Developing Optimised Vertebroplasty Treatments for Vertebral Fractures in Multiple Myeloma

2005年，联合王国报告了大约22万例新发癌症，同时还有大约15万例癌症死亡（联合王国癌症研究中心）。骨转移是继肺部和肝脏受累之后第三种最常见的继发性肿瘤，是许多癌症的严重衰弱和疼痛特征。这些骨性病变最常见的部位是脊柱，一些研究报告多达30%的患者表现出这种类型的浸润。事实上，癌症的最初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，脊髓受累的比例超过75%，脊柱骨折的风险增加了9倍。在这些患者中，骨破坏非常严重，正常的生理负荷会导致椎体骨折，从而导致疼痛和畸形，并大大降低患者的生活质量。随着包括MM在内的许多癌症治疗的改善，继发性肿瘤的可能性将增加，因此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，以加强骨骼和克服疼痛的骨折。到目前为止，关于脊髓MM浸润的力学后果的研究很少，也没有关于这种病理学的研究报道。事实上，所有癌症的研究都是稀疏的，并且由于样本量小和混合转移的使用而受到阻碍，混合转移具有不同的生物力学特征。生物力学信息的缺乏阻碍了预测MM患者骨折的临床模型的发展，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。目前治疗脊髓损伤的MM患者往往只有轻微的效果，慢性疼痛在这些人可能会持续。然而，一种被称为椎体成形术的新型锁眼手术技术正被广泛应用于骨质疏松症患者，它可能为MM患者提供一种更好的减轻疼痛和加强椎体的方法。最近一项由主要提案人进行的关于浸润MM病变脊柱的初步研究表明，这些样本与骨质疏松性骨中观察到的椎体骨形态存在相当大的差异。特别是，MM椎体有许多局灶性病变，需要增强，而骨质疏松症表现为更广泛的骨质流失。这一发现表明，如果要对不同的疾病进行成功的干预，则需要不同的PVP治疗。该研究计划首次对与MM相关的脊柱转移进行了大规模研究。在第一阶段，对患病组织的骨结构和骨折数据进行分析，将为这些患者的骨折评估提供临床相关的指南。在这一阶段，还将产生椎体成形术治疗这些骨折的有效性的初步数据。在第二阶段，将使用更现实的实验模型，在常规PVP治疗椎体压缩性骨折和预防性治疗中，评估椎段在日益苛刻的载荷下增强后的行为。最后，将利用从前几个阶段获得的信息开发计算模型。一旦得到验证，这些模型将用于系统研究可能影响椎体强度或增强的重要参数，如病变浸润水平、骨质流失和水泥体积。这些模型将成为开发更多患者特异性模型的先导，这些模型可用于临床治疗MM病变和更广泛的脊柱转移。

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.