Impact of the Autonomic Nervous System on the Skeleton.

It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton transitioned from a mere histological observation to the mechanism whereby neurons of the central nervous system communicate with cells of the bone microenvironment and regulate bone homeostasis. This shift in paradigm sparked new preclinical and clinical investigations aimed at defining the contribution of sympathetic, parasympathetic, and sensory nerves to the process of bone development, bone mass accrual, bone remodeling, and cancer metastasis. The aim of this article is to review the data that led to the current understanding of the interactions between the autonomic and skeletal systems and to present a critical appraisal of the literature, bringing forth a schema that can put into physiological and clinical context the main genetic and pharmacological observations pointing to the existence of an autonomic control of skeletal homeostasis. The different types of nerves found in the skeleton, their functional interactions with bone cells, their impact on bone development, bone mass accrual and remodeling, and the possible clinical or pathophysiological relevance of these findings are discussed.

Early versus delayed weight-bearing following operatively treated ankle fracture (WAX): a non-inferiority, multicentre, randomised controlled trial.

BACKGROUND: After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early weight-bearing) might be a safe and preferable rehabilitation strategy. This study aimed to determine the clinical and cost effectiveness of an early weight-bearing strategy compared with a delayed weight-bearing strategy. METHODS: This was a pragmatic, multicentre, randomised, non-inferiority trial including 561 participants (aged ≥18 years) who received acute surgery for an unstable ankle fracture in 23 UK National Health Service (NHS) hospitals who were assigned to either a delayed weight-bearing (n=280) or an early weight-bearing rehabilitation strategy (n=281). Patients treated with a hindfoot nail, those who did not have protective ankle sensation (eg, peripheral neuropathy), did not have the capacity to consent, or did not have the ability to adhere to trial procedures were excluded. Neither participants nor clinicians were masked to the treatment. The primary outcome was ankle function measured using the Olerud and Molander Ankle Score (OMAS) at 4 months after randomisation, in the per-protocol population. The pre-specified non-inferiority OMAS margin was -6 points and superiority testing was included in the intention-to-treat population in the event of non-inferiority. The trial was prospectively registered with ISRCTN Registry, ISRCTN12883981, and the trial is closed to new participants. FINDINGS: Primary outcome data were collected from 480 (86%) of 561 participants. Recruitment was conducted between Jan 13, 2020, and Oct 29, 2021. At 4 months after randomisation, the mean OMAS score was 65·9 in the early weight-bearing and 61·2 in the delayed weight-bearing group and adjusted mean difference was 4·47 (95% CI 0·58 to 8·37, p=0·024; superiority testing adjusted difference 4·42, 95% CI 0·53 to 8·32, p=0·026) in favour of early weight-bearing. 46 (16%) participants in the early weight-bearing group and 39 (14%) in the delayed weight-bearing group had one or more complications (adjusted odds ratio 1·18, 95% CI 0·80 to 1·75, p=0·40). The mean costs from the perspective of the NHS and personal social services in the early and delayed weight-bearing groups were £725 and £785, respectively (mean difference -£60 [95% CI -342 to 232]). The probability that early weight-bearing is cost-effective exceeded 80%. INTERPRETATION: An early weight-bearing strategy was found to be clinically non-inferior and highly likely to be cost-effective compared with the current standard of care (delayed weight-bearing). FUNDING: National Institute for Health and Care Research (NIHR), NIHR Barts Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley.

Structural and molecular characteristics of weight-bearing volar skin can be reconstituted by micro skin tissue column grafting.

