Tensile Yield Strain of Human Cortical Bone from the Femoral Diaphysis Is Constant among Healthy Adults and across the Anatomical Quadrants.

The literature suggests that the yield strain of cortical bone is invariant to its stiffness (elastic modulus) and strength (yield stress). However, data about intra-individual variations, e.g., the influence of different collagen/mineral organisations observed in bone aspects withstanding different habitual loads, are lacking. The hypothesis that the yield strain of human cortical bone tissue, retrieved from femoral diaphyseal quadrants subjected to different habitual loads, is invariant was tested. Four flat dumbbell-shaped specimens were machined from each quadrant of the proximal femoral diaphysis of five adult donors for a total of 80 specimens. Two extensometers attached to the narrow specimen region were used to measure deformation during monotonic tensile testing. The elastic modulus (linear part of the stress-strain curve) and yield strain/stress at a 0.2% offset were obtained. Elastic modulus and yield stress values were, respectively, in the range of 12.2-20.5 GPa and 75.9-136.6 MPa and exhibited a positive linear correlation. All yield strain values were in the narrow range of 0.77-0.87%, regardless of the stiffness and strength of the tissue and the anatomical quadrant. In summary, the results corroborate the hypothesis that tensile yield strain in cortical bone is invariant, irrespective also of the anatomical quadrant. The mean yield strain value found in this study is similar to what was reported by inter-species and evolution studies but slightly higher than previous reports in humans, possibly because of the younger age of our subjects. Further investigations are needed to elucidate a possible dependence of yield strain on age.

Does a novel bridging collar in endoprosthetic replacement optimise the mechanical environment for osseointegration? A finite element study.

Introduction: Limb-salvage surgery using endoprosthetic replacements (EPRs) is frequently used to reconstruct segmental bone defects, but the reconstruction longevity is still a major concern. In EPRs, the stem-collar junction is the most critical region for bone resorption. We hypothesised that an in-lay collar would be more likely to promote bone ongrowth in Proximal Femur Reconstruction (PFR), and we tested this hypothesis through validated Finite Element (FE) analyses simulating the maximum load during walking. Methods: We simulated three different femur reconstruction lengths (proximal, mid-diaphyseal, and distal). For each reconstruction length one in-lay and one traditional on-lay collar model was built and compared. All reconstructions were virtually implanted in a population-average femur. Personalised Finite Element models were built from Computed Tomography for the intact case and for all reconstruction cases, including contact interfaces where appropriate. We compared the mechanical environment in the in-lay and on-lay collar configurations, through metrics of reconstruction safety, osseointegration potential, and risk of long-term bone resorption due to stress-shielding. Results: In all models, differences with respect to intact conditions were localized at the inner bone-implant interface, being more marked in the collar-bone interface. In proximal and mid-diaphyseal reconstructions, the in-lay configuration doubled the area in contact at the bone-collar interface with respect to the on-lay configuration, showed less critical values and trends of contact micromotions, and consistently showed higher (roughly double) volume percentages of predicted bone apposition and reduced (up to one-third) percentages of predicted bone resorption. In the most distal reconstruction, results for the in-lay and on-lay configurations were generally similar and showed overall less favourable maps of the bone remodelling tendency. Discussion: In summary, the models corroborate the hypothesis that an in-lay collar, by realising a more uniform load transfer into the bone with a more physiological pattern, creates an advantageous mechanical environment at the bone-collar interface, compared to an on-lay design. Therefore, it could significantly increase the survivorship of endo-prosthetic replacements.

High-resolution peripheral quantitative computed tomography: research or clinical practice?

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.

Applying a homogeneous pressure distribution to the upper vertebral endplate: Validation of a new loading system, pilot application to human vertebral bodies, and finite element predictions of DIC measured displacements and strains.

Image-based personalized Finite Element Models (pFEM) could detect alterations in physiological deformation of human vertebral bodies, but their accuracy has been seldom reported. Meaningful validation experiments should allow vertebral endplate deformability and ensure well-controlled boundary conditions. This study aimed to (i) validate a new loading system to apply a homogeneous pressure on the vertebral endplate during vertebral body compression regardless of endplate deformation; (ii) perform a pilot study on human vertebral bodies measuring surface displacements and strains with Digital Image Correlation (DIC); (iii) determine the accuracy of pFEM of the vertebral bodies. Homogeneous pressure application was achieved by pressurizing a fluid silicone encased in a rubber silicone film acting on the cranial endplate. The loading system was validated by comparing DIC-measured longitudinal strains and lower-end contact pressures, measured on three homogeneous pseudovertebrae of constant transversal section at 2.0 kN, against theoretically calculated values. Longitudinal strains and contact pressures were rather homogeneous, and their mean values close to theoretical calculations (5% underestimation). DIC measurements of surface longitudinal and circumferential displacements and strains were obtained on three human vertebral bodies at 2.0 kN. Complete displacement and strain maps were achieved for anterolateral aspects with random errors ≤0.2 µm and ≤30 µstrain, respectively. Venous plexus and double curvatures limited the completeness and accuracy of DIC data in posterior aspects. pFEM of vertebral bodies, including cortical bone mapping, were built from computed tomography images. In anterolateral aspects, pFEM accuracy of the three vertebrae was: (i) comparable to literature in terms of longitudinal displacements (R2>0.8); (ii) extended to circumferential displacements (pooled data: R2>0.9) and longitudinal strains (zero median error, 95% error: <27%). Circumferential strains were overestimated (median error: 39%). The new methods presented may permit to study how physiological and pathologic conditions influence the ability of vertebral endplates/bodies to sustain loads.

