Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from -5.6 to -1.7 ms for T1ρ, and -2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

Technologically advanced running shoes reduce oxygen cost and cumulative tibial loading per kilometer in recreational female and male runners.

Technologically advanced running shoes (TARS) improve performance compared to classical running shoes (CRS). Improved race performance has been attributed to metabolic savings in male runners, but it remains unclear if these same benefits are experienced among females and in recreational runners. The mechanisms behind these benefits are still not fully understood despite the need for optimisation, and their influence on injury mechanisms has not been explored. Here we combined biomechanical, physiological, and modelling approaches to analyse joint mechanics, oxygen uptake, and tibial load in nineteen male and female recreational runners running with CRS and TARS at their individual lactate threshold speed (12.4 ± 1.9 km/h). Oxygen uptake was 3.0 ± 1.5% lower in TARS than in CRS. Ankle dorsiflexion, joint moment and joint power were reduced in TARS compared to CRS at various phases of stance including midstance, while knee joint mechanics were mostly similar throughout. There were no significant differences for tibial bending moment during the stance phase but cumulative tibial damage per kilometre was 12 ± 9% lower in TARS compared to CRS. Our results suggest that running with TARS reduces oxygen cost in recreational female and male runners, which may partly be explained by differences in lower limb joint mechanics. The lower cumulative tibial bone load with TARS may allow runners to run longer distances in this type of shoe compared to CRS.

Spatial variations in the osteocyte lacuno-canalicular network density and analysis of the connectomic parameters.

Osteocyte lacuno-canalicular network (LCN) is comprised of micrometre-sized pores and submicrometric wide channels in bone. Accumulating evidence suggests multiple functions of this network in material transportation, mechanobiological signalling, mineral homeostasis and bone remodelling. Combining rhodamine staining and confocal laser scanning microscopy, the longitudinal cross-sections of six mouse tibiae were imaged, and the connectome of the network was quantified with a focus on the spatial heterogeneities of network density, connectivity and length of canaliculi. In-vivo loading and double calcein labelling on these tibiae allowed differentiating the newly formed bone from the pre-existing regions. The canalicular density of the murine cortical bone varied between 0.174 and 0.243 µm/µm3, and therefore is three times larger than the corresponding value for human femoral midshaft osteons. The spatial heterogeneity of the network was found distinctly more pronounced across the cortex than along the cortex. We found that in regions with a dense network, the LCN conserves its largely tree-like character, but increases the density by including shorter canaliculi. The current study on healthy mice should serve as a motivating starting point to study the connectome of genetically modified mice, including models of bone diseases and of reduced mechanoresponse.

Treadmill exercise promotes bone tissue recovery in rats subjected to high + Gz loads.

INTRODUCTION: High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks. MATERIALS AND METHODS: To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR. RESULTS: The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis. CONCLUSION: This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts.

Tibial strains are sensitive to speed perturbations, but not grade perturbations, during running.

A fatigue-failure process is hypothesized to govern the development of tibial stress fractures, where bone damage is highly dependent on the peak strain magnitude. To date, much of the work examining tibial strain during running has ignored uphill and downhill running despite the prevalence of this terrain. This study examined the sensitivity of tibial strain to changes in running grade and speed using a combined musculoskeletal-finite element modelling routine. Seventeen participants ran on a treadmill at ±10, ±5 and 0 deg; at each grade, participants ran at 3.33 m s-1 and at a grade-adjusted speed of 2.50 and 4.17 m s-1 for uphill and downhill grades, respectively. Force and motion data were recorded in each grade and speed combination. Muscle and joint contact forces were estimated using inverse-dynamics-based static optimization. These forces were applied to a participant-adjusted finite element model of the tibia. None of the strain variables (50th and 95th percentile strain and strained volume ≥4000 µÎµ) differed as a function of running grade; however, all strain variables were sensitive to running speed (F1≥9.59, P≤0.03). In particular, a 1 m s-1 increase in speed resulted in a 9% (∼260 µÎµ) and 155% (∼600 mm3) increase in peak strain and strained volume, respectively. Overall, these findings suggest that faster running speeds, but not changes in running grade, may be more deleterious to the tibia.

