青少年特發性脊柱側凸(Adolescent Idiopathic Scoliosis, AIS) 是一種脊柱三維結構性畸形，其病因至今未明。它主要出現於11-13歲的青少年女性，其發病率為4%。由於目前此病的臨床治療效果未能盡如人意，因此必須明確其發病機制，以便能夠制定更有效的治療方案及預防措施。 / 既往有研究指出30%AIS患者存在系統性骨密度減低，且已證實骨密度的減少能夠預測其病情進展的情況。之前的研究主要通過傳統的雙能量X光骨質密度吸收儀（DXA）檢測骨密度，其測量結果僅局限於面積骨密度。然而，三維容積骨密度以及骨質微結構的分析對於深入了解患者的骨質量及其與發病機制的聯繫尤為重要。通過現代影像掃描技術發展，使我們可以通過高分辨率外周骨定量X-線斷層掃描儀（HR-pQCT）進行人體骨品質的無創定量檢測。其參數包括骨形態，容積骨密度以及鬆質骨的微結構。 / 本研究分為兩部分，研究目的為： 1）研究AIS患者與年齡，性別匹配的正常青少年骨品質的差異；2）評估及比較在AIS患者及其對照組中骨品質跟骨密度減少之關係。 / 未經治療AIS 患者214例，正常對照組187例，均為11-13歲的女性。 AIS患者及正常對照組均採用DXA掃描評估股骨頸的面積骨密度。此外，所有參加計劃者通過非優勢側橈骨遠端HR-pQCT 掃描，定量測量其骨形態，容積骨密度以及鬆質骨的微結構。 / 第一部分的結果顯示在校正年齡後AIS患者的皮質骨面積(p=0.048)，皮質骨容積骨密度(p=0.014)及鬆質骨骨小樑數目(p=0.003) 低於對照組，並且存在較高的骨小樑分離度(p=0.006)。通過多元線性回歸分析校正了年齡，鈣攝入量及體育活動後，仍顯示AIS患者皮質骨容積骨密度(p=0.032)及鬆質骨骨小樑數目(p=0.005) 顯著低於對照組，骨小樑分離度（p=0.010）顯著高於對照組。而皮質骨週長的比較則未見顯著差異。皮質骨中骨質量的異常提示AIS患者內皮質成骨時可能存在骨礦堆積障礙。並且這種較低的皮質骨面積及容積骨密度預示著較弱的骨機械強度，從而誘發AIS患者脊柱的不隱定以至畸形。此外，AIS中較少的骨小樑數目反映了骨小樑形成的缺陷，這可能是由於患者存在軟骨內成骨及骨礦化的異常調節。 / 在第二部分，根據DXA測量及計算的Z值，參加者被分為骨量偏低組（Z值≤-1)及正常骨量組（Z值>-1)。研究結果顯示，AIS的骨量偏低組與對照組具有顯著差異。通過骨量偏低組及正常骨量組的比較，結果顯示鬆質骨品質與骨量偏低的關係只存在於AIS組中。本研宄發現，在AIS患者中的骨量偏低組存在鬆質骨容積骨密度，骨體積分數顯著減少及骨小梁變薄。並且結果顯示AIS患者骨小梁模型指數（SMI）較大（p<0.001)，提示骨小梁更接近柱收結構，而先前研究已經證明柱狀結構較板狀結構在力學上更不穩定。通常鬆質骨對於代謝及生物力學的改變更加敏感。骨量偏低的AIS患者松質骨中骨品質的異常改變提示AIS患者可能存在骨代謝功能障礙，從而導致異常的骨形成及重塑。鬆質骨中骨微結構的改變可能會引起骨強度的下降，從而導致脊柱在機械力學上的不穩定及側凸進展。因此本研究的重要臨床意義在於需要形成一個融合了骨品質及骨密度相關指標的複合預測因素，在AIS的臨床治療過程中預測側凸進展。 / 此體內研究首次對AIS患者的骨品質進行了報導。研究結果表明AIS患者存在骨品質異常，並且首次提出骨量下降的AIS患者存在鬆質骨的異常改變。骨品質異常的本質和原因及其在AIS的發病機制中的作用值得進一步研究。 / Adolescent Idiopathic Scoliosis is a three-dimensional spinal deformity of unknown etiology. It occurs mainly in girls between 11 to 13-year-old with a prevalence rate of 4%. This common spinal condition can be associated with significant cosmetic and clinical morbidities in severe cases. Since the treatment for AIS remains unsatisfactory, it is imperative to elucidate the etiopathogenesis of AIS so that effective therapeutic and preventive measures can be devised. Towards this end, Cheng et al. investigated and noted that osteopenia was present in 30% of AIS subjects. Osteopenia was found to be a significant prognostic factor for curve progression in AIS. In previous studies, only Dual energy X-ray Absorptiometry (DXA) was available and the measurement was confined to areal-BMD (aBMD). For in-depth understanding of the bone quality and its link to the etiopathogenesis of AIS, three-dimensional volumetric evaluation of bone mass and measurement of key parameters of bone quality would be important. With the advancement of imaging techniques and the availability of high-resolution pQCT (HR-pQCT), it is now possible to have in vivo measurement of bone quality including Bone Morphometry, Volumetric BMD (vBMD) and Trabecular Bone Micro-architecture in human subjects. / The current study utilized HR-pQCT with the following objectives: 1) to investigate bone quality in AIS vs. age- and sex-matched normal controls and 2) to evaluate and compare the correlation of bone quality with osteopenia between AIS and non-AIS control subjects. / 214 untreated AIS and 187 non-AIS healthy girls between 11-13 years old were recruited. aBMD of bilateral femoral necks was measured by DXA. Bone Morphometry, vBMD and Trabecular Bone Micro-architecture were measured at the non-dominant distal radius using HR-pQCT. / In the first part, our findings demonstrated that AIS was associated with lower Cortical Bone Area (p=0.048), Cortical Bone vBMD (p=0.014), Trabecular Number (p=0.003) and greater Trabecular Separation (p=0.006) after adjustment for age. With multivariate linear regression analysis, after adjusted for age, calcium intake and physical activity levels, the association of AIS with lower Cortical Bone vBMD, (p=0.032), Trabecular Number (p=0.005) and greater Trabecular Separation (p=0.010) remained. In contrast, no difference was found in the Cortical Perimeter between AIS and controls. / The abnormalities in cortical bone quality in AIS suggested the possibility of defects in mineral accretion during endocortical apposition. We speculated that lower Cortical Area and vBMD could be associated with reduced bone mechanical strength thus predisposing to the development or progression of spinal deformity in AIS. Furthermore, the association between AIS and lower Trabecular Number reflected a defect in trabecular formation, which might be due to abnormal regulation and modulation of endochondral ossification and bone mineralization in AIS. / In the second part, subjects were classified into the osteopenic (Z-score≤-1) and non-osteopenic (Z-score>-1) group. Interestingly, we found that osteopenia in AIS was distinctly different from osteopenia in non-AIS controls. Alterations in trabecular bone quality in association with osteopenia were only detected in AIS. Osteopenic AIS was uniquely associated with lower Trabecular Bone vBMD, BV/TV, Trabecular Thickness (all p<0.001) and greater SMI (p=0.008) indicating predominance of rod-like trabeculae when compared with non-osteopenic AIS. / The trabecular compartment is generally more vulnerable and responsive to changes in the metabolic and biomechanical environment. The unique alterations of trabecular bone quality in osteopenic AIS suggested the presence of metabolic dysfunction resulting in abnormal modeling and remodeling processes in AIS. These altered trabecular bone micro-architecture might lead to reduced bone strength thus resulting in mechanical weakness of the spine and subsequent curve progression. Another clinical significance of the present study was the call for developing a composite prognostic factor incorporating both BMD and bone quality parameters for more accurate prediction of curve occurrence and progression in AIS in clinical practice. / In conclusion, this is the first series of in vivo studies evaluating bone quality in AIS. Our findings demonstrated abnormal bone quality in AIS and unique alteration of trabecular bone profile in osteopenic AIS. Further studies are warranted to better define the nature, origin and abnormal metabolic pathways and processes leading to the derangement in bone quality and its link to the etiopathogenesis of AIS. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yu, Wing Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 122-134). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese; appendixes includes Chinese. / ABSTRACT --- p.i / ABSTRACT (in Chinese) --- p.iv / ACKNOWLEDGEMENT --- p.vi / TABLE OF CONTENTS --- p.vii / LIST OF TABLES --- p.x / LIST OF FIGURES --- p.xi / LIST OF ABBREVIATIONS --- p.xii / Chapter Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1. --- General overview of scoliosis --- p.1 / Chapter 1.1.1. --- Classification of scoliosis --- p.1 / Chapter 1.1.2. --- Prevalence of AIS --- p.2 / Chapter 1.2. --- Natural History of AIS --- p.3 / Chapter 1.3. --- Curve progression --- p.4 / Chapter 1.4. --- Current treatment modalities --- p.5 / Chapter 1.5. --- Etiology of AIS --- p.6 / Chapter 1.5.1. --- Bone mass and bone development --- p.9 / Chapter 1.5.2. --- Measurement of bone mineral density --- p.10 / Chapter 1.5.3. --- Osteopenia in AIS --- p.11 / Chapter 1.6. --- Bone quality --- p.13 / Chapter 1.6.1. --- Limitation of two-dimensional BMD measurement by DXA --- p.13 / Chapter 1.6.2. --- Bone quality assessment --- p.14 / Chapter Chapter 2 --- METHODOLOGY --- p.22 / Chapter 2.1. --- Research questions and Objectives --- p.22 / Chapter 2.2. --- Study Design --- p.23 / Chapter 2.2.1. --- Study Flowchart --- p.24 / Chapter 2.3. --- Subject Recruitment --- p.29 / Chapter 2.3.1. --- AIS