Novel Methods to Assess Interfragmentary Motion: Quantifying a Critical Factor in Fracture Healing

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PROJECT SUMMARY/ABSTRACT We seek to understand how variations in surgical fixation and rehabilitation protocols for distal femur fractures impact the mechanical environment at the fracture and how this in turn influences healing. The concept of mechanotransduction, where physical forces are converted into biomechanical signals that guide cellular responses, is relevant to the healing of all human fractures. Distal femur fractures treated with locked plate fixation are an excellent model for study given a relatively high rate of healing complications (in up to 32% of cases) and a range of treatment strategies across a wide variety of mechanical conditions. The challenges faced when attempting to provide stable, yet biologically friendly (i.e., promoting secondary fracture healing) fixation at this site typify those encountered for all long bone fractures. Although the clinical importance of mechanotransduction in bone healing—in particular strain across a fracture site—has been qualitatively demonstrated, there is a lack of quantitative data. Its specific mechanisms are not fully characterized, and progress to improve related clinical outcomes [has been stagnant. A lack of quantitative clinical data limits our ability to design surgical techniques, implants, and rehabilitation protocols to optimize healing outcomes. Currently, a major obstacle in the field is an inability to assess interfragmentary strain or a clinically useful surrogate.] To overcome this, we aim to validate two novel, noninvasive, and complementary methods of quantifying clinical [fracture site motion]. Method 1) A case-specific computational model will be refined to estimate [fracture site motion] for 10 human subjects recently treated with locked plate fixation for a distal femur fracture. Method 2) Biplane fluoroscopy will be used to track [the proximal and distal bone fragments] during standing and walking for these same 10 patients. The proposed research provides two complementary methods of assessing [fracture site motion] in future translational research. These methods will be validated via cadaveric testing. Furthermore, unloaded and loaded CT measurements of [fracture site motion] in the test cohort will [allow in vivo validation]. Computational modeling provides an indirect, scalable method of estimating [fracture site motion] while biplane fluoroscopy will provide direct in vivo assessment. Both methods will support future translational research involving heretofore untestable hypotheses. This includes research into optimal fixation strategies and rehabilitation protocols, as well as the ability to control for confounding factors in studies of other aspects of fracture healing. This innovative work aims to overcome limitations in current research to develop two complementary methods of quantifying patient-specific [fracture site motion, which has been shown to be a clinically relevant surrogate for interfragmentary strain. A quantitative understanding of fracture site motion will inform observational studies and clinical trials directly targeting mechanotransduction and allow research targeting other aspects of fracture healing to account for a potential confounding effect of mechanotransduction. Further, quantifying fracture site motion is a necessary step toward future quantification of interfragmentary strain.] This translational study opens multiple avenues of mechanistic and clinical investigation with the potential for early and long-term clinical impact by decreasing the incidence of fracture [delayed union and] non-union. [The proposed work will support future Merit Review funding of a prospective observational study of optimizing fixation strategies and rehabilitation protocols for secondary fracture healing.]