Chlorpromazine alters bone metabolism of rats in vivo

The acute effect of chlorpromazine (CPZ) on metabolic changes in rats was investigated. CPZ was found to markedly suppress 45Ca incorporation into the calvarium and ileum in vitro. According to the serum and/or urinary levels of certain markers for bone metabolism, the increases of Ca and P in the serum and Ca, P, and gamma-carboxyglutamate (Gla) in the urine were observed in rats given 10 mg CPZ/kg of their body weight, whereas the amount of alkaline phosphatase (ALP) activity, ionized Ca, calcitonin, 25-hydroxyvitamin D3 (25(OH)D3), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) as clearly or slightly reduced, suggesting the inhibitory effect of their bone formation. This was well supported since only bone type ALP was detected in the urine and loss of the vertebral bone density from rats given daily CPZ administration for a week. Moreover, in this case, there is little if any difference in the levels of mid-molecule parathyroid hormone (mid-PTH), osteocalcin, and urinary cAMP for the nontreated and CPZ-treated animals, resulting in the fact that CPZ may mainly inhibit the hydroxylase for active vitamin D3.