imaging-of-the-microstructural-failure-mechanism-in-the-human-hip

Imaging of the Microstructural Failure Mechanism in the Human Hip

Imaging the bone microstructure under progressively increasing loads allows for observing the microstructural failure behavior of bone. Here, we describe ...

Queensland University of Technology

Flinders University

We review the literature on hip fracture mechanics and models of hip strain during exercise to postulate the exercise regimen for best promoting hip strength.

Modelling Human Locomotion to Inform Exercise Prescription for Osteoporosis.

The effect of tibiofemoral geometry on musculoskeletal function is important to movement biomechanics.

The relationship between tibiofemoral geometry and musculoskeletal function during normal activity.

We hypothesize that variations of body anthropometry, conjointly with the bone strength, determine the risk of hip fracture. To test the hypothesis, we compared, in a simulated sideways fall, the hip impact energy to the energy needed to fracture the femur. Ten femurs from elderly donors were tested using a novel drop-tower protocol for replicating the hip fracture dynamics during a fall on the side. The impact energy was varied for each femur according to the donor's body weight, height and soft-tissue thickness, by adjusting the drop height and mass. The fracture pattern, force, energy, strain in the superior femoral neck, bone morphology and microarchitecture were evaluated. Fracture patterns were consistent with clinically relevant hip fractures, and the superior neck strains and timings were comparable with the literature. The hip impact energy (11 - 95 J) and the fracture energy (11 - 39 J) ranges overlapped and showed comparable variance (CV = 69 and 61%, respectively). The aBMD-based definition of osteoporosis correctly classified 7 (70%) fracture/non-fracture cases. The incorrectly classified cases presented large impact energy variations, morphology variations and large subcortical voids as seen in microcomputed tomography. In conclusion, the risk of osteoporotic hip fracture in a sideways fall depends on both body anthropometry and bone strength.

Body Anthropometry and Bone Strength Conjointly Determine the Risk of Hip Fracture in a Sideways Fall.

Observations of elastic instability of trabecular bone cores supported the analysis of cortical thickness for predicting bone fragility of the hip in people over 60 years of age. Here, we falsified the hypothesis that elastic instability causes minimal energy fracture by analyzing, with a micrometric resolution, the deformation and fracture behavior of entire femora. Femur specimens were obtained from elderly women aged between 66 - 80 years. Microstructural images of the proximal femur were obtained under 3 - 5 progressively increased loading steps and after fracture. Bone displacements, strain, load bearing and energy absorption capacity were analyzed. Elastic instability of the cortex appeared at early loading stages in regions of peak compression. No elastic instability of trabecular bone was observed. The subchondral bone displayed local crushing in compression at early loading steps and progressed to 8 - 16% compression before fracture. The energy absorption capacity was proportional to the displacement. Stiffness decreased to near-zero values before fracture. Three-fourth of the fracture energy (10.2 - 20.2 J) was dissipated in the final 25% force increment. Fracture occurred in regions of peak tension and shear, adjacent to the location of peak compression, appearing immediately before fracture. Minimal permanent deformation was visible along the fracture surface. Elastic instability modulates the interaction between cortical and trabecular bone promoting an elastically stable fracture behavior of the femur organ, load bearing capacity, toughness, and damage tolerance. These findings will advance current methods for predicting hip fragility.

Damage tolerance and toughness of elderly human femora.

