COBRE in Mesenchymal & Neural
Regulation of Metabolic Networks

Building research excellence in understanding causes of metabolic disease

COBRE in Mesenchymal and Neural Regulation of Metabolic Networks


Project 4:  Neural and metabolic mechanisms of atypical antipsychotic drug-induced bone loss. Dr. Katie Motyl

Project significance – Atypical antipsychotic drugs are prescribed to adolescents, adults, and the elderly for schizophrenia, bipolar disorder and other off-label purposes such as depression and dementia. Patients taking these drugs have an increased fracture risk, impaired bone accrual, metabolic syndrome and circadian disruption. This project will study the mechanisms by which antipsychotics cause bone loss. In addition, antipsychotic drugs affect the sympathetic nervous system (SNS), which in turn regulates brown fat in the body. We will also examine the role of brown fat in bone loss due to antipsychotic drugs.

From Motyl et al. 2017

The antipsychotic risperidone causes bone loss. Eight week old mice were either sham operated or ovariectomized (OVX), which models hypogonadism leading to bone loss. Mice were treated with vehicle or risperidone daily for 8 weeks to study effects on bone. Shown are microCT images of the distal trabecular bone. Risperidone alone and ovariectomy alone lead to bone loss (compare to sham vehicle), but risperidone causes additional bone loss in ovariectomized mice.

This project’s collaborators include:  Kristy Townsend— University of Maine; and Karen Houseknecht – University of New England.

The Science Sketch video below demonstrates how the metabolic consequences of antipsychotic drugs relate to changes in bone remodeling.