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.

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.

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.

Comparison of Motion Grading in 1,000 Patients by First- and Second-Generation HR-pQCT: A Propensity Score Matched Cohort Study.

In-vivo bone microstructure measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) is gaining importance in research and clinical practice. Second-generation HR-pQCT (XCT2) shows improved image quality and shorter measurement duration compared to the first generation (XCT1). Predicting and understanding the occurrence of motion artifacts is crucial for clinical practice. We retrospectively analyzed data from HR-pQCT measurements at the distal radius and tibia of 1,000 patients (aged 20 to 89) evenly distributed between both generations of HR-pQCT. Motion artifacts were graded between 1 (no motion) and 5 (severe motion), with grades greater 3 considered unusable. Additionally, baseline characteristics and patients' muscle performance and balance were measured. Various group comparisons between the two generations of HR-pQCT and regression analyses between patient characteristics and motion grading were performed. The study groups of XCT1 and XCT2 did not differ by age (XCT1: 64.9 vs. XCT2: 63.8 years, p = 0.136), sex (both 74.5% females, p > 0.999), or BMI (both 24.2 kg/m2, p = 0.911) after propensity score matching. XCT2 scans exhibited significantly lower motion grading in both extremities compared to XCT1 (Radius: p < 0.001; Tibia: p = 0.002). In XCT2 motion-corrupted scans were more than halved at the radius (XCT1: 35.3% vs. XCT2: 15.5%, p < 0.001), and at the tibia the frequency of best image quality scans was increased (XCT1: 50.2% vs. XCT2: 63.7%, p < 0.001). The strongest independent predictor for motion-corrupted images is the occurrence of high motion grading at the other scanning site during the same consultation. The association between high motion grading in one scan and a corresponding high motion grading in another scan within the same session suggests a non-resting patient. Additionally, aged, female, and patients with smaller stature tend towards higher motion grading, requiring special attention to a correct extremity fixation.

Runners' responses to a biofeedback intervention aimed to reduce tibial acceleration differ within and between individuals.

An increment in peak tibial acceleration (PTA) may be related to an increased risk of running-rated injury. Many authors believe that reducing PTA through improved shock-absorption could, therefore, help prevent injury. The aim of the current study was, therefore, to investigate the individual responses of participants to a biofeedback intervention aimed at reducing PTA.11 participants (two females, nine males; 43 ±â€¯10 years; stature: 1.74 ±â€¯0.07 m; body mass: 74 ±â€¯11 kg; distance running a week: 19 ±â€¯14 km; 5 km time: 24 ±â€¯3 min) received an intervention of six sessions of multisensory biofeedback aimed at reducing PTA. Mean PTA and kinematic patterns were measured at baseline, directly after the feedback intervention and a month after the end of the intervention. Group as well as single-subject analyses were performed to quantify differences between the sessions. A significant decrease of 26 per cent (effect size: Hedges' g = 0.94) in mean PTA was found a month after the intervention. No significant changes or large effect sizes were found for any group differences in the kinematic variables. However, on an individual level, shock-absorbing solutions differed both within and between participants. The data suggest participants did not learn a specific solution to reduce PTA but rather learned the concept of reducing PTA. These results suggest future research in gait retraining should investigate individual learning responses and focus on the different strategies participants use both between and within sessions. For training purposes, participants should not focus on learning one running strategy, but they should explore several strategies.

Elasticity and material anisotropy of lamellar cortical bone in adult bovine tibia characterized via AFM nanoindentation.

The research focuses on the evaluation of the mechanical properties of osteonal cortical bone at the lamellar level. Elastic properties of the mid-diaphysis region of the bovine tibia are investigated via cantilever-based nanoindentation at the submicron length scale utilizing Atomic Force Microscopy, where the force-displacement curves are used for the elastic assessment using the Derjaguin-Muller-Toropov model to calculate indentation modulus. Variations of the modulus and the directional mechanical response of the osteonal bone at different distances from the Haversian canal are investigated. Additionally, the effects of demineralization on the indentation modulus are discussed. It was found that in the axial direction, the first and last untreated thick lamella layers show a significant indentation modulus difference compared to all other layers (4.26 ± 0.4 and 4.6 ± 0.3 GPa vs ∼3.5 GPa). On the other hand, the indentation modulus of transverse thick lamella layers shows a periodic variation between ∼3 ± 0.7 GPa and ∼4 ± 0.3 GPa from near the Haversian canal to near the interstitial bone. A periodic variation in the anisotropy ratio was found. Mineral content was quantified via energy-dispersive X-ray microanalysis at different levels of mineralization and shows a positive correlation with the indentation modulus.

