Simulated Lytic Defects Research Articles

Noninvasive Failure Load Prediction of Vertebrae with Simulated Lytic Defects and Biomaterial Augmentation.

The spine is the most common site for secondary bone metastases, and clinical management for fractures is based on size and geometry of the defect. About 75% of the bone needs to be damaged before lesions are detectable, so clinical tools should measure changes in both geometry and material properties. We have developed an automated, user-friendly, Spine Cancer Assessment (SCA) image-based analysis method that builds on a platform designed for clinical practice providing failure characteristics of vertebrae. The objectives of this study were to (1) validate SCA predictions with experimental failure load outcomes; (2) evaluate the planning capabilities for prophylactic vertebroplasty procedures; and (3) investigate the effect of computed tomography (CT) protocols on predicted failure loads. Twenty-one vertebrae were randomly divided into two groups: (1) simulated defect without treatment (negative control) [n = 9] and (2) with treatment [n = 12]. Defects were created and a polymeric biomaterial was injected into the vertebrae in the treated-defect group. Spines were scanned, reconstructed with two algorithms, and analyzed for fracture loads. To virtually plan for prophylactic intervention, vertebrae with empty lesions were simulated to be augmented with either poly(methyl methacrylate) (PMMA) or a novel bone replacement copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)]. Axial rigidities were calculated from the CT images. Failure loads, determined from the cross section with the lowest axial rigidity, were compared with experimental values. Predicted loads correlated well with experimental outcomes (R(2) = 0.73, p < 0.0001). Predictions from negative control specimens highly correlated with measured values (R(2) = 0.90, p < 0.0001). Although a similar correlation was obtained using both algorithms, the smooth reconstruction (B30) tended to underestimate predicted failure loads by ∼50% compared with the ∼10% underestimate of the sharp reconstruction (B70). Percent increase in failure loads after virtual vertebroplasty showed a higher increase in samples with PMMA compared with those with copolymer. The SCA method developed in this study calculated failure loads from quantitative computed tomography scans in vertebrae with simulated metastatic lytic defects, with or without treatment, facilitating clinical applicability and providing more reliable guidelines for physicians to select appropriate treatment options. Furthermore, the analysis could accommodate augmentation planning procedures that aimed to determine the optimum material that would increase vertebral body failure load.

Finite element analysis and CT-based structural rigidity analysis to assess failure load in bones with simulated lytic defects

There is an urgent need to improve the prediction of fracture risk for cancer patients with bone metastases. Pathological fractures that result from these tumors frequently occur in the femur. It is extremely difficult to determine the fracture risk even for experienced physicians. Although evolving, fracture risk assessment is still based on inaccurate predictors estimated from previous retrospective studies. As a result, many patients are surgically over-treated, whereas other patients may fracture their bones against expectations.We mechanically tested ten pairs of human cadaveric femurs to failure, where one of each pair had an artificial defect simulating typical metastatic lesions. Prior to testing, finite element (FE) models were generated and computed tomography rigidity analysis (CTRA) was performed to obtain axial and bending rigidity measurements. We compared the two techniques on their capacity to assess femoral failure load by using linear regression techniques, Student's t-tests, the Bland–Altman methodology and Kendall rank correlation coefficients.The simulated FE failure loads and CTRA predictions showed good correlation with values obtained from the experimental mechanical testing. Kendall rank correlation coefficients between the FE rankings and the CTRA rankings showed moderate to good correlations. No significant differences in prediction accuracy were found between the two methods.Non-invasive fracture risk assessment techniques currently developed both correlated well with actual failure loads in mechanical testing suggesting that both methods could be further developed into a tool that can be used in clinical practice. The results in this study showed slight differences between the methods, yet validation in prospective patient studies should confirm these preliminary findings.

