Influence of sidewall retention and interference fit in total ankle replacement on implant-bone micromotion: A finite element study.

The success of uncemented total ankle replacement (TAR) is linked to initial stability because bony ingrowth depends upon limited early micromotion. Tibial implant design fixation features resist micromotion aided by bony sidewall retention and interference fit. Our goal was to investigate factors influencing implant-bone micromotion in TAR. Two TAR tibial components were virtually inserted into CT-derived computer models of two distal tibias from patients with end-stage ankle arthritis. Density-based inhomogeneous material assignment was used to model bone compaction during press-fit. Finite element analysis (FEA) was used to simulate three fixation cases: (1) no sidewalls + line-to-line fit, (2) sidewalls + line-to-line fit, and (3) sidewalls + 50, 100, or 200 µm interference fit. Kinetic profiles from the stance phase of gait were simulated and micromotions computed from FEA output. Without sidewalls or interference fit, micromotions were largest in early and late stance, with largest micromotions (averaging ~150-250 µm) observed near heel strike. Micromotions decreased 39%-62% when sidewalls were retained. When interference fit was also modeled, micromotions decreased another 37%-61% to ~10 µm. Micromotion differences between patients persisted with sidewall retention but largely disappeared with interference fit. This study presents new insights into the effects of TAR fixation features on implant-bone micromotion. Stability appeared to be influenced by surrounding bone quality, but this influence was greatly diminished when interference fit was introduced. More complete understanding of TAR implant features and performance is needed, but our results show the importance of bone quality and interference fit in the stability of uncemented TAR.

Effects of Radiotherapy Upon Bone Structure-Strength Relationships Vary With Sex and Fractionation of Dosing.

Background: Radiotherapy for tumor treatment in or near bones often causes osteopenia and/or osteoporosis, and the resulting increased bone fragility can lead to pathologic fractures. Bone mineral density (BMD) is often used to screen for fracture risk, but no conclusive relationship has been established between BMD and the microstructural/ biomechanical changes in irradiated bone. Understanding the effects of radiation dosing regimen on the bone structure-strength relationship would improve the ability to reduce fracture-related complications resulting from cancer treatment. Methods: Thirty-two C57B6J mice aged 10 - 12 weeks old were randomized to single dose (1 x 25 Gy) and fractionated dose (5 x 5 Gy) irradiation groups. Right hindlimbs were irradiated while the contralateral hindlimbs served as the non-irradiated control. Twelve weeks after irradiation, BMD and bone microstructure were assessed with micro-computed tomography, and mechanical strength/stiffness was assessed with a torsion test. The effects of radiation dosing regimen on bone microstructure and strength were assessed using ANOVA, and bone strength-structure relationships were investigated through correlation analysis of microstructural and mechanical parameters. Results: Fractionated irradiation induced significantly greater losses in BMD in the femur (23% - male mice, p=0.016; 19% - female mice) and the tibia (18% - male mice; 6% - female mice) than the single-dose radiation. The associated reductions in trabecular bone volume (-38%) and trabecular number (-34% to -42%), and the increase in trabecular separation (23% to 29%) were only significant in the male mice with fractionated dosing. There was a significant reduction in fracture torque in the femurs of male (p=0.021) and female (p=0.0017) mice within the fractionated radiation group, but not in the single dose radiation groups. There was moderate correlation between bone microstructure and mechanical strength in the single-dose radiation group (r = 0.54 to 0.73), but no correlation in the fractionated dosing group (r=0.02 to 0.03). Conclusion: Our data indicate more detrimental changes in bone microstructure and mechanical parameters in the fractionated irradiation group compared to the single dose group. This may suggest the potential for protecting bone if a needed therapeutic radiation dose can be delivered in a single session rather than administered in fractions.

Finite Element Model-Computed Mechanical Behavior of Femurs with Metastatic Disease Varies Between Physiologic and Idealized Loading Simulations.

