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Adaptive elasticity in cortical bone has traditionally been modeled using Strain Energy Density (SED). Recent studies have highlighted the importance of interstitial fluid in bone adaptation, yet no research has quantified the role of interstitial fluid pressure and its effects, specifically incorporating both SED and interstitial fluid pressure in the adaptation process. This study introduces a novel formulation combining theory of porous media and theory of adaptive elasticity that considers both SED and interstitial fluid's pressure in cortical bone adaptation. The formulation is solved using ANSYS Fluent and a MATLAB script, and sensitivity analyses were conducted, analyzing various porosities, loading magnitudes, anisotropic properties of cortical bone, and involvement coefficients of interstitial fluid's pressure. This study reveals that bones with different vascular porosities (PV) tend to achieve similar density distributions under uniform loading over time. This highlights the significant role of interstitial fluid pressure in accelerating the convergence to optimal bone properties, especially in specimens with larger PV porosities. The findings emphasize the importance of fluid pressure in bone remodeling, aligning with previous studies. Furthermore, this study demonstrates that considering transversely isotropic material properties can significantly alter the remodeling configuration compared to isotropic material properties. This highlights the importance of accurately representing the anisotropic nature of cortical bone in models to better predict its adaptive responses. However, aspects such as fluid density variations and bone geometry changes remain unexplored, suggesting directions for future research. Overall, this research enhances the understanding of cortical bone adaptation and its mechanical interactions., Competing Interests: Declaration of competing interest None Declared, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The primary function of the tetrapod jaw is to transmit jaw muscle forces to bite points. The routes of force transfer in the jaw have never been studied but can be quantified using load paths - the shortest, stiffest routes from regions of force application to support constraints. Here, we use load path analysis to map force transfer from muscle attachments to bite point and jaw joint, and to evaluate how different configurations of trabecular and cortical bone affect load paths. We created three models of the mandible of the Virginia opossum, Didelphis virginiana, each with a cortical bone shell, but with different material properties for the internal spaces: (1) a cortical-trabecular model, in which the interior space is modeled with bulk properties of trabecular bone; (2) a cortical-hollow model, in which trabeculae and mandibular canal are modeled as hollow; and (3) a solid-cortical model, in which the interior is modeled as cortical bone. The models were compared with published in vivo bite force and bone strain data, and the load paths calculated for each model. The trabecular model, which is preferred because it most closely approximates the actual morphology, was best validated by in vivo data. In all three models, the load path was confined to cortical bone, although its route within the cortex varied depending on the material properties of the inner model. Our analysis shows that most of the force is transferred through the cortical, rather than trabecular bone, and highlights the potential of load path analysis for understanding form-function relationships in the skeleton., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: High-performance polymers are used in different fixed prosthesis treatments due to their many advantages such as biocompatibility, shock absorption ability, high fracture resistance. The effects of marginal design on the forces on high-performance polymers are unknown. This study aimed was to investigate the stress distribution of different marginal designs on Polyetheretherketone (PEEK) and Polyetherketoneketone (PEKK) substructure materials, cortical bone and cancellous bone by finite element analysis., Methods: A first maxillary molar tooth was modeled in 3D using the "3D Complex Render" method. Considering the ideal preparation conditions (Taper angle was 6°, step depth was 1 mm, occlusal reduction was 2 mm), four different configurations were modeled by changing the marginal design (chamfer, deep chamfer, shoulder 90°, shoulder 135°). PEEK, PEKK substructure, and composite superstructure were designed on created models. A total of 150 N oblique force from two points and a total of 300 N vertical force from three points were applied from occlusall. and the maximum principal stress, minimum principal stress, von Mises stress findings in the cortical bone, spongiose bone, and substructure were examined. The study was carried out by static linear analysis with a three-dimensional finite element stress analysis method., Results: The highest maximum principal stress value in the cortical bone was observed when the PEEK + Shoulder 135° step at vertical force. The highest minimum principal stress value in the cortical bone was observed when the PEEK + Shoulder 90° step, and PEEK + deep chamfer step at oblique force. The highest maximum principal stress value in spongiose bone was observed when the PEEK + Shoulder 90° step. The highest minimum principal stress value in spongiose bone was observed when the PEEK + deep chamfer step at vertical force. The highest von Mises stress value in the substructure was observed when the PEKK + Deep chamfer step at oblique force. The lowest maximum principal stress value in the cortical bone was observed when the PEKK + Shoulder 135° step at oblique force. The lowest minimum principal stress value in the cortical bone was observed when the PEEK + Shoulder 135° step, and PEKK + shoulder 135° step at vertical force. The lowest maximum principal stress value in spongiose bone was observed when the PEEK + Shoulder 90° step. The lowest minimum principal stress value in spongiose bone was observed when the PEEK + Shoulder 135° step and PEKK + Shoulder 135° step at vertical force. The lowest von Mises stress value in the substructure was observed when the PEEK + Deep chamfer step at vertical force., Conclusion: When cortical and spongiose bone stress were evaluated, no destructive stress was observed. Considering the stresses occurring in the substructure the highest stress was observed in the chamfer step., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Server mutluay unal reports financial support was provided by Investigation of the effect of different step design on stress by using finite element analysis when PEEK and PEKK substructure materials are used. Server mutluay unal reports a relationship with Afyonkarahisar Health Sciences University that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Over the past few decades, early osteoporosis detection using ultrasonic bone quality evaluation has gained prominence. Specifically, various studies focused on axial transmission using ultrasonic guided waves and have highlighted this technique's sensitivity to intrinsic properties of long cortical bones. This work aims to demonstrate the potential of low-frequency ultrasonic guided waves to infer the properties of the bone inside which they are propagating. A proprietary ultrasonic transducer, tailored to transmit ultrasonic guided waves under 500 kHz, was used for the data collection. The gathered data underwent two-dimensional fast Fourier transform processing to extract experimental dispersion curves. The proposed inversion scheme compares experimental dispersion curves with simulated dispersion curves calculated through the semi-analytical iso-geometric analysis (SAIGA) method. The numerical model integrates a bone phantom plate coupled with a soft tissue layer on its top surface, mimicking the experimental bone phantom plates. Subsequently, the mechanical properties of the bone phantom plates were estimated by reducing the misfit between the experimental and simulated dispersion curves. This inversion leaned heavily on the dispersive trajectories and amplitudes of ultrasonic guided wave modes. Results indicate a marginal discrepancy under 5% between the mechanical properties ascertained using the SAIGA-based inversion and those measured using bulk wave pulse-echo measurements., (© 2024 Acoustical Society of America.)

