Developing Optimised Vertebroplasty Treatments for Vertebral Fractures in Multiple Myeloma

开发针对多发性骨髓瘤椎体骨折的优化椎体成形术治疗方法

• 批准号: EP/H013385/1
• 负责人: Richard Hall
• 金额: $ 75.34万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FH013385%2F1
• 关键词: Developing; Optimised; Vertebroplasty; Treatments; Vertebral

In the UK in 2005 approximately 220,000 new cancers were reported together with approximately 150,000 cancer deaths (Cancer Research UK). Bony metastases are the third most common type of secondary tumour, after pulmonary and hepatic involvement, and are a severely debilitating and painful feature of many cancers. The most frequent site for these bony lesions is the spine with some studies reporting as many as 30 % of patients displaying this type of infiltration. Indeed, initial diagnosis of cancer may result from investigations of back pain which turns out to be a spinal metastases. In sufferers of multiple myeloma (MM), the pathology that is the focus of this study, the figure for spinal involvement is over 75 % with a nine fold increase in the risk of spinal fracture. In these patients the bone destruction can be so severe that normal physiological loads can fracture the vertebra, which leads to pain and deformity as well as a considerable reduction in the quality of life of the individual. With improvements in the treatment of many cancers, including MM, the likelihood of secondary tumours will increase and there is an urgency to investigate the biomechanical consequences of lesion infiltration together with possible interventions that can strengthen the bone and overcome painful fractures. Up to now there has been little research on the mechanical consequences of spinal MM infiltration, with no reported studies focusing on this pathology. Indeed, studies across all cancers have been sparse and hampered by their small samples size and the use of mixed metastases, which have different biomechanical characteristics. This lack of biomechanical information has hampered the development of clinical models to predict fracture in MM patients and investigate, in more systematic manner, treatments to reduce fracture risk or treat the fractures themselves. The current treatments for spinal lesions in MM patients are often only marginally effective and chronic pain in these individuals may persist. However, a new key-hole surgery technique called vertebroplasty, which is becoming widely used in osteoporotic patients, may provide a superior method for pain reduction as well as strengthening the vertebral body in the MM sufferer. A recent pilot study by the lead proposer on a spine infiltrated with MM lesions showed considerable differences in vertebral bone morphology between these samples and that observed within osteoporotic bone. In particular, the MM vertebrae has numerous focal lesions which need to be augmented whilst the ostteoporotic bone shows a more generalised bone loss. This finding suggests that different PVP treatments are required if the intervention is to be successful for different diseases This research proposal sets out for the first time, a large scale study of spinal metastases focusing on those associated with MM. In the first phase, analysis of the bony structure of the diseased tissue together with the fracture data will allow the generation of clinically relevant guidelines for fracture assessment in these patients. During this phase initial data will also be produced on the effectiveness of vertebroplasty to treat these fractures. In phase two, more realistic experimental models will be utilised that will assess post augmentation behaviour of the segment with increasingly demanding loads in both the conventional PVP treatment of vertebral compression fractures and in a preventative manner. Finally, computational models will be developed using information gained from the previous phases . Once validated, these models will be used to make a systematic study of important parameters that may effect the vertebral strength or augmentation such as level of lesion infiltration, bone loss and cement volume. These models will be pre-cursor to the development of more patient specific models that can be used clinically in the treatment of lesions in MM and spinal metastases more generally.

2005年，英国报告了大约220，000例新癌症病例，以及大约150，000例癌症死亡病例（英国癌症研究中心）。骨转移是继肺和肝受累之后第三种最常见的继发性肿瘤，并且是许多癌症的严重衰弱和疼痛特征。这些骨病变最常见的部位是脊柱，一些研究报告多达30%的患者显示这种类型的浸润。事实上，癌症的初步诊断可能是由于背部疼痛的调查，结果是脊柱转移。在多发性骨髓瘤（MM）患者中，病理学是本研究的重点，脊柱受累的数字超过75%，脊柱骨折的风险增加了9倍。在这些患者中，骨破坏可能如此严重，以至于正常的生理负荷可能使椎骨骨折，这导致疼痛和畸形以及个体生活质量的显著降低。随着许多癌症（包括MM）治疗的改善，继发性肿瘤的可能性将增加，迫切需要研究病变浸润的生物力学后果以及可能的干预措施，以加强骨骼并克服疼痛性骨折。到目前为止，关于脊柱MM浸润的机械后果的研究很少，没有报道关注这种病理学的研究。事实上，所有癌症的研究都很少，并且受到样本量小和使用具有不同生物力学特征的混合转移灶的阻碍。这种生物力学信息的缺乏阻碍了临床模型的开发，以预测MM患者的骨折，并以更系统的方式研究降低骨折风险或治疗骨折本身的治疗方法。目前对MM患者脊柱病变的治疗通常仅轻微有效，这些患者的慢性疼痛可能持续存在。然而，一种被称为椎体成形术的新的锁孔手术技术，正在广泛用于骨质疏松患者，可能为MM患者提供一种减轻疼痛和增强椎体的上级方法。最近由主要提议者对浸润MM病变的脊柱进行的一项初步研究显示，这些样本之间的椎骨形态与在骨质疏松骨内观察到的椎骨形态存在相当大的差异。特别是，MM椎骨有许多需要增强的局灶性病变，而骨质疏松性骨显示出更广泛的骨丢失。这一发现表明，如果干预要成功治疗不同的疾病，需要不同的PVP治疗。这项研究提案首次提出了一项大规模的脊柱转移研究，重点是与MM相关的转移。在第一阶段，对患病组织的骨结构以及骨折数据的分析将允许产生用于骨折评估的临床相关指南，这些病人。在此阶段，还将产生关于椎体成形术治疗这些骨折的有效性的初始数据。在第二阶段，将使用更真实的实验模型，以评估椎体压缩性骨折的传统PVP治疗和预防性方式中，随着载荷要求越来越高，节段的加固后行为。最后，将利用从前几个阶段获得的信息开发计算模型。一旦确认，这些模型将用于对可能影响椎体强度或增强的重要参数进行系统研究，例如病变浸润水平、骨丢失和骨水泥体积。这些模型将成为开发更多患者特异性模型的前体，这些模型可用于临床治疗多发性骨髓瘤和脊柱转移瘤。

项目成果

Novel methodology for assessing biomaterial-biofluid interaction in cancellous bone.

评估松质骨中生物材料-生物流体相互作用的新方法。

• DOI: 10.1016/j.jmbbm.2015.02.027
• 发表时间: 2015
• 期刊: Journal of the mechanical behavior of biomedical materials
• 影响因子: 3.9
• 作者: Bou-Francis A