D-CRSE: Diminishing chemotherapy-related side effects through patient education, a mixed-methods pilot study.

OBJECTIVES: Patient education materials regarding self-management of chemotherapy-related side effects are limited, which may result in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address problems themselves, and guidance on when to contact their oncologist or seek emergency care. This mixed-methods study conducted at Penn State Cancer Institute evaluates the feasibility of using an educational brochure to improve patient outcomes through education. METHODS: Chemotherapy naïve patients with breast or gastrointestinal (GI) cancer were enrolled in a single-arm clinical trial from December 2021 to 2022. Participants received the educational brochure and were asked to provide their initial impressions. They completed The Emotional Thermometer Scale (ETS) and the Memorial Symptom Assessment Scale (MSAS) to measure changes in patient symptoms and mental health throughout their chemotherapy course at 0, 6, and 12-week intervals. The drop-out rate was recorded as a measure of study feasibility. RESULTS: The study participants were split between the following cancer types: 77.8% breast and 22.2% GI cancer. A significant decrease in overall mean ETS score was observed between baseline and week 6 (p = 0.001) and 12 (p = 0.0004), respectively. Moreover, the mean MSAS psychological symptoms decreased significantly at week 12 compared to baseline (p = 0.005), while no change was observed in physical symptoms (p = 0.101). Of the 40 participants who completed baseline surveys, 37 had at least one additional visit for a drop-out rate of 7.5%. CONCLUSION: This mixed-methods pilot study was successful in demonstrating the feasibility of distributing a standardized educational brochure as an intervention for chemotherapy patients. While participants' emotional scores and psychological symptoms decreased over time, physical symptoms did not, which aligns with side effect progression from cumulative chemotherapy burden.

Torsion constants and virtual mechanical tests are valid image-based surrogate measures of ovine fracture healing.

In large animal studies, the mechanical reintegration of the bone fragments is measured using postmortem physical testing, but these assessments can only be performed once, after sacrifice. Image-based virtual mechanical testing is an attractive alternative because it could be used to monitor healing longitudinally. However, the procedures and software required to perform finite element analysis (FEA) on subject-specific models for virtual mechanical testing can be time consuming and costly. Accordingly, the goal of this study was to determine whether a simpler image-based geometric measure-the torsion constant, sometimes known as polar moment of inertia-can be reliably used as a surrogate measure of bone healing in large animals. To achieve this, postmortem biomechanical testing and microCT scans were analyzed for a total of 33 operated and 20 intact ovine tibiae. An image-processing procedure to compute the attenuation-weighted torsion constant from the microCT scans was developed in MATLAB and this code has been made freely available. Linear regression analysis was performed between the postmortem biomechanical data, the results of virtual mechanical testing using FEA, and the torsion constants measured from the scans. The results showed that virtual mechanical testing is the most reliable surrogate measure of postmortem torsional rigidity, having strong correlations and high absolute agreement. However, when FEA is not practical, the torsion constant is a viable alternative surrogate measure that is moderately correlated with postmortem torsional rigidity and can be readily calculated.

Embracing ethical research: Implementing the 3R principles into fracture healing research for sustainable scientific progress.

As scientific advancements continue to reshape the world, it becomes increasingly crucial to uphold ethical standards and minimize the potentially adverse impact of research activities. In this context, the implementation of the 3R principles-Replacement, Reduction, and Refinement-has emerged as a prominent framework for promoting ethical research practices in the use of animals. This article aims to explore recent advances in integrating the 3R principles into fracture healing research, highlighting their potential to enhance animal welfare, scientific validity, and societal trust. The review focuses on in vitro, in silico, ex vivo, and refined in vivo methods, which have the potential to replace, reduce, and refine animal experiments in musculoskeletal, bone, and fracture healing research. Here, we review material that was presented at the workshop "Implementing 3R Principles into Fracture Healing Research" at the 2023 Orthopedic Research Society (ORS) Annual Meeting in Dallas, Texas.

Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep.