The aim of this study was to evaluate the bone tissue effects under dynamic loading using finite element analysis (FEA) for four angled abutments with different deviated palatal lateral tilt angles. A three-dimensional model of the posterior maxillary region and an implant crown model were reconstructed and assembled with a three-dimensional model of the implant, angled abutment, and central screw to create a total of 10 three-dimensional finite element models tilted at 15 ∘ , 20 ∘ , 25 ∘ , and 30 ∘ in three groups, and the dynamic loads simulating oral mastication were loaded on the implant crown to analyze the equivalent stresses and strains in the peri-implant bone tissues. Under the dynamic loading, the cortical bone on the buccal side of the implant neck showed different degrees of stress concentration, and the cortical bone stress was much higher than the cancellous bone, and the strain concentration area of each model was located in the bone tissue around the implant neck and base. For the use of angular abutment, under the premise that the cortical bone stresses and strains of the 10 models meet the requirements for use, the peak stresses of 2.907 MPa, 3.018 MPa, and 2.164 MPa were achieved by using the 20 ∘ angular abutment to achieve the tilt angles of 20 ∘ , 25 ∘ , and 30 ∘ implantation, which is more advantageous compared with other models., (© 2024. International Federation for Medical and Biological Engineering.)

Finite element analysis (FEA) has been used to analyze the behavior of dental materials, mainly in implantology. However, FEA is a mechanical analysis and few studies have tried to simulate the biological characteristics of the healing process of loaded implants. This study used the rule of mixtures to simulate the biological healing process of immediate implants in an alveolus socket and bone-implant junction interface through FEA. Three-dimensional geometric models of the structures were obtained, and material properties were derived from the literature. The rule of mixtures was used to simulate the healing periods-immediate and early loading, in which the concentration of each cell type, based on in vivo studies, influenced the final elastic moduli. A 100 N occlusal load was simulated in axial and oblique directions. The models were evaluated for maximum and minimum principal strains, and the bone overload was assessed through Frost's mechanostat. There was a higher strain concentration in the healing regions and cortical bone tissue near the cervical portion. The bone overload was higher in the immediate load condition. The method used in this study may help to simulate the biological healing process and could be useful to relate FEA results to clinical practice., (© 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