Background and objectives: Femurs affected by metastatic bone disease (MBD) frequently undergo surgery to prevent impending pathologic fractures due to clinician-perceived increases in fracture risk. Finite element (FE) models can provide more objective assessments of fracture risk. However, FE models of femurs with MBD have implemented strain- and strength-based estimates of fracture risk under a wide variety of loading configurations, and "physiologic" loading models typically simulate a single abductor force. Due to these variations, it is currently difficult to interpret mechanical fracture risk results across studies of femoral MBD. Our aims were to evaluate (1) differences in mechanical behavior between idealized loading configurations and those incorporating physiologic muscle forces, and (2) differences in the rankings of mechanical behavior between different loading configurations, in FE simulations to predict fracture risk in femurs with MBD. Methods: We evaluated 9 different patient-specific FE loading simulations for a cohort of 54 MBD femurs: strain outcome simulations-physiologic (normal walking [NW], stair ascent [SA], stumbling), and joint contact only (NW contact force, excluding muscle forces); strength outcome simulations-physiologic (NW, SA), joint contact only, offset torsion, and sideways fall. Tensile principal strain and femur strength were compared between simulations using statistical analyses. Results: Tensile principal strain was 26% higher (R 2 = 0.719, P < .001) and femur strength was 4% lower (R 2 = 0.984, P < .001) in simulations excluding physiologic muscle forces. Rankings of the mechanical predictions were correlated between the strain outcome simulations (ρ = 0.723 to 0.990, P < .001), and between strength outcome simulations (ρ = 0.524 to 0.984, P < .001). Conclusions: Overall, simulations incorporating physiologic muscle forces affected local strain outcomes more than global strength outcomes. Absolute values of strain and strength computed using idealized (no muscle forces) and physiologic loading configurations should be used within the appropriate context when interpreting fracture risk in femurs with MBD.

Mechanical Gains Associated With Virtual Prophylactic Intramedullary Nail Fixation in Femurs With Metastatic Disease.

Background: Many patients with metastatic bone disease (MBD) of the femur undergo prophylactic surgical fixation for impending pathologic fractures; intramedullary nailing (IMN) being the most common fixation type. However, surgeons often question if IMN fixation provides sufficient improvements in mechanical strength for particular metastatic lesions. Our goal was to use patient-specific finite element (FE) modeling to computationally evaluate the effects of simulated IMN fixation on the mechanics of femurs affected with MBD. Methods: Computed tomography (CT) scans were available retrospectively from 48 patients (54 femurs) with proximal femoral metastases. The CT scans were used to create patient-specific, non-linear, voxel-based FE models of the femur, simulating the instant of peak hip joint contact force during normal walking. FE analyses were repeated after incorporating virtual IMN fixation (Smith and Nephew, TRIGEN INTERTAN) into the same femurs. Femur strength and load-to-strength ratio (LSR; lower LSR indicates lower fracture risk) were compared between untreated and IMN conditions using statistical analyses. Results: IMN fixation resulted in a very modest average 10% increase in mechanical strength (p<0.001), which was associated with a slight 7% reduction in fracture risk (p<0.001). However, there was considerable variation in fracture risk reduction between individual femurs (0.13-50%). In femurs with the largest reduction in fracture risk (>10%), IMN hardware directly passed through a considerable section of that femur's metastatic lesion. Femurs with lytic (10%) and diffuse (9%) metastases tended to have greater reductions in fracture risk compared to femurs with blastic (5%) and mixed (4%) metastases (p=0.073). Conclusion: Given the mechanically strong baseline condition of most femurs in this cohort, evident by the low fracture risk at the time of CT scanning, the relative increase in stiffness with the addition of the IMN hardware may not make a substantial contribution to overall mechanical strength. The mechanical gains of IMN fixation in femurs with MBD appear most beneficial when the hardware traverses an adequate section of the lesion. Level of Evidence: III.

Finite element analysis potentially identifies nonessential prophylactic stabilization in femurs with metastatic disease.

