risedronate ameliorated the decrease of femoral BMD and cancellous bone mass at the proximal tibial metaphysis in HX rats without affecting the serum IGF-I level, as a result of not causing a significant elevation of serum pyridinoline. Vitamin K(2) and risedronate combined had an additive effect on the femoral bone area, BMC and BMD, and the combined treatment group did not show any significant reduction of the total tissue and cortical areas at the tibial diaphysis, as well as a reduced serum pyridinoline level compared with untreated rats and an increased serum ALP level compared with untreated or risedronate-treated rats. These results suggest that risedronate had a positive effect on the BMD and cancellous bone mass of long bones in HX rats. Despite the lack of a significant effect of vitamin K(2) on bone mass parameters, it had an additive effect with risedronate on the BMC, BMD and cortical bone mass of long bones in HX rats.
垂体切除术（HX）会抑制大鼠长骨的生长并导致骨质减少。本研究调查了维生素K₂和利塞膦酸盐对HX大鼠长骨质量的联合作用，以确定这两种药物治疗是否具有相加效应。40只雌性Sprague-Dawley大鼠在6周龄时由供应商进行垂体切除，并在术后三天与10只作为年龄匹配对照的完整大鼠一起运至我们的实验室。研究在大鼠接收当天开始。由于垂体切除失败，3只HX大鼠被排除在研究之外。47只（6周龄）大鼠通过分层体重随机化方法分为以下5组：完整对照、单纯HX、HX + 维生素K₂（30 mg/kg，口服，每日）、HX + 利塞膦酸盐（2.5 μg/kg，皮下注射，每周5天）以及HX + 维生素K₂ + 利塞膦酸盐。给药期为4周。HX导致股骨骨面积、骨矿物质含量（BMC）和骨矿物质密度（BMD）降低，以及胫骨近端干骺端松质骨质量、胫骨骨干总组织面积和皮质面积减少。这些变化与血清胰岛素样生长因子（IGF）-I水平显著降低以及血清碱性磷酸酶（ALP）和吡啶啉升高有关。给予维生素K₂可提高HX大鼠的血清ALP水平，但不影响其他任何参数。另一方面，利塞膦酸盐改善了HX大鼠股骨BMD降低以及胫骨近端干骺端松质骨质量减少的情况，且不影响血清IGF-I水平，这是因为未导致血清吡啶啉显著升高。维生素K₂和利塞膦酸盐联合使用对股骨骨面积、BMC和BMD具有相加效应，联合治疗组胫骨骨干的总组织面积和皮质面积未出现任何显著减少，与未治疗大鼠相比血清吡啶啉水平降低，与未治疗或利塞膦酸盐治疗大鼠相比血清ALP水平升高。这些结果表明，利塞膦酸盐对HX大鼠长骨的BMD和松质骨质量具有积极作用。尽管维生素K₂对骨质量参数没有显著影响，但它与利塞膦酸盐对HX大鼠长骨的BMC、BMD和皮质骨质量具有相加效应。