Physical exercise induces spatially heterogeneous bone changes in the proximal femur. Recent advances have enabled 3D dual-energy X-ray Absorptiometry (DXA)-based finite element (FE) models to estimate bone strength. However, its ability to detect exercise-induced BMD and strength changes is unclear. The aim of this study was to quantify the repeatability of vBMD and femoral neck strength obtained from 3D-DXA images and determine the changes due an exercise intervention. The DXA scans included pairs of same-day repeated scans from ten healthy females and pre- and post-exercise intervention scans of 26 males. FE models with element-by-element correspondence were generated by morphing a template mesh to each bone. BMD and femoral strength under single-leg-stance and sideways fall loading configurations were obtained for both groups and compared. In the repeated images, the total hip vBMD difference was 0.5 ± 2.5%. Element-by-element BMD differences reached 30 ± 50%. The strength difference in single-leg stance was 2.8 ± 13% and in sideways fall was 4.5% ± 19%. In the exercise group, strength changes were 6 ± 19% under single-leg stance and 1 ± 18% under sideways fall. vBMD parameters were weakly correlated to strength (R < 0.31). The exercise group had a mean bone accrual exceeding repeatability values in the femoral head and cortical regions. The case with the highest vBMD change (6.4%) caused 18% and -7% strength changes under single-leg stance and sideways fall. 3D-DXA technology can assess the effect of exercise interventions in large cohorts but its validity in individual cases should be interpreted with caution.

Assessment of femoral neck strength and bone mineral density changes following exercise using 3D-DXA images.

The aim of the current study was to quantify the local effect of mechanical loading on cortical bone formation response at the periosteal surface using previously obtained μCT data from a mouse tibia mechanical loading study. A novel image analysis algorithm was developed to quantify local cortical thickness changes (ΔCt.Th) along the periosteal surface due to different peak loads (0N ≤ F ≤ 12N) applied to right-neurectomised mature female C57BL/6 mice. Furthermore, beam analysis was performed to analyse the local strain distribution including regions of tensile, compressive, and low strain magnitudes. Student's paired -test showed that ΔCt.Th in the proximal (25%), proximal/middle (37%), and middle (50%) cross-sections (along the z-axis of tibia) is strongly associated with the peak applied loads. These changes are significant in a majority of periosteal positions, in particular those experiencing high compressive or tensile strains. No association between F and ΔCt.Th was found in regions around the neutral axis. For the most distal cross-section (75%), the association of loading magnitude and ΔCt.Th was not as pronounced as the more proximal cross-sections. Also, bone formation responses along the periosteum did not occur in regions of highest compressive and tensile strains predicted by beam theory. This could be due to complex experimental loading conditions which were not explicitly accounted for in the mechanical analysis. Our results show that the bone formation response depends on the load magnitude and the periosteal position. Bone resorption due to the neurectomy of the loaded tibia occurs throughout the entire cross-sectional region for all investigated cortical sections 25, 37, 50, and 75%. For peak applied loads higher than 4 N, compressive and tensile regions show bone formation; however, regions around the neutral axis show constant resorption. The 50% cross-section showed the most regular ΔCt.Th response with increased loading when compared to 25 and 37% cross-sections. Relative thickness gains of approximately 70, 60, and 55% were observed for F = 12 N in the 25, 37, and 50% cross-sections. ΔCt.Th at selected points of the periosteum follow a linear response with increased peak load; no lazy zone was observed at these positions.

Cortical Thickness Adaptive Response to Mechanical Loading Depends on Periosteal Position and Varies Linearly With Loading Magnitude.

In vitro real-time replication of three-dimensional, time-varying load profiles acting on human bones during physical activity can advance bone and implant testing protocols. This study aimed to develop a novel protocol for applying the three-dimensional, time-varying hip contact force while walking to a human femur specimen. The target force profile was obtained from the literature. A proximal femur from an elderly female donor was instrumented using ten rosette strain gages and tested using a custom-made hexapod robot. A load-control algorithm determined the robot position generating the target force at low frequency (0.0004 Hz). Five cycles of the robot position were played back at five intermediate frequencies up to real-time (0.04, 0.08, 0.16, 0.4, and 0.8 Hz). The hip reaction force, the length of the actuators (position), and cortical strains were compared. The error in the load-control force was 0.3 ± 4.2 N (mean ± SD). The last three force, position, and strain cycles varied by less than 1.1% for every frequency analyzed. Across frequencies, the force increased by 28% at 0.8 Hz as a logarithmic function of frequency (R = 0.98). The position and strain error linearly increased with frequency up to 0.4 Hz. The median position error and the interquartile range of the strain error reached 15% and 13% at 0.8 Hz. Changes of force and cortical strain at increasing frequencies were linearly related (R = 0.99). Therefore, the protocol developed can provide repeatable three-dimensional time-varying load profiles, although the comparison of the specimen deformation obtained across frequencies should be considered with care, particularly in the higher frequency range. This information supports the design of dynamic tests of bone and implants.