This study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers, which represented osteons and interstitial tissue, loaded in uniaxial tension. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber "families." Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created by modeling aging via the following changes to the input parameters: (i) increasing porosity from 5% to 15%, (ii) increasing the ratio of the number of osteon fibers relative to interstitial fibers from 40% to 50%, and (iii) changing the fiber material properties from representing mature bone samples to representing elderly bone samples (i.e., increased strength and decreased toughness of interstitial fibers together with decreased toughness of osteon fibers). To understand the respective contributions of these changes, additional models isolating one or two of each of these were also created. From the computed stress-strain curve for the fiber bundle, the yield point (ϵ y , σ y ), ultimate point (ϵ u , σ u ), and toughness (U T ) for the bundle as a whole were measured. We found that changes to all three input parameters were required for the model to capture the aging-related decline in cortical bone mechanical properties consistent with those previously reported in the literature. In both mature and elderly bundles, rupture of the interstitial fibers drove the initial loss of strength following the ultimate point. Plasticity and more gradual rupture of the osteons drove the remainder of the response. Both the onset and completion of interstitial fiber rupture occurred at lower strains in the elderly vs. mature case. These findings point to the importance of studying microstructural changes beyond porosity, such as the area fraction of osteons and the material properties of osteon and interstitial tissue, in order to further understanding of aging-related changes in bone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Daily physiological activities subject our skeletal system to cyclic loading with varying frequencies and magnitudes. These loadings interact with the microstructure of bone and create microdamage, which can cause stress-induced injuries if not repaired on the time. The early detection is required to prevent the complications associated with these fractures. In the present study, to examine fatigue loading-induced damage in cortical bone, the sensitivity of four different indentation devices was investigated. For this, cortical bone samples were fatigued in four-point bending configuration at 0.5 Hz, 2 Hz and 4 Hz frequencies. Following the fatigue loading, cyclic reference point indentation (cRPI), impact reference point indentation (iRPI), Vickers microhardness and nanoindentation tests were performed on the bone samples. Results show that indentation devices are sensitive to detect fatigue loading induced damage only in 0.5 Hz group samples on compressive region. On the other hand, the sensitivity of indentation devices for tensile stress-induced damage is not clear. Also, histological examination of fatigued bone samples shows a significant increase in the crack density and crack length with fatigue loading only for the 0.5 Hz group samples. The present study provides insight into the sensitivity of different indentation devices to fatigue loading induced damage, which could be helpful in the development of new devices for the early diagnosis of stress induced injuries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mechanical loading on the skeleton stimulates bone formation. Although the exact mechanism underlying this process remains unknown, a growing body of evidence indicates that the Wnt signaling pathway is necessary for the skeletal response to loading. Recently, we showed that Wnts produced by osteoblast lineage cells mediate the osteo-anabolic response to tibial loading in adult mice. Here, we report that Wnt1 specifically plays a crucial role in mediating the mechano-adaptive response to loading. Independent of loading, short-term loss of Wnt1 in the Osx-lineage resulted in a decreased cortical bone area in the tibias of 5-month-old mice. In females, strain-matched loading enhanced periosteal bone formation in Wnt1F/F controls, but not in Wnt1F/F; OsxCreERT2 knockouts. In males, strain-matched loading increased periosteal bone formation in both control and knockout mice; however, the periosteal relative bone formation rate was 65% lower in Wnt1 knockouts versus controls. Together, these findings show that Wnt1 supports adult bone homeostasis and mediates the bone anabolic response to mechanical loading., (© 2022 Federation of American Societies for Experimental Biology.)

Disuse-induced bone loss is seen following spinal cord injury, prolonged bed rest, and exposure to microgravity. We performed whole transcriptomic profiling of cortical bone using RNA sequencing (RNAseq) and RNA molecular barcoding (NanoString) on a hindlimb unloading (HLU) mouse model to identify genes whose mRNA transcript abundances change in response to disuse. Eleven-week old female C57BL/6 mice were exposed to ambulatory loading or HLU for 7 days (n = 8/group). Total RNA from marrow-flushed femoral cortical bone was analyzed on HiSeq and NanoString platforms. The expression of several previously reported genes associated with Wnt signaling and metabolism was altered by HLU. Furthermore, the increased abundance of transcripts, such as Pfkfb3 and Mss51, after HLU imply these genes also have roles in the cortical bone's response to altered mechanical loading. Our study demonstrates that an unbiased approach to assess the whole transcriptomic profile of cortical bone can reveal previously unidentified mechanosensitive genes and may eventually lead to novel targets to prevent disuse-induced osteoporosis., Competing Interests: No authors have competing interests.

