Synergistic effect of vitamin K2 and prostaglandin E2 on cancellous bone mass in hypophysectomized young rats

Hypophysectomy (HX) results in cessation of bone growth and cancellous osteopenia in rats. It has been reported that prostaglandin E2 (PGE2) improves cortical and cancellous bone mass in HX rats. The purpose of the present study was to examine whether combined administration of vitamin K2 and PGE2 would have a more beneficial effect on bone than single administration of either alone in HX rats. Forty-three female Sprague-Dawley rats, 6 weeks of age, were randomized by the stratified weight method into five groups: intact controls, HX, HX + vitamin K2 (30 mg/kg, p.o., daily), HX + PGE2 (0.83 mg/kg, i.m., 5 days a week), and HX + vitamin K2 + PGE2. The duration of the experiment was 4 weeks. There was a reduction in cancellous bone volume/total tissue volume (BV/TV) of the proximal tibial metaphysis and a reduction in total tissue area and cortical area (Ct.Ar) of the tibial diaphysis. Vitamin K2 did not affect cancellous BV/TV or Ct.Ar. On the other hand, PGE2 attenuated the loss of cancellous BV/TV in association with higher bone formation rate/bone surface (BFR/BS) and eroded surface (ES)/BS compared with intact controls. PGE2 also increased percent Ct.Ar compared with nontreated HX rats as a result of attenuation of a decrease in periosteal BFR/BS. Vitamin K2 had a synergistic effect with PGE2 on cancellous BV/TV as a result of the suppression of an increase in ES/BS observed by PGE2 treatment. These results suggested that PGE2 had an anabolic action on cancellous and cortical bone and that despite no apparent effect of vitamin K2 on bone, it had a synergistic effect with PGE2 on cancellous bone mass in young HX rats.