Dr. Nazarian and research assistant Shohreh Behrouzi review a patient’s CT-based rigidity analysis results.
Courtesy of Mr. Ohan Manoukian


Published 11/1/2014
Jay D. Lenn

Bone Rigidity: Assessing the Impact of Malignant Lesions

OREF grant recipient wants to predict fractures in patients with metastatic bone disease

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, “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 since his days as a PhD student with his mentor Brian Snyder, MD, PhD.

Prospective Clinical Research Grants provide $50,000 per year for up to 3 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 oncologic treatments. Therefore, an accurate prediction of fracture risk is critical in guiding treatment goals and strategies.

“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,” said Dr. Nazarian.

Assessing rigidity
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 to optimize 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 study has the following aims:

  • 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

To establish normative rigidity values, Dr. Nazarian and his research team will use data from 1,000 CT scans on healthy individuals, 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 person’s vertebrae, femora, and humeri. 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 4-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 be asked to develop a treatment plan based on the two different 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
Dr. Nazarian noted that the OREF grant was awarded at a critical juncture in his research. “Generating the normative database is very labor intensive,” he said. “This grant moves the goalpost forward, so that we can have all the pieces in place, finish our programming component, and get to the point where we have freestanding, robust software that we can use in a clinical setting.”

He also noted that OREF grants are important due to 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.

Jay D. Lenn is a contributing writer for OREF and can be reached at communications@oref.org