TAXOL INHIBITS OSTEOCLASTIC BONE-RESORPTION

We have examined the effect of the anti-tumor compound taxol, on osteo clastic bone resorption. In the bone slice assay, taxol (0.1 - 0.001 m u M) dose-dependently inhibited bone resorption with an IC50 of 0.08 m u M. Osteoclast survival on bone slices was unaffected by 0.01 - 1 mu M taxol, but 10 mu M was cytotoxic. Taxol (1 mu M) also inhibited oste oclast spreading (45%) on fibronectin-coated slides. The anti-prolifer ative effects of taxol are due to its unique ability to stabilize micr otubules. Primary osteoclasts are proliferating end cells, so taxol pr obably inhibits resorption by interfering with other microtubule-depen dent functions such as cell polarization, motility or vesicle exocytos is. Since these inhibitory effects on osteoclasts in vitro are seen wi th therapeutically relevant concentrations, taxol therapy may have ben eficial side-effects e.g. inhibition of hypercalcemia and bone metasta ses.