Metastatic bone disease (MBD) is often managed by non-specialized orthopedic surgeons who rely on Mirels' criteria to predict pathologic fracture risk. However, low specificity of Mirels' criteria implies many lesions are scored at high fracture risk when the actual mechanical fracture risk is minimal. Our goal was to retrospectively compare mechanical fracture risk in MBD patients to Mirels' score and clinical treatment received. Using a CT-based finite element (FE) model of the proximal femur affected by MBD, femur strength and load-to-strength ratio (LSR) were determined for 52 femurs from 48 patients. Associations of femur strength with pain and Mirels' scores (Pearson r/Spearman ρ correlations), and the decision to operate (percentile analysis), and associations of LSR with pain and Mirels' scores (Spearman correlations) were determined. Nineteen of 52 femurs (37%) had a very low computed mechanical fracture risk (LSR < 0.4); 5 of those 19 underwent prophylactic stabilization, suggesting that clinical decision-making in MBD is substantially influenced by non-mechanical factors that likely overestimate pathologic fracture risk. Of the 30 femurs managed non-operatively, 24 had a low computed mechanical fracture risk (LSR ≤ 0.5), none of which (0%) experienced a fracture within 9 months. Patient-reported pain did not correlate with femur strength (r = -0.05, p = 0.748) nor with LSR (ρ = 0.07, p = 0.632). Mirels' score correlated weakly with femur strength (ρ = -0.32, p = 0.019) and with LSR (ρ = 0.29, p = 0.034). Computational mechanical tools like this FE model could be used as a clinical decision aid when considering non-surgical management in appropriate patients, potentially alleviating nonessential surgical treatment in some patients with femur MBD.

Return of Scapulohumeral Rhythm in Patients After Reverse Shoulder Arthroplasty: A Midterm Stereoradiographic Imaging Analysis.

Background: Reverse shoulder arthroplasty (RSA) is associated with high rates of midterm complications including scapular notching, implant wear, and mechanical impingement. Scapulo-humeral rhythm (SHR), described by Codman in the 1920's, is defined as the ratio of glenohumeral motion to scapulothoracic motion. SHR is used as an indicator of shoulder dysfunction, as alterations in SHR can have profound implications on shoulder biomechanics. The determination of SHR can be hindered by soft-tissue motion artifacts and high radiation burdens associated with traditional surface marker or fluoroscopic analysis. EOS low dose stereoradiographic imaging analysis utilizing 3D model construction from a 2D X-ray series may offer an alternative modality for characterizing SHR following RSA. Methods: Patients (n=10) underwent an EOS imaging analysis to determine SHR at six and twelve months post-RSA. Leveraging 3D models of the implants, 2D/3D image registration methods were used to calculate relative glenohumeral and scapulothoracic positioning at 60, 90 and 120° of shoulder elevation. Subject-specific SHR curves were assessed and midterm changes in post-RSA SHR associated with follow-up time and motion phase were evaluated. Pearson correlations assessed associations between patient-specific factors and post-RSA SHR. Results: Mean post-RSA SHR was 0.81:1 across subjects during the entire midterm postoperative period. As a cohort, post-RSA SHR was more variable for 60-90° of shoulder motion. SHR for 90-120° of motion decreased (0.43:1) at twelve months post-RSA. Post-RSA SHR could be categorized using three relative motion curve patterns, and was not strongly associated with demographic factors such as BMI. 50% of subjects demonstrated a different SHR relative motion curve shape at twelve months post-RSA, and SHR during the 90120° of motion was found to generally decrease at twelve months. Conclusion: Midterm post-RSA SHR was successfully evaluated using EOS technology, revealing lower SHR values (i.e., greater scapulothoracic motion) compared to normal values reported in the literature. SHR continued to change for some subjects during the midterm post-RSA period, with the greatest change during 90-120° of shoulder motion. Study findings suggest that future post RSA rehabilitation efforts to address elevated scapulothoracic motion may benefit from being patient-specific in nature and targeting scapular stabilization during 90-120° of shoulder motion. Level of Evidence: IV.

Influence of subscapularis stiffness with glenosphere lateralization on physiological external rotation limits after reverse shoulder arthroplasty.

BACKGROUND: Repair of the subscapularis following reverse shoulder arthroplasty (RSA) remains a controversial topic among surgeons. Poor rotator cuff muscle quality is associated with increased musculotendinous stiffness, and the subsequent effect of compromised tissue repair on RSA functional outcomes remains unclear. The objective was to investigate the influence of subscapularis stiffness together with glenoid component lateralization on pre- and postimpingement joint mechanics during external rotation after RSA. METHODS: A validated finite element model incorporating the Zimmer Trabecular Metal reverse system was used. The deltoid and subscapularis tendon were tensioned and wrapped around the joint prior to controlled shoulder external rotation. Baseline subscapularis stiffness, determined from cadaveric testing, was varied to 80%, 120% and 140% of baseline, to simulate a range of pliability associated with fatty infiltration and fibrosis. We evaluated the effects of varying subscapularis stiffness and the corresponding variation in joint tension with varying glenosphere lateralization (2, 4, and 10 mm) on the torque required to externally rotate the shoulder and the impingement/subluxation risk. RESULTS: Prior to any impingement, the torques required to externally rotate the shoulder ranged from 22-47 Nm across the range of parameters studied, with the greatest torques required for the 10-mm glenosphere lateralization. The impact of increasing subscapularis stiffness on torque requirements was most pronounced at the 10-mm lateralization, as well. A 20% increase in subscapularis stiffness necessitated a 7%-14% increase in preimpingement torque, whereas a 40% stiffness increase was associated with a 12%-27% increase in torque. Torque was proportional to lateralization. When lateralization was increased from 2 to 4 mm, the preimpingement torque increased by 10%-13%, whereas a 10-mm lateralization necessitated a 35%-62% torque increase relative to 2 mm of lateralization. Increased subscapularis stiffness did not limit impingement-free range of motion or substantially decrease postimpingement subluxation in this model. DISCUSSION: Mechanical gains achieved through lateralization may be hindered by increased torque demands, especially when a stiffer subscapularis is repaired. As lateralization increases subscapularis tension, greater torque is required to externally rotate the shoulder. The torque required for external rotation has been reported between 15-50 Nm. Subscapularis repair with the simulated increases in stiffness requires relative increases in torque that the reconstructed shoulder may not be able to physically produce to rotate the glenohumeral joint, particularly at 10-mm lateralization. These results suggest that subscapularis repair may not be indicated in cases where a lateralized glenoid component is used and the subscapularis is compromised.

Dominant and nondominant distal radius microstructure: Predictors of asymmetry and effects of a unilateral mechanical loading intervention.

Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral high resolution peripheral quantitative computed tomography (HRpQCT) data collected over a 12-month period as part of a clinical trial that prescribed a well-controlled, compressive loading task to the nondominant forearm. Baseline data from 102 women age 21-40, and longitudinal data from 66 women who completed the 12-month trial, were examined to determine factors responsible for side-to-side asymmetries in bone structure and change in structure over time. Cross-sectionally, the dominant radius had 2.4%-2.7% larger cross-sectional area, trabecular area, and bone mineral content than the nondominant radius, but no other differences were noted. Those who more strongly favored their dominant arm had significantly more, thinner, closely spaced trabecular struts in their dominant versus nondominant radius. Individuals assigned to a loading intervention had significant bilateral gains in total bone mineral density (2.0% and 1.2% in the nondominant versus dominant sides), and unilateral gains in the nondominant (loaded) cortical area (3.1%), thickness (3.0%), bone mineral density (1.7%) and inner trabecular density (1.3%). Each of these gains were significantly predicted by loading dose, a metric that included bone strain, number of cycles, and strain rate. Within individuals, change was negatively associated with age, meaning that women closer to age 40 experienced less of a gain in bone versus those closer to age 21. We believe that dominant/nondominant asymmetries in bone structure reflect differences in habitual loads during growth and past ability to adapt, while response to loading reflects current individual physiologic capacity to adapt.

Simulated lesions representative of metastatic disease predict proximal femur failure strength more accurately than idealized lesions.

Metastatic disease in bone is characterized by highly amorphous and variable lesion geometry, with increased fracture risk. Assumptions of idealized lesion geometry made in previous finite element (FE) studies of metastatic disease in the proximal femur may not sufficiently capture effects of local stress/strain concentrations on predicted failure strength. The goal of this study was to develop and validate a FE failure model of the proximal femur incorporating artificial defects representative of physiologic metastatic disease. Data from 11 cadaveric femur specimens were randomly divided into either a training set (n = 5) or a test set (n = 6). Clinically representative artificial defects were created, and the femurs were loaded to failure under offset torsion. Voxel-based FE models replicating the experimental setup were created from the training set pre-fracture computed tomography data. Failure loads from the linear model with maximum principal strain failure criterion correlated best with the experimental data (R2 = 0.86, p = 0.024). The developed model was found to be reliable when applied to the test dataset with a relatively low RMSE of 46.9 N, mean absolute percent error of 12.7 ± 17.1%, and cross-validation R2 = 0.88 (p < 0.001). Models simulating realistic lesion geometry explained an additional 26% of the variance in experimental failure load compared to idealized lesion models (R2 = 0.62, p = 0.062). Our validated automated FE model representative of physiologic metastatic disease may improve clinical fracture risk prediction and facilitate research studies of fracture risk during functional activities and with treatment interventions.