BACKGROUND: Therapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions. METHODS: Combined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively). Control groups received no CEMF treatment. Bone healing was evaluated radiographically, morphometrically (micro-CT), biomechanically and histologically. RESULTS: In the 3-mm gap model, the CEMF group (n = 6) exhibited higher callus mineral density compared to the Control group (n = 6), two-fold higher biomechanical torsional rigidity and a histologically more advanced callus maturity (no statistically significant differences). In the 17-mm graft model, differences between the Control (n = 6) and CEMF group (n = 6) were more pronounced. The CEMF group showed a radiologically more advanced callus, a higher callus volume (p = 0.003) and a 2.6 × higher biomechanical torsional rigidity (p = 0.024), combined with a histologically more advanced callus maturity and healing. CONCLUSIONS: This study showed that CEMF therapy notably enhanced bone healing resulting in better new bone structure, callus morphology and superior biomechanical properties. This technology could transform a standard inert orthopedic implant into an active device stimulating bone tissue for accelerated healing and regeneration.

Evaluating Adequacy of VTE Prophylaxis Dosing with Enoxaparin for Overweight and Obese Patients on an Orthopedic-Medical Trauma Comanagement Service.

OBJECTIVES: Venous thromboembolism (VTE) is a common nosocomial condition, developing frequently in overweight and obese patients. VTE prophylaxis with weight-based enoxaparin dosing may be more effective than the standard dosing regimen for overweight and obese patients; however, weight-based dosing is not practiced routinely. In this pilot study we sought to evaluate prophylactic anticoagulation regimens used for VTE prevention in overweight and obese patients on the Orthopedic-Medical Trauma (OMT) service to inform the need for modification of dosing practices. METHODS: This prospective, observational study evaluated the adequacy of current VTE prophylaxis practice at an academic tertiary center, including overweight and obese patients admitted during 2017-2018 to an OMT comanagement service. It included patients hospitalized for at least 3 days with a body mass index (BMI) of ≥25 and prescribed enoxaparin. Steady-state antifactor Xa trough and peak levels were monitored after three doses. Frequency of in prophylactic range (0.2-0.44) antifactor Xa levels and VTE events were compared by BMI groups and enoxaparin dosing using the χ2 test. RESULTS: There were 404 inpatients included: 41.1% were overweight (BMI 25-29), 43.4% were obese (BMI 30-39), and 15.6% were morbidly obese (BMI ≥40). A total of 351 patients (86.9%) received standard dose enoxaparin 30 mg 2 times per day (BID), and 53 patients received enoxaparin 40 mg BID or more. A number of patients (213; 52.7%) did not achieve prophylactic range antifactor Xa levels. A significantly higher number of patients in the overweight group achieved prophylactic range antifactor Xa compared with obese and morbidly obese groups (58.4% vs 41.7% and 33%, P = 0.002 and 0.0007, respectively). Morbidly obese patients treated with enoxaparin 40 mg BID or higher versus enoxaparin 30 mg BID had fewer VTE events (4% vs 10.8%, P = 0.18). CONCLUSIONS: The current practice of VTE enoxaparin prophylaxis may not be adequate for overweight and obese OMT patients. Further guidelines are needed to implement weight-based VTE prophylaxis in overweight and obese hospitalized patients.

Mechanical Biomarkers in Bone Using Image-Based Finite Element Analysis.

PURPOSE OF REVIEW: The purpose of this review is to summarize insights gained by finite element (FE) model-based mechanical biomarkers of bone for in vivo assessment of bone development and adaptation, fracture risk, and fracture healing. RECENT FINDINGS: Muscle-driven FE models have been used to establish correlations between prenatal strains and morphological development. Postnatal ontogenetic studies have identified potential origins of bone fracture risk and quantified the mechanical environment during stereotypical locomotion and in response to increased loading. FE-based virtual mechanical tests have been used to assess fracture healing with higher fidelity than the current clinical standard; here, virtual torsion test data was a better predictor of torsional rigidity than morphometric measures or radiographic scores. Virtual mechanical biomarkers of strength have also been used to deepen the insights from both preclinical and clinical studies with predictions of strength of union at different stages of healing and reliable predictions of time to healing. Image-based FE models allow for noninvasive measurement of mechanical biomarkers in bone and have emerged as powerful tools for translational research on bone. More work to develop nonirradiating imaging techniques and validate models of bone during particularly dynamic phases (e.g., during growth and the callus region during fracture healing) will allow for continued progress in our understanding of how bone responds along the lifespan.

