Novel Methodology for Using Radiostereometric Analysis to Monitor Fracture Healing

Background: Radiostereometric Analysis (RSA) is a method for performing highly accurate three-dimensional measurements in-vivo using sequential radiographs. RSA has been used extensively for monitoring prosthesis fixation in hip and knee replacements. Recently, there has been increasing interest in applying RSA towards the monitoring of fracture healing. Objective: The objective of this study was to evaluate the feasibility of using RSA to measure strain, stress, and plate migration in a distal femur fracture model. Methods: Femoral sawbones with a distal femur fracture were used as models. A distal femur condylar locking compression plate (LCP) was used to reduce the fracture model. Stainless steel screws were used to fasten the plate to the sawbone. In addition, translucent polyester screws were composed, embedded with 1mm steel beads, and fastened to the most proximal and distal portions of the plate. This allowed for recognition by the RSA imaging modality. The femoral sawbones were then placed in a mechanical testing complex and RSA X-rays taken at different forces of compression. The radiographs were analyzed for plate migration using the 1mm steel beads as points of reference. Results: Preliminary data indicate that it is possible to use a plate model that incorporates a micro-bead system to measure migration. Further analysis will quantify the amount of migration to determine whether significant changes occur at different stages of compression. Conclusion: The ability to measure plate migration in a Radiostereometric Analysis X-ray model is an important step towards improving the ability of orthopedic surgeons to monitor fracture healing and prevent non-union. The next stage of this research will involve using this model in clinical trials of distal femur fractures and building a database to correlate levels of plate migration with surgical outcome

A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes

PURPOSE: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. EXPERIMENTAL DESIGN: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth. RESULTS: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone. CONCLUSION: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease