Housing Temperature Influences Atypical Antipsychotic Drug‐Induced Bone Loss in Female C57BL/6J Mice. (7th September 2021)

• Record Type: Journal Article
• Authors: Kunst, Roni F; Langlais, Audrie L; Barlow, Deborah; Houseknecht, Karen L; Motyl, Katherine J
• Other Names: Johnson Rachelle W guestEditor.; Weivoda Megan guestEditor.
• Is Part Of: JBMR plus. Volume 5:Number 10(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-07
• Subjects: ANIMAL MODELS -- PRECLINICAL STUDIES -- SYSTEMS BIOLOGY—BONE INTERACTORS -- BONE‐BRAIN‐NERVOUS SYSTEM INTERACTIONS -- SYSTEMS BIOLOGY—BONE INTERACTORS -- BONE‐FAT INTERACTIONS; Bones -- Diseases -- Periodicals; Bones -- Metabolism -- Periodicals; Orthopedics -- Periodicals; 612.75104
• DOI: 10.1002/jbm4.10541
• Languages: English
• ISSNs: 2473-4039

Abstract

ABSTRACT: Atypical antipsychotic (AA) drugs, such as risperidone, are associated with endocrine and metabolic side effects, including impaired bone mineral density (BMD) acquisition and increased fracture risk. We have previously shown that risperidone causes bone loss through the sympathetic nervous system and that bone loss is associated with elevated markers of thermogenesis in brown and white adipose tissue. Because rodents are normally housed in sub‐thermoneutral conditions, we wanted to test whether increasing housing temperature would protect against bone loss from risperidone. Four weeks of risperidone treatment in female C57BL/6J mice at thermoneutral (28°C) housing attenuated risperidone‐induced trabecular bone loss and led to a low‐turnover bone phenotype, with indices of both bone formation and resorption suppressed in mice with risperidone treatment at thermoneutrality, whereas indices of bone resorption were elevated by risperidone at room temperature. Protection against trabecular bone loss was not absolute, however, and additional evidence of cortical bone loss emerged in risperidone‐treated mice at thermoneutrality. Taken together, these findings suggest thermal challenge may be in part responsible for bone loss with risperidone treatment and that housing temperature should be considered when assessing bone outcomes of treatments that impact thermogenic pathways. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. Abstract : Room‐temperature housing (left panel, 23°C) mounts a thermogenic stress response (large spark) to maintain body temperature. The atypical antipsychotic (AA) risperidone (RIS) also induces thermogenesis, accompanied by trabecular bone loss. Increasing housing temperature (right panel, 28°C) rescues RIS‐induced trabecular bone loss. Findings support an understudied thermogenic mechanism of bone loss side effects from AA drugs. Created with BioRender.com .