Load carriage changes tibiofemoral arthrokinematics during ambulatory tasks in recruit-aged women.

The introduction of women into U.S. military ground close combat roles requires research into sex-specific effects of military training and operational activities. Knee osteoarthritis is prevalent among military service members; its progression has been linked to occupational tasks such as load carriage. Analyzing tibiofemoral arthrokinematics during load carriage is important to understand potentially injurious motion and osteoarthritis progression. The study purpose was to identify effects of load carriage on knee arthrokinematics during walking and running in recruit-aged women. Twelve healthy recruit-aged women walked and ran while unloaded (bodyweight [BW]) and carrying additional + 25%BW and + 45%BW. Using dynamic biplane radiography and subject-specific bone models, tibiofemoral arthrokinematics, subchondral joint space and center of closest contact location between subchondral bone surfaces were analyzed over 0-30% stance (separate one-way repeated measures analysis of variance, load by locomotion). While walking, medial compartment contact location was 5% (~ 1.6 mm) more medial for BW than + 45%BW at foot strike (p = 0.03). While running, medial compartment contact location was 4% (~ 1.3 mm) more lateral during BW than + 25%BW at 30% stance (p = 0.04). Internal rotation was greater at + 45%BW compared to + 25%BW (p < 0.01) at 30% stance. Carried load affects tibiofemoral arthrokinematics in recruit-aged women. Prolonged load carriage could increase the risk of degenerative joint injury in physically active women.

A Method to Track 3D Knee Kinematics by Multi-Channel 3D-Tracked A-Mode Ultrasound.

This paper introduces a method for measuring 3D tibiofemoral kinematics using a multi-channel A-mode ultrasound system under dynamic conditions. The proposed system consists of a multi-channel A-mode ultrasound system integrated with a conventional motion capture system (i.e., optical tracking system). This approach allows for the non-invasive and non-radiative quantification of the tibiofemoral joint's six degrees of freedom (DOF). We demonstrated the feasibility and accuracy of this method in the cadaveric experiment. The knee joint's motions were mimicked by manually manipulating the leg through multiple motion cycles from flexion to extension. To measure it, six custom ultrasound holders, equipped with a total of 30 A-mode ultrasound transducers and 18 optical markers, were mounted on various anatomical regions of the lower extremity of the specimen. During experiments, 3D-tracked intra-cortical bone pins were inserted into the femur and tibia to measure the ground truth of tibiofemoral kinematics. The results were compared with the tibiofemoral kinematics derived from the proposed ultrasound system. The results showed an average rotational error of 1.51 ± 1.13° and a translational error of 3.14 ± 1.72 mm for the ultrasound-derived kinematics, compared to the ground truth. In conclusion, this multi-channel A-mode ultrasound system demonstrated a great potential of effectively measuring tibiofemoral kinematics during dynamic motions. Its improved accuracy, nature of non-invasiveness, and lack of radiation exposure make this method a promising alternative to incorporate into gait analysis and prosthetic kinematic measurements later.

Learning effects in over-ground running gait retraining: A six-month follow-up of a quasi-randomized controlled trial.

