A comparison of the effects of inhibitors of carbonic anhydrase on osteoclastic bone resorption and purified carbonic anhydrase isozyme II.

We have assessed the effects of five sulfonamides with widely varying inhibitory activity for carbonic anhydrase (CA) in the bone slice assay using disaggregated rat osteoclasts (OCs), and in the Maren assay where the catalytic activity of purified CA isozyme II (CA II) was measured. There was an excellent correlation between the relative potencies of the compounds in the two assays: ethoxzolamide (ETH) greater than acetazolamide (AZ) greater than M&B 21659 greater than M&B 9811 greater than M&B 7973. In the bone slice assay, ETH and AZ were found to be the most potent inhibitors of OC bone resorption, with IC50 values of 0.09 and 0.8 microM, respectively (from plan surface area of bone resorbed). These results support previous observations showing that OCs use CA II to generate protons during bone resorption and that CA II activity is essential for OCs to be able to resorb bone.