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Investigating the Effects of Aging and Prolonged Opioid Use on Bone Histomorphometry, Quality, and Biomechanics

Davis, Reed A
http://orcid.org/0000-0003-2735-2295
http://rave.ohiolink.edu/etdc/view?acc_num=akron1657368881832428

Abstract Details

2022, Doctor of Philosophy, University of Akron, Integrated Bioscience.
Opioids have become one of the most misused classes of prescribed medication. Synthetic opioids (e.g., fentanyl) have been responsible for most opioid overdose deaths since 2017. As this epidemic shows no signs of slowing, it is imperative to study the effects of opioids on various aspects of health including bone maintenance. Endogenous opioids (e.g., met-enkephalin) are involved in osteogenesis and bone remodeling. Exogenous opioids can interfere with bone maintenance directly through binding to osteoblasts, limiting bone formation, or indirectly through a cascade of effects limiting sex hormone production. To understand how opioids affect bone microarchitectural and biomechanical properties we first examine bone microstructure throughout the human lifespan to see natural changes occurring without the effects of opioids. Using both Synchrotron Radiation micro-Computed Tomography and confocal laser microscopy, we found bone and lacunar volume fractions to decrease with advancing age while pore diameter increased in the anterior midshaft femur. After finding how bone changes with age under normal circumstances, we sought to examine how prolonged opioid administration affected trabecular microstructure in a model organism (rabbit). We used μCT to examine the proximal tibia by anatomical quadrant (e.g., anterior, posterior). We found that morphine animals had greater bone volume fraction and less trabecular separation than controls. Fentanyl animals had significantly thicker trabeculae and increased trabecular spacing than controls. Detected differences by anatomical region followed the same overall pattern, suggesting biomechanical or anatomical variation rather than due to opioids. We finally examined overall bone strength in a non-weight bearing bone (rib) of the rabbit using uniaxial compression testing to determine how opioids affect overall mechanical competency. We found no difference in mechanical variables between opioid and control groups. Only rib span length was significantly greater in fentanyl animals compared to controls. Our stress-strain curves appeared remarkably similar to that of the standard curve derived from rocks. These results suggest that there is a complex response in bone to prolonged opioid administration and further work is necessary to elucidate such responses.
Brian Bagatto (Advisor)
Janna Andronowski (Committee Co-Chair)
Henry Astley (Committee Member)
David Cooper (Committee Member)
Christine Dengler-Crish (Committee Member)
Nita Sahai (Committee Member)
169 p.
Biology; Biomechanics; Histology; Pharmaceuticals; Physiology
Bone; Opioids; 3D Imaging; Micro-CT; Synchrotron; Rabbit; Porosity; Lacuno-Canalicular Network; Trabecular; Cortical; Rib; Femur; Tibia

Recommended Citations

Citations

  • Davis, R. A. (2022). Investigating the Effects of Aging and Prolonged Opioid Use on Bone Histomorphometry, Quality, and Biomechanics [Doctoral dissertation, University of Akron]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=akron1657368881832428

    APA Style (7th edition)

  • Davis, Reed. Investigating the Effects of Aging and Prolonged Opioid Use on Bone Histomorphometry, Quality, and Biomechanics. 2022. University of Akron, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=akron1657368881832428.

    MLA Style (8th edition)

  • Davis, Reed. "Investigating the Effects of Aging and Prolonged Opioid Use on Bone Histomorphometry, Quality, and Biomechanics." Doctoral dissertation, University of Akron, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=akron1657368881832428

    Chicago Manual of Style (17th edition)

akron1657368881832428
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