Investigation of Characteristic Motion Patterns of the Knee Joint During a Weightbearing Flexion.

This study aimed to develop and validate a novel flexion axis concept by calculating the points on femoral condyles that could maintain constant heights during knee flexion. Twenty-two knees of 22 healthy subjects were investigated when performing a weightbearing single leg lunge. The knee positions were captured using a validated dual fluoroscopic image system. The points on sagittal planes of the femoral condyles that had minimal changes in heights from the tibial plane along the flexion path were calculated. It was found that the points do formulate a medial-lateral flexion axis that was defined as the iso-height axis (IHA). The six degrees of freedom (6DOF) kinematics data calculated using the IHA were compared with those calculated using the conventional transepicondylar axis and geometrical center axis. The IHA measured minimal changes in proximal-distal translations and varus-valgus rotations along the flexion path, indicating that the IHA may have interesting clinical implications. Therefore, identifying the IHA could provide an alternative physiological reference for improvement of contemporary knee surgeries, such as ligament reconstruction and knee replacement surgeries that are aimed to reproduce normal knee kinematics and medial/lateral soft tissue tensions during knee flexion.

Comparison of muscle activity of hamstrings as knee flexors and hip extensors and effect of tibial and hip rotation on the contribution of hamstrings.

BACKGROUND: Limited studies have compared the muscle activity of the medial and lateral hamstrings as knee flexors with tibial internal and external rotation and hip extensors with hip internal and external rotation. In particular, hamstring activity during hip extension with hip rotation has rarely been investigated. OBJECTIVE: This study aimed to compare the muscle activity of the medial and lateral hamstrings as knee flexors and hip extensors and to compare the activity of these muscles according to tibial rotation during isometric knee flexion and hip rotation during isometric hip extension. METHODS: A total of 23 healthy adults participated in the study. The electromyographic (EMG) activity of the hamstrings was measured during maximal isometric knee flexion and maximal isometric hip extension. In addition, tibial rotation was applied actively during maximal isometric knee flexion, whereas hip rotation was applied actively during maximal isometric hip extension. RESULTS: EMG activity during maximal isometric knee flexion with tibial internal and external rotation was significantly higher than that during maximal isometric hip extension with hip internal and external rotation, respectively. For EMG activity according to tibial and hip rotation, there was no significant difference between tibial internal and external rotation during maximal isometric knee flexion, whereas there was a significant difference between hip internal and external rotation during maximal isometric hip extension. CONCLUSION: Hamstring activity was higher for knee flexors than for hip extensors. However, hip rotation during maximal isometric hip extension is an effective intervention for selective muscle activation of the medial and lateral hamstrings.

The effects of myostatin mutation on the tibia bone quality in female Japanese quail before and after sexual maturation.

In the modern layer industry, improvement of bone quality is one of the prior tasks to solve from economic and welfare standpoints. In addition to nutritional and environmental factors, genetic factors have been considered major factors regulating bone quality in layers but are yet to be fully investigated due to limitations on available animal models. Initially, the myostatin (MSTN) gene was genetically edited in quail to investigate the effect of MSTN mutation on economic traits in meat producing poultry species. In the current study, the function of the MSTN gene on regulation of bone quality in layers was investigated using MSTN mutant female quail as an animal model. Tibia bones were collected from wild-type (WT) and MSTN mutant female quail at 5 wk old and 4 mo old, representing prelaying and actively laying stages, respectively. Left tibia bones were analyzed by microcomputed tomography scanning to evaluate the architectural characteristics, while bone breaking strength (BBS) was measured using right tibia bones. At 5 wk of age, MSTN mutant female quail showed higher BBS and values on parameters related to bone quality such as bone mineral contents (BMC), bone mineral density (BMD), bone volume (BV), and/or trabecular bone thickness in whole diaphysis, whole metaphysis, and metaphyseal trabecular bone, compared to WT female quail. Although BBS and BMD became similar between the 2 groups at 4 mo of age, higher TV and TS in whole metaphysis and higher BMC and TV in whole diaphysis of MSTN mutant group compared to those of WT group suggested that the improved tibia bone quality by MSTN mutation before sexual maturation lasted to a certain degree even after sexual maturation. The use of the MSTN mutant female model provided new insights into genetic regulation on female quail bone quality depending on physiological changes.

Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis.

Rodent hindlimb unloading (HU) model was developed to elucidate responses/mechanisms of adverse consequences of space weightlessness. Multipotent mesenchymal stromal cells (MMSCs) were isolated from rat femur and tibia bone marrows and examined ex vivo after 2 weeks of HU and subsequent 2 weeks of restoration of load (HU + RL). In both bones, decrease of fibroblast colony forming units (CFU-f) after HU with restoration after HU + RL detected. In CFU-f and MMSCs, levels of spontaneous/induced osteocommitment were similar. MMSCs from tibia initially had greater spontaneous mineralization of extracellular matrix but were less sensitive to osteoinduction. There was no recovery of initial levels of mineralization in MMSCs from both bones during HU + RL. After HU, most bone-related genes were downregulated in tibia or femur MMSCs. After HU + RL, the initial level of transcription was restored in femur, while downregulation persisted in tibia MMSCs. Therefore, HU provoked a decrease of osteogenic activity of BM stromal precursors at transcriptomic and functional levels. Despite unidirectionality of changes, the negative effects of HU were more pronounced in stromal precursors from distal limb-tibia. These observations appear to be on demand for elucidation of mechanisms of skeletal disorders in astronauts in prospect of long-term space missions.

Impact loading intensifies cortical bone (re)modeling and alters longitudinal bone growth of pubertal rats.

Physical exercise is important for musculoskeletal development during puberty, which builds bone mass foundation for later in life. However, strenuous levels of training might bring adverse effects to bone health, reducing longitudinal bone growth. Animal models with various levels of physical exercise were largely used to provide knowledge to clinical settings. Experiments from our previous studies applied different levels of mechanical loading on rat tibia during puberty accompanied by weekly in vivo micro-CT scans. In the present article, we apply 3D image registration-based methods to retrospectively analyze part of the previously acquired micro-CT data. Longitudinal bone growth, growth plate thickness, and cortical bone (re)modeling were evaluated from rats' age of 28-77 days. Our results show that impact loading inhibited proximal bone growth throughout puberty. We hypothesize that impact loading might bring different growth alterations to the distal and proximal growth plates. High impact loading might lead to pathological consequence of osteochondrosis and catch-up growth due to growth inhibition. Impact loading also increased cortical bone (re)modeling before and after the peak proximal bone growth period of young rats, of which the latter case might be caused by the shift from modeling to remodeling as the dominant activity toward the end of rat puberty. We confirm that the tibial endosteum is more mechano-sensitive than the periosteum in response to mechanical loading. To our knowledge, this is the first study to follow up bone growth and bone (re)modeling of young rats throughout the entire puberty with a weekly time interval.

Regional modular responses in different bone compartments to the anabolic effect of PTH (1-34) and axial loading in mice.

Beneficial effects of intermittent parathyroid hormone (PTH) on bone mass and architecture are described to either simply add to, or to synergise with those of mechanical loading. We evaluate whether interaction with in vivo loading is reinforced by PTH dosing regimen and exhibits compartment-specific sensitivities. Female 12-week-old C57Bl6 mice received daily (7/7) or interrupted 5 day/week (5/7) PTH for 3 weeks (two vehicle groups). All mice had six loading episodes (12N) applied to right tibia (left, non-loaded) for the last 2 weeks. Micro-CT scans were used to evaluate mass and architecture in almost the entire cortical and proximal trabecular regions. Epiphyseal cortical, trabecular and marrow space volumes, and bony growth-plate bridge incidence were evaluated. Statistical analyses employed a linear mixed-effects model at each percentile and 2-way ANOVA with post-hoc test for epiphyses and bridging. We found that daily PTH enhances cortical mass and modifies shape along almost the entire tibia and that these effects are partly mitigated by brief interruption in treatment. Mechanical loading alone augments cortical mass and modifies shape but only in a region proximal to the tibiofibular junction. The effect of combining load and daily PTH dosing is solely additive for cortical bone mass with no significant load: PTH interaction, but exhibits clear synergy with interrupted PTH treatment. Daily, not interrupted PTH stimulates trabecular bone gains, yet load:PTH interaction is present at limited regions with both daily and interrupted treatment. PTH treatment, but not loading, modifies epiphyseal bone but, in contrast, only loading modifies bridge number and areal density. Our findings demonstrate impressive local effects on tibial mass and shape of combined loading and PTH that are sensitive to dosing regimen and exert their effects modularly. These findings emphasise a need to clarify PTH dosing regimens and that advantages could be accrued by aligning treatment accordingly to patient requirements and life-style.

