Developing Optimised Vertebroplasty Treatments for Vertebral Fractures in Multiple Myeloma

Lead Research Organisation: University of Leeds
Department Name: Mechanical Engineering


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.


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Description Key discovery aspect of the project include:
(1) First large scale analysis of the morphological and material characteristics of bone which has been infiltrated by multiple myeloma.
(2) First in vitro assessment of the use of vertebroplasty for MM.
(3) The construction of a finite element model representing the MM infiltration.
Exploitation Route (1) Utilised by the project partners.
(2) We are currently considering a project database for the imaging and loading data and make this available to researchers globally. This access would aid researchers and advanced the training of researchers across a number of fields.
Sectors Healthcare

Description FP7 integrated project
Amount £13,317,000 (GBP)
Funding ID LifeLongJoints - NMP-310477 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 04/2013 
End 03/2018
Description NIHR i4i Challenge Award
Amount £1,130,863 (GBP)
Funding ID II-C3-0714-20001 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2015 
End 10/2017
Title Loading methodologies 
Description In collaboration with technical university of Vienna and the University of Berne we were able to develop of more realistic loading scenarios together with greater depth of data corresponding to the vertebral fracture process. These enhanced processes were applied to the myeloma material. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Provided To Others? No  
Impact We were able to detail more precisely the fracture mechanics in mulitiple myeloma, the first time this had been achieved. 
Title Utilisation of cadaveric spinal materials for assessment of intervertebral devices 
Description Novel models were developed using both single vertebrae and two vertebra segments which allowed the student to investigate subsidence of TDRs and interbody fusion devices in a controlled, experimental manner. The models were used to ascertain the volume and positioning of cement within the vertebral body to prevent subsidence. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2012 
Provided To Others? Yes  
Impact The models have been used to optimise the position and volume of cement required to prevent subsidence, the latter being a problem when using intervertebral devices such as total disc replacements or interbody fusion devices. Subsidence is particularly common in the elderly who's bone may be osteoporotic or osteopenic. 
Description Sunnybrook 
Organisation Sunnybrook Health Sciences Centre
Country Canada 
Sector Academic/University 
PI Contribution Provision of experimental data with regard to failure in multiple myeloma vertebrae.
Collaborator Contribution Provision of knowledge for the development of novel finite element models.
Impact Outputs from the collaboration include the delivery of new knowledge around myeloma and the development of novel finite element models.
Start Year 2010
Description Uppsala University 
Organisation Uppsala University
Department Department of Physics and Astronomy
Country Sweden 
Sector Academic/University 
PI Contribution Data arising from the grant is being used in collaboration with Uppsala University. In particular, we are supplying the microCT data from which to develop the models and the loading characteristics. Further the collaboration resulted in an €18.3 M funding award through the EU where UU and Leeds (PI and Co-ordinator) are two of the main protagonists.
Collaborator Contribution Contribution of a student and Finite Element capability.
Impact The following publications have results from the extended collaboration:Maria Pettersson, Michael Bryant, Susann Schmidt, Håkan Engqvist, Richard M. Hall, Anne Neville, Cecilia Persson, Dissolution behaviour of silicon nitride coatings for joint replacements, Materials Science and Engineering: C, 62 (2016), 497-505. Oladokun, A. O., Pettersson, M. P., Bryant, M. B., Engqvist, H. E., Persson, C. P., Hall, R. H., & Neville, A. N. (2015). Fretting of CoCrMo and Ti6Al4V Alloys in Modular Prostheses. Tribology - Materials, Surfaces & Interfaces, 9(4), 165-173. doi:10.1179/1751584X15Y.0000000014
Start Year 2012