Predicting pathologic fractures of long bones caused by metastatic disease continues to be a challenging clinical problem. We assessed the ability of noninvasive imaging and computational techniques to predict the strength of bones with osteolytic lesions. A murine model of induced tumor osteolysis to the distal femur was used as a model system resulting in a wide range of lesion sizes. Microcomputed tomography scans were obtained and specimen-specific, voxel-based, finite element analyses were performed and results were compared with direct measurement of biomechanical strength via axial compressive loading of the distal femur. Additional indirect surrogates of bone strength included dual-energy xray absorptiometry to determine bone mineral density, radiographic scoring, and computed tomography volume/ mineral estimates. Predicted bone strength was weakest (r 2 = 0.55) for the dual-energy xray absorptiometry measure and strongest (r 2 = 0.91) for the direct computed tomography voxel-based, finite element analysis. The relative success of the voxel-based, finite element modeling approach to estimate bone strength in a murine osteolytic tumor model indicates this approach, with further development and validation, could serve as a way to nondestructively estimate bone strength in a clinical setting.
Treatment of an osteolytic bone with radiation therapy plus zoledronic acid restores normal bone qualities with respect to bone density, microarchitecture, and biomechanical strength.
Many patients with symptomatic bone metastases receive radiation therapy, even though radiation is known to have potential adverse effects on bone. We hypothesized that the concurrent use of a bisphosphonate drug (zoledronic acid, ZA) or a combination of ZA plus an anabolic agent (parathyroid hormone, PTH) would lead to improvements in the microarchitecture and mechanical properties of irradiated bone. Human breast cancer cells were injected into the distal femur of 56 female nude mice, which were then divided into four groups: no treatment (0 Gy), radiation administered 4 weeks postinjection (20 Gy), radiation plus ZA (12.5 microg/kg weekly from weeks 4 to 12) (20 Gy + ZA), and radiation followed by ZA (25 microg/kg weekly from weeks 4 to 8) and PTH(1-34) (100 microg microg/kg daily from weeks 8 to 12) (20 Gy + ZA + PTH). Left limbs served as normal control bones. Bone loss over the 12-week study was tracked with serial radiography and bone densitometry. At the end of the study, micro-computed tomography and mechanical testing were used to quantify bone microarchitecture and bone strength. Radiation alone failed to prevent tumor-induced decreases in bone mineral density (BMD), trabecular bone volume, and bone strength. Treatment with 20 Gy + ZA or 20 Gy + ZA + PTH as adjuncts to radiation was effective at preserving trabecular bone architecture and bone strength at normal levels. ZA reduced the risk of mechanical fragility following irradiation of a lytic bone lesion. Supplemental use of PTH did not result in further increases in bone strength but was associated with significant increases in BMD and bone mass, suggesting that it may be beneficial in enhancing bone architecture following radiation therapy.
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