Bone Adaptation in Adult Women Is Related to Loading Dose: A 12-Month Randomized Controlled Trial.

Although strong evidence exists that certain activities can increase bone density and structure in people, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical trial design. The degree to which strain rate and magnitude govern bone adaptation in humans has never been prospectively tested. Here, we studied the effects of a voluntary upper extremity compressive loading task in healthy adult women during a 12-month prospective period. A total of 102 women age 21 to 40 years participated in one of two experiments: (i) low (n = 21) and high (n = 24) strain magnitude; or (ii) low (n = 21) and high (n = 20) strain rate. Control (n = 16) no intervention. Strains were assigned using subject-specific finite element models. Load cycles were recorded digitally. The primary outcome was change in ultradistal radius integral bone mineral content (iBMC), assessed with QCT. Interim time points and secondary outcomes were assessed with high resolution pQCT (HRpQCT) at the distal radius. Sixty-six participants completed the intervention, and interim data were analyzed for 77 participants. Likely related to improved compliance and higher received loading dose, both the low-strain rate and high-strain rate groups had significant 12-month increases to ultradistal iBMC (change in control: -1.3 ± 2.7%, low strain rate: 2.7 ± 2.1%, high strain rate: 3.4 ± 2.2%), total iBMC, and other measures. "Loading dose" was positively related to 12-month change in ultradistal iBMC, and interim changes to total BMD, cortical thickness, and inner trabecular BMD. Participants who gained the most bone completed, on average, 128 loading bouts of (mean strain) 575 µÎµ at 1878 µÎµ/s. We conclude that signals related to strain magnitude, rate, and number of loading bouts contribute to bone adaptation in healthy adult women, but only explain a small amount of variance in bone changes. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Effects of loading rate on the of mechanical behavior of the femur in falling condition.

The Surgeon General estimates that by 2020, half of all Americans could have weak bones due to bone loss. Osteoporosis causes more than 1.5 million fractures every year. Identifying effective interventions based on individual patient characteristics remains a major challenge. Proximal femur fractures are common and devastating events for individuals with osteoporosis. Since fracture is primarily a mechanical event, noninvasive predictions of fracture strength and location would be useful both for identifying at-risk individuals and evaluating treatment effects. However, bone fracture prediction is complicated due to the complex microstructure and nanostructure of bone. Bone is a highly heterogeneous material with rate-dependent mechanical behavior and large inter-individual variation. In this study, we designed two mechanical test procedures to understand the mechanical response of bone under impact and quasi-static load tests. The boundary conditions of the tests were designed in a way to simulate a fall to the side. The present study consists of three main parts: cadaver testing, quantitative image analysis, and finite element (FE) modeling. We obtained ten human femur bones and used high-resolution CT to quantify the microstructure and density of each sample. Specimen-specific FE models were created to evaluate the ability of various failure criteria to predict experimental fracture. Afterward, the samples were tested and their failure patterns were recorded. The fractured samples were rescanned to analyze the fractured surfaces. Our experimental results show that the loading necessary to fracture the femur samples is much higher in the impact tests. However, the toughening mechanisms are more pronounced in quasi-static tests. We found that FE model formulations were able to accurately predict femur stiffness and strength for quasi-static and impact conditions separately, but that no single formulation could account for the rate-dependent outcomes.

Moderate-to-heavy smoking in women is potentially associated with compromised cortical porosity and stiffness at the distal radius.