Dual-zone material assignment method for correcting partial volume effects in image-based bone models.

In image-based finite element analysis of bone, partial volume effects (PVEs) arise from image blur at tissue boundaries and as a byproduct of geometric reconstruction and meshing during model creation. In this study, we developed and validated a material assignment approach to mitigate partial volume effects. Our validation data consisted of physical torsion testing of intact tibiae from N = 20 Swiss alpine sheep. We created finite element models from micro-CT scans of these tibiae using three popular element types (10-node tetrahedral, 8-node hexahedral, and 20-node hexahedral). Without partial volume management, the models over-predicted the torsional rigidity compared to physical biomechanical tests. To address this problem, we implemented a dual-zone material model to treat elements that overlap low-density surface voxels as soft tissue rather than bone. After in situ inverse optimization, the dual-zone material model produced strong correlations and high absolute agreement between the virtual and physical tests. This suggests that with appropriate partial volume management, virtual mechanical testing can be a reliable surrogate for physical biomechanical testing. For maximum flexibility in partial volume management regardless of element type, we recommend the use of the following dual-zone material model for ovine tibiae: soft-tissue cutoff density of 665 mgHA/cm3 with a soft tissue modulus of 50 MPa (below cutoff) and a density-modulus conversion slope of 10,225 MPa-cm3/mgHA for bone (above cutoff).

Rethinking the 10% strain rule in fracture healing: A distal femur fracture case series.

Since the 1970s, the 2%-10% rule has been used to describe the range of interfragmentary gap closure strains that are conducive for secondary bone healing. Interpreting the available evidence for the association between strain and bone healing remains challenging because interfragmentary strain is impossible to directly measure in vivo. The question of how much strain occurs within and around the fracture gap is also difficult to resolve using bench tests with osteotomy models because these do not reflect the complexity of injury patterns seen in the clinic. To account for these challenges, we used finite element modeling to assess the three-dimensional interfragmentary strain in a case series of naturally occurring distal femur fractures treated with lateral plating under load conditions representative of the early postoperative period. Preoperative computed tomography scans were used to construct patient-specific finite element models and plate fixation constructs to match the operative management of each patient. The simulations showed that gap strains were within 2%-10% only for the lowest load application level, 20% static body weight (BW). Moderate loading of 60% static BW and above caused gap strains that far exceeded 10%, but in all cases, strains in the periosteal region external to the fracture line remained low. Comparing these findings with postoperative radiographs suggests that in vivo secondary healing of distal femur fractures may be robust to early gap strains much greater than 10% because formation of new bone is initiated outside the gap where strains are lower, followed by later consolidation within the gap.

Enhanced cycling of nitrogen and metals during rapid infiltration: Implications for managed recharge.

We present results from a series of plot-scale field experiments to quantify physical infiltration dynamics and the influence of adding a carbon-rich, permeable reactive barrier (PRB) for the cycling of nitrogen and associated trace metals during rapid infiltration for managed aquifer recharge (MAR). Recent studies suggest that adding a bio-available carbon source to soils can enhance denitrification rates and associated N load reduction during moderate-to-rapid infiltration (≤1 m/day). We examined the potential for N removal during faster infiltration (>1 m/day), through coarse and carbon-poor soils, and how adding a carbon-rich PRB (wood chips) affects subsurface redox conditions and trace metal mobilization. During rapid infiltration, plots amended with a carbon-rich PRB generally demonstrated modest increases in subsurface loads of dissolved organic carbon, nitrite, manganese and iron, decreases in loads of nitrate and ammonium, and variable changes in arsenic. These trends differed considerably from those seen during infiltration through native soil without a carbon-rich PRB. Use of a carbon-rich soil amendment increased the fraction of dissolved N species that was removed at equivalent inflowing N loads. There is evidence that N removal took place primarily via denitrification. Shifts in microbial ecology following infiltration in all of the plots included increases in the relative abundances of microbes in the families Comamonadaceae, Pseudomonadaceae, Methylophilaceae, Rhodocyclaceae and Sphingomonadaceae, all of which contain genera capable of carrying out denitrification. These results, in combination with studies that have tested other soil types, flow rates, and system scales, show how water quality can be improved during infiltration for managed recharge, even during rapid infiltration, with a carbon-rich soil amendment.