For patients with lower limb amputations, prostheses are immensely helpful for mobility and the ability to perform job-related or recreational activities. However, the skin covering the amputation stump is typically transposed from adjacent areas of the leg and lacks the weight-bearing capacity that is only found in the specialized skin covering the palms and soles (a.k.a. volar skin). As a result, the skin tissue in direct contact with the prosthesis frequently breaks down, leading to the development of painful sores and other complications that limit, and often preclude, the use of prostheses. Transplanting volar skin onto amputation stumps could be a solution to these problems, but traditional skin transplantation techniques cause substantial morbidity at the donor site, such as pain and scarring, which are especially problematic for volar skin given the critical functional importance of the volar skin areas. We previously developed the technology to collect and engraft full-thickness skin tissue while avoiding long-term donor site morbidity, by harvesting the skin in the form of small (~0.5 mm diameter) cores that we termed "micro skin tissue columns" (MSTCs), so that each donor wound is small enough to heal quickly and without clinically appreciable scarring or other long-term abnormalities. The goal of this study was to establish whether a similar approach could be used to confer the structural and molecular characteristics of volar skin ectopically to other skin areas. In a human-to-mouse xenograft model, we show the long-term persistence of various human plantar MSTC-derived cell types in the murine recipient. Then in an autologous porcine model, we harvested MSTCs from the bottom of the foot and transplanted them onto excision wounds on the animals' trunks. The healing processes at both the donor and graft sites were monitored over 8 weeks, and tissue samples were taken to verify volar-specific characteristics by histology and immunohistochemistry. The volar donor sites were well-tolerated, healed rapidly, and showed no signs of scarring or any other long-term defects. The graft sites were able to maintain volar-specific histologic features and expression of characteristics protein markers, up to the 8-week duration of this study. These results suggest that MSTC grafting could be a practical approach to obtain autologous donor volar skin tissue, confer volar skin characteristics ectopically to nonvolar skin areas, improve the load-bearing capacity of amputation stump skin, and ultimately enhance mobility and quality-of-life for lower limb amputees.

Foot callus thickness does not trade off protection for tactile sensitivity during walking.

Until relatively recently, humans, similar to other animals, were habitually barefoot. Therefore, the soles of our feet were the only direct contact between the body and the ground when walking. There is indirect evidence that footwear such as sandals and moccasins were first invented within the past 40 thousand years1, the oldest recovered footwear dates to eight thousand years ago2 and inexpensive shoes with cushioned heels were not developed until the Industrial Revolution3. Because calluses-thickened and hardened areas of the epidermal layer of the skin-are the evolutionary solution to protecting the foot, we wondered whether they differ from shoes in maintaining tactile sensitivity during walking, especially at initial foot contact, to improve safety on surfaces that can be slippery, abrasive or otherwise injurious or uncomfortable. Here we show that, as expected, people from Kenya and the United States who frequently walk barefoot have thicker and harder calluses than those who typically use footwear. However, in contrast to shoes, callus thickness does not trade-off protection, measured as hardness and stiffness, for the ability to perceive tactile stimuli at frequencies experienced during walking. Additionally, unlike cushioned footwear, callus thickness does not affect how hard the feet strike the ground during walking, as indicated by impact forces. Along with providing protection and comfort at the cost of tactile sensitivity, cushioned footwear also lowers rates of loading at impact but increases force impulses, with unknown effects on the skeleton that merit future study.

Self-assembled nanocomposites of high water content and load-bearing capacity.

Biological tissues, such as cartilage, tendon, ligament, skin, and plant cell wall, simultaneously achieve high water content and high load-bearing capacity. The high water content enables the transport of nutrients and wastes, and the high load-bearing capacity provides structural support for the organisms. These functions are achieved through nanostructures. This biological fact has inspired synthetic mimics, but simultaneously achieving both functions has been challenging. The main difficulty is to construct nanostructures of high load-bearing capacity, characterized by multiple properties, including elastic modulus, strength, toughness, and fatigue threshold. Here we develop a process that self-assembles a nanocomposite using a hydrogel-forming polymer and a glass-forming polymer. The process separates the polymers into a hydrogel phase and a glass phase. The two phases arrest at the nanoscale and are bicontinuous. Submerged in water, the nanocomposite maintains the structure and resists further swelling. We demonstrate the process using commercial polymers, achieving high water content, as well as load-bearing capacity comparable to that of polyethylene. During the process, a rubbery stage exists, enabling us to fabricate objects of complex shapes and fine features. We conduct further experiments to discuss likely molecular origins of arrested phase separation, swell resistance, and ductility. Potential applications of the nanocomposites include artificial tissues, high-pressure filters, low-friction coatings, and solid electrolytes.

