Altered bone turnover in chlorpromazine-challenged rats and its effect on 1α-hydroxyvitamin D3 administration in vivo

We reported previously that Ca and Pi levels are elevated and alkaline phosphatase (ALP) activity and 1α,25(OH)₂D₃ levels are reduced in chlorpromazine (CPZ)-challenged rats. In the present study, we determined the serum levels of interleukin (IL)-6 and acid phosphatase (ACP) in CPZ-challenged rats, in addition to levels of ALP protein. ALP mRNA and coccyx morphology were examined in CPZ-challenged rats as well as the effect of CPZ on 1α(OH)D₃ production in vivo. Although Ca, Pi, IL-6, and ACP activity levels in CPZ-challenged rats were markedly increased on day 30, the elevated serum levels were restored to within normal ranges by the in vivo addition of 1α(OH)D₃ to CPZ administration. The gain in body weight in CPZ-treated rats was significantly improved by the addition of 1α(OH)D₃. Reduced levels of 1α,25(OH)₂D₃ in CPZ-treated rats were restored to normal levels by the administration of 1α(OH)D₃. Moreover, the decreased ALP activity and ALP mRNA levels in the rat coccyx marrow in CPZ-treated rats were also restored by the administration of 1α(OH)D₃ with CPZ. However, the molecular sizes of rat ALP molecules and ALP mRNA were the same for each group. Furthermore, bone morphometry showed that trabecular bone in the rat coccyx was decreased in CPZ-treated rats. However, the reduced volume of trabecular bone in CPZ-treated rats was restored by the addition of 1α(OH)D₃ to CPZ administration. Taken together, altered bone metabolism in CPZ-treated rats can be improved by the addition of 1α(OH)D₃. Received: January 11, 2001 / Accepted: July 18, 2001