Bone density and its relation to the development of acromial stress fracture following reverse total shoulder arthroplasty.

Background: Postoperative acromial stress fracture is a troublesome postoperative complication after reverse shoulder arthroplasty. Our study aims to utilize routinely performed preoperative computed tomography scans to identify differences in the material properties of the acromion in patients who did and did not develop a postoperative acromial stress fracture. Methods: Treatment records and computed tomography scans for 99 reverse shoulder arthroplasties were collected. Scans were calibrated using a phantom and transferred for post-processing where the acromion, full scapula, and humeral head were isolated. The final segmented model was used to assess acromial volume and volumetric bone mineral density for each region of interest. Results: There was no association between age and volumetric bone mineral density in any region of interest (all R 2 ≤ 0.048, all p > 0.082). Patients who developed an acromial stress fracture were not significantly different from those who did not in terms of age, acromial volume, or acromial volumetric bone mineral density (all p > 0.559). Patients with known osteoporosis or osteopenia had slightly lower volumetric bone mineral density, but the differences were not significant (all p ≥ 0.072). Conclusion: Postoperative acromial fractures following reverse shoulder arthroplasty cannot be predicted by computed tomography-derived volumetric bone mineral density or volume. These mechanical characteristics also do not predictably decrease with age or osteoporosis diagnosis.

Biomechanical duality of fracture healing captured using virtual mechanical testing and validated in ovine bones.

Bone fractures commonly repair by forming a bridging structure called callus, which begins as soft tissue and gradually ossifies to restore rigidity to the bone. Virtual mechanical testing is a promising technique for image-based assessment of structural bone healing in both preclinical and clinical settings, but its accuracy depends on the validity of the material model used to assign tissue mechanical properties. The goal of this study was to develop a constitutive model for callus that captures the heterogeneity and biomechanical duality of the callus, which contains both soft tissue and woven bone. To achieve this, a large-scale optimization analysis was performed on 2363 variations of 3D finite element models derived from computed tomography (CT) scans of 33 osteotomized sheep under normal and delayed healing conditions. A piecewise material model was identified that produced high absolute agreement between virtual and physical tests by differentiating between soft and hard callus based on radiodensity. The results showed that the structural integrity of a healing long bone is conferred by an internal architecture of mineralized hard callus that is supported by interstitial soft tissue. These findings suggest that with appropriate material modeling, virtual mechanical testing is a reliable surrogate for physical biomechanical testing.

Boundary Conditions Matter-Impact of Test Setup on Inferred Construct Mechanics in Plated Distal Femur Osteotomies.

The mechanics of distal femur fracture fixation has been widely studied in bench tests that employ a variety of approaches for holding and constraining femurs to apply loads. No standard test methods have been adopted for these tests and the impact of test setup on inferred construct mechanics has not been reported. Accordingly, the purpose of this study was to use finite element models to compare the mechanical performance of a supracondylar osteotomy with lateral plating under conditions that replicate several common bench test methods. A literature review was used to define a parameterized virtual model of a plated distal femur osteotomy in axial compression loading with four boundary condition sets ranging from minimally to highly constrained. Axial stiffness, fracture gap closure, and transverse motion at the fracture line were recorded for a range of applied loads and bridge spans. The results showed that construct mechanical performance was highly sensitive to boundary conditions imposed by the mechanical test fixtures. Increasing the degrees of constraint, for example, by potting and rigidly clamping one or more ends of the specimen, caused up to a 25× increase in axial stiffness of the construct. Transverse motion and gap closure at the fracture line, which is an important driver of interfragmentary strain, was also largely influenced by the constraint test setup. These results suggest that caution should be used when comparing reported results between bench tests that use different fixtures and that standardization of testing methods is needed in this field.