Stem integrity in Arabidopsis thaliana requires a load-bearing epidermis.

Because plant cells are glued to each other via their cell walls, failure to coordinate growth among adjacent cells can create cracks in tissues. Here, we find that the unbalanced growth of inner and outer tissues in the clavata3 de-etiolated3 (clv3 det3) mutant of Arabidopsis thaliana stretched epidermal cells, ultimately generating cracks in stems. Stem growth slowed before cracks appeared along clv3 det3 stems, whereas inner pith cells became drastically distorted and accelerated their growth, yielding to stress, after the appearance of cracks. This is consistent with a key role of the epidermis in restricting growth. Mechanical property measurements recorded using an atomic force microscope revealed that epidermal cell wall stiffness decreased in det3 and clv3 det3 epidermises. Thus, we hypothesized that stem integrity depends on the epidermal resistance to mechanical stress. To formally test this hypothesis, we used the DET3 gene as part of a tissue-specific strategy to complement cell expansion defects. Epidermis-driven DET3 expression restored growth and restored the frequency of stem cracking to 20% of the clv3 det3 mutant, demonstrating the DET3-dependent load-bearing role of the epidermis.

Osteochondral fluid transport in an ex vivo system.

OBJECTIVE: Alterations to bone-to-cartilage fluid transport may contribute to the development of osteoarthritis (OA). Larger biological molecules in bone may transport from bone-to-cartilage (e.g., insulin, 5 kDa). However, many questions remain about fluid transport between these tissues. The objectives of this study were to (1) test for diffusion of 3 kDa molecular tracers from bone-to-cartilage and (2) assess potential differences in bone-to-cartilage fluid transport between different loading conditions. DESIGN: Osteochondral cores extracted from bovine femurs (N = 10 femurs, 10 cores/femur) were subjected to either no-load (i.e., pure diffusion), pre-load only, or cyclic compression (5 ± 2% or 10 ± 2% strain) in a two-chamber bioreactor. The bone was placed into the bone compartment followed by a 3 kDa dextran tracer, and tracer concentrations in the cartilage compartment were measured every 5 min for 120 min. Tracer concentrations were analyzed for differences in beginning, peak, and equilibrium concentrations, loading effects, and time-to-peak tracer concentration. RESULTS: Peak tracer concentration in the cartilage compartment was significantly higher compared to the beginning and equilibrium tracer concentrations. Cartilage-compartment tracer concentration and maximum fluorescent intensity were influenced by strain magnitude. No time-to-peak relationship was found between strain magnitudes and cartilage-compartment tracer concentration. CONCLUSION: This study shows that bone-to-cartilage fluid transport occurs with 3 kDa dextran molecules. These are larger molecules to move between bone and cartilage than previously reported. Further, these results demonstrate the potential impact of cyclic compression on osteochondral fluid transport. Determining the baseline osteochondral fluid transport in healthy tissues is crucial to elucidating the mechanisms OA pathology.

Hip contact forces can be predicted with a neural network using only synthesised key points and electromyography in people with hip osteoarthritis.

