Six week old male Sprague-Dawley rats were administered intravenous clozapine, quetiapine, haloperidol or vehicle once daily for a period of 42 days with access to only high fat diet and their weight was monitored regularly. At the end of the study the rats were killed and the tibiae excised and bone mineral density (BMD) measured with dual X-ray absorptiometry and bone architecture assessed with micro-computed tomography (micro-CT) and associated software. Results were subjected to one-way ANOVA and post hoc Dunnetts multiple comparison test. All treatment groups were compared to control. There were no significant differences in body weight between the different groups at completion of the study. Clozapine treated animals alone showed a significant reduction in bone mineral density (p<0.05) however no differences were seen with haloperidol and quetiapine. Both haloperidol and quetiapine, but not clozapine, treatment showed a significant reduction in the bone to tissue volume ratio (BV/TV) by approximately 23% (p<0.05) and an increase in trabecular number (TbN) by approximately 21% (p<0.05). Trabecular bone architecture parameters for haloperidol and quetiapine, but not clozapine, showed more rod like and disconnected structure as reflected in the increases in structure model index (SMI) of around 15% (p<0.05) and trabecular pattern factor (TbPf) by 22% (p<0.05). This data demonstrates that in rats receiving a high fat diet, haloperidol and quetiapine have an adverse effect on bone micro-architecture without significant change in whole body bone mineral density. Clozapine did not affect bony architecture in a significant manner as reported in our earlier study, though bone mineral density was reduced. Reasons for the different effect of clozapine in this study are still uncertain but may be related to the significant weight loss seen at the end point of the previous study. Causes for osteoporosis and increased fracture risk in schizophrenia may include smoking history, malnutrition, limited sun exposure and compliance. Long term administration of both typical and atypical anti-psychotics may have a negative effect on bone and is a further factor that can influence this risk. An awareness of this relationship is useful in the orthopaedic management of schizophrenic patients.