Though smokers have poor clinical outcomes after treatment for fractures, the skeletal effects of smoking are still debated. Our results showed that female smokers had 33% higher cortical bone porosity. Smoking targets cortical compartment microstructure and mechanics, and micron-scale variables are essential to better understand the specific effects of smoking. PURPOSE: Smokers have poor outcomes in the clinic after treatment for fractures. However, skeletal effects of smoking are still debated. Inconsistencies in published data are likely due to macro-scale variables used to characterize bone differences due to smoking. Therefore, our goal was to characterize distal radius microstructure and macrostructure differences between smokers and non-smokers, and determine the degree to which smoking is associated with compartment-specific mechanical differences resulting from compromised cortical-trabecular microstructure. METHODS: Data were acquired from 46 female smokers (35 to 64 years old), and 45 age- and body mass-matched female non-smokers. Distal radius microstructure and mechanical variables were determined from high-resolution peripheral quantitative computed tomography (HR-pQCT) images and multiscale finite element analysis. Distal radius macro-scale variables (bone volume, bone mineral content, volumetric bone mineral density [vBMD]) were determined from low-resolution images. RESULTS: Age- and body mass index-adjusted results showed that cortical porosity was 33% higher (p < 0.01), and that cortical vBMD and stiffness were 3% and 8% lower, respectively (p < 0.05), among smokers. We also observed unloading of the cortical compartment in smokers. There were no differences in the macro-scale variables. Average HR-pQCT-derived vBMD was 8% lower (p < 0.05) in smokers corresponding to 5 years of postmenopausal loss. CONCLUSION: Skeletal effects of smoking become evident at the micron level through a structurally and mechanically compromised cortical compartment, which partially explains the inconsistent results observed at the macro-level, and the poor clinical outcomes. Smoking may also compound postmenopausal effects on bone potentially placing women having undergone menopause at a greater risk for fracture.

Distal radius microstructure and finite element bone strain are related to site-specific mechanical loading and areal bone mineral density in premenopausal women.

While weight-bearing and resistive exercise modestly increases aBMD, the precise relationship between physical activity and bone microstructure, and strain in humans is not known. Previously, we established a voluntary upper-extremity loading model that assigns a person's target force based on their subject-specific, continuum FE-estimated radius bone strain. Here, our purpose was to quantify the inter-individual variability in radius microstructure and FE-estimated strain explained by site-specific mechanical loading history, and to determine whether variability in strain is captured by aBMD, a clinically relevant measure of bone density and fracture risk. Seventy-two women aged 21-40 were included in this cross-sectional analysis. High resolution peripheral quantitative computed tomography (HRpQCT) was used to measure macro- and micro-structure in the distal radius. Mean energy equivalent strain in the distal radius was calculated from continuum finite element models generated from clinical resolution CT images of the forearm. Areal BMD was used in a nonlinear regression model to predict FE strain. Hierarchical linear regression models were used to assess the predictive capability of intrinsic (age, height) and modifiable (body mass, grip strength, physical activity) predictors. Fifty-one percent of the variability in FE bone strain was explained by its relationship with aBMD, with higher density predicting lower strains. Age and height explained up to 31.6% of the variance in microstructural parameters. Body mass explained 9.1% and 10.0% of the variance in aBMD and bone strain, respectively, with higher body mass indicative of greater density. Overall, results suggest that meaningful differences in bone structure and strain can be predicted by subject characteristics.

Exercise Early and Often: Effects of Physical Activity and Exercise on Women's Bone Health.

In 2011 over 1.7 million people were hospitalized because of a fragility fracture, and direct costs associated with osteoporosis treatment exceeded 70 billion dollars in the United States. Failure to reach and maintain optimal peak bone mass during adulthood is a critical factor in determining fragility fracture risk later in life. Physical activity is a widely accessible, low cost, and highly modifiable contributor to bone health. Exercise is especially effective during adolescence, a time period when nearly 50% of peak adult bone mass is gained. Here, we review the evidence linking exercise and physical activity to bone health in women. Bone structure and quality will be discussed, especially in the context of clinical diagnosis of osteoporosis. We review the mechanisms governing bone metabolism in the context of physical activity and exercise. Questions such as, when during life is exercise most effective, and what specific types of exercises improve bone health, are addressed. Finally, we discuss some emerging areas of research on this topic, and summarize areas of need and opportunity.

Simplified boundary conditions alter cortical-trabecular load sharing at the distal radius; A multiscale finite element analysis.