OBJECTIVE: To develop and validate a neural network to estimate hip contact forces (HCF), and lower body kinematics and kinetics during walking in individuals with hip osteoarthritis (OA) using synthesised anatomical key points and electromyography. To assess the capability of the neural network to detect directional changes in HCF resulting from prescribed gait modifications. DESIGN: A calibrated electromyography-informed neuromusculoskeletal model was used to compute lower body joint angles, moments, and HCF for 17 participants with mild-to-moderate hip OA. Anatomical key points (e.g., joint centres) were synthesised from marker trajectories and augmented with bias and noise expected from computer vision-based pose estimation systems. Temporal convolutional and long short-term memory neural networks (NN) were trained using leave-one-subject-out validation to predict neuromusculoskeletal modelling outputs from the synthesised key points and measured electromyography data from 5 hip-spanning muscles. RESULTS: HCF was predicted with an average error of 13.4 ± 7.1% of peak force. Joint angles and moments were predicted with an average root-mean-square-error of 5.3 degrees and 0.10 Nm/kg, respectively. The NN could detect changes in peak HCF that occur due to gait modifications with good agreement with neuromusculoskeletal modelling (r2 = 0.72) and a minimum detectable change of 9.5%. CONCLUSION: The developed neural network predicted HCF and lower body joint angles and moments in individuals with hip OA using noisy synthesised key point locations with acceptable errors. Changes in HCF magnitude due to gait modifications were predicted with high accuracy. These findings have important implications for implementation of load-modification based gait retraining interventions for people with hip OA in a natural environment (i.e., home, clinic).

Transient receptor potential vanilloid 4 regulates extracellular matrix composition and mediates load-induced intervertebral disc degeneration in a mouse model.

OBJECTIVE: Transient receptor potential vanilloid 4 (TRPV4) is a multi-modally activated cation channel that mediates mechanotransduction pathways by which musculoskeletal tissues respond to mechanical load and regulate tissue health. Using conditional Trpv4 knockout mice, we investigated the role of Trpv4 in regulating intervertebral disc (IVD) health and injury-induced IVD degeneration. METHODS: Col2-Cre;Trpv4fl/f (Trpv4 KO) mice were used to knockout Trpv4 in all type 2 collagen-expressing cells. Effects of gene targeting alone was assessed in lumbar spines, using vertebral bone length measurement, histological, immunohistochemistry and gene expression analyses, and mechanical testing. Disc puncture was performed on caudal IVDs of wild-type (WT) and Trpv4 KO mice at 2.5- and 6.5-months-of-age. Six weeks after puncture (4- and 8-months-of-age at sacrifice), caudal spines were assessed using histological analyses. RESULTS: While loss of Trpv4 did not significantly alter vertebral bone length and tissue histomorphology compared to age-matched WT mice, Trpv4 KO mice showed decreased proteoglycan and PRG4 staining in the annulus fibrosus compared to WT. At the gene level, Trpv4 KO mice showed significantly increased expression of Acan, Bgn, and Prg4 compared to WT. Functionally, loss of Trpv4 was associated with significantly increased neutral zone length in lumbar IVDs. Following puncture, both Trpv4 KO and WT mice showed similar signs of degeneration at the site of injury. Interestingly, loss of Trpv4 prevented mechanically-induced degeneration in IVDs adjacent to sites of injury. CONCLUSION: These studies suggest a role for Trpv4 in regulating extracellular matrix synthesis and mediating the response of IVD tissues to mechanical stress.

The relationship between bone strain index, bone mass, microarchitecture and mechanical behavior in human vertebrae: an ex vivo study.

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.

Adaptive gait responses to varying weight-bearing conditions: Inferences from gait dynamics and H-reflex magnitude.

This study investigates the effects of varying loading conditions on excitability in neural pathways and gait dynamics. We focussed on evaluating the magnitude of the Hoffman reflex (H-reflex), a neurophysiological measure representing the capability to activate motor neurons and the timing and placement of the foot during walking. We hypothesized that weight manipulation would alter H-reflex magnitude, footfall and lower body kinematics. Twenty healthy participants were recruited and subjected to various weight-loading conditions. The H-reflex, evoked by stimulating the tibial nerve, was assessed from the dominant leg during walking. Gait was evaluated under five conditions: body weight, 20% and 40% additional body weight, and 20% and 40% reduced body weight (via a harness). Participants walked barefoot on a treadmill under each condition, and the timing of electrical stimulation was set during the stance phase shortly after the heel strike. Results show that different weight-loading conditions significantly impact the timing and placement of the foot and gait stability. Weight reduction led to a 25% decrease in double limb support time and an 11% narrowing of step width, while weight addition resulted in an increase of 9% in step width compared to body weight condition. Furthermore, swing time variability was higher for both the extreme weight conditions, while the H-reflex reduced to about 45% between the extreme conditions. Finally, the H-reflex showed significant main effects on variability of both stance and swing phases, indicating that muscle-motor excitability might serve as feedback for enhanced regulation of gait dynamics under challenging conditions.

Long-term effects of non-weight bearing and immobilization after anterior cruciate ligament reconstruction on joint contracture formation in rats.

PURPOSE: Non-weight bearing improves and immobilization worsens contracture induced by anterior cruciate ligament reconstruction (ACLR), but effect persistence after reloading and remobilization remains unclear, and the combined effects of these factors on ACLR-induced contracture are unknown. We aimed to determine 1) whether the effects of short-term (2-week) non-weight bearing or immobilization after ACLR on contracture would be sustained by reloading or remobilization during a 10-week observation period, and 2) how the combination of both interventions compared to the outcome of either alone. METHODS: We divided 88 ACL-reconstructed male rats into four groups: non-intervention, non-weight bearing, joint immobilization, and both interventions. Interventions were performed for 2 weeks, followed by rearing without intervention. Twelve untreated rats were used as controls. At 2, 4, and 12 weeks post-surgery, we assessed range of motion (ROM) and histological changes. RESULTS: ACLR resulted in persistent loss of ROM, accompanied by synovial shortening, capsule thickening, and osteophyte formation. Two weeks of non-weight bearing increased ROM and reduced osteophyte size, but the beneficial effects disappeared within 10 weeks after reloading. Two-week immobilization decreased ROM and facilitated synovial shortening. After remobilization, ROM partially recovered but remained below non-intervention levels at 12 weeks. When both interventions were combined, ROM was similar to immobilization alone. CONCLUSIONS: The beneficial effects of 2-week non-weight bearing on contracture diminished within 10 weeks after reloading. The adverse effects of 2-week immobilization on contracture persisted after 10 weeks of remobilization. The effects of the combined use of both interventions on contracture were primarily determined by immobilization.

Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.

BACKGROUND: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo. METHODS AND RESULTS: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages. CONCLUSION: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions.

The outer membrane is an essential load-bearing element in Gram-negative bacteria.

Gram-negative bacteria possess a complex cell envelope that consists of a plasma membrane, a peptidoglycan cell wall and an outer membrane. The envelope is a selective chemical barrier1 that defines cell shape2 and allows the cell to sustain large mechanical loads such as turgor pressure3. It is widely believed that the covalently cross-linked cell wall underpins the mechanical properties of the envelope4,5. Here we show that the stiffness and strength of Escherichia coli cells are largely due to the outer membrane. Compromising the outer membrane, either chemically or genetically, greatly increased deformation of the cell envelope in response to stretching, bending and indentation forces, and induced increased levels of cell lysis upon mechanical perturbation and during L-form proliferation. Both lipopolysaccharides and proteins contributed to the stiffness of the outer membrane. These findings overturn the prevailing dogma that the cell wall is the dominant mechanical element within Gram-negative bacteria, instead demonstrating that the outer membrane can be stiffer than the cell wall, and that mechanical loads are often balanced between these structures.

Numerical evaluation of internal femur osteosynthesis based on a biomechanical model of the loading in the proximal equine hindlimb.

Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a "gap" fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types.

Accuracy of Volumetric Bone Mineral Density Measurement in Weight Bearing, Cone Beam Computed Tomography.