This study evaluated learning and recall effects following a feedback-based retraining program. A 6-month follow-up of a quasi-randomized controlled trial was performed with and without recall. Twenty runners were assigned to experimental or control groups and completed a 3-week running program. A body-worn system collected axial tibial acceleration and provided real-time feedback on peak tibial acceleration for six running sessions in an athletic training facility. The experimental group received music-based biofeedback in a faded feedback scheme. The controls received tempo-synchronized music as a placebo for blinding purposes. The peak tibial acceleration and vertical loading rate of the ground reaction force were determined in a lab at baseline and six months following the intervention to assess retention and recall. The impacts of the experimental group substantially decreased at follow-up following a simple verbal recall (i.e., run as at the end of the program): peak tibial acceleration:-32%, p = 0.018; vertical loading rate:-34%, p = 0.006. No statistically significant changes were found regarding the retention of the impact variables. The impact magnitudes did not change over time in the control group. The biofeedback-based intervention did not induce clear learning at follow-up, however, a substantial impact reduction was recallable through simple cueing in the absence of biofeedback.

The biomechanical influence of transtibial Bone-Anchored limbs during walking.

Individuals with unilateral transtibial amputation (TTA) using socket prostheses demonstrate asymmetric joint biomechanics during walking, which increases the risk of secondary comorbidities (e.g., low back pain (LBP), osteoarthritis (OA)). Bone-anchored limbs are an alternative to socket prostheses, yet it remains unknown how they influence multi-joint loading. Our objective was to determine the influence of bone-anchored limb use on multi-joint biomechanics during walking. Motion capture data (kinematics, ground reaction forces) were collected during overground walking from ten participants with unilateral TTA prior to (using socket prostheses) and 12-months after bone-anchored limb implantation. Within this year, each participant completed a rehabilitation protocol that guided progression of loading based on patient pain response and optimized biomechanics. Musculoskeletal models were developed at each testing timepoint (baseline or 12-months after implantation) and used to calculate joint kinematics, internal joint moments, and joint reaction forces (JRFs). Analyses were performed during three stance periods on each limb. The between-limb normalized symmetry index (NSI) was calculated for joint moments and JRF impulses. Discrete (range of motion (ROM), impulse NSI) dependent variables were compared before and after implantation using paired t-tests with Bonferroni-Holm corrections while continuous (ensemble averages of kinematics, moments, JRFs) were compared using statistical parametric mapping (p < 0.05). When using a bone-anchored limb, frontal plane pelvic (residual: pre = 9.6 ± 3.3°, post = 6.3 ± 2.5°, p = 0.004; intact: pre = 10.2 ± 3.9°, post = 7.9 ± 2.6°, p = 0.006) and lumbar (residual: pre = 15.9 ± 7.0°, post = 10.6 ± 2.5°, p = 0.024, intact: pre = 17.1 ± 7.0°, post = 11.4 ± 2.8°, p = 0.014) ROM was reduced compared to socket prosthesis use. The intact limb hip extension moment impulse increased (pre = -11.0 ± 3.6 Nm*s/kg, post = -16.5 ± 4.4 Nm*s/kg, p = 0.005) and sagittal plane hip moment impulse symmetry improved (flexion: pre = 23.1 ± 16.0 %, post = -3.9 ± 19.5 %, p = 0.004, extension: pre = 29.2 ± 20.3 %, post = 8.7 ± 22.9 %, p = 0.049). Residual limb knee extension moment impulse decreased compared to baseline (pre = 15.7 ± 10.8 Nm*s/kg, post = 7.8 ± 3.9 Nm*s/kg, p = 0.030). These results indicate that bone-anchored limb implantation alters multi-joint biomechanics, which may impact LBP or OA risk factors in the TTA population longitudinally.

Statistical shape analysis and computational modeling reveal novel relationships between tibiofemoral bony geometry and knee mechanics in young, female athletes.

