Effect of levamisole on bone resorption in cultured mouse calvaria

The effects of levamisole (LT), dexamisole (DT), levo-p-bromotetramisole (LBT) and dextro-p-bromotetramisole (DBT) on bone were examined in an organ culture system using calvarial bones from newborn mice. LBT and DBT at concentrations 30 microM and greater and LT and DT at concentrations 100 microM and greater caused a dose-dependent, reversible inhibitory effect on mineral mobilization and matrix degradation. LBT, DBT (100 and 300 microM) as well as LT and DT (greater than or equal to 100 microM) reduced the spontaneous release of beta-glucuronidase without having any marked effect on the release of lactate dehydrogenase (LDH). LT and DT did not influence protein synthesis but LBT and LBT were inhibitory in concentrations at and above 100 microM. Mitotic activity, as assessed by incorporation of [3H]thymidine, was inhibited by LBT and DBT (0.1, 1 mM). LT and LBT caused a stereospecific inhibition of GPase, PPiase and ATPase. It is concluded that tetramisoles are potent, non-stereospecific inhibitors of bone resorption in vitro.