Saudi Cultural Missions Theses & Dissertations
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Item Restricted An investigation of a novel method for the diagnosis of osteoporosis using quantitative ultrasound(Exeter University, 2024) Asiri, Mohammed; Knapp, Karen; Fulford, Jonathan; Strain, DavidRationale: The rising global prevalence of osteoporosis and its significant financial and healthcare costs have prompted a revaluation of existing diagnostic procedures, mostly focused on dual-energy X-ray absorptiometry. Despite its popularity and usefulness, DXA has downsides that include radiation exposure, high prices, restricted availability in developing countries, and erroneous findings impacted by body fat composition. These limitations have led to the development of alternative diagnostics. Radiofrequency echographic multi-spectrometry (REMS) is a new method that uses ultrasound and advanced algorithms to evaluate bone health. However, its broad use and validation in varied therapeutic situations remain obstacles. Method: The precision error rate was measured to assess the ability of REMS to provide precise measurements. Seven operators scanned 61 participants' femur and lumbar spines to measure inter- and intra-operator reproducibility. Short-term precision tests were performed on 15 subjects, 10 continuing for medium- and long-term evaluations. Another 168 men and women were recruited to have REMS and DXA scans of the lumbar spine and femur. This set-up tested REMS' reliability and capacity to distinguish fracture patients. The study also compared REMS readings with DXA results in diabetes as a disease affecting bone density. A subset of 23 participants was scanned for abdominal fat thickness measurement to explore the influence of fat on REMS measurements. Finally, a survey assessed the acceptability of participants with REMS technology and examined how body composition affects measurement accuracy. Results: REMS had a better precision error rate than DXA in evaluating bone density in the lumbar spine and femur. REMS performed better in femoral evaluations than in the spine, in reasonable agreement with DXA and may detect osteoporosis and discriminate bone health states. Fracture risk prediction was more sensitive with DXA. The survey showed a negligible effect of body composition on the REMS measures and favourable participant approval. Despite these promising results, the study stressed the necessity to validate REMS in under-represented populations and diverse clinical settings. Conclusion: This Ph.D. project showed the promise of REMS as a novel osteoporosis diagnostic tool, highlighting its strengths and weaknesses. Based on the findings, REMS technology could potentially serve as a primary or supportive tool in the diagnosis and management of osteoporosis. Further research is essential to refine its diagnostic accuracy and efficacy in different demographics and clinical contexts. Expanding the evidence base will solidify the role of REMS in osteoporosis care.21 0Item Restricted OSTERIX - POSITIVE CELL-INTRINSIC IRE1α /XBP1 SIGNALING REGULATES THE POSTNATAL BONE DEVELOPMENT AND BONE MARROW HOMEOSTASIS(Saudi Digital Library, 2022) Alshalawy, Faisal; Ouyang, HongjiaoX-box binding protein-1 (XBP1) is a transcription factor that plays a critical role in managing cellular responses to endoplasmic reticulum (ER) stress. Under stress conditions, the transcriptionally active form of XBP1 is generated from unspliced Xbp1 by the inositol-requiring enzyme-1 (IRE1), an endoplasmic reticulum (ER) stress sensor and an ER-membrane residing endoribonuclease and kinase. The IRE1/XBP1s signaling is implicated in the development and homeostasis of many professional secretory cells and organs. Herein, In the second chapter of the dissertation, we demonstrate that deficiency of IRE1α, an IRE1 isoform that is expressed by osteoblast-lineage cells (Osterix-expressing cells), e.g., osteoblasts and skeletal progenitor cells, leads to osteoporosis/osteopenia with reduced bone formation/osteoblastogenesis and bone resorption/osteoclastogenesis, as well as enhanced bone marrow adipogenesis, in vivo. IRE1 deficiency results in compromised XBP1s signaling in osteolineage cells. In order to determine whether XBP1 is an important biological mediator of IRE1α in regulating postnatal bone development and bone hemostasis. In the third chapter of the dissertation, we showed that functional deficiency of XBP1 in Osterix-expressing cells, e.g., osteoblasts and skeletal progenitor cells, leads to osteoporosis/osteopenia with a significant compromised osteoblastogenesis and osteoclastogenesis, and increased bone marrow adipogenesis, in vivo. XBP1 deficiency results in both direct reduction in mRNA levels of XBP1 spliced and XBP1 total. Our study provides mouse genetic evidence demonstrating that Osx+ cell-intrinsic IRE1α/XBP1 is a physiological regulator for the postnatal bone development and bone marrow homeostasis.28 0