Haloperidol for modelling osteoporosis in rats

Introduction: Various experimental models of osteoporosis are well-known and presented in the literature, yet we did not find a description in the available literature of the possibility of using antipsychotics to induce osteoporosis in rats. The aim of the study: We aimed to develop a “haloperidol model” of osteoporosis and to evaluate its efficiency in rats. Materials and Methods: Wistar rats were divided into 2 groups (20 animals each): control (saline) and experimental (haloperidol). Haloperidol was administered intraperitoneally for 90 days according to the regimen from 15 mg/kg/day to 5 mg/kg/day as 1 mL per 100 mg of rat body weight of saline solutions in corresponding concentrations. We performed blood tests for total calcium, alkaline phosphatase, and urine tests for oxyproline to demonstrate that bone metabolism changes in rats were consistent with osteoporosis. After 90 days, we finalized the experiment and performed a histomorphometry assessment of the bone tissue of rats’ vertebrae (the average diameter of the spongy trabecula, the thickness of the cortical plate and the area of the intertrabecular space were evaluated) and microelement analysis (Ca, Sr, Zn, Cu). Results: We found that haloperidol induced a decrease in the level of total calcium by 2.2 times and alkaline phosphatase by 1.6 times in the blood, an increase in oxyproline in the urine by 1.7 times; a reduction in the average diameter of trabeculae by 2.2 times and the thickness of the cortical layer by 2 times, an increase in the area of the intertrabecular space by 2 times; a deficiency in the content of Ca, Zn and Cu, and an increase in the content of Sr, as compared with such in the control group. Conclusion: Prolonged administration of haloperidol to rats intraperitoneally for 90 days according to the regimen from 15 mg/kg/day to 5 mg/kg/day causes the bone metabolism changes with all characteristics of bone destruction, detected by biochemical, histomorphometry and microelement analyses of bone tissue and blood. Haloperidol could be used to model experimental osteoporosis and the “haloperidol model” could be used to study potential of new antiresorptive agents.