Modulating mechanobiology and blood supply to improve bone strength in Paget's disease

调节机械生物学和血液供应以改善佩吉特病的骨强度

• 批准号: 1938335
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1938335
• 关键词: Modulating; mechanobiology; blood; supply; improve

aget's disease of bone (PDB) is a metabolic bone disease characterised by very high rates of bone remodelling which lead to bone expansion, trabecular disorganisation with a consequent decreases in strength and quality. Blood flow to bone lesions present in PDB has been reported to be nine times the normal levels, and warmth to the skin over Pagets bone is common, however targeting the vasculature in the treatment of PDB remains to be investigated. Fracture is a well-recognised complication of PDB and accurate, early diagnosis is key to successful treatment but remains difficult, improving fracture predication in PDB is our long term research goal.3D image-based computational modelling or finite element (FE) analysis is perceived to be a highly promising tool clinically to predict stresses throughout the bone which are related to impact forces, important determinants of fracture risk. Computed tomography (CT) can provide input to FE analyses, assessing the 3D bone geometry and bone density distribution in order to estimate bone strength in vitro. However, for in vivo application of FE analysis, major methodological challenges are unsolved, since in vivo images are frequently impaired by the presence of soft tissue or motion artefacts and mechanical loading conditions are not known. To combat this problem we have recently developed a novel bone loading system which promotes a robust anabolic response ex vivo. This system allows for CT scans to be undertaken before and after exposure to predetermined strain magnitudes and can better inform FE analyses to accurately predict sites of biomechanical stress and fracture within bone.The main aim of this interdisciplinary studentship between Biological Sciences and Engineering will be to combine ex vivo loading and finite element analysis in the study of Pagetic bones to better predict fracture risk at local sites during the disease. This will allow us to establish for the first time the role of microstructural organisation and vascularisation in determining bone quality in Paget's disease, as well as offer potential treatments. We will also utilise these techniques to test how effective inhibitors of angiogenesis will be in treating the disease and reducing fractures (in collaboration with Roche).

aget's disease of bone （PDB）是一种代谢性骨病，其特征是骨重塑率非常高，导致骨扩张、骨小梁紊乱，从而导致强度和质量下降。据报道，在PDB中，流向骨骼病变的血流量是正常水平的9倍，Pagets骨骼上的皮肤发热是常见的，然而，针对血管系统治疗PDB仍有待研究。骨折是一种公认的PDB并发症，准确、早期诊断是成功治疗的关键，但仍然很困难，提高PDB的骨折预测是我们的长期研究目标。基于三维图像的计算建模或有限元（FE）分析被认为是一种非常有前途的临床工具，用于预测整个骨骼的应力，这些应力与冲击力有关，是骨折风险的重要决定因素。计算机断层扫描（CT）可以为有限元分析提供输入，评估三维骨几何形状和骨密度分布，以估计体外骨强度。然而，对于有限元分析的体内应用，主要的方法挑战尚未解决，因为体内图像经常因软组织或运动伪影的存在而受损，并且不知道机械载荷条件。为了解决这个问题，我们最近开发了一种新的骨负荷系统，它可以促进体内合成代谢反应。该系统允许在暴露于预定应变量级之前和之后进行CT扫描，可以更好地为有限元分析提供信息，以准确预测骨内生物力学应力和骨折的位置。这个生物科学和工程跨学科的研究项目的主要目的是将体外载荷和有限元分析结合在Pagetic骨骼的研究中，以更好地预测疾病期间局部部位的骨折风险。这将使我们首次确定微结构组织和血管化在决定佩吉特病骨质量中的作用，并提供潜在的治疗方法。我们还将利用这些技术来测试血管生成抑制剂在治疗疾病和减少骨折方面的效果（与罗氏公司合作）。