patients --- p.29 / Chapter 2.3.2. --- Normal Controls --- p.29 / Chapter 2.4. --- Patients Consents --- p.30 / Chapter 2.5. --- Radiological Assessment --- p.30 / Chapter 2.5.1. --- Curve severity --- p.30 / Chapter 2.6. --- Anthropometric and pubertal assessments --- p.31 / Chapter 2.6.1. --- Body weight --- p.31 / Chapter 2.6.2. --- Body height --- p.31 / Chapter 2.6.3. --- Arm span --- p.32 / Chapter 2.6.4. --- Sitting height --- p.32 / Chapter 2.6.5. --- Body mass index --- p.32 / Chapter 2.7. --- Menstrual status and pubertal maturity --- p.33 / Chapter 2.8. --- Dietary calcium intake --- p.33 / Chapter 2.9. --- Physical activities --- p.34 / Chapter 2.10. --- Bone mineral density (BMD) measurements --- p.34 / Chapter 2.10.1. --- Areal BMD measured by Dual energy X-ray Absorptiometry (DXA) --- p.34 / Chapter 2.10.2. --- Definition of osteopenia or low bone mass --- p.35 / Chapter 2.11. --- Bone quality assessment --- p.36 / Chapter 2.11.1. --- Positioning --- p.36 / Chapter 2.11.2. --- Standardization of the Region of Interest (ROI) for Scan Acquisition --- p.36 / Chapter 2.11.3. --- Analysis of the Scan Results --- p.38 / Chapter 2.12. --- Statistical analysis --- p.41 / Chapter Chapter 3 --- RESULTS --- p.55 / Chapter 3.1. --- Subject characteristics --- p.55 / Chapter 3.2. --- Age of menarche, breast development and pubic hair development --- p.55 / Chapter 3.3. --- Anthropometric assessment --- p.55 / Chapter 3.4. --- Dietary calcium intake --- p.56 / Chapter 3.5. --- Physical activities --- p.56 / Chapter 3.6. --- aBMD and prevalence of osteopenia in AIS and controls --- p.56 / Chapter 3.7. --- Comparison of bone quality between AIS and controls --- p.57 / Chapter 3.7.1. --- Bone Morphometry --- p.57 / Chapter 3.7.2. --- Volumetric BMD --- p.58 / Chapter 3.7.3. --- Trabecular Bone Micro-architecture --- p.59 / Chapter 3.7.4. --- Short summary --- p.59 / Chapter 3.8. --- Comparison of bone quality Vs. Osteopenia between AIS and Controls --- p.61 / Chapter 3.8.1. --- Demographic characteristic of osteopenic and non-osteopenic AIS and controls --- p.61 / Chapter 3.8.2. --- Bone quality Vs Osteopenia in AIS and controls --- p.62 / Chapter 3.8.3. --- Short summary --- p.64 / Chapter Chapter 4 --- OVERALL DISCUSSION and CONCLUSION --- p.81 / Chapter 4.1. --- Low bone mineral density in AIS --- p.82 / Chapter 4.2. --- Comparison of bone quality between AIS and controls --- p.83 / Chapter 4.2.1. --- Alterations of Cortical Bone Morphometry and vBMD in AIS --- p.84 / Chapter 4.2.2. --- Lower Trabecular Number and greater Trabecular Separation in AIS --- p.88 / Chapter 4.3. --- Correlation between bone quality and osteopenia in AIS Vs normal controls --- p.90 / Chapter 4.3.1. --- Unique alteration of bone quality of trabecular bone in osteopenic AIS subjects --- p.90 / Chapter 4.3.2. --- Effect of the alterations in trabecular bone quality on bone strength in osteopenic AIS and its possible relationship with curve progression --- p.92 / Chapter 4.4. --- Justification of the Methodology --- p.95 / Chapter 4.4.1. --- Site of BMD measurement --- p.95 / Chapter 4.5. --- Summary and clinical significance --- p.97 / Chapter 4.6. --- Limitations and further studies --- p.99 / APPENDIX --- p.101 / BIBLIOGRAPHY --- p.122 / CONFERENCES AND PUBLICATIONS --- p.136
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_328088 |
| Date | January 2012 |
| Contributors | Yu, Wing Sze., Chinese University of Hong Kong Graduate School. Division of Orthopaedics and Traumatology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | electronic resource, electronic resource, remote, 1 online resource (xiii, 139 leaves) : ill. (some col.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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