Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Calcif Tissue Int. 2010 Mar;86(3):234-41. doi: 10.1007/s00223-010-9333-8. Epub 2010 Jan 29.
The purpose of the present preclinical study was to determine whether vitamin K(2) would promote bone healing in a rat femoral osteotomy model with or without glucocorticoid (GC) treatment. Thirty-eight 6 week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation and then were randomized into four groups that received the following treatment schedules: vehicle, vitamin K(2), GC + vehicle, and GC + vitamin K(2). GC (prednisolone, 2.5 mg/kg) was administered subcutaneously twice a week. Vitamin K(2) (menatetrenone, 30 mg/kg) was administered orally five times a week. After 8 weeks of treatment, the wires were removed and a bone histomorphometric analysis was performed on the bone tissue inside the callus. Vitamin K(2) administration to GC-untreated rats decreased the osteoclast surface/bone surface (OcS/BS), osteoblast surface (ObS)/BS, eroded surface (ES)/BS, and bone formation rate (BFR)/BS and increased the lamellar area/bone area. Although GC treatment increased the ES/BS and decreased the ObS/BS, BFR/BS, and lamellar area/bone area, vitamin K(2) administration to GC-treated rats decreased the OcS/BS and prevented an increase in the ES/BS and a decrease in the lamellar area/bone area. These results suggested that vitamin K(2) downregulated bone turnover and stimulated lamellar bone formation in GC-untreated rats and prevented an increase in bone resorption while maintaining bone formation and prevented a decrease in lamellar bone formation in GC-treated rats. Thus, vitamin K(2) appears to be effective for promoting bone healing in a rat femoral osteotomy model with or without GC treatment.
本临床前研究的目的是确定维生素 K(2) 是否会促进糖皮质激素（GC）治疗或不治疗的大鼠股骨切开模型中的骨愈合。38 只 6 周龄雌性 Sprague-Dawley 大鼠接受单侧股骨骨干切开术，随后进行髓内钢丝固定，然后随机分为四组，分别接受以下治疗方案：载体、维生素 K(2)、GC+载体和 GC+维生素 K(2)。GC（泼尼松龙，2.5mg/kg）每周皮下给药两次。维生素 K(2)（甲萘醌，30mg/kg）每周口服给药五次。治疗 8 周后，取出钢丝，并对骨痂内的骨组织进行骨组织形态计量学分析。维生素 K(2) 给药可降低 GC 未治疗大鼠的破骨细胞表面/骨表面（OcS/BS）、成骨细胞表面（ObS/BS）、侵蚀表面（ES/BS）和骨形成率（BFR/BS），并增加板层面积/骨面积。虽然 GC 治疗增加了 ES/BS 并降低了 ObS/BS、BFR/BS 和板层面积/骨面积，但维生素 K(2) 给药可降低 OcS/BS 并防止 ES/BS 增加和板层面积/骨面积减少。这些结果表明，维生素 K(2) 下调了未接受 GC 治疗的大鼠的骨转换并刺激了板层骨形成，防止了骨吸收的增加，同时维持了骨形成，并防止了 GC 治疗的大鼠板层骨形成的减少。因此，维生素 K(2) 似乎可有效促进大鼠股骨切开模型中的骨愈合，无论是否存在 GC 治疗。
