Promethazine inhibits osteoclastic bone resorption in vitro.

Several studies have shown that promethazine can reduce age-related osteopenia in mice. Furthermore, prolonged treatment with promethazine (50 mg/day) increases bone mineral content in the lumbar spine in post-menopausal women with osteopenia. However, the mechanism of action of promethazine has not been elucidated. The present study shows that promethazine HCl (0.01-10 microM) dose-dependently inhibits bone resorption by isolated rat osteoclasts in the bone slice assay with an IC50 of approximately 1 microM. Since these concentrations are likely to be achieved in vivo, it is suggested that the beneficial effect of promethazine on osteopenia is at least partly due to a direct inhibitory effect on osteoclast activity.