Effect of Vitamin K2 on Three-Dimensional Trabecular Microarchitecture in Ovariectomized Rats

Abstract

Menatetrenone, a vitamin K 2 with four isoprene units, has been reported to improve osteoporotic bone loss. The purpose of this investigation was to clarify the effect of menatetrenone on the three-dimensional (3D) trabecular microarchitecture in ovariectomized (OVX) rats by using microcomputed tomography (MCT). Forty-two 13-week-old female rats were used and divided into four groups: the OVX (OVX ؉ MK-4) group treated with menatetrenone, the (OVX untreated) group, the sham-operated (Sham ؉ MK-4) group treated with menatetrenone, and the sham-operated group not treated with menatetrenone (Sham untreated) group. OVX rats were fed a calcium-deficient diet. Menatetrenone treatment was begun just after the ovariectomy, and the mean menatetrenone oral intake over the 8-week period was adjusted to 30 mg/kg BW per day. The proximal metaphyseal region of the right tibia was evaluated by dual X-ray absorptiometry (DXA) and MCT. A parametric analysis of the reconstructed trabecular volume was carried out using bone volume fractions, the fractal dimension calculated by the 3D box-counting method, and the connectivity density as determined by topological analysis. Menatetrenone significantly increased the trabecular bone volume, fractal dimension, and connectivity in the OVX ؉ MK-4 group compared with the OVX-untreated group ( p < 0.01). Our results suggest that an 8-week administration of menatetrenone protects against the loss of trabecular bone volume and its connectivity when treatment is begun just after the ovariectomy. Despite this apparent protection, it remains unknown whether it is possible to reestablish trabecular connectivity if therapeutic intervention occurs after the trabecular connectivity has been lost. (J Bone Miner Res 2000;15:1810 -1817)

Additive Effect of Vitamin K2 and Risedronate on Long Bone Mass in Hypophysectomized Young Rats

“…Risedronate (Aventis Pharma, Tokyo, Japan) was dissolved in 10 ml of PBS to make a working stock solution with a concentration of 200 µg/ ml and was administered subcutaneously at a dose of 2.5 µg/kg, 5 days per week. The selected dose of vitamin K 2 was effective according to the results of a previous study [29], although the influence of this vitamin on the bones seems to be modest. The dose of risedronate was set in accordance with previously published data [28].…”

Menatetrenone Ameliorates Reduction in Bone Mineral Density and Bone Strength in Sciatic Neurectomized Rats

“…Recent clinical studies have suggested that MK-4 effectively prevents the occurrence of new frac tures in patients with postmenopausal osteoporosis (6 -8) and ameliorates osteoporosis associated with Parkin son's disease (9). The effects of MK-4 on bone metabo lism were demonstrated in a model of postmenopausal osteoporosis (10)(11)(12). It is generally accepted that bone resorption is increased in ovariectomized rats.…”

“…MK-4 (menatetrenone; Eizai Co. Ltd., Tokyo, Japan) was given as a dietary supplement 30mg/100g, 85mg/100g of the diet, respectively. The dosages of MK-4 were set based on the results of earlier studies (10,12,13 Bone mineral densitometry (BMD). At the designed determination points, bone samples were taken and all the connective tissues were carefully removed.…”

Role of vitamin K in the regulation of calcification

“…Of the two published studies on phylloquinone supplementation in rodents, neither demonstrated a positive effect on bone turnover or bone mineral density (BMD) [46,47]. In contrast, of the 17 published studies on MK-4 supplementation in rodents that were reviewed, 13 reported positive effects, ranging from inhibition of BMD or bone mineral content (BMC) loss [43,[48][49][50][51][52][53][54][55][56][57] to increased bone formation [58] and preservation of mechanical properties [59]. The average daily dose used in these studies was 30 mg/kg diet.…”