Finite element analysis and computed tomography based structural rigidity analysis of rat tibia with simulated lytic defects

Finite element analysis (FEA), CT based structural rigidity analysis (CTRA) and mechanical testing is performed to assess the compressive failure load of rat tibia with simulated lytic defects.Twenty rat tibia were randomly assigned to four equal groups (n=5). Three of the groups included a simulated defect at various locations: anterior bone surface (Group 1), posterior bone surface (Group 2) and through bone defect (Group 3). The fourth group was a control group with no defect (Group 4). Microcomputed tomography was used to assess bone structural rigidity properties and to provide 3D model data for generation of the finite element models for each specimen.Compressive failure load calculated using CT derived rigidity parameters (FCTRA) was well correlated to failure load recorded in mechanical testing (R2=0.96). The relationships between mechanical testing failure load and the axial rigidity (R2=0.61), bending rigidity (R2=0.71) and FEA calculated failure loads, considering bone as an elastic isotropic (R2=0.75) and elastic transversely isotropic (R2=0.90) are also well correlated. CTRA stress, calculated adjacent to the defect, were also shown to be well correlated with yield stresses calculated using the minimum density at the weakest cross section (R2=0.72). No statistically significant relationship between apparent density and mechanical testing failure load was found (P=0.37).In summary, the results of this study indicate that CTRA analysis of bone strength correlates well with both FEA and results obtained from compression experiments. In addition there exist a good correlation between structural rigidity parameters and experimental failure loads. In contrast, there was no correlation between average bone density and failure load.

Non-invasive assessment of failure torque in rat bones with simulated lytic lesions using computed tomography based structural rigidity analysis

This study applies CT-based structural rigidity analysis (CTRA) to assess failure torque of rat femurs with simulated lytic defects at different locations (proximal and distal femur) and diameters (25% and 50% of the cross-section at the site), and compared the results to those obtained from mechanical testing. Moreover, it aims to compare the correlation coefficients between CTRA-based failure torque and DXA-based aBMD versus actual failure torque. Twenty rats were randomly assigned to four equal groups of different simulated lesions based on size and location. Femurs from each animal underwent micro-computed tomography to assess three-dimensional micro-structural data, torsional rigidity using structural rigidity analysis and dual energy X-ray absorptiometry to assess bone mineral density. Following imaging, all specimens were subjected to torsion. Failure torque predicted from CT-derived structural rigidity measurements was better correlated with mechanically derived failure torque [ R 2=0.85] than was aBMD from DXA [ R 2=0.32]. In summary, the results of this study suggest that computed tomography based structural rigidity analysis can be used to accurately and quantitatively measure the mechanical failure torque of bones with osteolytic lesions in an experimental rat model. Structural rigidity analysis can provide more accurate predictions on maximal torque to mechanical failure than dual energy X-ray absorptiometry based on bone mineral density.

Application of Structural Rigidity Analysis to Assess Fidelity of Healed Fractures in Rat Femurs with Critical Defects

Approximately 6 million fractures occur each year in the United States, with an estimated medical and loss of productivity cost of $99 billion. As our population ages, it can only be expected that these numbers will continue to rise. While there have been recent advances in available treatments for fractures, assessment of the healing process remains a subjective process. This study aims to demonstrate the use of micro-computed tomography (microCT)-based structural rigidity analysis to accurately and quantitatively assess the progression of fracture healing over time in a rat model. The femora of rats with simulated lytic defects were injected with human BMP-2 cDNA at various time points postinjury (t = 0, 1, 5, 10 days) to accelerate fracture healing, harvested 56 days from time of injury, and subjected to microCT imaging to obtain cross-sectional data that were used to compute torsional rigidity. The specimens then underwent torsional testing to failure using a previously described pure torsional testing system. Strong correlations were found between measured torsional rigidity and computed torsional rigidity as calculated from both average (R2 = 0.63) and minimum (R2 = 0.81) structural rigidity data. While both methods were well correlated across the entire data range, minimum torsional rigidity was a better descriptor of bone strength, as seen by a higher Pearson coefficient and smaller y-intercept. These findings suggest considerable promise in the use of structural rigidity analysis of microCT data to accurately and quantitatively measure fracture-healing progression.

