Tadashi S. Kaneko

Predicting proximal femoral strength using structural engineering models.

Hip fracture related to osteoporosis and metastatic disease is a major cause of morbidity and mortality. An accurate and precise method of predicting proximal femoral strength and fracture location would be useful for research and clinical studies of hip fracture. The goals of this study were to develop a structural modeling technique that accurately predicts proximal femoral strength; to evaluate the accuracy and precision of this predicted strength on an independent data set; and to evaluate the ability of this technique to predict fracture location. Fresh human cadaveric proximal femora with and without metastatic lesions were studied using computed tomography scan-based three-dimensional structural models and mechanical testing to failure under single-limb stance-type loading. The models understated proximal femoral strength by an average of 444 N, and the precision of the predicted strength was ± 1900 N. Therefore, the ability to predict hip strength in an individual subject is limited primarily by the level of precision, rather than accuracy. This level of precision is likely to be sufficient for many studies of hip strength. Finally, these models predict fractures involving the subcapital and cervical regions, consistent with most fractures produced experimentally under single-limb stance-type loading.

Relationships between material properties and CT scan data of cortical bone with and without metastatic lesions

Breast, prostate, lung, and other cancers can metastasize to bone and lead to pathological fracture. To lay the groundwork for new clinical techniques for assessing the risk of pathological fracture, we identified relationships between density measured using quantitative computed tomography (rhoQCT), longitudinal mechanical properties, and ash density (rhoAsh) of cortical bone from femoral diaphyses with and without metastatic lesions from breast, prostate, and lung cancer (bone with metastases from six donors; bone without metastases from one donor with cancer and two donors without cancer). Moderately strong linear relationships between rhoQCT and elastic modulus, strength, and rhoAsh were found for bone with metastases (0.73<r<0.93, P<0.05). After accounting for differences in rhoQCT, the elastic modulus, compressive strength, tensile yield strain, and rhoAsh of bone with metastatic lesions differed from those of bone from donors without cancer (P<0.01). However, differences in tensile strength or compressive yield strain, after controlling for rhoQCT, were not found. Thus, these cancers degrade the elastic modulus and compressive strength, but not the tensile strength, of cortical bone beyond the amount that would be expected from decreased density alone. The rhoQCT-mechanical property relationships reported may be useful for evaluating bone integrity and assessing the risk of fracture of bone with metastases.

Predicting the strength of femoral shafts with and without metastatic lesions.

To evaluate a potential tool for assessing the risk of a pathologic fracture of the femoral shaft, we examined whether fracture loads computed by our computed tomography scan-based finite element models are predictive of measured fracture loads. We also evaluated whether the precision of the computed fracture loads for shafts with metastases is altered if models are generated using mechanical property-density relationships for bone without metastases. We investigated whether femoral shafts with a hemispheric defect and shafts with metastases have qualitatively similar structural behavior. Using identical four-point bending loading conditions, we computed and measured fracture loads of femoral shafts with and without metastases and with a burred hemispheric defect to simulate a tumor. Finite element model fracture loads were strongly predictive of the measured fracture loads (range, 0.92-0.98) even when the models of bones with metastases used mechanical property relationships for bone without metastases. Specimens with hemispheric defects behaved structurally differently than specimens with metastases, indicating that these defects do not accurately simulate the effects of metastases. Results of our study show that these computed tomography scan-based finite element models can be used to estimate the strength of femoral shafts with and without metastases. These models may be useful for assessing the risk of pathologic fractures of femoral shafts.

