Risperidone Accelerates Bone Loss in Mice with Autistic-Like Deficits Induced by Maternal Lipopolysaccharides Exposure

Patients with neurodevelopmental disorders, usually suffer from low bone density. Many studies have revealed a higher risk of fractureafter treatment with the atypical antipsychotic drug Risperidone (RIS), which is used to treat such disorders. It remains debatable whether neurodevelopmental disorders are considered by low bone mass or pharmacotherapy may be the reason. This study evaluated the effects of risperidone on different aspects of bones in mice with lipopolysaccharide (LPS)-induced autistic-like deficits. Materials and Methods: Fivegroups of male mice were examined: LPS+Saline, which were exposed to LPS prenatally and received saline on days 28-56 postnatal; Saline +RIS, which received RIS orally in the same days; LPS+RIS, which were exposed to LPS prenatally then received RIS; Saline + Salineand Saline + RIS Vehicle, which were included as control groups. On the 56th day postnatal, animals were assessed for autistic-like behaviors. Then their bones were taken for biomechanical, immunohistological, stereological, and molecular evaluations. Results: Maternal LPS exposure resulted in deficits in all behavioral tests and RIS ameliorated these behaviors (p<0.01) & (p<0.05). The administration of LPS andRIS individually caused reduction in the biomechanical factors of bone. The numerical density of osteocalcinpositive cells was significantly decreased in the mice in these groups. These mice also had decreased RUNX2 and osteocalcin gene expression. When LPS micewere treated with Risperidone, these conditions were accelerated(p=0.000). Conclusion: In the LPS mice model of neurodevelopmental disorders, bone stability and mass were reduced. This condition worsened when these animals were treated with Risperidone