Date of Award
Spring 5-10-2025
Level of Access Assigned by Author
Open-Access Thesis
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Sciences
First Committee Advisor
Katherine Motyl
Second Committee Member
Calvin Vary
Third Committee Member
Anyonya Guntur
Additional Committee Members
Matthew Lynes
Diana Goode
Abstract
Osteoporosis is a skeletal disease that results from low bone density and strength leading to fracture and ultimately, reduced quality of life and increased mortality. An estimated 1 in 10 adults over the age of 50 in the U.S. have osteoporosis. One of many factors that impact skeletal health includes the use of certain medications that have the unwanted side effect of increased fracture. Referred to as fracture associated drugs (FADs), many FADs are taken to treat nervous system disorders.
/="/"> Utilizing pharmacologic mouse models of atypical antipsychotic (AA) drug, opioid, and selective serotonin reuptake inhibitor (SSRI) treatment, this thesis explores how the nervous system effects bone remodeling evidenced by changes in brown fat activation, micro-RNA expression, and circulating extracellular vesicles related to osteoclast resorption and osteoblast bone formation. Key findings include the propensity for olanzapine, an atypical antipsychotic, to cause trabecular bone loss across different housing temperatures as a modulator of sympathetic and brown fat activation. In contrast, the SSRI sertraline benefits trabecular bone in young wildtype mice, which is distinct from findings from human studies that show SSRI use decreases bone density. Furthermore, this thesis sets a framework to continue to identify novel signaling between nerves and bone via extracellular vesicles using transgenic fluorescent reporter mice. Addressing root causes of bone loss by FADs is important as it may offer new therapeutic targets and prevention strategies and increase overall understanding of signaling between the nervous system and bone.
Recommended Citation
Langlais, Audrie L., "Sympathetic and Sensory Mechanisms of Bone Loss from Common Neuropharmaceuticals" (2025). Electronic Theses and Dissertations. 4142.
https://digitalcommons.library.umaine.edu/etd/4142