Real-time replication of three-dimensional and time-varying physiological loading cycles for bone and implant testing: A novel protocol demonstrated for the proximal human femur while walking.

The effect of force amount, age, body weight and bone mineral density (BMD) on the femur's force relaxation response was analysed for 12 donors (age: 56-91 years). BMD and fracture load,  , were estimated from clinical CT images. The 30 min force relaxation was obtained using a constant compression generating an initial force   between 7% and 78% of  . The stretched decay function (() =  ×   ) proposed earlier for bone tissue was fitted to the data and analysed using robust linear regression. The relaxation function fitted well to all the recordings (  = 0.99). The relative initial force was bilinearly associated (  = 0.83) to the shape factor, , and the characteristic time, , when  /  was less than 0.4, although  was no longer associated with  /  by pooling all the data. The characteristic time  increased with age (  = 0.37,  = 0.03) explaining 35% of the variation of  in the entire dataset. In conclusion, the relative initial force mostly determines the femur's force relaxation response, although the early relaxation response under subcritical loading is variable, possibly due to damage occurring at subcritical loading levels.

The effect of age and initial compression on the force relaxation response of the femur in elderly women.

The assessment of shoulder kinematics and kinetics are commonly undertaken biomechanically and clinically by using rigid-body models and experimental skin-marker trajectories. However, the accuracy of these trajectories is plagued by inherent skin-based marker errors due to marker misplacements (offset) and soft-tissue artifacts (STA). This paper aimed to assess the individual contribution of each of these errors to kinematic and kinetic shoulder outcomes computed using a shoulder rigid-body model. Baseline experimental data of three shoulder planar motions in a young healthy adult were collected. The baseline marker trajectories were then perturbed by simulating typically observed population-based offset and/or STA using a probabilistic Monte-Carlo approach. The perturbed trajectories were then used together with a shoulder rigid-body model to compute shoulder angles and moments and study their accuracy and variability against baseline. Each type of error was studied individually, as well as in combination. On average, shoulder kinematics varied by 3%, 6% and 7% due to offset, STA or combined errors, respectively. Shoulder kinetics varied by 11%, 27% and 28% due to offset, STA or combined errors, respectively. In conclusion, to reduce shoulder kinematic and kinetic errors, one should prioritise reducing STA as they have the largest error contribution compared to marker misplacements.

Statistical Quantification of the Effects of Marker Misplacement and Soft-Tissue Artifact on Shoulder Kinematics and Kinetics.

Joint motion calculated using multi-body models and inverse kinematics presents many advantages over direct marker-based calculations. However, the sensitivity of the computed kinematics is known to be partly caused by the model and could also be influenced by the participants' anthropometry and sex. This study aimed to compare kinematics computed from an anatomical shoulder model based on medical images against a scaled-generic model and quantify the effects of anatomical errors and participants' anthropometry on the calculated joint angles. Twelve participants have had planar shoulder movements experimentally captured in a motion lab, and their shoulder anatomy imaged using an MRI scanner. A shoulder multi-body dynamics model was developed for each participant, using both an image-based approach and a scaled-generic approach. Inverse kinematics have been performed using the two different modelling procedures and the three different experimental motions. Results have been compared using Bland-Altman analysis of agreement and further analysed using multi-linear regressions. Kinematics computed via an anatomical and a scaled-generic shoulder models differed in average from 3.2 to 5.4 degrees depending on the task. The MRI-based model presented smaller limits of agreement to direct kinematics than the scaled-generic model. Finally, the regression model predictors, including anatomical errors, sex, and BMI of the participant, explained from 41 to 80% of the kinematic variability between model types with respect to the task. This study highlighted the consequences of modelling precision, quantified the effects of anatomical errors on the shoulder kinematics, and showed that participants' anthropometry and sex could indirectly affect kinematic outcomes.

