Graduation Semester and Year
Summer 2024
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Materials Science and Engineering
Department
Materials Science and Engineering
First Advisor
Harry Fred Tibbals
Second Advisor
Efstathios Meletis
Abstract
Abstract
Investigation of Bone Structure and Composition Differences in Osteofibrous Dysplasia and Neurofibromatosis Type 1
Farzaneh Fereidouni, Ph.D.
The University of Texas at Arlington, 2024
Supervising Professor: Harry F. Tibbals
Bone genetic diseases such as Osteofibrous Dysplasia (OFD) and Neurofibromatosis type 1 (NF1) present significant challenges, particularly in children, due to their effects on skeletal homeostasis. This study aims to apply advanced material analysis to elucidate the biological disparities associated with OFD and NF1 bone dysplasia and contribute to developing diagnostic protocols and remediation approaches for these and similar bone disorders.
By employing various analytical methods, including analysis of mineral-to-matrix ratio, bone mineral density, bone hardness, and micromechanical architecture, this study compares normal rat bones with those affected by OFD and NF1. The pre-clinical mouse models of these disorders investigate potential mechanisms and pathways involved in these conditions.
The findings suggest that OFD and NF1 significantly alter bone composition and mineral-to-matrix structure, leading to decreased trabecular bone score, bone mineralization, and bone mineral density. These diseases are hypothesized to involve a common mechanism related to the MEK pathway and mineral phosphate disruption. The mineral-to-matrix ratio, in combination with bone density, is proposed as a potential diagnostic marker for these diseases.
To achieve these objectives, several techniques are employed, including Micro-CT, Raman spectroscopy, Raman 2D mapping, Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS), Micro Hardness Testing, and staining to identify abnormalities in composition and structure. We examined knockout bone which is defined as OFD and NF1 Bone. The collected data indicates that the mineral-to-matrix ratio is significantly lower in knockout mice affected by OFD and NF1, while microhardness test results show higher values in normal bones. Additionally, bone density was lower in knockout bones as compared to normal bones; furthermore, histology results showed that the OFD knockout bones are weaker and have a higher risk of fracture compared to normal bones due to the increased percentage of empty lacunae and trabeculation of cortical bone.
This research yields three significant findings: evidence of abnormalities in apatite mineralization in OFD and NF1 knockout bones from Raman spectra, elevated inorganic mineral forms of calcium and phosphorous in OFD and NF1 knockout bones from Raman and EDS/SEM analyses, and disorganization of bone microstructure in OFD and NF1 knockout bones revealed by 2D Raman mapping. These results support reported differences in bone density and mineral-to-matrix ratios between normal, OFD, and NF1-affected bone, demonstrating the potential utility of 2D Raman for high-resolution mapping of bone microstructure.
Overall, this study provides valuable insights into the pathophysiology of OFD and NF1, offering potential diagnostic techniques for early detection and quantification of bone morphology and composition in these and similar bone diseases.
Keywords: Bone; Mineral-to-matrix Ratio; Bone Density; Raman Spectroscopy; SEM/EDS; Micro-CT; Hardness Test; Histology.
Keywords
Bone; Mineral-to-matrix Ratio; Bone Density; Raman Spectroscopy; SEM/EDS; Micro-CT; Hardness Test; Histology.
Disciplines
Biology and Biomimetic Materials | Structural Materials
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Fereidouni, Farzaneh, "INVESTIGATION OF BONE STRUCTURE AND COMPOSITION DIFFERENCES IN OSTEOFIBROUS DYSPLASIA AND NEUROFIBROMATOSIS TYPE 1" (2024). Material Science and Engineering Dissertations. 85.
https://mavmatrix.uta.edu/materialscieng_dissertations/85