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High-resolution peripheral quantitative CT (HR-pQCT) is a low-dose three-dimensional imaging technique, originally developed for in vivo assessment of bone microarchitecture at the distal radius and tibia in osteoporosis. HR-pQCT has the ability to discriminate trabecular and cortical bone compartments, providing densitometric and structural parameters. At present, HR-pQCT is mostly used in research settings, despite evidence showing that it may be a valuable tool in osteoporosis and other diseases. This review summarizes the main applications of HR-pQCT and addresses the limitations that currently prevent its integration into routine clinical practice. In particular, the focus is on the use of HR-pQCT in primary and secondary osteoporosis, chronic kidney disease (CKD), endocrine disorders affecting bone, and rare diseases. A section on novel potential applications of HR-pQCT is also present, including assessment of rheumatic diseases, knee osteoarthritis, distal radius/scaphoid fractures, vascular calcifications, effect of medications, and skeletal muscle. The reviewed literature seems to suggest that a more widespread implementation of HR-pQCT in clinical practice would offer notable opportunities. For instance, HR-pQCT can improve the prediction of incident fractures beyond areal bone mineral density provided by dual-energy X-ray absorptiometry. In addition, HR-pQCT may be used for the monitoring of anti-osteoporotic therapy or for the assessment of mineral and bone disorder associated with CKD. Nevertheless, several obstacles currently prevent a broader use of HR-pQCT and would need to be targeted, such as the small number of installed machines worldwide, the uncertain cost-effectiveness, the need for improved reproducibility, and the limited availability of reference normative data sets.

We re-evaluated clinical applications of image-to-FE models to understand if clinical advantages are already evident, which proposals are promising, and which questions are still open.CT-to-FE is useful in longitudinal treatment evaluation and groups discrimination. In metastatic lesions, CT-to-FE strength alone accurately predicts impending femoral fractures. In osteoporosis, strength from CT-to-FE or DXA-to-FE predicts incident fractures similarly to DXA-aBMD. Coupling loads and strength (possibly in dynamic models) may improve prediction. One promising MRI-to-FE workflow may now be tested on clinical data. Evidence of artificial intelligence usefulness is appearing. CT-to-FE is already clinical in opportunistic CT screening for osteoporosis, and risk of metastasis-related impending fractures. Short-term keys to improve image-to-FE in osteoporosis may be coupling FE with fall risk estimates, pool FE results with other parameters through robust artificial intelligence approaches, and increase reproducibility and cross-validation of models. Modeling bone modifications over time and bone fracture mechanics are still open issues.

BACKGROUND AND AIMS Vascular calcifications (VCs), a known risk factor for cardiovascular disease and mortality, are strongly linked to vertebral fractures (VFs) [1]. The coronary calcium score from computer tomography (CT) is the gold standard to measure VCs [2], but this implies high radiation doses and costs. Although, several calcifications scores at the abdominal aorta have been developed from lower-dose and low-cost lateral spine RX projections. These scores are widely applied (the 0–24 score): Kauppila Score (KS) [3]. Most RX scores are semi-quantitative implying an error-prone visual assessment. Indeed, so far, repeatability studies could not estimate the minimum detectable difference (MDD). Based on this knowledge, we developed a new RX-based computer-assisted VCs score with the aim to test its precision (repeatability and reproducibility metrics and MDD estimate) compared to KS. METHOD New Quantitative Score (QS), computer-assisted tracking of calcifications, considers both abdominal aorta calcification and column length (range 0–1), then multiplied by 24 to easily compare with the standard score: KS. Dedicated software developed with ALBA framework (https://github.com/IOR-BIC/ALBA) to subsequently record standard and new scores (see Figure 1). We enrolled 44 patients with VCs from an earlier study and the anonymous recorded data were randomized in two series. Five experts from four specialties in two institutions evaluated the data twice, with 1-month interval between series. Additional test-retest evaluation was performed on eight subjects with a second RX within 2 weeks. RESULTS Intra-observer analysis (Bland-Altman plots and regression analysis between series): both scores seem not biased; QS showed higher reproducibility [95% confidence interval (95% CI) of differences almost halved]. Inter-observer [Intra Class Correlation Coefficient (ICC)]: ICC higher for QS in the first series (0.78 versus 0.64); a lower difference was observed in the second evaluation (0.84 versus 0.82). MDD (Standard Error of the Mean): reduced by around 25% for the QS (2.98 versus 4, in the 0–24 scale). Test-retest (Wilcoxon paired test): not significantly different for both scores. Agreement (Bland-Altman plots): scores are discordant. The QS shows significantly higher values and an increasing trend with calcification severity. CONCLUSION Our new quantitative computer-assisted score improved the precision of RX scores in the estimate of VCs. Furthermore, it showed higher intra-observer repeatability than KS and we reported for the first time an estimate of MDD in the VCs assessment. In detail, MDD was 25% lower for the new score. An ongoing study will determine whether this lower MDD may reduce follow-up times to check for VCs progression and whether this new VCs score may act as a risk alert for the development/worsening of VFs.

