Boyd, Steven KyleKhan, AnealSidhu, Karamjot Kaur2020-09-042020-09-042020-08-27Sidhu, K. K. (2020). Spectrum of Microarchitectural Bone Disease in Inborn Errors of Metabolism (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/112496Inborn errors of metabolism (IBEMs) are a heterogeneous group of inherited disorders caused by a defect in the synthesis, metabolism, transport, and/or storage of metabolites. Diagnosed patients can often present with compromised bone health and an increased risk for fragility fractures. The current standard for measuring bone health in the general population is bone density assessed by dual-energy X-ray absorptiometry (DXA). However, its utilization in understanding bone status in IBEMs is limited. The primary limiting factor is DXA’s inability to assess cortical and trabecular bone independently, which is important in understanding bone loss that is a result of complex disease processes. In this thesis, macro- and microarchitectural properties of bone were monitored in a wide range of IBEM disorders using new three-dimensional technology, high-resolution peripheral quantitative computed tomography (HR- pQCT). Moreover, bone strength was estimated by employing finite element techniques on HR- pQCT image data. A further examination of these measurements in relationship to genetic mutations, clinical history, and treatment status was investigated in Gaucher disease and hypophosphatasia as a case report and cohort study, respectively. In IBEM patients, both bone density and microarchitecture were impaired when compared to a reference database. The degree of impairment varied between IBEM subtypes, and was significantly greater in IBEMs associated with decreased bone mass mineralization, including hypophosphatasia. Cortical bone density and microarchitecture were also significantly lower in IBEM patients with previous fractures when compared to IBEM patients with no fracture history. Estimated bone strength was also significantly lower in certain IBEM disorders when compared to a reference database, including IBEM disorders of metabolism requiring diet restrictions and disorder of the nervous or muscular system resulting in impaired mobility. Investigations in Gaucher disease and hypophosphatasia suggested disease-targeting therapy may aid in preventing or delaying accelerated bone mass loss that is thought to occur from the IBEM diagnosis. In conclusion, bone density and microarchitecture are largely affected in IBEMs. Future work in understanding how therapeutic interventions, such as bone-altering therapies, impact bone density and microarchitecture in IBEMs may be highly valuable.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Rare diseasesHigh-resolution quantitative computed tomographyGaucher diseaseHypophosphatasiaBone densityBone microarchitectureGeneticsRadiologyEngineering--Biomedicalmaster thesis10.11575/PRISM/38168