SBIR-STTR Award

With over 400,000 patients undergoing spine fusion surgery each year, many of whom have low bone density because of their advanced age, it is now clear that failure of the bone after a fusion procedure is a serious and increasingly common problem. This negative outcome of the primary fusion surgery requires the patient have a second surgery, and arises because the patient's vertebral bone is too weak to sustain the loads applied to it after the primary fusion surgery. The bone can fail in different ways, the mostcommon modes of bone failure being: 1) fracture of the adjacent-level vertebra; 2) loosening of a pedicle screw due to local failure of the supporting bone; and 3) subsidence or fracture of the vertebral endplates. These failure modes have been difficult to avoid because, although spine surgeons have a variety of both surgical and non-surgical approaches to reduce the risk of bone failure, these risk-mitigating measures add complexity and expense to the surgery and surgeons do not have an objective test to justify their use or identify which measures would be most suitable for a given high-risk patient. Thus, in the larger context of minimizing the incidence of bone failure after a spine fusion surgery, the long-term goal of this overall SBIR project is to develop new clinical tests that: 1) pre-operatively identify patients at high-risk of bone failure secondary to a fusion surgery; and 2) assess risk for each potential mode of bone failure (fracture of the adjacent-level vertebra; loosening of a pedicle screw; subsidence or fracture of the vertebral endplates). Our overall approach is based on providing a detailed biomechanical analysis of the patient's vertebrae, performed as an 'add-on' analysis of the patient's pre-operative diagnostic computed tomography (CT) scan of their spine. For this Phase-I portion of the project, Aim 1 will develop a set of 'virtual stress tests' of the patient's vertebrae, using fnite element analysis of the patient's CT scan. These biomechanical tests will probe each of the different types of failure modes and will account also for patient-specific measures of spine curvature and loading as well as disc morphology. These multiple tests will then be used in Aim 2, in which we will perform a retrospective blinded case-control study on over 300 spine fusion patients, for whom pre-operative CT scans have previously been acquired and clinical outcomes are on file. Finally, in Aim 3, we will perform statistical analyses to identify which of the test outcomes are most predictive of the clinical outcomes, accounting also for various clinical risk factors. We also seek to test the hypothesis that prediction of clinical outcomes by our biomechanics-based test is better than by the current best practices, setting the stage for furtherdevelopment of the technology in a subsequent Phase-II project. Bone failure secondary to spine fusion surgery is a serious problem. If successful, these new tests would be cost-effective to implement and would have substantial positive impact on patient care.

Thesaurus Terms:
Accounting;Address;Age;Base;Biomechanics;Blinded;Bone;Bone Density;Bone Quality;Bone Strength;Bone Turnover;Case-Control Studies;Clinical;Clinical Practice;Clinical Risk;Cohort;Cohort Studies;Collaborations;Cost;Cost Effective;Cost Effectiveness Analysis;Coupled;Diagnostic;Disease;Elderly;Elements;Equilibrium;Evaluation;Experience;Failure (Biologic Function);Fatigue;Female;Finite Element Analysis;Fracture;Geometry;Goals;Health Care Costs;High Risk;Implant;Improved;Incidence;Individual;Instrument;Instrumentation;Kyphosis Deformity Of Spine;Length;Logistic Regressions;Lordosis;Measures;Modeling;Morphology;Older Patient;Operative Surgical Procedures;Outcome;Patient Care;Patients;Phase;Population;Primary Outcome;Principal Component Analysis;Procedures;Pseudarthrosis;Public Health Relevance;Radiologist;Recording Of Previous Events;Research Clinical Testing;Retrospective Studies;Risk;Risk Factors;Scanning;Secondary To;Sensitivity And Specificity;Series;Sex;Small Business Innovation Research Grant;Smoking History;Spinal;Spinal Curvatures;Spinal Fractures;Spinal Fusion;Spine Bone Structure;Staging;Stress Tests;Surgeon;Technology;Technology Development;Teriparatide;Testing;Tool;United States;Validation Studies;Vertebral Bone;Vertebral Column;Virtual;X-Ray Computed Tomography;