A Novel Quantitative Computer-Assisted Score Can Improve Repeatability in the Estimate of Vascular Calcifications at the Abdominal Aorta.

In CKD and in the elderly, Vascular Calcifications (VC) are associated to cardiovascular events and bone fractures. VC scores at the abdominal aorta (AA) from lateral spine radiographs are widely applied (the 0-24 semiquantitative discrete visual score (SV) being the most used). We hypothesised that a novel continuum score based on quantitative computer-assisted tracking of calcifications (QC score) can improve the precision of the SV score. This study tested the repeatability and reproducibility of QC score and SV score. In forty-four patients with VC from an earlier study, five experts from four specialties evaluated the data twice using a dedicated software. Test-retest was performed on eight subjects. QC results were reported in a 0-24 scale to readily compare with SV. The QC score showed higher intra-operator repeatability: the 95% CI of Bland-Altman differences was almost halved in QC; intra-operator R2 improved from 0.67 for SV to 0.79 for QC. Inter-observer repeatability was higher for QC score in the first (Intraclass Correlation Coefficient 0.78 vs. 0.64), but not in the second evaluation (0.84 vs. 0.82), indicating a possible heavier learning artefact for SV. The Minimum Detectable Difference (MDD) was smaller for QC (2.98 vs. 4 for SV, in the 0-24 range). Both scores were insensitive to test-retest procedure. Notably, QC and SV scores were discordant: SV showed generally higher values, and an increasing trend of differences with VC severity. In summary, the new QC score improved the precision of lateral spine radiograph scores in estimating VC. We reported for the first time an estimate of MDD in VC assessment that was 25% lower for the new QC score with respect to the usual SV score. An ongoing study will determine whether this lower MDD may reduce follow-up times to check for VC progression.

Individual Trajectories of Bone Mineral Density Reveal Persistent Bone Loss in Bone Sarcoma Patients: A Retrospective Study.

Multiagent chemotherapy offers an undoubted therapeutic benefit to cancer patients, but is also associated with chronic complications in survivors. Osteoporosis affects the quality of life of oncologic patients, especially at the paediatric age. However, very few studies have described the extent of loss of bone mineral density (BMD) in bone sarcoma patients. We analysed a retrospective series of children and adolescents with primary malignant bone tumours (52 osteosarcoma and 31 Ewing sarcoma) and retrieved their BMD at diagnosis and follow-up as Hounsfield units (HU). We studied their individual BMD trajectories before and after chemotherapy up to 5 years, using routine chest CT scan and attenuation thresholds on T12 vertebrae ROI. At one year, bone sarcoma patients showed significant bone loss compared to diagnosis: 17.6% and 17.1% less for OS and EW, respectively. Furthermore, a bone loss of more than 49.2 HU at one-year follow-up was predictive of the persistence of a reduced bone mass over the following 4 years, especially in patients with EW. At 4 years, only 26% and 12.5% of OS and EW, respectively, had recovered or improved their BMD with respect to the onset, suggesting a risk of developing morbidities related to a low BMD in those subjects.

Finite Element Assessment of Bone Fragility from Clinical Images.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.

The Vessels-Bone Axis: Iliac Artery Calcifications, Vertebral Fractures and Vitamin K from VIKI Study.

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 >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 < 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.

A taper-fit junction to improve long bone reconstruction: A parametric In Silico model.

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 exvivo experiments to further corroborate the proposed taper-fit junction concept and to refine its surgical implementation.

Cortical bone mapping improves finite element strain prediction accuracy at the proximal femur.

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.

nmsBuilder: Freeware to create subject-specific musculoskeletal models for OpenSim.

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.

Bone adaptation of a biologically reconstructed femur after Ewing sarcoma: Long-term morphological and densitometric evolution.