BACKGROUND: Weight bearing computed tomography (WBCT) utilizes cone beam CT technology to provide assessments of lower limb joint structures while they are functionally loaded. Grey-scale values indicative of X-ray attenuation that are output from cone beam CT are challenging to calibrate, and their use for bone mineral density (BMD) measurement remains debatable. To determine whether WBCT can be reliably used for cortical and trabecular BMD assessment, we sought to establish the accuracy of BMD measurements at the knee using modern WBCT by comparing them to measurements from conventional CT. METHODS: A hydroxyapatite phantom with three inserts of varying densities was used to systematically quantify signal uniformity and BMD accuracy across the acquisition volume. We evaluated BMD in vivo (n = 5, female) using synchronous and asynchronous calibration techniques in WBCT and CT. To account for variation in attenuation along the height (z-axis) of acquisition volumes, we tested a height-dependent calibration approach for both WBCT and CT images. RESULTS: Phantom BMD measurement error in WBCT was as high as 15.3% and consistently larger than CT (up to 5.6%). Phantom BMD measures made under synchronous conditions in WBCT improved measurement accuracy by up to 3% but introduced more variability in measured BMD. We found strong correlations (R = 0.96) as well as wide limits of agreement (-324 mgHA/cm3 to 183 mgHA/cm3) from Bland-Altman analysis between WBCT and CT measures in vivo that were not improved by height-dependent calibration. CONCLUSION: Whilst BMD accuracy from WBCT was found to be dependent on apparent density, accuracy was independent of the calibration technique (synchronous or asynchronous) and the location of the measurement site within the field of view. Overall, we found strong correlations between BMD measures from WBCT and CT and in vivo measures to be more accurate in trabecular bone regions. Importantly, WBCT can be used to distinguish between anatomically relevant differences in BMD, however future work is necessary to determine the repeatability and sensitivity of BMD measures in WBCT.

Enhanced Outcomes in Femoral Subtrochanteric Fractures Using Long INTERTAN Nails with Titanium Cable Cerclage: A Retrospective Analysis.

BACKGROUND The evidence on use of supplementary titanium cable cerclage (TCC) in treating femoral subtrochanteric fractures (FSF) remains scarce. Therefore, this study aimed to investigate the potential therapeutic effects for FSF patients using TCC. MATERIAL AND METHODS A retrospective study of 68 FSF patients treated by a long intramedullary (IM) nailing with (Observation group, n=41) or without (Control group, n=27) TCC was conducted from January 2020 to December 2021. The primary outcome measure was time to postoperative full weight-bearing. Secondary outcome measures were operation time, intraoperative blood loss, number of blood transfusions needed, varus angle loss, excellent and good rate of fracture reduction, Harris score, and survival rate. RESULTS Patients were followed up for 13 to 36 months. The excellent and good rate of fracture reduction was 100% in the Observation group versus 92.6% in the Control group (P=0.013), and the varus angle loss and time to postoperative full weight-bearing in the Observation group were significantly less than in the Control group (P<0.05). The intraoperative blood loss in the Observation group was significantly higher than in the Control group (P<0.001). No differences were noted between groups for Harris scores and survival rates at last follow-up. CONCLUSIONS TCC fixation combined with IM nailing can improve the excellent and good rate of fracture reduction and reduce varus angle loss, as well as shorten the time to full weight-bearing and promote early functional exercise, which offers an effective treatment option for FSF patients who have failed closed reduction.

Per-step and cumulative load at three common running injury locations: The effect of speed, surface gradient, and cadence.