Young female athletes participating in sports requiring rapid changes of direction are at heightened risk of suffering traumatic knee injury, especially noncontact rupture of the anterior cruciate ligament (ACL). Clinical studies have revealed that geometric features of the tibiofemoral joint are associated with increased risk of suffering noncontact ACL injury. However, the relationship between three-dimensional (3D) tibiofemoral geometry and knee mechanics in young female athletes is not well understood. We developed a statistically augmented computational modeling workflow to determine relationships between 3D geometry of the knee and tibiofemoral kinematics and ACL force in response to an applied loading sequence of compression, valgus, and anterior force, which is known to load the ACL. This workflow included 3D characterization of tibiofemoral bony geometry via principal component analysis and multibody dynamics models incorporating subject-specific knee geometries. A combination of geometric features of both the tibia and the femur that spanned all three anatomical planes was related to increased ACL force and to increased kinematic coupling (i.e., anterior, medial, and distal tibial translations and internal tibial rotation) in response to the applied loads. In contrast, a uniplanar measure of tibiofemoral geometry that is associated with ACL injury risk, sagittal plane slope of the lateral tibial plateau subchondral bone, was not related to ACL force. Thus, our workflow may aid in developing mechanics-based ACL injury screening tools for young, active females based on a unique combination of bony geometric features that are related to increased ACL loading.

Impact of hindlimb length variation on jumping dynamics in the Longshanks mouse.

Distantly related mammals (e.g. jerboa, tarsiers, kangaroos) have convergently evolved elongated hindlimbs relative to body size. Limb elongation is hypothesized to make these species more effective jumpers by increasing their kinetic energy output (through greater forces or acceleration distances), thereby increasing take-off velocity and jump distance. This hypothesis, however, has rarely been tested at the population level, where natural selection operates. We examined the relationship between limb length, muscular traits and dynamics using Longshanks mice, which were selectively bred over 22 generations for longer tibiae. Longshanks mice have approximately 15% longer tibiae and 10% longer femora compared with random-bred Control mice from the same genetic background. We collected in vivo measures of locomotor kinematics and force production, in combination with behavioral data and muscle morphology, to examine how changes in bone and muscle structure observed in Longshanks mice affect their hindlimb dynamics during jumping and clambering. Longshanks mice achieved higher mean and maximum lunge-jump heights than Control mice. When jumping to a standardized height (14 cm), Longshanks mice had lower maximum ground reaction forces, prolonged contact times and greater impulses, without significant differences in average force, power or whole-body velocity. While Longshanks mice have longer plantarflexor muscle bodies and tendons than Control mice, there were no consistent differences in muscular cross-sectional area or overall muscle volume; improved lunge-jumping performance in Longshanks mice is not accomplished by simply possessing larger muscles. Independent of other morphological or behavioral changes, our results point to the benefit of longer hindlimbs for performing dynamic locomotion.

Application of ultrasound to monitor in vivo residual bone movement within transtibial prosthetic sockets.

Transtibial prosthetic users do often struggle to achieve an optimal prosthetic fit, leading to residual limb pain and stump-socket instability. Prosthetists face challenges in objectively assessing the impact of prosthetic adjustments on residual limb loading. Understanding the mechanical behaviour of the pseudo-joint formed by the residual bone and prosthesis may facilitate prosthetic adjustments and achieving optimal fit. This study aimed to assess the feasibility of using B-mode ultrasound to monitor in vivo residual bone movement within a transtibial prosthetic socket during different stepping tasks. Five transtibial prosthesis users participated, and ultrasound images were captured using a Samsung HM70A system during five dynamic conditions. Bone movement relative to the socket was quantified by tracking the bone contour using Adobe After-Effect. During the study a methodological adjustment was made to improve data quality, and the first two participants were excluded from analysis. The remaining three participants exhibited consistent range of motion, with a signal to noise ratio ranging from 1.12 to 2.59. Medial-lateral and anterior-posterior absolute range of motion varied between 0.03 to 0.88 cm and 0.14 to 0.87 cm, respectively. This study demonstrated that it is feasible to use B-mode ultrasound to monitor in vivo residual bone movement inside an intact prosthetic socket during stepping tasks.

Genome-wide association study for bone quality of ducks during the laying period.

The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

Successful Powerlifting in a Unilateral, Transtibial Amputee: A Descriptive Case Series.