The mineralization level is heterogeneous in cortical bone extracellular matrix as a consequence of remodeling. Models of the effective elastic properties at the millimeter scale have been developed based on idealizations of the vascular pore network and matrix properties. Some popular models do not take into account the heterogeneity of the matrix. However, the errors on the predicted elasticity when the difference in elastic properties between osteonal and interstitial tissues is not modeled have not been quantified. This work provides an estimation of the maximum error. We compare the effective elasticity of a representative volume element (RVE) assuming (1) different elastic properties in osteonal and interstitial tissues vs. (2) average matrix properties. In order to account for the variability of bone microstructure, we use a collection of high resolution images of the pore network to build RVEs. In each RVE we assumed a constant osteonal wall thickness and we artificially varied this thickness between 35 and 140 [Formula: see text]m to create RVEs with different amounts of osteonal tissue. The homogenization problem was solved with a fast Fourier transform (FFT)-based numerical scheme. We found that the error depends on pore volume fraction and varies on average from 1 to [Formula: see text] depending on the assumed diameter of the osteons. The results suggest that matrix heterogeneity may be disregarded in cortical bone models in most practical cases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cortical bone structure is a crucial determinant of bone strength, yet for many years studies of novel genes and cell signalling pathways regulating bone strength have focused on the control of trabecular bone mass. Here we focus on mechanisms responsible for cortical bone development, growth, and degeneration, and describe some recently described genetic-driven modifications in humans and mice that reveal how these processes may be controlled. We start with embryonic osteogenesis of preliminary bone structures preceding the cortex and describe how this structure consolidates then matures to a dense, vascularised cortex containing an increasing proportion of lamellar bone. These processes include modelling-induced, and load-dependent, asymmetric cortical expansion, which enables the cortex's transition from a highly porous woven structure to a consolidated and thickened highly mineralised lamellar bone structure, infiltrated by vascular channels. Sex-specific differences emerge during this process. With aging, the process of consolidation reverses: cortical pores enlarge, leading to greater cortical porosity, trabecularisation and loss of bone strength. Each process requires co-ordination between bone formation, bone mineralisation, vascularisation, and bone resorption, with a need for locational-, spatial- and cell-specific signalling pathways to mediate this co-ordination. We will discuss these processes, and a number of cell-signalling pathways identified in both murine and human genetic studies to regulate cortical bone mass, including signalling through gp130, STAT3, PTHR1, WNT16, NOTCH, NOTUM and sFRP4., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 yr) physical activity on trabecular microarchitectural properties and microfinite element analyses of estimated bone strength., Methods: Female collegiate-level tennis players (n = 15; age = 20.3 ± 0.9 yr) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral quantitative computed tomography. The distal tibia and the tibial diaphysis in both legs were also assessed, and cross-country runners (n = 15; age = 20.8 ± 1.2 yr) included as controls., Results: The distal radius of the racquet arm had 11.8% (95% confidence interval [CI] = 7.9% to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than that in the nonracquet arm (all P < 0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI = 13.0% to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI = 6.7% to 12.6%) greater in the racquet versus nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI = 1.7% to 7.1%) greater strength than the contralateral leg., Conclusion: Chronically elevated physical activity enhances trabecular microarchitecture and microfinite element estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate that tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared with in the contralateral leg., (Copyright © 2020 by the American College of Sports Medicine.)

Osteoporosis is a common skeletal disease, with increased risk of fractures. Currently available osteoporosis treatments reduce the risk of vertebral fractures, mainly dependent on trabecular bone, whereas the effect on nonvertebral fractures, mainly dependent on cortical bone, is less pronounced. WNT signaling is a crucial regulator of bone homeostasis, and the activity of WNTs is inhibited by NOTUM, a secreted WNT lipase. We previously demonstrated that conditional inactivation of NOTUM in all osteoblast lineage cells increases the cortical but not the trabecular bone mass. The aim of the present study was to determine if NOTUM increasing cortical bone is derived from osteoblast precursors/early osteoblasts or from osteocytes/late osteoblasts. First, we demonstrated Notum mRNA expression in Dmp1- expressing osteocytes and late osteoblasts in cortical bone using in situ hybridization. We then developed a mouse model with inactivation of NOTUM in Dmp1 -expressing osteocytes and late osteoblasts ( Dmp1-creNotum flox/flox mice). We observed that the Dmp1-creNotum flox/flox mice displayed a substantial reduction of Notum mRNA in cortical bone, resulting in increased cortical bone mass and decreased cortical porosity in femur but no change in trabecular bone volume fraction in femur or in the lumbar vertebrae L5 in Dmp1-creNotum flox/flox mice as compared with control mice. In conclusion, osteocytes and late osteoblasts are the principal source of NOTUM in cortical bone, and NOTUM derived from osteocytes/late osteoblasts reduces cortical bone mass. These findings demonstrate that inhibition of osteocyte/late osteoblast-derived NOTUM might be an interesting pharmacological target to increase cortical bone mass and reduce nonvertebral fracture risk. NEW & NOTEWORTHY NOTUM produced by osteoblasts is known to regulate cortical bone mass. Our new findings show that NOTUM specifically derived by DMP1 -expressing osteocytes and late osteoblasts regulates cortical bone mass and not trabecular bone mass.