Anatomical custom-made prostheses make it possible to reconstruct complicated bone defects following excision of bone tumors, thanks to 3D-printed technology. To date, clinical measures have been used to report clinical-functional outcome and provide evidence for the effectiveness of this new surgical approach. However, there are no studies that quantified the achievable recovery during common activities by using instrumental clinical-functional evaluation in these patients.What is the motor performance, functional outcome and quality of life in patients with custom-made 3D-printed pelvic prostheses following bone tumor?To analyze motor performance, six patients performed motion analysis during five motor activities at follow-up of 32 ± 18 months. Joint angles, ground reaction forces and joint moments of the operated and contralateral limbs were compared. On-off activity of lower-limb muscles were calculated from electromyography and compared to a healthy matched population. To analyze functional outcome and quality of life, differences in measured hip abductor strength between limbs were evaluated, as well as clinical-functional scores (Harris Hip Score, Barthel Index, Musculoskeletal Tumor Society score), and quality of life (SF-36 health survey).We found only slight differences in joint kinematics when comparing operated and contralateral limb. The activity of gluteal muscles was normal, while hamstrings showed out-of-phase activities. Ground reaction forces and hip moments showed asymmetries between limbs, particularly in more demanding motor activities. We found a mean difference in hip abductor strength of 48 ± 82 N between limbs, good clinical-functional scores, and quality of life scores within normative.Our study showed optimal long-term results in functional recovery, mainly achieved through recovery of the gluteal function, although minor impairments were found, which may be considered for future improvement of this innovative surgery. The effect of a more loaded contralateral limb on internal loads and long-term performance of the implant remains unknown and deserves further investigation.

Resection of sarcomas around the acetabulum presents major challenges. The resulting bone effect can be reconstructed with personalized custom-made prostheses. Patient-specific instruments (PSIs) have been demonstrated to be of added value for bone-cutting accuracy, and they may improve pelvic surgery. The authors describe a novel ileo-adductor approach for pelvic tumor surgery and report the preliminary results of 5 reconstructions using custom 3D-printed prostheses associated with PSI surgical guides. This combined technique allows an optimal restoration of the anatomy with reduced surgical time and reduced postoperative complications such as infections and wound healing problems. [ Orthopedics . 2022;45(2):e110–e114.]

Vascular calcification and fragility fractures are associated with high morbidity and mortality, especially in end-stage renal disease. We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aortic calcifications (AACs) with the risk for vertebral fractures (VFs) in hemodialysis patients. The VIKI study was a multicenter cross-sectional study involving 387 hemodialysis patients. The biochemical data included bone health markers, such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, and phosphate. VF, IACs and AACs was determined through standardized spine radiograms. VF was defined as &gt, 20% reduction of vertebral body height, and VC were quantified by measuring the length of calcium deposits along the arteries. The prevalence of IACs and AACs were 56.1% and 80.6%, respectively. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p = 0.028), whereas we found no association (p = 0.294) for AACs. IACs were associated with VF irrespective of calcification severity. Patients with IACs had lower levels of vitamin K2 and menaquinone 7 (0.99 vs. 1.15 ng/mL, p = 0.003), and this deficiency became greater with adjustment for triglycerides (0.57 vs. 0.87 ng/mL, p &lt, 0.001). IACs, regardless of their extent, are a clinically relevant risk factor for VFs. The association is enhanced by adjusting for vitamin K, a main player in bone and vascular health. To our knowledge these results are the first in the literature. Prospective studies are needed to confirm these findings both in chronic kidney disease and in the general population.

Background Vascular calcification and fragility fractures are common age-related disorders, associated with high morbidity and mortality especially in end-stage renal disease. Skeletal disorders occur in dialysis patients. Few studies have provided data on the prevalence of vertebral fractures (VF) and their association with large artery calcifications. Purpose We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aorta calcifications (AACs) with the risk for VFs in hemodialysis (HD) patients. Methods The VIKI Study is a cross-sectional study involving 387 HD patients from 18 Italian dialysis centers, assessing demographic, clinical and biochemical data in such patients. Biochemical data included bone health markers such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, phosphate, Bone Gla Protein and Matrix Gla Protein. The presence of VF, IACs and AACs were determined through standardized radiograms of the spine. A >20% reduction of vertebral body height was considered a VF. We quantified vascular calcifications by measuring the length of calcium deposits along the abdominal arteries, classifying the degree of severity for the IACs and AACs with a specific score (mild: 0.1–3 cm; moderate: 3.1–5 cm; and severe >5 cm) previously validated for AACs. Results The prevalence of IACs was 56.1%, and of AACs 80.6%. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p=0.028), whereas we found no association (p=0.294) for AACs. The presence of IACs associated with VF irrespective of calcification severity. Patients with IACs had lower levels of the vitamin K2, menaquinone 7 (0.99 vs 1.15 ng/ml; p=0.003), and deficiency of this marker became greater when adjusting for triglyceride levels (0.57 vs 0.87 ng/ml; p Conclusions The presence of IACs, regardless of their extent, appears to be a clinically relevant risk factor for VFs. The association is further enhanced by including vitamin K, a main player in bone and vascular health, in the model. Prospective studies are needed to confirm these findings both in chronic kidney disease patients and in the general population. Funding Acknowledgement Type of funding sources: None.