ABSTRACT: Beausejour, JP, Guinto, G, Artrip, C, Corvalan, A, Mesa, MF, Lebron, MA, and Stock, MS. Successful powerlifting in a unilateral, transtibial amputee: A descriptive case series. J Strength Cond Res 38(5): e243-e252, 2024-There are no reports in the literature of powerlifting success after amputation. We had the unique opportunity to characterize functional outcomes, strength, muscle contractility and size, and corticospinal excitability in an accomplished, competitive powerlifter (best competition squat = 205.0 kg, deadlift = 262.7 kg) with a unilateral, transtibial amputation relative to amputee controls. Four men (age range = 23-49 years) with unilateral, lower-limb amputation (3 transtibial, 1 transfemoral) participated in 1 laboratory visit. We assessed 10-m gait speed, the timed up and go (TUG) test, 5-time sit-to-stand performance (5TSTS), contractile properties of the vastus lateralis (VL) and medial gastrocnemius by tensiomyography, and VL cross-sectional area (CSA) by ultrasonography. Unilateral assessments for the intact limb included isokinetic knee extension and flexion torque and power and transcranial magnetic stimulation derived corticospinal excitability. An interview with the powerlifter provided contextual perspective. Compared with the control subjects, the powerlifter performed the 5TSTS faster (6.8%), exhibited faster VL contraction times (intact limb = 12.2%; residual limb = 23.9%), and showed larger VL CSA for the intact limb (46.7%). The powerlifter exhibited greater knee extension and flexion peak torque and mean power, particularly at 180°·s -1 , as well as greater corticospinal excitability for the intact VL (65.6%) and tibialis anterior (79.6%). By contrast, the control subjects were faster in the TUG (18.3%) and comfortable (13.0%) and fast (21.4%) in the 10-m walk test. The major themes of our interview included needing to modify lifting mechanics, persistence, and remarkable pain tolerance. Our findings highlight the impressive neuromuscular adaptations that are attainable after lower-limb amputation.

Effect of meniscus modelling assumptions in a static tibiofemoral finite element model: importance of geometry over material.

Finite element studies of the tibiofemoral joint have increased use in research, with attention often placed on the material models. Few studies assess the effect of meniscus modelling assumptions in image-based models on contact mechanics outcomes. This work aimed to assess the effect of modelling assumptions of the meniscus on knee contact mechanics and meniscus kinematics. A sensitivity analysis was performed using three specimen-specific tibiofemoral models and one generic knee model. The assumptions in representing the meniscus attachment on the tibia (shape of the roots and position of the attachment), the material properties of the meniscus, the shape of the meniscus and the alignment of the joint were evaluated, creating 40 model instances. The values of material parameters for the meniscus and the position of the root attachment had a small influence on the total contact area but not on the meniscus displacement or the force balance between condyles. Using 3D shapes to represent the roots instead of springs had a large influence in meniscus displacement but not in knee contact area. Changes in meniscus shape and in knee alignment had a significantly larger influence on all outcomes of interest, with differences two to six times larger than those due to material properties. The sensitivity study demonstrated the importance of meniscus shape and knee alignment on meniscus kinematics and knee contact mechanics, both being more important than the material properties or the position of the roots. It also showed that differences between knees were large, suggesting that clinical interpretations of modelling studies using single geometries should be avoided.

A framework based on subject-specific musculoskeletal models and Monte Carlo simulations to personalize muscle coordination retraining.

