Reveromycin A Inhibits Bone Loss in Ovariectomized Mice 

Author(s): Yasuhiro Ozasa, Takuro Wada, Toshihiko Yamashita, Yasuo Kokai

Background and objectives: Reveromycin A inhibits bone metastasis of lung cancer cells in natural killer cell-depleted immunodeficient mice with increasing apoptosis of osteoclasts. This knowledge suggests that reveromycin A is a potent inhibitor for osteoclasts in vivo. To determine the activity of bone loss in acute estrogen deficiency, we studied ovariectomized mice treated with reveromycin A. 

Materials and Methods: Eight-week-old female C57BL/6 mice were either ovariectomized or sham-operated. Reveromycin A was continuously administered for the first 2 weeks (Group RA) or the last 2 weeks (Group RP) using a subcutaneous mini osmotic pump. Mice were sacrificed 4 weeks after surgery. Inhibition was detected by images as well as serum carboxyterminal telopeptide of type I collagen (CTX). 

Results: BMD reduction in the RA group was significantly inhibited and was comparable with that in the sham group. In contrast, the RP group failed to inhibit BMD reduction. The plasma CTX level at the 28th day of the experiment was significantly increased in the RP and OVX groups compared with that in the sham group, while the increase was inhibited in the RA group. Morphometric analysis revealed that absorption of trabecular bone was strongly inhibited in the RA group. 

Conclusion: The inhibitory effects of reveromycin A administered immediately after ovariectomy was the most effective at the early phase of bone loss than at the later stage. A new reagent that inhibits bone loss in acute estrogen deficiency might be a new tool to experimentally study osteoporosis and may have clinical implications.

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