The effects of anatomical errors on shoulder kinematics computed using multi-body models.

Postoperative weight bearing has the potential to generate fragmental motion of surgically repaired tibial plateau fractures (TPFs), which may contribute to loss of fracture reduction. The effect of loading on the internal distribution of fragmentary displacements is currently unknown. The aim of this study was to determine the internal displacements of surgically repaired split TPFs due to a three-bodyweight load, using large-volume micro-CT imaging and image correlation. Fractures were generated and surgically repaired for two cadaveric specimens. Load was applied to the specimens inside a large-volume micro-CT system and scanned at 0.046 mm isotropic voxel size. Pre- and post-loading images were paired, co-registered, and internal fragmentary displacements quantified. Internal fragmental displacements of the cadaveric bones were compared to in vivo displacements measured in the lateral split fragments of TPFs in a clinical cohort of patients who had similar surgical repair and were prescribed pain tolerated postoperative weight bearing. The split fragments of cadaveric specimens displaced, on average, less than 0.3 mm, consistent with in vivo measurements. Specimen one rotated around the mediolateral axis, while specimen two displaced consistently caudally. Specimen two also had varying displacements along the mediolateral axis where, at the fracture site, the fragment displaced caudally and laterally, while the most lateral edge of the tibial plateau displaced caudally and medially. The methods applied in this study can be used to measure internal fragmental motion within TPFs.

Ex vivo assessment of surgically repaired tibial plateau fracture displacement under axial load using large-volume micro-CT.

Physical exercise induces spatially heterogeneous adaptation in bone. However, it remains unclear where the changes in BMD and geometry have the greatest impact on femoral neck strength. The aim of this study was to determine the principal BMD-and-geometry changes induced by exercise that have the greatest effect on femoral neck strength. Pre- and post-exercise 3D-DXA images of the proximal femur were collected of male participants from the LIFTMOR-M exercise intervention trial. Meshes with element-by-element correspondence were generated by morphing a template mesh to each bone to calculate changes in BMD and geometry. Finite element (FE) models predicted femoral neck strength changes under single-leg stance and sideways fall load. Partial least squares regression (PLSR) models were developed with BMD-only, geometry-only, and BMD-and-geometry changes to determine the principal modes that explained the greatest variation in neck strength changes. The PLSR models explained over 90% of the strength variation with 3 PLS components using BMD-only (R > 0.92, RMSE < 0.06 N) and 8 PLS components with geometry-only (R > 0.93, RMSE < 0.06 N). Changes in the superior neck and distal cortex were most important during single-leg stance while the superior neck, medial head, and lateral trochanter were most important during a sideways fall. Local changes in femoral neck and head geometry could differentiate the exercise groups from the control group. Exercise interventions may target BMD changes in the superior neck, inferior neck, and greater trochanter for improved femoral neck strength in single-leg stance and sideways fall.

Geometry and bone mineral density determinants of femoral neck strength changes following exercise.

Tibiofemoral geometry influences knee passive motion and understanding their relationship can provide insight into knee function and mechanisms of injury. However, the complexity of the geometric constraints has made characterizing the relationship challenging. The aim of this study was to determine the tibiofemoral bone geometries that explain the variation in passive motion using a partial least squares regression (PLSR) model. The PLSR model was developed for 29 healthy cadaver specimens (10 female, 19 male) with femur and tibia geometries retrieved from MRI images and six degree-of-freedom tibiofemoral kinematics determined during a flexion cycle with minimal medial pressure. The first 13 partial least squares (PLS) components explained 90% of the variation in the kinematics and accounted for 89% of the variation in geometry. The first three PLS components which shared geometric changes to particular surface congruencies of the tibial and femoral condyles explained the most amount of variation in the kinematics, primarily in anterior-posterior translation. Meanwhile, variations in femoral condyle width and the intercondylar space, tibia plateau size and conformity, and tibia eminences heights in PLS 2 and 4 explained the greatest amount of variation in internal-external rotation. PLS 4 exhibiting variation in overall size of the knee accounted for greatest amount of variation in geometry (50%) and had the greatest influence on the abduction-adduction motion and some on internal-external rotation but, overall, explained only a small proportion of the kinematics (10%). Elucidating the complex relationship between tibiofemoral bone geometry and passive kinematics may help personalize treatments for improved functional outcomes in patients.