Excessive loads at lower limb joints can lead to pain and degenerative diseases. Altering joint loads with muscle coordination retraining might help to treat or prevent clinical symptoms in a non-invasive way. Knowing how much muscle coordination retraining can reduce joint loads and which muscles have the biggest impact on joint loads is crucial for personalized gait retraining. We introduced a simulation framework to quantify the potential of muscle coordination retraining to reduce joint loads for an individuum. Furthermore, the proposed framework enables to pinpoint muscles, which alterations have the highest likelihood to reduce joint loads. Simulations were performed based on three-dimensional motion capture data of five healthy adolescents (femoral torsion 10°-29°, tibial torsion 19°-38°) and five patients with idiopathic torsional deformities at the femur and/or tibia (femoral torsion 18°-52°, tibial torsion 3°-50°). For each participant, a musculoskeletal model was modified to match the femoral and tibial geometry obtained from magnetic resonance images. Each participant's model and the corresponding motion capture data were used as input for a Monte Carlo analysis to investigate how different muscle coordination strategies influence joint loads. OpenSim was used to run 10,000 simulations for each participant. Root-mean-square of muscle forces and peak joint contact forces were compared between simulations. Depending on the participant, altering muscle coordination led to a maximum reduction in hip, knee, patellofemoral and ankle joint loads between 5 and 18%, 4% and 45%, 16% and 36%, and 2% and 6%, respectively. In some but not all participants reducing joint loads at one joint increased joint loads at other joints. The required alteration in muscle forces to achieve a reduction in joint loads showed a large variability between participants. The potential of muscle coordination retraining to reduce joint loads depends on the person's musculoskeletal geometry and gait pattern and therefore showed a large variability between participants, which highlights the usefulness and importance of the proposed framework to personalize gait retraining.

Cortical bone adaptation response is region specific, but not peak load dependent: insights from µ CT image analysis and mechanostat simulations of the mouse tibia loading model.

The two major aims of the present study were: (i) quantify localised cortical bone adaptation at the surface level using contralateral endpoint imaging data and image analysis techniques, and (ii) investigate whether cortical bone adaptation responses are universal or region specific and dependent on the respective peak load. For this purpose, we re-analyse previously published µ CT data of the mouse tibia loading model that investigated bone adaptation in response to sciatic neurectomy and various peak load magnitudes (F = 0, 2, 4, 6, 8, 10, 12 N). A beam theory-based approach was developed to simulate cortical bone adaptation in different sections of the tibia, using longitudinal strains as the adaptive stimuli. We developed four mechanostat models: universal, surface-based, strain directional-based, and combined surface and strain direction-based. Rates of bone adaptation in these mechanostat models were computed using an optimisation procedure (131,606 total simulations), performed on a single load case (F = 10 N). Subsequently, the models were validated against the remaining six peak loads. Our findings indicate that local bone adaptation responses are quasi-linear and bone region specific. The mechanostat model which accounted for differences in endosteal and periosteal regions and strain directions (i.e. tensile versus compressive) produced the lowest root mean squared error between simulated and experimental data for all loads, with a combined prediction accuracy of 76.6, 55.0 and 80.7% for periosteal, endosteal, and cortical thickness measurements (in the midshaft of the tibia). The largest root mean squared errors were observed in the transitional loads, i.e. F = 2 to 6 N, where inter-animal variability was highest. Finally, while endpoint imaging studies provide great insights into organ level bone adaptation responses, the between animal and loaded versus control limb variability make simulations of local surface-based adaptation responses challenging.

Combining PTH(1-34) and mechanical loading has increased benefit to tibia bone mechanics in ovariectomised mice.

Combined treatment with PTH(1-34) and mechanical loading confers increased structural benefits to bone than monotherapies. However, it remains unclear how this longitudinal adaptation affects the bone mechanics. This study quantified the individual and combined longitudinal effects of PTH(1-34) and mechanical loading on the bone stiffness and strength evaluated in vivo with validated micro-finite element (microFE) models. C57BL/6 mice were ovariectomised at 14-week-old and treated either with injections of PTH(1-34), compressive tibia loading or both interventions concurrently. Right tibiae were in vivo microCT-scanned every 2 weeks from 14 until 24-week-old. MicroCT images were rigidly registered to reference tibia and the cortical organ level (whole bone) and tissue level (midshaft) morphometric properties and bone mineral content were quantified. MicroCT images were converted into voxel-based homogeneous, linear elastic microFE models to estimate the bone stiffness and strength. This approach allowed us for the first time to quantify the longitudinal changes in mechanical properties induced by combined treatments in a model of accelerated bone resorption. Both changes of stiffness and strength were higher with co-treatment than with individual therapies, consistent with increased benefits with the tibia bone mineral content and cortical area, properties strongly associated with the tibia mechanics. The longitudinal data shows that the two bone anabolics, both individually and combined, had persistent benefit on estimated mechanical properties, and that benefits (increased stiffness and strength) remained after treatment was withdrawn.