Combining bone allografts and vascularized fibular autografts in intercalary reconstructions after resection of bone sarcomas is of particular interest in young patients as it facilitates bone healing and union and helps reduce fractures. However, adverse events related to bone adaptation still occur. Bone adaptation is driven by mechanical loading, but no quantitative biomechanical studies exist that would help surgical planning and rehabilitation. We analyzed the bone adaptation of a successful femoral reconstruction after Ewing sarcoma during 76-month follow-up using a novel methodology that allows CT-based quantification of morphology and density. The results indicated that the vital allograft promoted bone adaptation in the reconstruction. However, an overall negative balance of bone remodeling and a progressive mineral density decrease in the femoral neck might threaten long-term bone safety. These concerns seem related to both surgical technique and mechanical stimuli, where a stiff metal implant may determine load sharing, which negatively affects bone remodeling.

Relationship between bone adaptation and in-vivo mechanical stimulus in biological reconstructions after bone tumor: A biomechanical modeling analysis.

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.

Can CT image deblurring improve finite element predictions at the proximal femur?

The aim of this study was to determine if a CT image deblurring algorithm can improve CT-based FE modelling accuracy at the proximal femur. Experimental data (CT scans of fourteen proximal fresh-frozen cadaveric femurs, non-destructive surface strain measurements in stance and sideways fall loading configurations on all femurs, and failure loads obtained in stance for seven specimens, in sideways fall for the other seven) were taken from a recent study (Schileo et al., 2014). An estimate of the 3D Point Spread Function for each CT scan was used within a deconvolution solver to perform the deblurring. The most proximal regions of three specimens were scanned using an HRpQCT scanner and compared to the original and deblurred CT images to quantify errors in bone contour estimates and determine correlation of intensity values within the bone contours. Subject-specific FE models of the proximal femur were generated. The accuracy of deblurred FE predictions against experimental measurements was compared to the published (non-deblurred) FE results. When compared to HRpQCT, CT deblurring led to lower mean surface distances (0.31 vs. 0.49mm) and higher CT intensity correlations with respect to the original CT. All indicators of strain prediction accuracy were significantly improved in deblurred FE models, more markedly at the femoral neck (peak error reduced by 38%). Failure load prediction, based on a simple elastic limit model, was also improved in deblurred FE models, although differently for stance and sideways fall loading conditions. In stance, correlation was unchanged, but specimen-wise errors were reduced (mean error 10% vs. 15%). In sideways fall, correlation notably increased (R(2)=0.95 vs. 0.81), despite a general overestimation of failure load. In summary, the proposed CT deblurring technique yielded moderate but significant improvements in FE predictions, and may thus be considered a first step toward the improvement of CT-based FE models of the human femur.

Navigation in Orthognathic Surgery: 3D Accuracy.

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 < 1 mm was 61.88% and median reproducibility < 2 mm was 85.46%. For the point-based analysis, with sign, the median distance was 0.75 mm in the frontal axis, -0.05 mm in the caudal-cranial axis, -0.35 mm in the lateral axis. In absolute value, the median distance was 1.19 mm in the frontal axis, 0.59 mm in the caudal-cranial axis, and 1.02 mm in the lateral axis. We suggest that simulation-guided navigation makes accurate postoperative outcomes possible for maxillary repositioning in orthognathic surgery, if compared with the surgical computer-designed project realized with a dedicated software, particularly for the vertical dimension, which is the most challenging to manage.

European Society of Biomechanics S.M. Perren Award 2014: Safety factor of the proximal femur during gait: a population-based finite element study.

It has been suggested that the mechanical competence of the proximal femur is preserved with respect to physiological loading conditions rather than accidental overloading, but the consequences of this adaptation for fracture risk in the elderly remain unclear. The goal of the present study was to analyse the safety factor of the human femur in the two most frequent daily activities, level walking and stair climbing, and to understand the dependence, if any, of this safety factor on age, volumetric bone mineral density (vBMD), and gender. To this aim, a finite element study was performed on 200 subjects (116 women and 84 men), spanning a large range of age (23-84 years) and vBMD levels (T-score from 0 to -3.59). For the first time, finite element models that included a subject-specific description of the anatomy and mineral density distribution of each bone were coupled with a personalisation of the loads acting on the proximal femur during movement, including the action of the muscles and their variability across the population. The results demonstrate that the human proximal femur is characterised by a high safety factor (on average five, never reaching fracture threshold), even in the presence of advanced age and low mineral content. These results corroborate the hypothesis that the relationship between loading and mechanical competence is generally preserved in the elderly population for the most frequent motor activities, walking and stair climbing. Interestingly, a decrease of the safety factor was observed with increasing lifespan and reduced mineral content in women but not in men.

To what extent can linear finite element models of human femora predict failure under stance and fall loading configurations?

