Research Summary
Research topic: Assessing the utility of CT-based rigidity analysis to predict fractures and guide treatment plans for patients with metastatic bone disease.
Research results: Determination of accuracy of fracture risk predictions using CT-based rigidity analysis versus predictions using standard guidelines
Patient care application of results: Software that would enable orthopaedic surgeons to make a quick and reliable analysis of a patient's fracture risk.
Simplified patient care application: For patients with metastatic bone disease, accurate prediction of fracture risk that leads to preventive interventions and better outcomes.
Bone rigidity
OREF grant recipient looks at new method to predict fractures in patients with metastatic bone disease
Jay D. Lenn
In mechanical engineering, beam theory is a calculation that factors in both the geometric and material properties of a beam to determine its rigidity. A change in either property affects the loadbearing abilities of the beam.
In metastatic bone disease, malignant lesions affect both the geometric and material properties of bone. Ara Nazarian, DrSc, and his colleagues are using the principles of beam theory to design a computerized tomography (CT)-based rigidity analysis that can determine the risk of fractures in bones with metastasized lesions. He explained, "We think that if you are designing a system to assess fracture risk, it needs to analyze changes in both material and geometric components of the bone."
Dr. Nazarian, an assistant professor of orthopaedic surgery at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, was awarded a 2012 Orthopaedic Research and Education Foundation (OREF) Prospective Clinical Research Grant to conduct a multicenter study assessing the utility of CT-based rigidity analysis to predict fractures and guide treatment plans. He has been working on this project from his days as a PhD student with his mentor Dr. Brian Snyder.
Prospective Clinical Research Grants provide $50,000 per year for up to three years to fund promising prospective clinical studies in areas of high importance in orthopaedic surgery.
The value of fracture prediction
Metastatic bone disease damages bone, causes pain, and increases the risk of fractures. Metastatic lesions in the spine can damage nerves and cause paralysis.
Surgery to prevent fractures generally results in better outcomes than surgery to repair fractures, and preventive interventions often enable better coordination of surgical and oncological treatments. Therefore, an accurate prediction of fracture risk is critical in guiding treatment goals and strategies.
Dr. Nazarian explained, "Our hope is to make a system available to physicians that would enable them to make a quick and reliable analysis of a patient's fracture risk based on sound engineering principles rather than current guidelines, which are more subjective and based on parameters that aren't necessarily accurate."
Assessing rigidity in healthy and diseased bone
Dr. Nazarian has tested the rigidity analysis system in animal models and in a number of small clinical studies. He said, "We have gone through many steps of optimizing a robust algorithm to predict fractures, but we also want a system that's user-friendly and cost-effective—an analysis that a physician can conduct on a laptop in less than 25 minutes."
The next step—funded by the OREF grant—is testing the predictive value of the tool at 11 medical centers in the United States and Canada in collaboration with the Musculoskeletal Tumor Society. The aims of study are:
• To establish normative rigidity values for healthy bones
• To compare the accuracy of fracture risk predictions using CT-based rigidity analysis with predictions using standard guidelines
• To evaluate whether treatment plans based on standard guidelines are changed by the use of rigidity analysis
Dr. Nazarian and his research team will use a set of CT data to establish normative rigidity values from 1,000 CT scans from healthy subjects, ages 40 to 60, from Be Well Body Scans at Beth Israel Deaconess Medical Center.
Rigidity analysis will be conducted on sequential cross sections of each vertebra, femur and humerus. Factoring in such variables as body mass index (BMI), gender and age, the analysis will result in a database of normalized axial, bending and torsional rigidities at multiple cross-sectional sites along each bone. The location of each section will be defined as a percentage of the entire bone length.
Each of the 11 medical centers will recruit 30 patients with metastatic bone disease. The CT-based rigidity analysis will identify the minimum axial, bending and torsional rigidity of each affected bone—the minimum value being the rigidity of the most vulnerable cross section in a given bone. Based on preliminary clinical data, a bone will be considered at risk for imminent fracture if the reduction in rigidity is more than 33 percent when compared with the norm for that particular cross section. Fracture risk will also be assessed using standard clinical and radiographic guidelines.
During a four-month follow-up, affected bones will be monitored for fractures. Subsequent data analysis will compare how well the CT-based rigidity analysis predicted fractures compared with the standard guidelines.
Finally, the orthopaedic oncologist for each patient will choose a treatment plan based on two separate methods: standard guidelines or rigidity analysis. Cases in which the treatment plans are divergent will be included in a second-phase, randomized trial that compares the clinical outcomes of treatments based on the two methods.
The value of funding for research continuity
Dr. Nazarian noted that the OREF grant was awarded at a critical juncture in his research. He said, "Generating the normative database is very labor intensive. This grant moves the goalpost forward, so that we can have all the pieces in place, finish our programming component, and get to a point , where we have a free-standing and robust software that we can use in a clinical setting."
He notes that OREF grants are important because of current uncertainties in research budgets. "The rollercoaster ride of funding is exactly the opposite of what you need. You lose continuity of work, and it becomes difficult to plan ahead." Dr. Nazarian hopes the data from the current study will enable his group to conduct a larger, multicenter trial with funding from the National Institutes of Health.
Photo courtesy of Mr. Ohan Manoukian