A multi-scale study of bone mineralization and bone quality in adolescent idiopathic scoliosis

• Other Authors: Wang, Zhiwei (author.)
• Format: Others
• Language: English; Chinese; Chinese
• Published: 2015
• Subjects: Bones > Growth; Scoliosis > Etiology; Bone Density; Scoliosis > etiology
• Online Access: http://repository.lib.cuhk.edu.hk/en/item/cuhk-1291247

Introduction. The etiology of adolescent idiopathic scoliosis (AIS) is largely unknown. AIS was well-documented to be associated with low bone mineral density (BMD) and abnormal bone quality. We hypothesized that bone matrix mineralization is abnormally low in AIS and that the abnormality could lead to the observed osteopenia and abnormal bone quality that might contribute to the etiopathogenesis of AIS. === Objectives. 1. To verify the abnormal bone mass and bone quality in AIS Vs normal matched controls 2. To study the bone matrix mineralization status, micro-architecture and mechanical property in AIS Vs controls 3. To study the cellular and molecular characterization of bone formation and resorption in AIS Vs controls 4. To study the possible association of abnormal bone quality with the curve progression === Methods. 1. The case-control study in Chapter 3 included 257 AIS and 187 age- and gender-matched normal controls. BMD and bone quality were measured with dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) in vivo. 2. Chapter 4 studied iliac crest bone biopsies from 28 AIS and 9 controls. Bone mineral status was measured with DXA, micro-computed tomography (micro-CT) and energy dispersive X-ray spectroscopy; bone micro-architecture and mechanical property were measured with micro-CT, individual trabeculae segmentation analysis and finite element analysis (FEA). 3. Chapter 5 included 46 AIS and 23 controls. The mRNA expression of the bone tissue and primary osteoblastic and osteoclastic activities related to bone mineralization were studied. 4. Chapter 6 included 82 AIS patients. Bone quality was measured with HR-pQCT in vivo at baseline. Comparison was made between the stable and the progressive patients followed for more than 1.5 years after skeletal maturity. === Results. 1. In Chapter 3, both osteopenic and non-osteopenic AIS had lower areal BMD (aBMD) and trabecular and cortical volumetric BMD (vBMD) than their matched normal controls, with the non-osteopenic AIS reaching statistical significance (P<0.05). Osteopenic AIS had larger cortical perimeter and trabecular area than the osteopenic controls after adjustments of confounding factors (P<0.05); non-osteopenic AIS had significantly lower cortical area, thickness and vBMD than the non-osteopenic controls (P<0.05), and marginally significant cortical area and thickness after adjustments. 2. In Chapter 4, AIS had lower bone calcium content (Ca/C ratio) in trabecular bone than controls (P<0.05); moreover, AIS had significantly lower trabeculae rod number and thickness and mechanical property (P<0.05). Osteopenic AIS had significantly lower rod and plate micro-architecture (P<0.05) and 11.3% of decline of FEA mechanical property than non-osteopenic AIS. 3. In Chapter 5, AIS had lower expression of osteogenic markers (ALP and RUNX2) (P=0.009-0.132) and higher expression of extracellular matrix markers (COL1 and BGLAP) (P =0.109-0.132) in bone formation, and higher expression of bone resorption markers (TRAP and CTSK) (P =0.045-0.100). AIS also showed lower osteogenic differentiation potential and calcium nodule formation ability than controls. Within the subgroups, osteopenic AIS showed lower osteoblastic differentiation (P=0.009) and 41.8% decline of calcium formation abilities (P =0.186). The primary osteoblasts from the osteopenic AIS had higher pro-osteoclastogenic potential (P =0.034) and higher osteoclastogenic differentiation potential on osteoclasts. 4. In Chapter 6, progressive AIS had significantly lower aBMD, total vBMD and lower cortical area and thickness after adjustments (P<0.05). The predictive model showed that bone quality model was more predictive than the aBMD model which was more predictive than the basic model on curve progression. === Discussions The present study verified all the AIS had lower BMD and abnormal bone quality. It provided a direct evidence of lower calcium content in AIS which might contribute to the observed lower BMD. Therefore, these abnormalities in AIS could represent a spectrum of severity which is labeled as osteopenic or non-osteopenic with DXA and partly explained by the cellular and molecular studies. The longitudinal study showed AIS with poorer bone quality have significantly higher probability of curve progression. In summary, the present findings supported and confirmed our proposed hypothesis. === 引言：有研究提示AIS低骨量與骨質量異常與病因學有關。我們推測，AIS的骨基質礦化可能異常降低，進而導致低骨量和異常骨質量發生，這可能與AIS病因学有關。 === 目的：1. 驗證AIS的低骨量及骨質量異常 2. 调查AIS骨基質礦化、骨微結構和機械性能狀態 3. 研究AIS關於骨礦化的細胞分子功能 4. 探讨AIS骨質量與側彎進展間的關聯 === 方法：1. 通過雙能吸收儀和高分辨率外周定量CT比较低骨量和非低骨量AIS与其正常對照間骨密度和骨質量的差异 2. 通過雙能吸收儀、顯微CT和掃描電鏡與能量色散光譜儀檢測骨礦物質含量，及顯微CT、骨小梁個體分割和有限元分析法檢測骨微結構和力學性能，比較AIS和正常對照及AIS亞組間的差異。3. 通過檢測與骨礦化相關的mRNA，和原代成骨和破骨細胞培養，比較AIS和正常對照及AIS亞組間的差異。4. 通過高分辨率外周定量CT縱向隨診AIS患者，比較進展組和穩定組間骨質量差異。 === 結果：1. 低骨量和非低骨量AIS均比正常對照組骨密度和骨質量降低。2. AIS骨鈣含量降低，骨微結構和機械性能顯著異常。3. AIS骨形成標記物降低、骨吸收標記物升高，成骨分化潛能降低。低骨量AIS比非低骨量AIS成骨細胞分化能力降低和親破骨分化潛能升高。4. 側彎進展AIS骨密度和骨質量顯著異常。 === 討論：本研究結果支持我們的假設：AIS骨基質礦化異常，導致低骨量和異常骨質量，提示與AIS發病機理相關聯。 === Wang, Zhiwei. === Thesis Ph.D. Chinese University of Hong Kong 2015. === Includes bibliographical references (leaves 243-261). === Abstracts also in Chinese; appendixes includes Chinese. === Title from PDF title page (viewed on 09, September, 2016). === 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.