Risperidone accelerates bone loss in mice models of schizophrenia by inhibiting osteoblast autophagy

Risperidone (RIS) is the first-line drug in the clinical treatment of schizophrenia, and long-term use may lead to bone loss and even osteoporosis. This study investigated whether the mechanism of RIS-induced bone loss is related to autophagy.

The schizophrenia mice were established with the administration of MK-801. Then, RIS were injected, or autophagy inducer rapamycin (RAPA) co-injected for 8 weeks. Cognitive performance was determined by the novel object recognition and Open field tests. Bone loss of schizophrenia mice were assessed using microCT, H&E staining, ALP staining, ARS staining and WB, respectively. Autophagy of schizophrenia mice were detected by immunofluorescence, transmission electron microscopy (TEM) and WB, respectively. In addition, osteogenic differentiation of MC3T3-E1 and BMSCs cells were assessed using H&E staining, ALP staining, ARS staining and WB, respectively.

In the present study, we found that RIS treatment can promote bone loss in schizophrenia mice and inhibit osteogenic differentiation of MC3T3-E1 and BMSCs cells. Interesting, the number of autophagosome and autophagy-related protein expression were decreased after RIS treatment. However, the bone loss and inhibition of osteogenic differentiation induced by RIS in schizophrenia mice were reversed by autophagy inducer RAPA.

RIS significantly increased bone loss and inhibited osteogenic differentiation in schizophrenia mice; the underlying mechanism entails suppressing osteoblast autophagy.