Image-based radiodensity profilometry measures early remodeling at the bone-callus interface in sheep.

Bone healing has been traditionally described as a four-phase process: inflammatory response, soft callus formation, hard callus development, and remodeling. The remodeling phase has been largely neglected in most numerical mechanoregulation models of fracture repair in favor of capturing early healing using a pre-defined callus domain. However, in vivo evidence suggests that remodeling occurs concurrently with repair and causes changes in cortical bone adjacent to callus that are typically neglected in numerical models of bone healing. The objective of this study was to use image processing techniques to quantify this early-stage remodeling in ovine osteotomies. To accomplish this, we developed a numerical method for radiodensity profilometry with optimization-based curve fitting to mathematically model the bone density gradients in the radial direction across the cortical wall and callus. After assessing data from 26 sheep, we defined a dimensionless density fitting function that revealed significant remodeling occurring in the cortical wall adjacent to callus during early healing, a 23% average reduction in density compared to intact. This fitting function is robust for modeling radial density gradients in both intact bone and fracture repair scenarios and can capture a wide variety of the healing responses. The fitting function can also be scaled easily for comparison to numerical model predictions and may be useful for validating future mechanoregulatory models of coupled fracture repair and remodeling.

Bone Marrow Aspirate Concentrate as a Reliable Adjunct in Tibiotalocalcanal Fusion: A Radiographic Modified RUST Score Analysis.

BACKGROUND: Tibiotalar and subtalar arthritis requiring tibiotalocalcaneal (TTC) fusion can be technically challenging and is dependent on reliable fusion for a good clinical outcome. Initial data regarding bone marrow aspirate concentrate (BMAC) has shown promise in use as an aide in both fracture and fusion healing. The purpose of this study is to determine the outcomes in TTC fusion when utilizing BMAC as an adjunct. METHODS: Twenty consecutive patients who underwent TTC fusion with BMAC adjunct between March 2013 and November 2017 were retrospectively screened for inclusion. Patients were included regardless of comorbidities or risk factors for non-union, and only excluded if they did not have a minimum of 12 months of clinical and/or radiographic chart data. Follow-up was obtained at regular intervals of 6 weeks, 3 months, 6 months and 1 year. Modified RUST scores were applied to grade bony union in a blinded fashion by two orthopedic trauma fellowship-trained surgeons and agreement was assessed via intraclass correlation coefficient (ICC). RESULTS: Twenty patients were screened and 12 met inclusion criteria for analysis. Majority were male (66.6%) at a mean age of 55.4 years and they were all treated via TTC fusion for a diagnosis of tibiotalar and subtalar arthritis. There were no postoperative complications and no reoperations in this cohort; no donor site morbidity was associated with BMAC. By the 3-month follow-up timepoint, all but one patient received a minimum modified RUST score of 10 indicating bony union (ICC 0.91); by the 6-month time point (ICC 0.94), all 12 patients were deemed united. CONCLUSION: BMAC as an adjunct in the setting of TTC fusion is a safe treatment option that can promote reliable, consistent bony fusion with minimal complications.

Pilot study of micromotion nailing for mechanical stimulation of tibial fracture healing.