Determining the relationship between tibiofemoral geometry and passive motion with partial least squares regression.

The surgical Latarjet procedure aims to stabilise the glenohumeral joint following anterior dislocations. Despite restoring joint stability, the procedure introduces alterations of muscle paths which likely modify the shoulder dynamics. Currently, these altered muscular functions and their implications are unclear. Hence, this work aims to predict changes in muscle lever arms, muscle and joint forces following a Latarjet procedure by using a computational approach. Planar shoulder movements of ten participants were experimentally assessed. A validated upper-limb musculoskeletal model was utilised in two configurations, i.e., a baseline model, simulating normal joint, and a Latarjet model simulating its related muscular alterations. Muscle lever arms and differences in muscle and joint forces between models were derived from the experimental marker data and static optimisation technique. Lever arms of most altered muscles, hence their role, were substantially changed after Latarjet. Altered muscle forces varied by up to 15% of the body weight. Total glenohumeral joint force increased by up to 14% of the body weight after Latarjet, mostly due to increase in compression force. Our simulation indicated that the Latarjet muscular alterations lead to changes in the muscular recruitment and contribute to the stability of the glenohumeral joint by increasing compression force during planar motions.

Article	Year
Modelling Human Locomotion to Inform Exercise Prescription for Osteoporosis. Current osteoporosis reports\| PubMed ID: 32335858	2020
The relationship between tibiofemoral geometry and musculoskeletal function during normal activity. Gait & posture\| PubMed ID: 32622207	2020
Body Anthropometry and Bone Strength Conjointly Determine the Risk of Hip Fracture in a Sideways Fall. Annals of biomedical engineering\| PubMed ID: 33184710	2021
Damage tolerance and toughness of elderly human femora. Acta biomaterialia\| PubMed ID: 33454384	2021
Assessment of femoral neck strength and bone mineral density changes following exercise using 3D-DXA images. Journal of biomechanics\| PubMed ID: 33636460	2021
Cortical Thickness Adaptive Response to Mechanical Loading Depends on Periosteal Position and Varies Linearly With Loading Magnitude. Frontiers in bioengineering and biotechnology\| PubMed ID: 34222215	2021
Real-time replication of three-dimensional and time-varying physiological loading cycles for bone and implant testing: A novel protocol demonstrated for the proximal human femur while walkin... Journal of the mechanical behavior of biomedical materials\| PubMed ID: 34536802	2021
The effect of age and initial compression on the force relaxation response of the femur in elderly women. Royal Society open science\| PubMed ID: 35592757	2022
Statistical Quantification of the Effects of Marker Misplacement and Soft-Tissue Artifact on Shoulder Kinematics and Kinetics. Life (Basel, Switzerland)\| PubMed ID: 35743850	2022
The effects of anatomical errors on shoulder kinematics computed using multi-body models. Biomechanics and modeling in mechanobiology\| PubMed ID: 35867281	2022
Ex vivo assessment of surgically repaired tibial plateau fracture displacement under axial load using large-volume micro-CT. Journal of biomechanics\| PubMed ID: 36063585	2022
Geometry and bone mineral density determinants of femoral neck strength changes following exercise. Biomechanics and modeling in mechanobiology\| PubMed ID: 36271264	2023
Determining the relationship between tibiofemoral geometry and passive motion with partial least squares regression. Journal of orthopaedic research : official publication of the Orthopaedic Research Society\| PubMed ID: 36722422	2023
Latarjet's muscular alterations increase glenohumeral joint stability: A theoretical study. Journal of biomechanics\| PubMed ID: 37245383	2023

Saulo Martelli

Biography

JoVE Journal Publications

Other Publications