Objective: In developmental hip dysplasia (DDH) patients, the chronic dislocation of the femoral head with respect to the true acetabulum determines muscle contracture and atrophy, particularly of the abductor muscles, and leads to secondary osteoarthritis (OA) with severe motor dysfunction, pain and disability. The correct positioning when a total hip replacement (THR) is performed is fundamental to the recovery of gait function. Also, inadequate rehabilitation of the abductor muscles for pelvic stabilisation can be responsible for residual dysfunction. Consensus on a programme for abductor muscle strengthening in these patients is not currently available. The aim of this study was to evaluate the effectiveness of a specific program of exercises for strengthening the abductor muscles in these patients. Methods: A multicentre, prospective, randomised clinical trial was carried out in an outpatient rehabilitation setting on 103 patients given THR for DDH through a minimally-invasive anterolateral approach. Patients were randomly divided into a Study Group, including 46 patients, and a Control Group, including 57 patients. All patients underwent standard early postoperative rehabilitation. In addition, the Study Group were given an extra 2-week rehabilitation once full weight-bearing on the operated limb was allowed, aimed at strengthening the abductor muscles. All patients were evaluated preoperatively, and at about 3 and 6 months postoperatively. Clinical measures (lower limb-length differences, hip range of motion, abductor muscle strength), and functional measures (WOMAC, HHS, 10mt WT, SF-12) were taken. Results: Hip range of motion and functional outcome measures showed a progressive improvement at follow ups in both groups, significantly higher in the Study Group. In particular, abductor strength at 6 months post-op improved by 92.5% with respect to 35.7% in the Control Group. Conclusion: In addition to standard rehabilitation, a rehabilitation programme for strengthening the gluteal muscles in DDH patients who underwent THR determined an increase in muscle strength that improved functional performance and patient satisfaction.

Purpose Critical size long bone defects represent a clinical challenge in orthopaedic surgery. Various grafting techniques have been developed through the years, but they all present several downsides. A key requirement of all grafting techniques is the achievement of a continuous interface between host bone and graft to enhance both biological processes and mechanical stability. This study used a parametric in silico model to quantify the biomechanical effect of the inaccuracies inherent to current osteotomy techniques, and to test a new concept of accurate taper-fit junction that may improve the biomechanical parameters of the reconstruction under load. Methods A population-based in-silico 3D model of the reconstruction of a long bone defect was built to represent a defect of the femoral mid-diaphysis. To fix the reconstruction a titanium plate was placed on the lateral aspect of the reconstruction. The model was modified to (i) quantify the biomechanical consequences of actual inaccuracies in the realization of a flat host-graft interface, (ii) compare the contact behaviour and bone strains among different taper angles of the new design and the current host-graft flat interface, (iii) evaluate the robustness of the taper-fit design to inter-subject variability in bone geometry and defect length. Results The influence of 2° single-plane misalignments of the host-graft interface is highly dependent on the misalignment orientation with respect to the metal plate. For some misalignment orientations, tangential micromotions of contact interfaces exceeded alert thresholds. When the angle of the taper-fit host-graft junction is changed from 10° to 30° and the results obtained are compared with the planar case, the overall stiffness is almost preserved, the bone strains are almost unchanged with safety factors higher than five, and full contact closure around the host-graft junction is achieved at 20°. Similarly, contact pressures decrease almost linearly with a 20% decrease at 30°. The host-graft micro motions are almost unchanged in both value and distribution up to 20° and never exceed the warning threshold of 50 μm. Conclusions The present in silico study developed quantitative biomechanical evidence that an osteotomy performed with attention to the perpendicularity of the cut planes is needed to reduce the risk of mismatch and possible complications of long bone reconstructions, and that a new concept of a taper-fit junction may improve the biomechanical environment of the interface between the graft and the host bone. The optimal taper-fit configuration is suggested to be around a 20° taper angle. These results will serve as an input to conduct ex vivo experiments to further corroborate the proposed taper-fit junction concept and to refine its surgical implementation.

Despite evidence of the biomechanical role of cortical bone, current state of the art finite element models of the proximal femur built from clinical CT data lack a subject-specific representation of the bone cortex. Our main research hypothesis is that the subject-specific modelling of cortical bone layer from CT images, through a deconvolution procedure known as Cortical Bone Mapping (CBM, validated for cortical thickness and density estimates) can improve the accuracy of CT-based FE models of the proximal femur, currently limited by partial volume artefacts. Our secondary hypothesis is that a careful choice of cortical-specific density-elasticity relationship may improve model accuracy. We therefore: (i) implemented a procedure to include subject-specific CBM estimates of both cortical thickness and density in CT-based FE models. (ii) defined alternative models that included CBM estimates and featured a cortical-specific or an independently optimised density-elasticity relationship. (iii) tested our hypotheses in terms of elastic strain estimates and failure load and location prediction, by comparing with a published cohort of 14 femurs, where strain and strength in stance and fall loading configuration were experimentally measured, and estimated through reference FE models that did not explicitly model the cortical compartment. Our findings support the main hypothesis: an explicit modelling of the proximal femur cortical bone layer including CBM estimates of cortical bone thickness and density increased the FE strains prediction, mostly by reducing peak errors (average error reduced by 30%, maximum error and 95th percentile of error distribution halved) and especially when focusing on the femoral neck locations (all error metrics at least halved). We instead rejected the secondary hypothesis: changes in cortical density-elasticity relationship could not improve validation performances. From these improved baseline strain estimates, further work is needed to achieve accurate strength predictions, as models incorporating cortical thickness and density produced worse estimates of failure load and equivalent estimates of failure location when compared to reference models. In summary, we recommend including local estimates of cortical thickness and density in FE models to estimate bone strains in physiological conditions, and especially when designing exercise studies to promote bone strength. ispartof: BONE vol:136 ispartof: location:United States status: published

