Browsing by Author "Schneider, Prism Steorra"

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    The assessment of fragility fracture risk using HR-pQCT as a novel tool for diagnosis of osteoporosis
    (2021-08) Whittier, Danielle Elizabeth Wein; Boyd, Steven Kyle; Schneider, Prism Steorra; Manske, Sarah Lynn; Edwards, William Brent; Forkert, Nils Daniel; Hallgrimsson, Benedikt; Jepsen, Karl
    Osteoporosis is a systemic skeletal disease, characterized by reduced bone density and deterioration of bone microarchitecture, leading to increased fracture risk. However, current diagnosis using dual-energy X-ray absorptiometry (DXA) only accounts for density and consequently fails to capture most individuals who fracture. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a medical imaging modality capable of characterizing three-dimensional bone microarchitecture at peripheral skeletal sites, and has demonstrated that bone microarchitecture can improve prediction of fracture risk. However, to date the improvement is modest, as interpretation of the interaction between fracture and the numerous parameters provided by HR-pQCT is complex. The objective of this dissertation was to elucidate the key microarchitectural characteristics that underpin bone fragility, and use these insights to improve assessment of fracture risk with HR-pQCT. First, reference data in the form of centile curves was established for HR-pQCT parameters using a population-based cohort (n=1,236, age 18–90 years), and a new intuitive parameter called void space was developed to capture localized regions of bone loss in HR-pQCT images. In a separate prospective multi-center cohort (n=5,873, age 40–90 years), unsupervised machine learning was implemented to identify common groupings (i.e., phenotypes) of bone microarchitecture in older adults. Three phenotypes were identified and characterized as low density, structurally impaired, and healthy bone, where the low density phenotype had the strongest association with incident osteoporotic fractures (hazard ratio = 3.28). Using the same cohort, a fracture risk assessment tool, called µFRAC, was developed using supervised machine learning methods to provide a 5-year risk of major osteoporotic fracture based on HR-pQCT parameters, and was demonstrated to significantly outperform DXA in predicting fracture risk. Finally, a new retrospective cohort of patients with fragility fractures at the hip (n=108, age 56–96 years) was used to characterize bone fragility. Hip fracture patients were significantly associated with the low density phenotype and had bone void spaces that were 2–3 times larger than controls. Together, these findings provide insight into the characteristics of bone that lead to osteoporotic fractures and introduces tools that enable insightful interpretation of HR-pQCT data for clinical use.
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    Studying Hypercoagulability in Hip Fracture Patients as Determined by Thrombelastography
    (2020-06-29) You, Daniel Zheng; Schneider, Prism Steorra; Salo, Paul T.; Fritzler, Marvin J.; Korley, Robert E. C.; Skeith, Leslie
    Hip fractures are the most devastating manifestation of osteoporosis with high venous thromboembolic (VTE) rates reported following surgery. Currently, there is no guideline consensus on the optimal duration of pharmacologic thromboprophylaxis or medication choice. Furthermore, some patients develop VTE despite being on anticoagulation. Thrombelastography (TEG) is a whole-blood viscoelastic hemostatic assay that has the potential to identify hypercoagulable patients at risk for developing VTE. The purpose of this study was to understand the utility of TEG analysis to quantify hypercoagulability and ensuing VTE risk in patients with hip fracture. Serial TEG analysis was performed in a cohort of patients with hip fracture every 24-hours from admission until post-operative day (POD) five, then at two and six weeks post-operatively. Hypercoagulability was quantified using a TEG maximal amplitude (MA) threshold over 65 mm. Multivariable logistic regression evaluated associations between elevated MA values and patient and surgical factors. In total, 121 patients (88 female) with a median age of 81 (range = 53 – 96) were recruited. Although admission TEG analysis revealed normal coagulation status (MA<65mm), patients transitioned to a hypercoagulable state by POD 3. Hypercoagulability peaked two weeks post-operatively. Furthermore, most patients remained hypercoagulable six weeks post-operatively, despite discontinuing anticoagulation one to two weeks prior. On admission, female sex and the presence of chronic kidney disease were associated with hypercoagulability (MA>65mm). Post-operatively, reduced mobility and treatment with arthroplasty were associated with hypercoagulability (MA>65mm). Results from this study support further investigation into individualized extended thromboprophylaxis regimens in patients with hip fracture. Additionally, TEG-identified patient and surgical factors associated with hypercoagulability should be given further consideration to mitigate VTE risk and in the development of future hip fracture specific VTE risk prediction models.
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    Using HR-pQCT and finite element analysis to inform clinical assessment of distal radius fractures
    (2020-08-05) Spanswick, Phillip; Schneider, Prism Steorra; Boyd, Steven Kyle; Manske, Sarah Lynn; Korley, Robert E. C.
    Distal radius fractures (DRFs) are commonly treated non-operatively with cast immobilization; however, there are no standardized clinical practice guidelines to direct optimal duration of immobilization following a DRF. Finite element (FE) modelling coupled with high-resolution peripheral quantitative computed tomography (HR-pQCT) allows for non-invasive in vivo assessment of bone density and stiffness throughout the fracture healing process, which may inform fracture healing progression and cast removal. Many fracture assessment instruments have been developed for clinical use, but a lack of validation and standardization has led to considerable variability in the assessment of fracture healing. We hypothesized that changes in bone stiffness and bone mineral density measured using HR-pQCT can better inform the duration of casting following a DRF. We aimed to identify clinical assessment instruments that were good predictors of fracture stiffness and could inform cast removal. Participants (n=30) with a stable DRF were followed for two week intervals from the time of fracture until two months post-fracture, then at three months and six months post-fracture. At each follow-up, participants underwent clinical, radiographic, and functional assessments, as well as had their fractured wrist scanned using HR-pQCT. Recovery of bone stiffness during fracture healing was determined from micro-FE (µFE) models generated from HR-pQCT image data. During fracture healing, significant longitudinal changes were found in µFE-estimated stiffness, patient-reported outcomes, grip strength, range of motion (ROM), tenderness, number of cortices healed based on radiographs, and fracture line visibility (p<0.05); however, no significant change was detected in HR-pQCT based total bone mineral density. Grip strength, ROM, and patient-reported outcomes such as the Patient-Rated Wrist Evaluation (PRWE) and the Quick Disability of the Arm, Shoulder and Hand (QuickDASH) questionnaire correlated strongly with µFE-estimated stiffness (0.61≥ rm ≥0.71). Based on µFE-estimated stiffness, PRWE and QuickDASH are the best predictors of stiffness recovery (p<0.05) and may be used to guide duration of cast immobilization in the clinical setting.