Cortical thickness adaptation to combined mechanical loading and parathyroid hormone treatments is site specific and synergistic in the mouse tibia model.

In this study, we aimed to quantify the localised effects of mechanical loading (ML), low (20 µg/kg/day), moderate (40 µg/kg/day) or high (80 µg/kg/day) dosages of parathyroid hormone (PTH), and combined (PTHML) treatments on cortical bone adaptation in healthy 19-week old female C57BL/6 mice. To this end, we utilise a previously reported image analysis algorithm on µCT data of the mouse tibia published by Sugiyama et al. (2008) to measure changes in cortical area, marrow cavity area and local cortical thickness measures (ΔCt.Ar, ΔMa.Ar, ΔCt.Th respectively), evaluated at two cross-sections within the mouse tibia (proximal-middle (37 %) and middle (50 %)), and are compared to a superposed summation (P + M) of individual treatments to determine the effectiveness of combining treatments in vivo. ΔCt.Ar analysis revealed a non-linear, synergistic interactions between PTH and ML in the 37 % cross-section that saturates at higher PTH dosages, whereas the 50 % cross-section experiences an approximately linear, additive adaptation response. This coincided with an increase in ΔMa.Ar (indicating resorption of the endosteal surface), which was only counteracted by combined high dose PTH with ML in the middle cross-section. Regional analysis of ΔCt.Th changes reveal localised cortical thinning in response to low dose PTH treatment in the posteromedial region of the middle cross-section, signifying that PTH does not provide a homogeneous adaptation response around the cortical perimeter. We observe a synergistic response in the proximal-middle cross-section, with regions of compressive strain experiencing the greatest adaptation response to PTHML treatments, (peak ΔCt.Th of 189.32, 213.78 and 239.30 µm for low, moderate and high PTHML groups respectively). In contrast, PTHML treatments in the middle cross-section show a similar response to the superposed P + M group, with the exception of the combined high dose PTHML treatment which shows a synergistic interaction. These analyses suggest that, in mice, adding mechanical loading to PTH treatments leads to region specific bone responses; synergism of PTHML is only achieved in some regions experiencing high loading, while other regions respond additively to this combined treatment.

Comparing three generic musculoskeletal models to estimate the tibiofemoral reaction forces during gait and sit-to-stand tasks.

The choice of musculoskeletal (MSK) model is crucial for performing MSK estimations to evaluate muscle demands and joint forces. This study compared two previously published generic MSK models and a modified model to estimate tibiofemoral reaction forces (TFRF) during gait, sit-to-stand, and stand-to-sit. The estimated tibiofemoral reaction forces were compared with an in vivo dataset from six patients using an instrumented knee prosthesis. A correlation and root mean square error (RMSE) in the time-series analysis and relative peak error (RPE) were evaluated. The results showed that the three MSK models were similar in estimating the vertical forces, with a large correlation, and RPE was found around 20 % during gait. The RMSE and the RPE indicated that the modified model had lower total and lateral compartment forces errors for sit-to-stand and stand-to-sit, showing the best performance. The shear forces for all tasks and models showed significant errors. Future MSK studies should consider these findings when researching functional tasks. The modified model was found to be more effective in estimating the vertical tibiofemoral joint reaction forces in tasks that impose greater demands on muscle forces and require high knee and hip flexion.