Housing Temperature Influences Atypical Antipsychotic Drug-Induced Bone Loss in Female C57BL/6J Mice.
Housing Temperature Influences Atypical Antipsychotic Drug-Induced Bone Loss in Female C57BL/6J Mice.
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作者：
Kunst RF;Langlais AL;Barlow D;Houseknecht KL;Motyl KJ
非典型抗精神病 (AA) 药物，如利培酮，与内分泌和代谢副作用相关，包括骨矿物质密度 (BMD) 获取受损和骨折风险增加。我们之前已经证明，利培酮通过交感神经系统导致骨质流失，并且骨质流失与棕色和白色脂肪组织中产热标志物的升高有关。由于啮齿类动物通常生活在亚热中性条件下，因此我们想测试提高饲养温度是否可以防止利培酮引起的骨质流失。对雌性 C57BL/6J 小鼠在热中性 (28°C) 环境下进行利培酮治疗 4 周，可减轻利培酮诱导的小梁骨丢失，并导致低周转骨表型，在热中性环境下接受利培酮治疗的小鼠的骨形成和吸收指数均受到抑制，而在室温下利培酮治疗的小鼠骨吸收指数升高。然而，对小梁骨丢失的保护并不是绝对的，并且在热中性条件下利培酮治疗的小鼠中出现了皮质骨丢失的额外证据。总而言之，这些发现表明热挑战可能是利培酮治疗导致骨质流失的部分原因，并且在评估影响生热途径的治疗结果时应考虑外壳温度。 © 2021 作者。 JBMR Plus 由 Wiley periodicals LLC 代表美国骨与矿物研究学会出版。室温外壳（左图，23°C）会产生热应激反应（大火花）以维持体温。非典型抗精神病药 (AA) 利培酮 (RIS) 也会诱导产热，并伴有小梁骨丢失。提高鸡舍温度（右图，28°C）可以挽救 RIS 引起的骨小梁流失。研究结果支持了 AA 药物导致骨质流失副作用的生热机制，这一机制尚未得到充分研究。使用 BioRender.com 创建。
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. 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.