Joint Coordinate System Using Functional Axes Achieves Clinically Meaningful Kinematics of the Tibiofemoral Joint as Compared to the International Society of Biomechanics Recommendation.

Quantification of clinically meaningful tibiofemoral motions requires a joint coordinate system (JCS) with motions free from kinematic crosstalk errors. The objectives were to use a JCS with literature-backed functional axes (FUNC) and a JCS recommended by the International Society of Biomechanics (ISB) to determine tibiofemoral kinematics of the native (i.e., healthy) knee, determine variability associated with each JCS, and determine whether the FUNC JCS significantly reduced kinematic crosstalk errors compared to the ISB JCS. Based on a kinematic model consisting of a three-cylindric joint chain, the FUNC JCS included functional flexion-extension (F-E) and internal-external (I-E) tibial rotation axes. In contrast, the ISB JCS included F-E and I-E axes defined using anatomic landmarks. Single-plane fluoroscopic images in 13 subjects performing a weighted deep knee bend were analyzed. Tibiofemoral kinematics using the FUNC JCS fell within the physiological range of motion in all six degrees-of-freedom. Internal tibial rotation averaged 13 deg for the FUNC JCS versus 10 deg for the ISB JCS and motions in the other four degrees-of-freedom (collectively termed off-axis motions) were minimal as expected based on biomechanical constraints. Off-axis motions for the ISB JCS were significantly greater; maximum valgus rotation was 4 deg and maximum anterior and distraction translations were 9 mm and 25 mm, respectively, which is not physiologic. Variabilities in off-axis motions were significantly greater with the ISB JCS (p < 0.0002). The FUNC JCS achieved clinically meaningful kinematics by significantly reducing kinematic crosstalk errors and is the more suitable coordinate system for quantifying tibiofemoral motions.

Effect of light intensity on growth performance and bone development of tibia in broilers.

Light management affects the health outcomes and growth performance of broiler chickens. However, the effects of different light intensities on growth performance and its association with tibia development of broilers remain unclear. In the present study, 462 Ross male broilers were divided into seven treatment groups with 6 replicates (11 birds per replicate), and then were subjected to different light intensity levels (0.5, 2, 5, 7, 9, 13 or 19 Lx) for 42 days. The results demonstrated that broilers under lower light intensity (2, 5Lx) obtained higher body weight (p < 0.05) and feed conversion ratio (p < 0.05). Lower light intensity exposure had no effects on the length, width, weight, breaking strength and the mineral density of the tibia (p > 0.05), but led to increased ash content and phosphorus during the starter phase (p < 0.05). Also, plasma levels of calcium (Ca), phosphorus (P) and alkaline phosphatase were increased in response to lower light intensity conditions (p < 0.05), but decreased under higher light intensity (p < 0.05), indicating dynamic mineral metabolic and depositional activity to light intensity. In addition, broilers exposed to lower intensity (0.5 Lx, 2 Lx and 5 Lx) during the starter phase had decreased hypertrophic chondrocytes (p < 0.05), but did not affect resting zone chondrocytes and proliferative chondrocytes of the growth plate (p > 0.05). In contrast, the light intensity did not affect the growth performance and the development of the tibia of broilers during the finishing phase. In summary, we demonstrated that lower light intensity promoted the growth performance and the bone development of broilers. Application of lower light intensity at the starter phase might be a management strategy for broiler industries.

Prediction of cortical bone mineral apposition rate in response to loading using an adaptive neuro-fuzzy inference system.