Background and objective Musculoskeletal modeling and simulations of movement have been increasingly used in orthopedic and neurological scenarios, with increased attention to subject-specific applications. In general, musculoskeletal modeling applications have been facilitated by the development of dedicated software tools; however, subject-specific studies have been limited also by time-consuming modeling workflows and high skilled expertise required. In addition, no reference tools exist to standardize the process of musculoskeletal model creation and make it more efficient. Here we present a freely available software application, nmsBuilder 2.0, to create musculoskeletal models in the file format of OpenSim, a widely-used open-source platform for musculoskeletal modeling and simulation. nmsBuilder 2.0 is the result of a major refactoring of a previous implementation that moved a first step toward an efficient workflow for subject-specific model creation. Methods nmsBuilder includes a graphical user interface that provides access to all functionalities, based on a framework for computer-aided medicine written in C++. The operations implemented can be used in a workflow to create OpenSim musculoskeletal models from 3D surfaces. A first step includes data processing to create supporting objects necessary to create models, e.g. surfaces, anatomical landmarks, reference systems; and a second step includes the creation of OpenSim objects, e.g. bodies, joints, muscles, and the corresponding model. Results We present a case study using nmsBuilder 2.0: the creation of an MRI-based musculoskeletal model of the lower limb. The model included four rigid bodies, five degrees of freedom and 43 musculotendon actuators, and was created from 3D surfaces of the segmented images of a healthy subject through the modeling workflow implemented in the software application. Conclusions We have presented nmsBuilder 2.0 for the creation of musculoskeletal OpenSim models from image-based data, and made it freely available via nmsbuilder.org. This application provides an efficient workflow for model creation and helps standardize the process. We hope this would help promote personalized applications in musculoskeletal biomechanics, including larger sample size studies, and might also represent a basis for future developments for specific applications.

Hip dysplasia patients after total hip replacement show worse functional performance compared to primary osteoarthritis patients, and unfortunately there is no research on muscle and joint loads that would help understand rehabilitation effects, motor dysfunctions and failure events. We tested the hypothesis that a higher functional improvement in hip dysplasia patients who received hip abductor strengthening after hip replacement, would result in different gait function and musculoskeletal loads during walking compared to patients who performed standard rehabilitation only. In vivo gait analysis and musculoskeletal modeling were used to analyze the differences in gait parameters and hip and muscle forces during walking between the two groups of patients. We found that, in a functional scenario of very mild abnormalities, the patients who performed muscle strengthening expressed a more physiological force pattern and a generally greater force in the operated limb, although statistically significant in limited portions of the gait cycle, and likely related to a higher gait speed. We conclude that in a low-demand task, the abductor strengthening program does not have a marked effect on hip loads, and further studies on hip dysplasia patients would help clarify the effect of muscle strengthening on loads.

Objective: Clinical application of computed tomography (CT) based finite element (FE) estimates of bone strength recently showed encouraging results [1]. However, model performance may be improved. In fact, in-vitro valida- tion studies showed systematic errors in strain prediction, especially where bone cortex is thin (i.e. the femoral neck) [2]. This work seeks to verify if, and to what extent, a CT deblurring algorithm restoring both geometry and intensity data in thin bone structures [3], can improve strain and failure load prediction accuracy of CT-based FE models of the prox- imal femur. Material and Methods: CT scans were acquired of 14 fresh-frozen human cadaveric femora. An estimate of the 3D Point Spread Function for each CT scan was used within a deconvolution solver to perform deblurring. Using the restored images, FE models of the proximal femur were generated [4]. Each femur was tested non- destructively in both stance and fall loading configurations to measure surface strains, and then loaded to failure in stance or fall. Deblurred FE predictions of strains and failure load were com- pared to experimental measurements, and FE predictions ob- tained from the original CT data (no deblurring). Results: An enhancement in strain prediction accuracy was obtained using deblurred FE models, with the Standard Error of Estimate reduced by 11 % with respect to reference FE models. Marked improvements at the femoral neck were achieved (e.g. peak error reduced by 38 %). Using deblurred models, the regression equation between FE-predicted and measured failure loads was characterized by a slope not sig- nificantly different from one, with R2 = 0.89, unchanged with respect to reference models. Absolute differences between estimated and measured failure loads were consistently re- duced by deblurring in stance (mean error 10 vs. 15 %) but not in fall (32 vs. 17 %). Conclusions: The proposed CT deblurring technique yielded moderate but significant improvements in femo- ral FE predictions, and can thus be seen as a first and worthwhile step in the improvement of CT-based FE models of the human femur.

Background In ceramic-on-ceramic (CoC) total hip arthroplasty (THA), component positioning demonstrated to influence the bearing damage: however the connection between angles and clinical outcomes at long-term follow-ups is currently lacking. Aims of this study were: the computer tomography (CT) assessment of component positioning in CoC THAs; the correlation analysis between positioning and ceramic damage; the identification of safe zones. Methods 91 consecutive post-operative CT scans including two types of CoC implants, with a mean follow-up of 12 ± 4.4 years, were evaluated. III generation (74.2%) and IV generation (25.8%) CoC surfaces were included. The angle measurements (cup abduction, anteversion, cup tilt, stem antetorsion, sacral slope) were automated using a CT-based software. The combined anteversion was assessed as well as the cup-neck position at −15°, 0°, 45° and 90° of flexion. Ceramic damage was diagnosed using synovial fluid analyses and radiological criteria. Results 63.7% of THAs was inside the cup abduction target 30°–45° and 68.1% was inside the cup anteversion target 5°–25°. 19 patients (20.9%) showed signs of ceramic damage. High cup abduction and high cup-neck 45° minimum angle (which stood for high abduction and extreme combined version) significantly correlated with ceramic damage. No demographical features apart III generation ceramic bearings influenced the results. No safe zones could be detected. Conclusions In CoC THA, no safe zones can be described. However it is important to avoid cup inclination over 45° and a combination of steep cup and extreme combined version.