Of the over 450,000 patients undergoing instrumented spinal fusion surgery each year in the United States, over 20,000 ultimately require a revision surgery, the majority of which are secondary to insufficient bone quality. Biomechanical problems associated with insufficient bone quality include pseudarthrosis, insufficiency fractures of the proximal adjacent vertebra, subsidence of any intervertebral implant-graft construct, and loosening of an implanted pedicle screw. No objective clinical test is currently available for surgeons to reliably identify a patient's risk of these adverse outcomes. A bone mineral density test is not enough, as "normal" bone may still have insufficient quality for high stresses near the implant. The overall goal of this Phase-II SBIR project is to clinically validate our virtual stress test (VST) technology for pre-operatively identifying spinal fusion patients who are at high risk of a failed surgery. VST utilizes the CT scan already acquired for the patient’s pre-operative assessment to construct a virtual, three-dimensional model of the fusion construct in order to investigate its mechanical response to loading. Our proposed pre-operative spinal fusion evaluation, based on VST, has three elements: a) Perform VST to assess pedicle screw loosening, endplate subsidence, and vertebral failure, all specific to the patient’s vertebrae and spinal fusion surgical plan. From that information, identify patients at high risk of a failed fusion surgery due to insufficient bone quality; b) For each vertebral level, specify optimal screw sizing and placement for each pedicle, and measure bone mineral density (BMD) and vertebral strength; c) Provide a comprehensive assessment of risk of a future vertebral fracture due to osteoporosis. Having developed the VST technology in our Phase-I study, this Phase-II study seeks to validate its use in the largest ever biomechanics study of spinal fusion patients. This case-cohort study will include 1,500 women and men who underwent spinal fusion surgery at Kaiser Permanente Southern California from 2009–2018, have a pre-surgical CT scan and at least 90 days of follow-up. Cases (n=500) will be patients with an adverse surgical outcome that required re-operation after the index procedure. Half of this cohort will be used to optimize the virtual stress tests for pedicle screw loosening, endplate subsidence, and vertebral failure. Using the remainder of the cohort, VST will be performed blinded to surgical outcomes in order to test the hypothesis that VST predicts failed surgery, independent of BMD and other clinical risk factors. If successful, this study would result in a biomechanics-based clinical tool for pre-operatively evaluating a patient's risk of spinal fusion failure due to insufficient bone quality. Given the options that now exist for addressing such issues, such as use of anabolic bone forming agents or prophylactic bone cement injection, such a tool could lead to a reduction in adverse surgical outcomes and thus fewer re-operations and revisions.

Public Health Relevance Statement:
Statement of Relevance Of the over 450,000 patients undergoing instrumented spine-fusion surgery each year in the United States, over 20,000 ultimately require a revision surgery. This project will produce a biomechanics-based tool to identify pre-operatively patients at risk of spine fusion failure secondary to insufficient bone quality. Given the options that now exist for addressing such issues, such as use of anabolic bone forming agents or prophylactic bone cement injection, such a tool could lead to a reduction in adverse surgical outcomes and thus fewer re- operations and revisions.

Project Terms:
Accounting; Address; adverse outcome; base; Biomechanics; Blinded; bone; Bone Density; bone quality; bone stress; California; Clinical; clinical risk; cohort; Cohort Studies; Collaborations; Complex; Congenital failure of fusion; Data; Databases; design; Dual-Energy X-Ray Absorptiometry; Elements; Ensure; Evaluation; Failure; Finite Element Analysis; follow-up; Fracture; fracture risk; Future; Goals; Guidelines; high risk; Implant; indexing; Injections; instrument; instrumentation; Lead; Measurement; Measures; Mechanics; Medical Records; men; Methods; Modeling; operation; Operative Surgical Procedures; Osteoporosis; osteoporosis with pathological fracture; Outcome; Patient risk; Patients; Performance; Pharmacotherapy; Phase; phase 1 study; phase 2 study; Polymethyl Methacrylate; predictive test; Procedures; prophylactic; Pseudarthrosis; Radiation; research clinical testing; Research Personnel; response; Risk; Risk Assessment; Risk Factors; Robotics; Roentgen Rays; Secondary to; Sensitivity and Specificity; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Spinal Fractures; Spinal Fusion; spine bone structure; Stress; Stress Tests; success; Surgeon; surgery outcome; System; Technology; Testing; three-dimensional modeling; tool; Training; United States; Validation; Vertebral column; virtual; Woman; Work; X-Ray Computed Tomography