In vivo Assessment of Bone Microarchitecture and Bone Strength in Systemic Lupus Erythematosus Patients by High-Resolution Peripheral Quantitative Computed Tomography and Finite Element Analysi

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic systemic inflammation and various organ damages. Patients with SLE are at a higher risk of bone loss and fragility fracture than normal population. Furthermore, a high prevalence of vertebral fracture in premenopausal patients with SLE was observed. Low areal bone mineral density (aBMD) is currently the most widely used surrogate marker of osteoporotic fracture risk. However, discrepancies between aBMD measured by dual energy X-ray absorptiometry (DXA) and fracture prevalence is recognized in senile osteoporosis, GC use and SLE, indicating how aBMD alone is not fully reflective of reduction in bone strength. That's possibly due to the limitations of DXA, a 2-dimensional projectional imaging technique. DXA measures integral aBMD of cortical and trabecular bone and is confounded by bone geometry, thus could not truly reflect bone quality including microarchitecture and bone strength.;Objectives: 1. To assess bone geometric, densitometric, microarchitectural and biomechanical properties in patients with SLE on long-term GC (SLE/GC) as compared with healthy controls. 2. To evaluate the correlation between bone geometric, densitometric, microarchitectural and biomechanical properties and organ damage in patients with SLE/GC. 3. To compare the bone geometric, densitometric, microarchitectural and biomechanical properties among SLE/GC, SLE patients without any GC therapy (SLE/non-GC) and healthy controls. 4. To evaluate the changes of bone geometric, densitometric, microarchitectural and biomechanical properties by HR-pQCT over time in patients with SLE/GC and identify potential predictors for bone deterioration.;Methods: The present thesis comprises three cross-sectional studies and one prospective observational study in 180 Chinese female patients with SLE/GC and 180 age- and sexmatched healthy controls as well as 30 patients with SLE/non-GC in Hong Kong. Bone geometry, vBMD and microarchitecture were measured by HR-pQCT at non-dominant distal radius. Biomechanical properties (bone strength) were estimated by HR-pQCTbased muFEA. Areal BMD was evaluated by DXA at left femoral neck, left hip, lumbar spine and non-dominant distal radius. Clinical assessments and review of medical records were performed to obtain information regarding disease status.;Conclusions: 1. In addition to the aBMD loss at axial skeletons, bone geometry, vBMD, microarchitecture and biomechanical properties (bone strength) at peripheral site are significantly deteriorated in SLE patients with or without GC therapy, most dramatic at the cortical compartment. Cortical thinning and increased CtPo without any increase in cortical perimeter in SLE patients are suggestive of an ongoing process of endocortical resorption ('trabecularization') and intracortical excavated porosity.;2. Measurements of HR-pQCT and muFE underscore the power of advanced imaging in elucidating the potential underlying pathophysiology of bone loss in SLE, and provide us additional information about alterations of bone quality at separated cortical and trabecular compartment which might better predict fracture risk beyond aBMD by DXA in SLE.;3. Since cumulative GC dose was significantly associated with many organ damages, the predominant role that SDI plays in the deterioration of bone quality might, at least partly, reflects the deleterious effect of GC on bone. Thus, disease per se (cumulative inflammatory burden [SDI]) or in combination with GC therapy plays an important role in the bone mass loss and bone quality deterioration in SLE patients.;4. HR-pQCT provides us an insight into the underlying mechanism of bone loss in SLE that may be due to the disease damage and might partly due to the chronic use of GC. Therefore, preventing organ damage in SLE patients by adequate suppression of inflammation may be beneficial for preserving bone density and microarchitecture. Therapies without deleterious effect on bone, which can effectively control disease activity and, at the same time, prevent organ damage should be explored. (Abstract shortened by UMI.).