This study assessed: (i) how the magnitude and direction of principal strains vary for different sideways fall loading directions; (ii) how the principal strains for a sideways fall differ from physiological loading directions; (iii) the fracture mechanism during a sideways fall. Eleven human femurs were instrumented with 16 triaxial strain gauges each. The femurs were non-destructively subjected to: (a) six loading configurations covering the range of physiological loading directions; (b) 12 configurations simulating sideways falls. The femurs were eventually fractured in a sideways fall configuration while high-speed cameras recorded the event. When the same force magnitude was applied, strains were significantly larger in a sideways fall than for physiological loading directions (principal compressive strain was 70% larger in a sideways fall). Also the compressive-to-tensile strain ratio was different: for physiological loading the largest compressive strain was only 30% larger than the largest tensile strain; but for the sideways fall, compressive strains were twice as large as the tensile strains. Principal strains during a sideways fall were nearly perpendicular to the direction of principal strains for physiological loading. In the most critical regions (medial part of the head−neck) the direction of principal strain varied by less than 9° between the different physiological loading conditions, whereas it varied by up to 17° between the sideways fall loading conditions. This was associated with a specific fracture mechanism during sideways fall, where failure initiated on the superior-lateral side (compression) followed by later failure of the medially (tension), often exhibiting a two-peak force−displacement curve.

Computed tomography (CT)-based finite element (FE) reconstructions describe shape and density distribution of bones. Both shape and density distribution, however, can vary a lot between individuals. Shape/density indexation (usually achieved by principal component analysis—PCA) can be used to synthesize realistic models, thus overcoming the shortage of CT-based models, and helping e.g. to study fracture determinants, or steer prostheses design. The aim of this study was to describe a PCA-based statistical modelling algorithm, and test it on a large CT-based population of femora, to see if it can accurately describe and reproduce bone shape, density distribution, and biomechanics. To this aim, 115 CT-datasets showing normal femoral anatomy were collected and characterized. Isotopological FE meshes were built. Shape and density indexation procedures were performed on the mesh database. The completeness of the database was evaluated through a convergence study. The accuracy in reconstructing bones not belonging to the indexation database was evaluated through (i) leave-one-out tests (ii) comparison of calculated vs. in-vitro measured strains. Fifty indexation modes for shape and 40 for density were necessary to achieve reconstruction errors below pixel size for shape, and below 10% for density. Similar errors for density, and slightly higher errors for shape were obtained when reconstructing bones not belonging to the database. The in-vitro strain prediction accuracy of the reconstructed FE models was comparable to state-of-the-art studies. In summary, the results indicate that the proposed statistical modelling tools are able to accurately describe a population of femora through finite element models.

Comparing the available electromyography (EMG) and the related uncertainties with the space of muscle forces potentially driving the same motion can provide insights into understanding human motion in healthy and pathological neuromotor conditions. However, it is not clear how effective the available computational tools are in completely sample the possible muscle forces. In this study, we compared the effectiveness of Metabolica and the Null-Space algorithm at generating a comprehensive spectrum of possible muscle forces for a representative motion frame. The hip force peak during a selected walking trial was identified using a lower-limb musculoskeletal model. The joint moments, the muscle lever arms, and the muscle force constraints extracted from the model constituted the indeterminate equilibrium equation at the joints. Two spectra, each containing 200,000 muscle force samples, were calculated using Metabolica and the Null-Space algorithm. The full hip force range was calculated using optimization and compared with the hip force ranges derived from the Metabolica and the Null-Space spectra. The Metabolica spectrum spanned a much larger force range than the NS spectrum, reaching 811 N difference for the gluteus maximus intermediate bundle. The Metabolica hip force range exhibited a 0.3—0.4 BW error on the upper and lower boundaries of the full hip force range (3.4—11.3 BW), whereas the full range was imposed in the NS spectrum. The results suggest that Metabolica is well suited for exhaustively sample the spectrum of possible muscle recruitment strategy. Future studies will investigate the muscle force range in healthy and pathological neuromotor conditions.

Composite bones are synthetic models made to simulate the mechanical behaviour of human bones. Finite element (FE) models of composite bone can be used to evaluate new and modified designs of joint prostheses and fixation devices. The aim of the current study was to create an FE model of a composite tibia and to validate it against results obtained from a comprehensive set of experiments. For this, 17 strain rosettes were attached to a composite tibia (model 3101, Pacific Research Laboratories, Vashon, Washington, USA). Surface strains and displacements were measured under 13 loading conditions. Two FE models were created on the basis of computed tomography scans. The models differed from each other in the mesh and material properties assigned. The experiments were simulated on them and the results compared with experimental results. The more accurate model was selected on the basis of regression analysis. In general, experimental strain measurements were highly repeatable and compared well with published results. The more accurate model, in which the inner elements representing the foam were assigned isotropic material properties and the elements representing the epoxy layer were assigned transversely isotropic material properties, was able to simulate the mechanical behaviour of the tibia with acceptable accuracy. The regression line for all axial loads combined had a slope of 0.999, an intercept of -6.24 microstrain, and an R2 value of 0.962. The root mean square error as a percentage was 5 per cent.