Daily activities such as aerobic movements and athletic events found effective in mitigating bone loss as it promotes osteogenesis. Computational model considered normal strain, or strain energy density as a stimulus to predict site specific osteogenesis. This model, however, fails to predict site specific osteogenesis as cortical bone surfaces exhibit different remodelling rate to mechanical loading. Remodelling rate or mineral apposition rate depends upon the loading parameters such as loading cycle, frequency, and magnitude of strain. Therefore, the present study aims to develop an adaptive neuro-fuzzy inference system (ANFIS) model for finding a robust relationship between loading parameters like strain magnitude, frequency, and cycle, and a bone remodelling parameter i.e. mineral apposition rate (MAR). The model is trained, tested, and checked with the experimental data. The results indicate that ANFIS model outperformed state of the art Artificial Neural Network (ANN) models during the prediction of MAR at periosteal and endosteal surface. A strong corelation R2 = 0.92 and R2 = 0.97 was observed at 70% of the input data at periosteal and endosteal surface respectively. Result concludes that endosteal surface was more promisable as compared to periosteal surface in predicting accurate MAR. The outcomes of present study may be used to precisely predict site-specific osteogenesis in cortical bone as function of loading parameters.

Determine the vertical ground reaction forces and knee mechanics with different gait inclinations in the sheep model.

Our current understanding of knee mechanics and anterior cruciate ligament (ACL) function is predominately based on data recorded during simulations of clinical examinations or the application of nonphysiologic loads and motions. These methodologies provide little information on knee and ACL mechanics during activities of daily living (ADLs). Additionally, researchers have not directly measured knee kinetics, knee contact pressures, and ACL forces, and it is unknown how these parameters change with different activities. This study quantified the effects of activity level on vertical ground reaction forces, knee kinematics, and joint and ligament forces during in vivo motions. Five female Suffolk sheep were walked twice weekly on a treadmill during level (0°), inclined (+6°), and declined (-6°) gait for 12 weeks. Electromagnetic (EM) trackers were surgically implanted onto the left distal femur and the left proximal tibia, and in vivo motions were recorded for all activities. Following sacrifice, the in vivo motions were applied to their respective knees using a serial robot with a multi-axis load cell. In vitro simulations were repeated to measure (a) total knee forces, (b) contact pressure maps, and (c) ACL-only forces. Declining the gait surface led to increased posterior translation during the swing phase and decreased flexion at hoof-strike, decreased medial contact pressure at push-off, decreased ACL force at hoof-strike and increased ACL force at push-off. This study established a system that can be used to examine knee mechanics and ACL forces during ADLs for different knee states to define design requirements for ACL reconstruction techniques.

PTH Treatment Increases Cortical Bone Mass More in Response to Compression than Tension in Mice.

Parathyroid hormone (PTH) is an anabolic osteoporosis treatment that increases bone mass and reduces fracture risk. Clinically, the effects of PTH are site-specific, increasing bone mass more at the spine than the hip and not increasing bone mass at the radius. Differences in local loading environment between the spine, hip, and radius may help explain the variation in efficacy, as PTH and mechanical loading have been shown to synergistically increase bone mass. We hypothesized that differences in loading mode might further explain these variations. Owing to the curvature of the mouse tibia, cyclic compression of the hindlimb causes bending at the tibial midshaft, placing the anterior surface under tension and the posterior surface under compression. We investigated the combination of PTH treatment and tibial loading in an osteoblast-specific estrogen receptor-alpha knockout mouse model of low bone mass (pOC-ERαKO) and their littermate controls (LCs) and analyzed bone morphology in the tensile, compressive, and neutral regions of the tibial midshaft. We also hypothesized that pretreating wild-type C57Bl/6J (WT) mice with PTH prior to mechanical loading would enhance the synergistic anabolic effects. Compression was more anabolic than tension, and PTH enhanced the effect of loading, particularly under compression. PTH pretreatment maintained the synergistic anabolic effect for longer durations than concurrent treatment and loading alone. Together these data provide insights into more effective physical therapy and exercise regimens for patients receiving PTH treatment. © 2022 American Society for Bone and Mineral Research (ASBMR).

Skeletal Effects of Sleeve Gastrectomy in Adolescents and Young Adults: A 2-Year Longitudinal Study.

CONTEXT: Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health. OBJECTIVE: This work aimed to evaluate the effect of VSG on bone health in youth. METHODS: An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture. RESULTS: VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls. CONCLUSION: VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.