Trabecular bone loss after administration of the second-generation antipsychotic risperidone is independent of weight gain

► Risperidone reduced trabecular and cortical bone mass in mice. ► Risperidone elevated bone resorption and suppressed bone formation. ► Risperidone induced osteoclast (but not osteoblast) differentiation in vitro. ► Weight gain did not contribute to risperidone-induced bone loss.