Vitamin K2 Promotes Bone Healing in a Rat Femoral Osteotomy Model with or without Glucocorticoid Treatment

Abstract

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.

Vitamin K₂ Improves Femoral Bone Strength without Altering Bone Mineral Density in Gastrectomized Rats

“…In the GX1vitamin K2 group, vitamin K2 (menaquinone-4, menatetrenone; Eisai Co. Ltd., Tokyo, Japan) was suspended in a fatty acid preparation (Miglyol 812; Mitsuba Trading Co. Ltd., Tokyo, Japan) at a dosage of 30 mg/mL/kg and administered by gavage five times a week. Although the dosage may be considered to be very high, treatment with vitamin K2 at 30 mg/kg five times a week has previously been reported to maintain bone health in rats without causing any adverse events (27,28). The weight of the rats was monitored weekly and the duration of the treatment was 6 wk.…”

Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

“…It is also suggested that vitamin K2 may improve osteocyte density and lacunar occupancy by viable osteocytes in the cortical bone of glucocorticoid-treated or sciatic neurectomized rats 73, 74. In addition, vitamin K2 may down-regulate bone turnover and stimulate lamellar bone formation, and prevent an increase in bone resorption with maintaince of bone formation and prevent a decrease in lamellar bone formation in glucocorticoid-treated rats 75. Further studies are required for the comprehensive assessment of the role of vitamin K in the development of T2DM.…”

A biomechanical, micro-computertomographic and histological analysis of the influence of diclofenac and prednisolone on fracture healing in vivo

“…However, the value was significantly higher than that of the diclofenac group. Concordantly, the prednisolone group of a recent rat femur fracture study showed an increased total bone area histologically generated by an increase of the woven bone, whereas the lamellar bone showed decreased values [34]. Compared with the control group, the authors described a slow remodelling of woven bone to lamellar bone within the callus; this is equivalent to a delay of fracture healing.…”

“…To date, there is no clear evidence that the fracture healing is restricted in patients who are under glucocorticoid medication [34]. Controversially, long-term medication of 5.5 weeks up to 3.5 months led to impaired fracture healing in rabbits (ulnar osteotomy) and rats (closed/open fracture of the femur) [7, 10, 19, 33–35], whereas short-term medication of 3-4 days in a femural osteotomy model of the rat did not affect the biomechanics or histology [16, 36].…”