The spine is the skeletal site most often affected by metastatic breast cancer, and 17-50% of patients with spinal metastasis sustain a vertebral fracture. Systemic treatments with cytotoxic agents, hormone manipulation, bisphosphonates and/or local treatment with radiation and/or surgical stabilization, constitute the range of therapies available to breast cancer patients with skeletal metastasis. However, there are no objective methods for selecting which treatment will best reduce the patient's risk for sustaining a pathologic fracture and for monitoring the patient's response to therapy. Therefore, establishing objective criteria to evaluate the load carrying capacity of the involved vertebrae can be used both to monitor changes in bone structure that reflect the interaction of the tumor with the host bone, and to guide treatment for fracture prevention. Objective measures of fracture risk will both enhance patient management and resource utilization. Our overall hypothesis is that the loss of structural integrity of the spine due to tumor induced osteolysis, assessed using CT based structural analysis protocol, can be restored using structural polymers deployed in a minimally invasive manner.
In Aim 1, in a series of in vitro tests, the ability of a QCT based structural analysis protocol to classify the fracture risk of thoracolumbar human spines with simulated critical osteolytic defects will be quantified under physiological loading conditions. Predicated fracture load, computed for the vertebrae, will be compared to the failure load measured by mechanical testing. The role of spinal ligaments in effecting the predicted failure load will be investigated.
In Aim 2, a novel image-based algorithm will be developed and integrated within the CT structural analysis protocol, to provide pre-operative planning for prophylactic augmentation of the affected vertebra. Specific anatomically and materially detailed computational models will be used to optimize the design rules incorporated within the image based module to achieve restoration of the structural integrity of the affected vertebra. Using a series of in vitro studies, we will characterize the dependencies of the mechanical properties of treated vertebrae on the material properties of the injectable biopolymer and the geometrical properties of the lytic defect. We will compare this performance to the use of Polymethylmetacrylate cement.
In Aim 3, the efficacy of the developed CT based pre-operative analysis, prediction and augmentation system, in restoring the structural integrity of thoracolumbar spines with simulated lytic defects, will be quantified. In summary, Drawing on principles of structural engineering, a novel CT based pre-operative analysis, prediction and augmentation system, will be developed to allow pre-operative planning for prophylactic augmentation of the human thoracolumbar spines with critical lytic defects.
|Alkalay, Ron N; Harrigan, Timothy P (2016) Mechanical assessment of the effects of metastatic lytic defect on the structural response of human thoracolumbar spine. J Orthop Res 34:1808-1819|
|Alkalay, Ron N; von Stechow, Dietrich; Hackney, David B (2015) Augmentation of failed human vertebrae with critical un-contained lytic defect restores their structural competence under functional loading: An experimental study. Clin Biomech (Bristol, Avon) 30:608-16|
|Alkalay, Ron N (2015) Effect of the metastatic defect on the structural response and failure process of human vertebrae: an experimental study. Clin Biomech (Bristol, Avon) 30:121-8|
|Alkalay, Ron Noah; Vader, David; Hackney, David (2015) The degenerative state of the intervertebral disk independently predicts the failure of human lumbar spine to high rate loading: an experimental study. Clin Biomech (Bristol, Avon) 30:211-8|
|Alkalay, Ron N; Burstein, Deborah; Westin, Carl-Fredrik et al. (2015) MR diffusion is sensitive to mechanical loading in human intervertebral disks ex vivo. J Magn Reson Imaging 41:654-64|