Inhibition of stimulated bone resorption by vanadate

We have previously reported that stimulated release of calcium (Ca) from bone is a sodium-dependent process. Partial support for this conclusion came from the observation that ouabain inhibited stimulated bone resorption as a result of inhibition of the Na,K-ATPase in bone. We now present additional supporting evidence from the results of experiments using vanadate, an ion known to inhibit the activity of Na,K-ATPase. Vanadate inhibited stimulated bone resorption in neonatal mouse calvaria. Inhibition occurred in a dose-dependent manner, and ortho-vanadate was 3-fold more potent than meta-vanadate. Ortho-vanadate was equally effective against several different stimulators of resorption, including PTH, prostaglandin E2, and 1,25-dihydroxycholecalciferol. PTH-stimulated bone resorption was inhibited with a Ki of about 9 microM. Stimulated Ca release was completely blocked whether vanadate was added at zero time or 24 h after the addition of a resorption-stimulating agent. Because the responses to vanadate were similar to those observed with ouabain, we conclude that vanadate is probably acting to inhibit stimulated resorption via inhibition of the Na,K-ATPase in bone.