Background Biomechanical interpretations of bone adaptation in biological reconstructions following bone tumors would be crucial for orthopedic oncologists, particularly if based on quantitative observations. This would help plan for surgical treatments, rehabilitative programs and communication with the patients. We aimed to analyze the biomechanical adaptation of a femoral reconstruction after Ewing sarcoma according to an increasingly-used surgical technique, and to relate in-progress bone resorption to the mechanical stimulus induced by different motor activities. Methods We created a multiscale musculoskeletal and finite element model from CT scans and motion analysis data at a 76-month follow-up of a patient, to analyze muscle and joint loads, and to compare the mechanical competence of the reconstructed bone with the contralateral limb, in the current real condition and in a possible revision surgery that removed proximal screws. Findings Our results showed strategies of muscle coordination that led to differences in joint loads between limbs more marked in more demanding motor activities, and generally larger in the contralateral limb. The operated femur presented a markedly low ratio of physiological strain due to load-sharing with the metal implant, particularly in the lateral aspect. The possible revision surgery would help restore a physiological strain configuration, while the safety of the reconstruction would not be threatened. Interpretation We suggest that bone resorption is related to load-sharing and to the internal forces exerted during movement, and the mechanical stimulus should be improved by adopting modifications in the surgical treatment and by promoting physical therapy aimed at specific muscle strengthening.

An innovative epiphyseal device has been recently proposed claiming an effective bone–prosthesis load transfer and a nearly physiological bone stresses distribution. However preliminary experimental tests showed a 23% weakening of the femoral neck after implantation. Aim of this study was to revise the prosthesis geometry with the goal of enhancing the femoral neck strength after implantation, while maintaining unchanged the initial conceptual design. To this aim, the risk of femoral neck fractures, prosthesis fractures, aseptic loosening and excessive bone resorption were addressed through a validated finite element procedure following a systematic approach. The initial prosthesis geometry was revised to reduce each investigated failure risk below the threshold of acceptance (100%). The new geometry was re-assessed to verify the effectiveness of the revision. The first design was predicted to locally induce high bone strains and cement stresses, which translated in a risk of bone and cement failure exceeding the threshold of acceptance (>100%). The revised design preserved a good stability of the device, contemporary reducing the risk for bone (45%) and cement (60%) failure. If results will be confirmed by statistical and clinical experimentations, current clinical indications for hip epiphyseal devices might be extended.

Bone biomechanics have been extensively investigated in the past both within vitroexperiments and numerical models. In most cases either approach is chosen, without exploiting synergies. Both experiments and numerical models suffer from limitations relative to their accuracy and their respective fields of application.In vitroexperiments can improve numerical models by: (i) preliminarily identifying the most relevant failure scenarios; (ii) improving the model identification with experimentally measured material properties; (iii) improving the model identification with accurately measured actual boundary conditions; and (iv) providing quantitative validation based on mechanical properties (strain, displacements) directly measured from physical specimens being tested in parallel with the modelling activity. Likewise, numerical models can improvein vitroexperiments by: (i) identifying the most relevant loading configurations among a number of motor tasks that cannot be replicatedin vitro; (ii) identifying acceptable simplifications for thein vitrosimulation; (iii) optimizing the use of transducers to minimize errors and provide measurements at the most relevant locations; and (iv) exploring a variety of different conditions (material properties, interface, etc.) that would require enormous experimental effort. By reporting an example of successful investigation of the femur, we show how a combination of numerical modelling and controlled experiments within the same research team can be designed to create a virtuous circle where models are used to improve experiments, experiments are used to improve models and their combination synergistically provides more detailed and more reliable results than can be achieved with either approach singularly.

This paper briefly summarises the most recent developments in multiscale modelling technology as applied to the generation of personalised multiscale models of the musculoskeletal system to be used for the prediction of the risk of bone fracture. We describe how the VHPOP European consortium is compositing all these groundbreaking methods into a radically innovative multiscale technology that can radically change the clinical practice in a few years. A concrete proof of concept, based on the multiscale data made available by the Living Human Digital Library (LHDL) project, is briefly described, showing how multiscale modelling can be used to predict the risk of fracture in specific subjects with much greater accuracy.

Absence of the fibula after harvesting to reconstruct an upper-limb segment increases loads on the donor-side tibia and thereby provides a unique opportunity to analyze the bone adaptation process in humans. We therefore quantified densitometric and morphologic changes of the donor-side tibia in three young patients (ages 8, 13, 16 years), on the basis of computed tomography (CT) examinations of both legs (one preoperatively and two postoperatively). The range of final followup was 27–43 months. Three-dimensional models of shank bones were generated from CT data and used to measure cross-sectional area, diaphyseal cortical thickness, and cross-sectional moment of inertia. In addition, density of the newly formed bone was evaluated. The donor-side tibia showed morphologic and density adaptation with time. New bone was deposited predominantly in the interosseous space and almost replaced the bone area lost by excision of the fibula. The second moment of area grew more in the donor-side tibia than in the intact one, without fully recovering the contralateral tibia-fibula complex values, and the principal axes rotated toward the preoperative direction. Thus, while considerable adaptation had occurred by 27–43 months in these young patients, the adaptation was incomplete; the mineral density of the newly formed bone recovered normal cortical bone values only in the patient with the longest followup (43 months). Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

In this paper, we present an approach to interactive out-of-core volume data exploration that has been developed to augment the existing capabilities of the LhpBuilder software, a core component of the European project LHDL ( http://www.biomedtown.org/biomed_town/lhdl ). The requirements relate to importing, accessing, visualizing and extracting a part of a very large volume dataset by interactive visual exploration. Such datasets contain billions of voxels and, therefore, several gigabytes are required just to store them, which quickly surpass the virtual address limit of current 32-bit PC platforms. We have implemented a hierarchical, bricked, partition-based, out-of-core strategy to balance the usage of main and external memories. A new indexing scheme is introduced, which permits the use of a multiresolution bricked volume layout with minimum overhead and also supports fast data compression. Using the hierarchy constructed in a pre-processing step, we generate a coarse approximation that provides a preview using direct volume visualization for large-scale datasets. A user can interactively explore the dataset by specifying a region of interest (ROI), which further generates a much more accurate data representation inside the ROI. If even more precise accuracy is needed inside the ROI, nested ROIs are used. The software has been constructed using the Multimod Application Framework, a VTK-based system; however, the approach can be adopted for the other systems in a straightforward way. Experimental results show that the user can interactively explore large volume datasets such as the Visible Human Male/Female (with file sizes of 3.15/12.03 GB, respectively) on a commodity graphics platform, with ease.