AIMS: The study objective was to prospectively assess clinical outcomes for a pilot cohort of tibial shaft fractures treated with a new tibial nailing system that produces controlled axial interfragmentary micromotion. The hypothesis was that axial micromotion enhances fracture healing compared to static interlocking. METHODS: Patients were treated in a single level I trauma centre over a 2.5-year period. Group allocation was not randomized; both the micromotion nail and standard-of-care static locking nails (control group) were commercially available and selected at the discretion of the treating surgeons. Injury risk levels were quantified using the Nonunion Risk Determination (NURD) score. Radiological healing was assessed until 24 weeks or clinical union. Low-dose CT scans were acquired at 12 weeks and virtual mechanical testing was performed to objectively assess structural bone healing. RESULTS: A total of 37 micromotion patients and 46 control patients were evaluated. There were no significant differences between groups in terms of age, sex, the proportion of open fractures, or NURD score. There were no nonunions (0%) in the micromotion group versus five (11%) in the control group. The proportion of fractures united was significantly higher in the micromotion group compared to control at 12 weeks (54% vs 30% united; p = 0.043), 18 weeks (81% vs 59%; p = 0.034), and 24 weeks (97% vs 74%; p = 0.005). Structural bone healing scores as assessed by CT scans tended to be higher with micromotion compared to control and this difference reached significance in patients who had biological comorbidities such as smoking. CONCLUSION: In this pilot study, micromotion fixation was associated with improved healing compared to standard tibial nailing. Further prospective clinical studies will be needed to assess the strength and generalizability of any potential benefits of micromotion fixation. Cite this article: Bone Jt Open 2021;2(10):825-833.

Enhancing hospitalists smoking cessation counseling and billing compliance by education intervention: a quality improvement project.

Smoking causes an estimated 480,000 deaths every year. At our institute, tobacco treatment services (TTS) provide inpatient counseling and hospitalists have an essential role in providing education and replacement medications at discharge. Our project focused on increasing knowledge among hospitalists to improve the frequency of smoking cessation consultation and utilization of pharmacotherapy, accompanied by appropriate documentation and billing. We used baseline data from March 2018 to February 2019. Educational intervention was implemented from March 2019 to June 2019. Post-intervention results are reported from July 2019 to February 2020. Pre- and post-intervention periods' results were compared. A significantly higher number of patients received TTS counseling during the post-intervention phase compared to pre-intervention (54 vs. 41%, p < 0.0001). A significantly higher number of patients were prescribed inpatient medications (42% to 48%, p = 0.004) and at the time of discharge (22% to 31%, p < 0.0001). However, there was a significant decrease in physician billing from pre-intervention to post-intervention, dropping from 19.5% to 16.2% (p = 0.012). Physicians' gender, experience level, and loss of incentives impacted their consultation and billing behaviors. Future studies should continue to address the importance of TTS and physician behavior on increasing inpatient smoking cessation counseling and treatment.

An Adaptable Computed Tomography-Derived Three-Dimensional-Printed Alignment Fixture Minimizes Errors in Radius Biomechanical Testing.

Biomechanical testing of long bones can be susceptible to errors and uncertainty due to malalignment of specimens with respect to the mechanical axis of the test frame. To solve this problem, we designed a novel, customizable alignment and potting fixture for long bone testing. The fixture consists of three-dimensional-printed components modeled from specimen-specific computed tomography (CT) scans to achieve a predetermined specimen alignment. We demonstrated the functionality of this fixture by comparing benchtop torsional test results to specimen-matched finite element models and found a strong correlation (R2 = 0.95, p < 0.001). Additional computational models were used to estimate the impact of malalignment on mechanical behavior in both torsion and axial compression. Results confirmed that torsion testing is relatively robust to alignment artifacts, with absolute percent errors less than 8% in all malalignment scenarios. In contrast, axial testing was highly sensitive to setup errors, experiencing absolute percent errors up to 50% with off-center malalignment and up to 170% with angular malalignment. This suggests that whenever appropriate, torsion tests should be used preferentially as a summary mechanical measure. When more challenging modes of loading are required, pretest clinical-resolution CT scanning can be effectively used to create potting fixtures that allow for precise preplanned specimen alignment. This may be particularly important for more sensitive biomechanical tests (e.g., axial compressive tests) that may be needed for industrial applications, such as orthopedic implant design.

Domain-independent simulation of physiologically relevant callus shape in mechanoregulated models of fracture healing.