Novel Approach of Predicting Fracture Load in the Human Proximal Femur Using Non-Invasive QCT Imaging Technique

This paper presents an analysis of predicting the load-bearing capacities of human femurs using quantitative computer tomography (QCT)-based beam theory. Cross-sectional images of 12 human cadaver femurs (intact bones, age: 39-77 years; male = 8, female = 4) were scanned in conjunction with a calcium hydroxyapatite phantom which has five chambers of known densities. The apparent densities obtained from the scans were used to evaluate the Young's modulus (E) by applying the established empirical relationships. The fracture load of a configuration that simulated single-legged stance was measured experimentally and compared with the predicted failure load using a composite beam theory, plane stress model of the femur. In this model, the failure was assumed to occur at the weakest cross-section through the bone determined from QCT-based structural analysis. In contrast to the other experimental investigations, the setup used in this study considers the entire length of a human femur and also incorporates a novel mechanical jig to mimic the realistic physiological scenario. In one of our earlier studies, simulated lytic defects of varying size were created at the inter-trochanteric region of femurs and their load-bearing capacities were calculated based on their structural properties. Both the results obtained from the current study as well as the ones from our previous study were used to assess the viability of the methodology. A high degree of correlation was observed when the predicted failure loads obtained from the intact femurs and previously studied defective femurs were compared with the ex vivo fracture loads. The coefficients of determination (R(2)) of QCT-derived predicted loads with respect to the measured failure loads were 0.80 for the intact femurs and 0.87 for the defective femurs. The results suggest that the QCT-derived beam analysis provides a viable approach for the assessment of load-bearing capacity in various clinical scenarios.

Lytic lesions in the femoral neck: Importance of location and evaluation of a novel minimally invasive repair technique

Proximal femoral metastases can lead to pathologic fracture. The goals of this study were to improve guidelines for assessing pathologic hip fracture risk by quantifying the effect of location of femoral neck metastases on hip strength under single-limb stance loading and to evaluate the effectiveness of a proposed minimally invasive surgical repair technique for restoring hip strength. Twelve matched pairs of human cadaveric proximal femora were used to create a total of 564 finite element models before and after introduction and repair of simulated lytic defects, modeled as spherical voids, at various locations within the femoral neck. Defect site greatly affected hip strength (p < 0.001). Defects in the inferomedial aspect of the neck and in the dense trabecular bone near the base of the femoral head had the greatest effect, with hip strengths 23% to 72% and 43% to 64% that of the intact strength, respectively, for 20-mm diameter defects. Even so, the proposed percutaneous repair technique restored static strength of femora with defects at all of the studied locations. These findings may lead to a reduction in the number of patients who suffer a preventable pathologic fracture, a decreased likelihood of unnecessary surgery, and a less invasive prophylactic surgical procedure.

Predicting Failure Load of the Femur with Simulated Osteolytic Defects using Noninvasive Imaging Technique in a Simplified Load Case

Currently, there is no proven sensitive or specific method for predicting pathological fracture of the femur. The clinical management of lytic femoral metastases is based on geometric measurement of the bone, of the defect, or both. However, the mechanical behavior of a structure depends on both its material and geometric properties. Our hypothesis is that a change in bone structural properties as the result of tumor induced osteolysis determines the fracture risk in bones with skeletal metastases. We developed a method of QCT (Quantitative Computed Tomography) combined with engineering beam analysis as a noninvasive tool for measuring the material and geometric properties of the femur with simulated lytic defects in the intertrochanteric region. In this ex-vivo study we prove that engineering beam structural analysis applied to serial transaxial QCT scans through human femora with simulated lytic defects at the proximal femur predicts the load at failure and location of fracture better than current clinical guidelines. Structural rigidity measured by QCT in this study may be used to predict the load carrying capacity of femurs with metastatic defects and, furthermore, may be used when the tumor has weakened the bone sufficiently such that pathological fracture is imminent and prophylactic stabilization is necessary.