There is significant interest in the stress—strain state in the proximal femoral metaphysis, because of its relevance for hip fractures and prosthetic replacements. The scope of this work was to provide a better understanding of the strain distribution, and of its correlation with the different directions of loading, and with bone quality. A total of 12 pairs of human femurs were instrumented with strain gauges. Six loading configurations were designed to cover the range of directions spanned by the hip joint force. Inter-specimen variability was reduced if paired specimens were considered. The principal strain magnitude varied greatly between loading configurations. This suggests that different loading configurations need to be simulated in vitro. The strain magnitude varied between locations but, on average, was compatible with the strain values measured in vivo. The strain magnitudes and the direction of principal tensile strain in the head and neck were compatible with the spontaneous fractures of the proximal femur reported in some subjects. The principal tensile strain was significantly larger where the cortical bone was thinner; the compressive strain was larger where the cortical bone was thicker. The direction of the principal strain varied significantly between measurement locations but varied little between loading configurations. This suggests that the anatomy and the distribution of anisotropic material properties enable the proximal femur to respond adequately to the changing direction of daily loading.

Background The Finite Element Method is at present the method of choice for strain prediction in bones from Computed Tomography data. However, accurate methods rely on the correct topological representation of the bone surface, which requires a massive operator effort, thus restricting their applicability to clinical practice. Meshless methods, which do not rely on a pre-defined topological discretisation of the domain, might greatly improve the numerical process automation, but currently their application to biomechanics is negligible. Methods A meshless implementation of an innovative numerical approach based on a direct discrete formulation of physical laws, the Cell Method, was developed to predict strains in a cadaver femur from Computed Tomography data. The model accuracy was estimated by comparing the predicted strains with those experimentally measured on the same specimen in a previous study. As a reference, the results were compared to those obtained with a state-of-the-art finite element model. Findings The Cell Method meshless model predicted strains highly correlated with the experimental measurements ( R 2 = 0.85) with a good global accuracy (RMSE = 15.6%). The model performed slightly worse than the finite element one, but this was probably due to the need to sub-sample the original data, and the lower order of the interpolation used (linear vs parabolic). Interpretation Although there is surely room for improvement, the accuracy already obtained with this meshless implementation of the Cell Method makes it a good candidate for some clinical applications, especially considering the full automation of the method, which does not require any data pre-processing.

An experimental-numerical study was performed to investigate the relationships between computed tomography (CT)-density and ash density, and between ash density and apparent density for bone tissue, to evaluate their influence on the accuracy of subject-specific FE models of human bones. Sixty cylindrical bone specimens were examined. CT-densities were computed from CT images while apparent and ash densities were measured experimentally. The CT/ash-density and ash/apparent-density relationships were calculated. Finite element models of eight human femurs were generated considering these relationships to assess their effect on strain prediction accuracy. CT and ash density were linearly correlated (R(2)=0.997) over the whole density range but not equivalent (intercep t0, slope1). A constant ash/apparent-density ratio (0.598+/-0.004) was found for cortical bone. A lower ratio, with a larger dispersion, was found for trabecular bone (0.459+/-0.100), but it became less dispersed, and equal to that of cortical tissue, when testing smaller trabecular specimens (0.598+/-0.036). This suggests that an experimental error occurred in apparent-density measurements for large trabecular specimens and a constant ratio can be assumed valid for the whole density range. Introducing the obtained relationships in the FE modelling procedure improved strain prediction accuracy (R(2)=0.95, RMSE=7%). The results suggest that: (i) a correction of the densitometric calibration should be used when evaluating bone ash-density from clinical CT scans, to avoid ash-density underestimation and overestimation for low- and high-density bone tissue, respectively; (ii) the ash/apparent-density ratio can be assumed constant in human femurs and (iii) the correction improves significantly the model accuracy and should be considered in subject-specific bone modelling.

The mechanical strength of human bones has often been investigated in the past. Bone failure is related to musculoskeletal loading, tissue properties, bone metabolism, etc. This is intrinsically a multiscale problem. However, organ-level performance in most cases is investigated as a separate problem, incorporating only part (if any) of the information available at a higher scale (body level) or at a lower one (tissue level, cell level). A multiscale approach is proposed, where models available at different levels are integrated. A middle-out strategy is taken: the main model to be investigated is at the organ level. The organ-level model incorporates as an input the outputs from the body-level (musculoskeletal loads), tissue-level (constitutive equations) and cell-level models (bone remodelling). In this paper, this approach is exemplified by a clinically relevant application: fractures of the proximal femur. We report how a finite-element model of the femur (organ level) becomes part of a multiscale model. A significant effort is related to model validation: a number of experiments were designed to quantify the model's sensitivity and accuracy. When possible, the clinical accuracy and the clinical impact of a model should be assessed. Whereas a large amount of information is available at all scales, only organ-level models are really mature in this perspective. More work is needed in the future to integrate all levels fully, while following a sound scientific method to assess the relevance and validity of such an integrated model.