High-resolution peripheral quantitative computed tomography (HR-pQCT) derived micro-finite element (FE) modeling is used to evaluate mechanical behavior at the distal radius microstructure. However, these analyses typically simulate non-physiologic simplified platen-compression boundary conditions on a small section of the distal radius. Cortical and trabecular regions contribute uniquely to distal radius mechanical behavior, and various factors affect these regions distinctly. Generalized strength predictions from standardized platen-compression analyses may not adequately capture region specific responses in bone. Our goal was to compare load sharing within the cortical-trabecular compartments between the standardized platen-compression BC simulations, and physiologic BC simulations using a validated multiscale approach. Clinical- and high-resolution images were acquired from nine cadaveric forearm specimens using an HR-pQCT scanner. Multiscale FE models simulating physiologic BCs, and micro-FE only models simulating platen-compression BCs were created for each specimen. Cortical and trabecular loads (N) along the length of the distal radius micro-FE section were compared between BCs using correlations. Principal strain distributions were also compared quantitatively. Cortical and trabecular loads from the platen-compression BC simulations were strongly correlated to the physiologic BC simulations. However, a 30% difference in cortical loads distally, and a 53% difference in trabecular loads proximally was observed under platen BC simulations. Also, distribution of principal strains was clearly different. Our data indicated that platen-compression BC simulations alter cortical-trabecular load sharing. Therefore, results from these analyses should be interpreted in the appropriate mechanical context for clinical evaluations of normal and pathologic mechanical behavior at the distal radius.

Validation of a new multiscale finite element analysis approach at the distal radius.

High-resolution peripheral computed tomography is commonly used to evaluate mechanical behavior of the distal radius microstructure using micro-finite element (FE) modeling. However, only a 9mm section is considered and boundary conditions (BCs) are usually simplified (platen-compression), and may not represent physiologic loading. Regardless, these methods are increasingly being used for clinical evaluations. Our goal was to develop and validate a novel multiscale solution that allows for physiologically relevant loading simulations (such as bracing during a fall), and show that mechanical behavior in the distal radius is different under platen BCs. Our approach incorporated bone microstructure together with organ-level radius geometry, by replacing matching continuum regions with micro-FE sections in user-defined regions of interest. Multiscale model predicted strains showed a strong correlation and a significant relationship with measured strains (r=0.836, p<0.001; slope=0.881, intercept=-12.17 µÎµ, p<0.001). Interestingly, platen BC simulated strains were almost 50% lower than measured strains (r=0.835, p<0.001), and strain distributions were clearly different. Our multiscale method demonstrated excellent potential as a computationally efficient alternative for observing true mechanical environment within distal radius microstructure under physiologically accurate loading.

Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats.

A wider diversity of drug treatments to aid smoking cessation is needed to help tailor the most efficacious treatment for different types of smokers. This study was conducted to determine whether amitifadine, which inhibits re-uptake of dopamine, norepinephrine and serotonin, would decrease nicotine self-administration at doses that do not cause adverse side effects. Adult female Sprague-Dawley rats were trained to self-administer nicotine intravenous (IV) and were given acute doses of amitifadine in a repeated measures counterbalanced design. Effects of amitifadine on locomotor activity and food motivated responding were also evaluated. Chronic amitifadine effects were also examined. The 30 mg/kg amitifadine dose significantly reduced nicotine self-administration. The 5 and 10 mg/kg doses reduced nicotine self-administration during the first 15 min of the session when the greatest amount of nicotine was self-administered. The 30 mg/kg amitifadine dose, but not the lower doses caused a significant reduction in locomotor activity averaged over the one-hour session and reduced food motivated responding. The 10 mg/kg dose caused hypoactivity at the beginning of the session, but 5 mg/kg did not cause any hypoactivity. The effects of chronic amitifadine treatment (10 mg/kg) over the course of 15 sessions was also determined. Amitifadine caused a significant reduction in nicotine self-administration, which was not seen to diminish over two consecutive weeks of treatment and a week after enforced abstinence. Amitifadine significantly reduced nicotine self-administration. This prompts further research to determine if amitifadine might be an effective treatment for smoking cessation.

Results of automatic image registration are dependent on initial manual registration.