Noninvasive Imaging Technique Predicts Failure Load of the Femur with Simulated Osteolytic Defects

Objective. To determine whether the load-carrying capacity of human proximal femora with simulated lytic defects can be predicted using QCT-derived simplified beam theory. Design. The predicted fracture load of simulated defects were calculated using new technique of QCT combined with engineering beam analysis. Patients. Simulated lytic defects were created using a surgical drill in the intertrochanteric region of twenty human cadaveric femora. QCT scans were conducted before and after creating defects on either AM (Anterior-Medial) or PL (Posterior-Lateral) regions. Results. A linear relation could be used to predict failure load from the proposed engineering analysis based on QCT scan. The coefficient of determination analysis of QCT-derived predicted load vs. the measured failure load was R2=0.73 (p&lt;0.0001). Conclusions. The data suggest that three quarters of human femoral failure can be predicted in vivo, i.e. using QCT scan. Combined with information on the loads associated with the activities of daily living, these data may be used to prevent pathologic fractures of patients who had prior surgery of removing tumors on proximal femurs.

Failure of trabecular bone with simulated lytic defects can be predicted non-invasively by structural analysis

Pathologic fracture is a significant risk for patients afflicted with metastatic or benign skeletal tumors. The quandary for physicians who treat these patients is that after making the diagnosis they must try to predict the load bearing capacity of the involved bone and the fracture risk from images seen in radiological examinations. Since bone fails at a relatively constant strain independent of density we demonstrate that using a mechanics of materials approach that the cross-sectional structural properties of the bone most affected by the lytic defect governs the load bearing capacity of the entire bone. Homogeneous cylindrical cores of trabecular bone were harvested from the vertebral bodies of whale spines, and prepared with circular or slotted through-hole defects of varying sizes to simulate lytic skeletal tumors. Each specimen was imaged using quantitative computed tomography (CT), dual energy X-ray absorptiometry (DXA), and magnetic resonance imaging (MRI) to obtain data for calculating cross-sectional structural properties: axial, flexural, and torsional rigidity. The specimens were then divided into groups uniformly distributed with respect to defect sizes and shapes, and subjected to uniaxial tension, four-point bending or torsion until failure. A strong positive relationship was found between measured tensile yield loads, bending, and torsional yield moments vs. axial, flexural and torsional structural rigidities respectively, calculated from QCT, DXA, and MRI data [QCT: tension r2 = 0.951, bending r2 = 0.909, torsion r2 = 0.914 (p < 0.001); DXA: tension r2 = 0.926, bending r2 = 0.841, torsion r2 = 0.916 (p < 0.001), MRI: tension r2 = 0.916; bending r2 = 0.856, torsion r2 = 0.852 (p < 0.001)]. For cylindrical cores of trabecular bone with simulated lytic defects, the load bearing capacity of the entire core was directly proportional to the axial, bending, or torsional rigidity at the weakest cross-section through the core containing the defect. Therefore structural rigidity analysis of cross-sectional geometric data measured non-invasively by QCT, DXA, and MRI of bones containing lytic defects may be used to predict the load bearing capacity of the involved bone and the relative fracture risk in vivo. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Failure of trabecular bone with simulated lytic defects can be predicted non-invasively by structural analysis