The effect of simulated metastatic lytic lesions on proximal femoral strength

Metastatic lesions in the proximal femur can reduce hip strength and lead to pathologic fracture. However, current methods for identifying patients at risk of pathologic fracture are inadequate. We hypothesized the percentage of intact proximal femoral strength remaining after formation of a simulated lytic defect within the femoral neck or at the level of the lesser trochanter depends on defect location within the respective region. Computed tomography scan-based finite element models of 12 cadaveric proximal femora were used to evaluate the effect of 20-mm-diameter spherical voids at various locations in the neck and at the level of the lesser trochanter. In both regions, the percentage of intact strength remaining depended on defect location (p < 0.001). In the neck, the strength of specimens with inferomedial defects (median, 50.4% of intact; range, 27.8-71.7%) was less than the strength of specimens with defects located in the center of the neck, superolaterally, or anteriorly (p < 0.05). Near the lesser trochanter, anteromedial defects resulted in the lowest strength (median, 66.6% of intact; range, 49.2-73.8%). Other defects at the level of the lesser trochanter had a markedly smaller effect. These findings may be helpful for evaluating pathologic fracture risk.

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.

Evaluation of a radiation transport modeling method for radioactive bone cement

Spinal metastases are a common and serious manifestation of cancer, and are often treated with vertebroplasty/kyphoplasty followed by external beam radiation therapy (EBRT). As an alternative, we have introduced radioactive bone cement, i.e. bone cement incorporated with a radionuclide. In this study, we present a Monte Carlo radiation transport modeling method to calculate dose distributions within vertebrae containing radioactive cement. Model accuracy was evaluated by comparing model-predicted depth-dose curves to those measured experimentally in eight cadaveric vertebrae using radiochromic film. The high-gradient regions of the depth-dose curves differed by radial distances of 0.3-0.9 mm, an improvement over EBRT dosimetry accuracy. The low-gradient regions differed by 0.033-0.055 Gy/h/mCi, which may be important in situations involving prior spinal cord irradiation. Using a more rigorous evaluation of model accuracy, four models predicted the measured dose distribution within the experimental uncertainty, as represented by the 95% confidence interval of the measured log-linear depth-dose curve. The remaining four models required modification to account for marrow lost from the vertebrae during specimen preparation. However, the accuracy of the modified model results indicated that, when this source of uncertainty is accounted for, this modeling method can be used to predict dose distributions in vertebrae containing radioactive cement.

SU‐FF‐T‐43: Feasibility of Using Radioactive Bone Cement to Treat Vertebral Metastases

Purpose: To evaluate the feasibility of using radioactive bone cement to delivertherapeuticradiation to the vertebral body without undue risk to the spinal cord, i.e. vertebral brachytherapy.Method and Materials: CT‐scan based Monte Carlo N‐Particle radiation transport models, consisting of a three‐dimensional rectangular lattice of 0.625×0.625×1.25‐mm voxels, were created of a T‐12 human cadaveric vertebra. Trabecular and cortical bone were both represented by a spectrum of thirty complementary volume fractions of solid cortical bone and bone marrow, and all soft tissue was represented as a single material. A cylindrical volume of radioactive bone cement was simulated within the model, and two candidate radioisotopes were studied: P‐32 and Sr‐89. Thirty million particle histories were simulated (MCNPX v.2.5.0) to characterize the dose distribution within the vertebral body. Results: The dose distributions for both radioisotopes were axisymmetric about the cement implant and rapidly decreased with increasing distance from the cement. Initial activities of 0.94 mCi and 0.51 mCi for P‐32 and Sr‐89, respectively, would deliver >300 Gy to bone within 1.6 mm of the cement implant and >80 Gy to bone within 2.8 mm, while keeping the dose at 3.4 mm under 45 Gy. Conclusion: The predicted dose distributions show that a therapeuticradiationdose would be delivered to all bone within ∼3 mm of the cement without undue risk to tissue beyond 3.4 mm (such as the spinal cord), indicating preliminary feasibility of this technique. With further development, this technology may yield a clinically‐feasible procedure that would eliminate the need for 10 radiotherapy sessions, making it convenient for the patient, while potentially improving the clinical outcome by delivering a higher dose to the tumor and a lower dose to the spinal cord than conventional radiotherapy. Conflict of Interest (only if applicable): Research sponsored by Bone‐Rad Therapeutics, Inc.