Measurement of static alignment of articulating joints is of clinical benefit and can be determined using image-based registration. We propose a method that could potentially improve the outcome of image-based registration by using initial manual registration. Magnetic resonance images of two wrist specimens were acquired in the relaxed position and during simulated grasp. Transformations were determined from voxel-based image registration between the two volumes. The volumes were manually aligned to match as closely as possible before auto-registration, from which standard transformations were obtained. Then, translation/rotation perturbations were applied to the manual registration to obtain altered initial positions, from which altered auto-registration transformations were obtained. Models of the radiolunate joint were also constructed from the images to simulate joint contact mechanics. We compared the sensitivity of transformations (translations and rotations) and contact mechanics to altering the initial registration condition from the defined standard. We observed that with increasing perturbation, transformation errors appeared to increase and values for contact force and contact area appeared to decrease. Based on these preliminary findings, it appears that the final registration outcome is sensitive to the initial registration.

Short-term bone formation is greatest within high strain regions of the human distal radius: a prospective pilot study.

Bone adaptation is understood to be driven by mechanical strains acting on the bone as a result of some mechanical stimuli. Although the strain/adaptation relation has been extensively researched using in vivo animal loading models, it has not been studied in humans,likely due to difficulties in quantifying bone strains and adaptation in living humans. Our purpose was to examine the relationship between bone strain and changes in bone mineral parameters at the local level. Serial computed tomography (CT) scans were used to calculate 14 week changes in bone mineral parameters at the distal radius for 23 women participating in a cyclic in vivo loading protocol (leaning onto the palm of the hand), and 12 women acting as controls. Strains were calculated at the distal radius during the task using validated finite element (FE) modeling techniques. Twelve subregions of interest were selected and analyzed to test the strain/adaptation relation at the local level. A positive relationship between mean energy equivalent strain and percent change in bone mineral density (BMD) (slope=0.96%/1000 le, p<0.05) was observed within experimental,but not control subjects. When subregion strains were grouped by quartile, significant slopes for quartile versus bone mineral content (BMC) (0.24%/quartile) and BMD(0.28%/quartile) were observed. Increases in BMC and BMD were greatest in the highest-strain quartile (energy equivalent strain>539 le). The data demonstrate preliminary prospective evidence of a local strain/adaptation relationship within human bone.These methods are a first step toward facilitating the development of personalized exercise prescriptions for maintaining and improving bone health.

Computationally efficient magnetic resonance imaging based surface contact modeling as a tool to evaluate joint injuries and outcomes of surgical interventions compared to finite element modeling.

Joint injuries and the resulting posttraumatic osteoarthritis (OA) are a significant problem. There is still a need for tools to evaluate joint injuries, their effect on joint mechanics, and the relationship between altered mechanics and OA. Better understanding of injuries and their relationship to OA may aid in the development or refinement of treatment methods. This may be partially achieved by monitoring changes in joint mechanics that are a direct consequence of injury. Techniques such as image-based finite element modeling can provide in vivo joint mechanics data but can also be laborious and computationally expensive. Alternate modeling techniques that can provide similar results in a computationally efficient manner are an attractive prospect. It is likely possible to estimate risk of OA due to injury from surface contact mechanics data alone. The objective of this study was to compare joint contact mechanics from image-based surface contact modeling (SCM) and finite element modeling (FEM) in normal, injured (scapholunate ligament tear), and surgically repaired radiocarpal joints. Since FEM is accepted as the gold standard to evaluate joint contact stresses, our assumption was that results obtained using this method would accurately represent the true value. Magnetic resonance images (MRI) of the normal, injured, and postoperative wrists of three subjects were acquired when relaxed and during functional grasp. Surface and volumetric models of the radiolunate and radioscaphoid articulations were constructed from the relaxed images for SCM and FEM analyses, respectively. Kinematic boundary conditions were acquired from image registration between the relaxed and grasp images. For the SCM technique, a linear contact relationship was used to estimate contact outcomes based on interactions of the rigid articular surfaces in contact. For FEM, a pressure-overclosure relationship was used to estimate outcomes based on deformable body contact interactions. The SCM technique was able to evaluate variations in contact outcomes arising from scapholunate ligament injury and also the effects of surgical repair, with similar accuracy to the FEM gold standard. At least 80% of contact forces, peak contact pressures, mean contact pressures and contact areas from SCM were within 10 N, 0.5 MPa, 0.2 MPa, and 15 mm2, respectively, of the results from FEM, regardless of the state of the wrist. Depending on the application, the MRI-based SCM technique has the potential to provide clinically relevant subject-specific results in a computationally efficient manner compared to FEM.