Mechanoregulatory models have been used to predict the progression of bone fracture healing for more than two decades. However, many published studies share the same fundamental limitation: callus development proceeds within a pre-defined domain that both restricts and directs healing and leads to some non-physiologic healing patterns. To address this limitation, we added two spatial proximity functions to an existing mechanoregulatory model of fracture healing to control the localization of callus within the healing domain. We tested the performance of the new model in an idealized ovine tibial osteotomy with medial plate fixation using three sizes of healing domains and multiple variations of the spatial proximity functions. All model variations produced outward callus growth and bridging weighted toward the far cortex, which is consistent with in vivo healing. With and without the proximity functions, there were marked differences in the predicted callus volume and shape. With no proximity functions, the callus produced was strongly domain dependent, with a 15% difference in volume between the smallest and largest initialization domains. With proximity function control, callus growth was restricted to near the fracture line and there was only 2% difference in volume between domain sizes. Superimposing both proximity functions - one to control outward growth and one representing a decay in periosteal activity away from the fracture - produced a predicted callus size that was within the physiologic range for sheep and had a realistic morphology when compared with fluorescent dye co-localization with calcium deposition over time and histology.

Virtual mechanical tests out-perform morphometric measures for assessment of mechanical stability of fracture healing in vivo.

Finite element analysis with models derived from computed tomography (CT) scans is potentially powerful as a translational research tool because it can achieve what animal studies and cadaver biomechanics cannot-low-risk, noninvasive, objective assessment of outcomes in living humans who have actually experienced the injury, or treatment being studied. The purpose of this study was to assess the validity of CT-based virtual mechanical testing with respect to physical biomechanical tests in a large animal model. Three different tibial osteotomy models were performed on 44 sheep. Data from 33 operated limbs and 20 intact limbs was retrospectively analyzed. Radiographic union scoring was performed on the operated limbs and physical torsional tests were performed on all limbs. Morphometric measures and finite element models were developed from CT scans and virtual torsional tests were performed to assess healing with four material assignment techniques. In correlation analysis, morphometric measures and radiographic scores were unreliable predictors of biomechanical rigidity, while the virtual torsion test results were strongly and significantly correlated with measured biomechanical test data, with high absolute agreement. Overall, the results validated the use of virtual mechanical testing as a reliable in vivo assessment of structural bone healing. This method is readily translatable to clinical evaluation for noninvasive assessment of the healing progress of fractures with minimal risk. Clinical significance: virtual mechanical testing can be used to reliably and noninvasively assess the rigidity of a healing fracture using clinical-resolution CT scans and that this measure is superior to morphometric and radiographic measures.

Mechanoregulation modeling of bone healing in realistic fracture geometries.

In bone fracture healing, new tissue gradually forms, ossifies, and eventually remodels itself to restore mechanical stiffness and strength across injury site. Mechanical strain at the fracture site has been implicated in controlling the process of healing and numerical mechanoregulation models with strain-based fuzzy logic rules have been applied to simulate bone healing for simple fracture geometries. However, many of these simplified models cannot capture in vivo observations such as delays in healing with torsional instability or differences in healing rate between different fracture types. Accordingly, the purpose of this work was to apply a fuzzy logic mechanoregulation fracture healing simulation technique to 3D models representing a range of clinically inspired fracture geometries with intramedullary nail fixation and multiaxial loading conditions. The models predicted that the rate of healing depends on the geometry of the fracture and that all fracture types experience a small healing delay with torsional instability. The results also indicated that when realistic torsional loading and fixator mechanics are included, previously published strain-based rules for tissue destruction lead to simulated nonunions that would not be expected in vivo. This suggested that fracture healing may be more robust to distortional strain than has been previously reported and that fuzzy logic models may require parameter tuning to correctly capture clinically relevant healing. The strengths of this study are that it includes fracture morphology effects, realistic implant mechanics, and an exploratory adaptation of the upper distortional strain threshold. These findings may help future researchers extend these methods into clinical fracture healing prediction.