Proximal femur strength estimates from computed tomography (CT)-based finite element (FE) models are finding clinical application. Published models reached a high in-vitro accuracy, yet many of them rely on nonlinear methodologies or internal best-fitting of parameters. The aim of the present study is to verify to what extent a linear FE modelling procedure, fully based on independently determined parameters, can predict the failure characteristics of the proximal femur in stance and sideways fall loading configurations. Fourteen fresh-frozen cadaver femora were CT-scanned. Seven femora were tested to failure in stance loading conditions, and seven in fall. Fracture was monitored with high-speed videos. Linear FE models were built from CT images according to a procedure already validated in the prediction of strains. An asymmetric maximum principal strain criterion (0.73% tensile, 1.04% compressive limit) was used to define a node-based risk factor (RF). FE-predicted failure load, mode (tensile/compressive) and location were determined from the first node reaching RF=1. FE-predicted and measured failure loads were highly correlated (R(2)=0.89, SEE=814N). In all specimens, FE models correctly identified the failure mode (tensile in stance, compressive in fall) and the femoral region where fracture started (supero-lateral neck aspect). The location of failure onset was accurately predicted in eight specimens. In summary, a simple FE model, adaptable in the future to multiple loads (e.g. including muscles), was highly correlated with experimental failure in two loading conditions on specimens ranging from normal to osteoporotic. Thus, it can be suitable for use in clinical studies.

Comprehensive evaluation of PCA-based finite element modelling of the human femur.

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.

Multiple loading conditions analysis can improve the association between finite element bone strength estimates and proximal femur fractures: a preliminary study in elderly women.

This is a preliminary case-control study on osteopenic/osteoporotic elderly women, testing the association of proximal femur fracture with minimum femoral strength, as derived from finite element (FE) analysis in multiple loading conditions. Fracture cases (n=22) in acute conditions were enrolled among low-trauma fractures admitted in various hospitals in the Emilia Romagna Region, Italy. Women with no history of low-trauma fractures were enrolled as controls (n=33). Patients were imaged with DXA to obtain aBMD, and with a bilateral full femur CT scan. FE-strength was derived in stance and fall configurations: (i) as the minimum strength among those obtained for multiple loading conditions spanning a domain of plausible force directions, and (ii) as the strength associated to the most commonly used single loading conditions. The association of FE-strength and aBMD with fractures was tested with logistic regression models, deriving odds ratios (ORs) and area under the receiver operating characteristic curve (AUC). FE-strength from multiple loading conditions better classified fracture cases from controls (OR per SD change=9.6, 95% CI=3.0-31.3, AUC=0.87 in stance; OR=9.5, 95% CI=2.9-31.2, AUC=0.88 in fall) compared to aBMD (OR=3.6, 95% CI=1.6-8.2, AUC=0.79 for total femur aBMD), while FE-strength results from the most commonly used single loading conditions were similar to aBMD. Only FE-strength from multiple loading conditions remained significant in age- and aBMD-adjusted models (OR=10.5, 95% CI=1.8-61.3, AUC=0.95). In summary, we highlighted the importance of considering different loading conditions to identify bone weakness, and confirmed that femoral FE-strength estimates may add value to aBMD predictions in elderly osteopenic/osteoporotic women.

Specimen-specific modeling of hip fracture pattern and repair.

Hip fracture remains a major health problem for the elderly. Clinical studies have assessed fracture risk based on bone quality in the aging population and cadaveric testing has quantified bone strength and fracture loads. Prior modeling has primarily focused on quantifying the strain distribution in bone as an indicator of fracture risk. Recent advances in the extended finite element method (XFEM) enable prediction of the initiation and propagation of cracks without requiring a priori knowledge of the crack path. Accordingly, the objectives of this study were to predict femoral fracture in specimen-specific models using the XFEM approach, to perform one-to-one comparisons of predicted and in vitro fracture patterns, and to develop a framework to assess the mechanics and load transfer in the fractured femur when it is repaired with an osteosynthesis implant. Five specimen-specific femur models were developed from in vitro experiments under a simulated stance loading condition. Predicted fracture patterns closely matched the in vitro patterns; however, predictions of fracture load differed by approximately 50% due to sensitivity to local material properties. Specimen-specific intertrochanteric fractures were induced by subjecting the femur models to a sideways fall and repaired with a contemporary implant. Under a post-surgical stance loading, model-predicted load sharing between the implant and bone across the fracture surface varied from 59%:41% to 89%:11%, underscoring the importance of considering anatomic and fracture variability in the evaluation of implants. XFEM modeling shows potential as a macro-level analysis enabling fracture investigations of clinical cohorts, including at-risk groups, and the design of robust implants.