Pathologic fracture is a significant risk for patients afflicted with metastatic or benign skeletal tumors. The quandary for physicians who treat these patients is that after making the diagnosis they must try to predict the load bearing capacity of the involved bone and the fracture risk from images seen in radiological examinations. Since bone fails at a relatively constant strain independent of density we demonstrate that using a mechanics of materials approach that the cross-sectional structural properties of the bone most affected by the lytic defect governs the load bearing capacity of the entire bone. Homogeneous cylindrical cores of trabecular bone were harvested from the vertebral bodies of whale spines, and prepared with circular or slotted through-hole defects of varying sizes to simulate lytic skeletal tumors. Each specimen was imaged using quantitative computed tomography (CT), dual energy X-ray absorptiometry (DXA), and magnetic resonance imaging (MRI) to obtain data for calculating cross-sectional structural properties: axial, flexural, and torsional rigidity. The specimens were then divided into groups uniformly distributed with respect to defect sizes and shapes, and subjected to uniaxial tension, four-point bending or torsion until failure. A strong positive relationship was found between measured tensile yield loads, bending, and torsional yield moments vs. axial, flexural and torsional structural rigidities respectively, calculated from QCT, DXA, and MRI data [QCT: tension r 2=0.951, bending r 2=0.909, torsion r 2=0.914 ( p<0.001); DXA: tension r 2=0.926, bending r 2=0.841, torsion r 2=0.916 ( p<0.001); MRI: tension r 2=0.916; bending r 2=0.856, torsion r 2=0.852 ( p<0.001)]. For cylindrical cores of trabecular bone with simulated lytic defects, the load bearing capacity of the entire core was directly proportional to the axial, bending, or torsional rigidity at the weakest cross-section through the core containing the defect. Therefore structural rigidity analysis of cross-sectional geometric data measured non-invasively by QCT, DXA, and MRI of bones containing lytic defects may be used to predict the load bearing capacity of the involved bone and the relative fracture risk in vivo.

A Biomechanical Analysis of Intravertebral Pressures During Vertebroplasty of Cadaveric Spines With and Without Simulated Metastases

A biomechanical cadaveric study of thoracic and lumbar vertebrae with simulated metastases quantifying intravertebral pressures during transpedicular vertebroplasty. To compare intravertebral pressures during percutaneous vertebroplasty in vertebrae with and without simulated lytic metastases. Percutaneous vertebroplasty is designed to provide stability to vertebrae weakened by osteoporosis or metastatic disease. The complication rate is higher when the procedure is used for the treatment of lytic vertebral lesions. The major complications reported are radiculopathy, spinal cord compression, and embolic phenomena. Ten fresh-frozen cadaveric vertebrae were tested intact (7 lumbar, 3 thoracic) and 7 were tested with simulated lytic defects (4 lumbar, 3 thoracic). Defects were created by replacing a core of cancellous bone with soft tumor tissue in the center of the vertebral body. Simplex P (Howmedica Osteonics, Mahwah, NJ) cement was injected into each vertebra through a unipedicular approach at a constant rate of 3 mL per minute. Cement volume, injection force, and intravertebral pressures at the posterior vertebral body wall were recorded. Following the procedure, the vertebrae were sectioned to visualize cement and tumor disbursement. There was no significant difference between the two groups for age, size, trabecular density, and cement volume. Vertebrae with simulated metastases generated an average maximum pressure of 39.66 kPa during cement injection versus 6.83 kPa in intact vertebrae (P < 0.05). Higher pressures were also generated in smaller vertebrae based on a power relationship (r2 = 0.71 intact, r2 = 0.43 tumor). Percutaneous vertebroplasty produces higher intravertebral pressures in vertebrae containing a simulated lytic metastasis than in intact vertebrae. Pressures generated in the tumor specimens are sufficiently elevated to cause embolic phenomena.

Density predicts the activity-dependent failure load of proximal femora with defects.

To determine whether the load-bearing capacity of human proximal femora with metastatic defects can be predicted from the bone mineral content. The bone mineral content (BMC) of the total proximal femur was measured by dual-energy X-ray absorptiometry (DXA). The femurs were loaded so as to simulate stair ascent or external rotation. Simulated lytic defects were created using specialized cutting tools in the intertrochanteric region of 32 human cadaveric femora. Bone density measurements were made before and after creating defects. A linear relation could be used to predict failure load from BMC or bone mineral density. The slope of the linear relation was greater for loads representing external rotation than for loads representing stair ascent. The linear relations suggest that the BMC measurements account for both the density of the host bone and the amount of bone removed by the defect. The data suggest that between 70% and 80% of the variation in failure load of human femora with lytic metastatic defects can be predicted from the BMC and that relations between BMC and failure load are sensitive to the type of loading. Combined with information on the loads associated with the activities of daily living, these data may be used to help identify patients in whom prophylactic stabilization might prevent a pathologic fracture.