Background In many published studies, elastic properties of bone are correlated to the bone density, in order to derive an empirical elasticity–density relationship. The most common use of these relationships is the prediction of the bone local properties from medical imaging data in subject-specific numerical simulation studies. The proposed relationships are substantially different one from the other. It is unclear whether such differences in elasticity–density relationships can be entirely explained in terms of methodological discrepancies among studies. Methods All relevant literature was reviewed. Only elasticity–density relationships derived from similarly controlled experiments were included and properly normalized. The resulting relationships were grouped according to the most important methodological differences: type of end support during testing, specimen geometry, and anatomical sampling location. Findings Even after normalization with respect to strain rate and densitometric measurement unit, substantial inter-study differences do exist, and they can only be partially explained by the methodological differences between studies. Interpretation Some recommendations are made for the application of elasticity–density relationships to subject-specific finite element studies. The importance of defining a standardized mechanical testing methodology for bone specimens is stressed, and some guidelines that emerged from the literature are proposed. To identify density–elasticity relationships suitable for use in subject-specific FE studies, the development of a benchmark study is also proposed, where the elasticity–density relationship is taken as the variable under study, and a numerical model of known numerical accuracy predicts experimental strain measurements.

Nowadays biomedical engineers regularly have to combine data from multiple medical imaging modalities, biomedical measurements and computer simulations and this can demand the knowledge of many specialised software tools. Acquiring this knowledge to the depth necessary to perform the various tasks can require considerable time and thus divert the researcher from addressing the actual biomedical problems. The aim of the present study is to describe a new application called the Multimod Data Manager, distributed as a freeware, which provides the end user with a fully integrated environment for the fusion and manipulation of all biomedical data. The Multimod Data Manager is generated using a software application framework, called the Multimod Application Framework, which is specifically designed to support the rapid development of computer aided medicine applications. To understand the general logic of the Data Manager, we first introduce the framework from which it is derived. We then illustrate its use by an example--the development of a complete subject-specific musculo-skeletal model of the lower limb from the Visible Human medical imaging data to be used for predicting the stresses in the skeleton during gait. While the Data Manager is clearly still only at the prototype stage, we believe that it is already capable of being used to solve a large number of problems common to many biomedical engineering activities.

This paper describes a new application framework (OpenMAF) for rapid development of multimodal applications in computer-aided medicine. MAF applications are multimodal in data, in representation, and in interaction. The framework supports almost any type of biomedical data, including DICOM datasets, motion-capture recordings, or data from computer simulations (e.g. finite element modeling). The interactive visualization approach (multimodal display) helps the user interpret complex datasets, providing multiple representations of the same data. In addition, the framework allows multimodal interaction by supporting the simultaneous use of different input-output devices like 3D trackers, stereoscopic displays, haptics hardware and speech recognition/synthesis systems. The Framework has been designed to run smoothly even on limited power computers, but it can take advantage of all hardware capabilities. The Framework is based on a collection of portable libraries and it can be compiled on any platform that supports OpenGL, including Windows, MacOS X and any flavor of Unix/linux.

Spontaneous fractures (i.e. caused by sudden loading and muscle contraction, not by trauma) represent a significant percentage of proximal femur fractures. They are particularly relevant as may occur in elderly (osteoporotic) subjects, but also in relation to epiphyseal prostheses. Despite its clinical and legal relevance, this type of fracture has seldom been investigated. Studies concerning spontaneous fractures are based on a variety of loading scenarios. There is no evidence, nor consensus on the most relevant loading scenario. The aim of this work was to develop and validate an experimental method to replicate spontaneous fractures in vitro based on clinically relevant loading. Primary goals were: (i) repeatability and reproducibility, (ii) clinical relevance. A validated numerical model was used to identify the most critical loading scenario that can lead to head–neck fractures, and to determine if it is necessary to include muscle forces when the head–neck region is under investigation. The numerical model indicated that the most relevant loading scenario is when the resultant joint force is applied to the head at 81 from the diaphysis. Furthermore, it was found that it is not essential to include the muscles when investigating head–neck fractures. The experimental setup was consequently designed. The procedure included high-speed filming of the fracture event. Clinically relevant fracture modes were obtained on 10 cadaveric femurs. Failure load should be reported as a fraction of donor’s body-weight to reduce variability. The proposed method can be used to investigate the reason and mechanism of failure of natural and operated proximal femurs. r 2007 Elsevier Ltd. All rights reserved.

This article aims to determine the absolute accuracy of maxillary repositioning during orthognathic surgery according to simulation-guided navigation, that is, the combination of navigation and three-dimensional (3D) virtual surgery. We retrospectively studied 15 patients treated for asymmetric dentofacial deformities at the Oral and Maxillofacial Surgery Unit of the S.Orsola-Malpighi University Hospital in Bologna, Italy, from January 2010 to January 2012. Patients were scanned with a cone-beam computed tomography before and after surgery. The virtual surgical simulation was realized with a dedicated software and loaded on a navigation system to improve intraoperative reproducibility of the preoperative planning. We analyzed the outcome following two protocols: (1) planning versus postoperative 3D surface analysis; (2) planning versus postoperative point-based analysis. For 3D surface comparison, the mean Hausdorff distance was measured, and median among cases was 0.99 mm. Median reproducibility