Age-related osteopenia in the mouse: effects of an H1 blocker, a phenothiazine, and promethazine.

Mature and old B6AF1 and B6D2F1 mice were given acidified tap water or promethazine HCl (a phenothiazine with H1 receptor blocking activity), chlorpheniramine (an H1 blocker) or trifluoperazine (a phenothiazine with no H1 blocking activity) in their drinking water, and the effects of these agents on bone mineral content were assessed by intermittently measuring the 24-h whole body retention of Tc 99m methylene diphosphonate (Tc 99m MDP, an indicator of bone metabolism) and at the end of the studies by determining ash weights of femur, ilium and sacrum. It was found that 24-h retention of Tc 99m MDP was elevated in old mice as it is in old osteopenic humans, that promethazine but not chlorpheniramine or trifluoperazine inhibited bone loss in aging mice, and that there was a correlation between decrease in retention of Tc 99m MDP and decreased bone loss. These preliminary results suggest that the ability of promethazine to inhibit age-related bone loss may not be mediated through its action as an H1 blocker or as a phenothiazine. However, more agents of each type need to be tested before this point can be established.