Understanding how loading and damage on common running injury locations changes across speeds, surface gradients, and step frequencies may inform training programs and help guide progression/rehabilitation after injuries. However, research investigating tissue loading and damage in running is limited and fragmented across different studies, thereby impairing comparison between conditions and injury locations. This study examined per-step peak load and impulse, cumulative impulse, and cumulative weighted impulse (hereafter referred to as cumulative damage) on three common injury locations (patellofemoral joint, tibia, and Achilles tendon) across different speeds, surface gradients, and cadences. We also explored how cumulative damage in the different tissues changed across conditions relative to each other. Nineteen runners ran at five speeds (2.78, 3.0, 3.33, 4.0, 5.0 m s-1 ), and four gradients (-6, -3, +3, +6°), and three cadences (preferred, ±10 steps min-1 ) each at one speed. Patellofemoral, tibial, and Achilles tendon loading and damage were estimated from kinematic and kinetic data and compared between conditions using a linear mixed model. Increases in running speed increased patellofemoral cumulative damage, with nonsignificant increases for the tibia and Achilles tendon. Increases in cadence reduced damage to all tissues. Uphill running increased tibial and Achilles tendon, but decreased patellofemoral damage, while downhill running showed the reverse pattern. Per-step and cumulative loading, and cumulative loading and cumulative damage indices diverged across conditions. Moreover, changes in running speed, surface gradient, and step frequency lead to disproportional changes in relative cumulative damage on different structures. Methodological and practical implications for researchers and practitioners are discussed.

Validity of spatiotemporal and ground reaction force estimates during resisted sprinting with a motorized loading device.

We aimed to examine the validity of estimating spatiotemporal and ground reaction force (GRF) parameters during resisted sprinting using a robotic loading device (1080 Sprint). Twelve male athletes (age: 20.9 ± 2.2 years; height: 174.6 ± 4.2 cm; weight: 69.4 ± 6.1 kg; means ± SDs) performed maximal resisted sprinting with three different loads using the device. The step frequency and length and step-averaged velocity, anteroposterior GRF (Fap ), and the ratio of Fap to resultant GRF (RF) were estimated using the velocity and towing force data measured using the device. Simultaneously, the corresponding values were measured using a 50-m force plate system. The proportional and fixed biases of the estimated values against those measured using the force plate system were determined using ordinary least product (OLP) regression analysis. Proportional and fixed biases were observed for most variables. However, the proportional bias was small or negligible except for the step frequency. Conversely, the fixed bias was small for step-averaged velocity (0.11 m/s) and step length (0.04 m), whereas it was large for step frequency (0.54 step/s), Fap (16N), and RF (2.22%). For all variables except step frequency, the prediction intervals in the OLP regression dramatically decreased when the corresponding values were smoothed using a two-step moving average. These results indicate that by using the velocity and force data recorded in the loading device, most of the spatiotemporal and GRF variables during resisted sprinting can be estimated with some correction of the fixed bias and data smoothing using the two-step moving average.

Investigating the impact of external load on muscle synergies during bipedal squats.

PURPOSE: A broad functional movement repertoire is crucial for engaging in physical activity and reducing the risk of injury, both of which are central aspects of lifelong health. As a fundamental exercise in both recreational and rehabilitative training regimes, the bipedal squat (SQBp) incorporates many everyday movement patterns. Crucially, SQBp can only be considered functional if the practitioner can meet the coordinative demands. Many factors affect coordinative aspects of an exercise, most notably external load. Since compound movements are assumed to be organized in a synergistic manner, we employed muscle synergy analysis to examine differences in muscle synergy properties between various external load levels during SQBp. METHODS: Ten healthy male recreational athletes were enrolled in the present study. Each participant performed three sets of ten SQBp on a smith machine at three submaximal load levels (50%, 62.5%, and 75% of 3 repetition maximum) across three non-consecutive days. Muscle activity was recorded from 12 prime movers of SQBp by way of electromyography (EMG). Muscle synergies were analyzed in terms of temporal activation patterns, i.e., waveform, as well as the relative input of each muscle into individual synergies, i.e., weight contribution. RESULTS: Waveforms of muscle synergies did not differ between loads. Weight contributions showed significant differences between load levels, albeit only for the gastrocnemius muscle in a single synergy. CONCLUSION: Taken together, our results imply mostly stable spatiotemporal composition of muscle activity during SQBp, underlining the importance of technical competence during compound movement performance in athletic and rehabilitative settings.