Vitamin K2 promotes bone healing in a rat femoral osteotomy model with or without glucocorticoid treatment.
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.
Iwamoto
Jun
J
Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. jiwamoto@sonata.plala.or.jp
Seki
Azusa
A
Sato
Yoshihiro
Y
Matsumoto
Hideo
H
Tadeda
Tsuyoshi
T
Yeh
James K
JK
D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005269:Femur / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D050723:Fractures, Bone / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D016268:Internal Fixators; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010027:Osteotomy; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D024482:Vitamin K 2 / Q000494:pharmacology* / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D000933:Antifibrinolytic Agents; D005938:Glucocorticoids; D024482:Vitamin K 2; D011239:Prednisolone