Mandibular cortical and trabecular bone abnormalities in patients with familial adenomatous polyposis (FAP) were evaluated using dental panoramic radiographs (DPR) radiomorphometric indices and fractal dimension (FD). Sixty DPRs from 15 FAP patients and 45 healthy controls were evaluated. FAP group was composed of 33.3% females and 66.6% males, age mean  = 37.2 years (SD 15.79). The non-FAP group was paired by gender and sex. The parameters analyzed were: FD of the trabecular bone in four regions of interest (ROI), mandibular cortical index (MCI) and width (MCW). FD values were lower for the FAP group. Statistically significance differences were shown by ROI 2 and 3 anteriorly to the mental foramen bilaterally, p = 0.001, and p = 0.006. The ROI 1 and 4, at the mandibular angle trabeculae, indicated statistical significances on the right side (p = 0.036) and no differences on the left side (p = 0.091). There was no significant difference in MCI and MCW when the groups were compared, MCW (L) p = 0.247, and MCW (R) p = 0.070. Fractal values of FAP patients' mandibular trabecular bone were lower than healthy controls. The radiomorphometric indices MCI and MCW were not useful for analyzing the cortical bone pattern. Therefore, FD is a promising tool for detection of abnormal bone structure in DPRs and for supporting the appropriate referral of FAP patients.

A large number of post mortem human subjects was used to investigate the relation between the micro-structure of rib cortical bone and the mechanical properties using Fractal Dimension. Uniaxial tensile tests were performed on coupons of rib cortical bone. Tensile strength, yield stress, Young's Modulus, maximum strain, and work to fracture were determined for each coupon. Fractal dimension was computed using CT images and Digital Image Correlation procedures. A highly significant effect of fractal dimension in the mechanical properties was found. In addition, the variation in mechanical properties was found to be adequately represented by Generalized Extreme Value type distributions.

Unstable pelvic ring fractures are severe and complex injuries, and surgical fixation is challenging and can be complicated by early failure due in part to difficulties with securely fixing screws in low-density bone. There is limited information in the literature about how the density distribution across the pelvic bones changes with age and sex. In this study, we used 60 sets of calibrated bone density measurements obtained opportunistically from clinical computed tomography scans of the pelvis. Three-dimensional models of the innominate bone were produced and the effects of age and sex on cortical bone density modeled. Overall trends and regions where these factors had a significant effect were identified, and the results visualized. Across the entire innominate bone, the mean loss of density was found to be 1.6 mg/cc per year, with several specific areas (pubic body, iliac fossa, posterior ilium, and anterior inferior iliac spine for example) showing significant rates of loss up to three times greater than the rest of the bone. Areas significantly affected by sex included the posterior pubic root, anterior aspect of the pubic body, and iliac crest. Despite overall trends of attenuation, there remains significant variability between individuals. This supports the need to further explore subject-specific planning tools for pelvic fracture repair. Statement of clinical significance: Bone density changes across the innominate bone due to age and sex tend to vary between individuals, although consistent effects were seen at specific regions. This information may help in surgical planning of unstable fracture repairs., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Objectives: Variation in trabecular and cortical bone properties is often used to infer habitual behavior in the past. However, the structures of both types of bone are rarely considered together and may even contradict each other in functional interpretations. We examine trabecular and cortical bone properties in various athletes and sedentary controls to clarify the associations between combinations of cortical and trabecular bone properties and various loading modalities., Materials and Methods: We compare trabecular and cortical bone properties using peripheral quantitative computed tomography scans of the tibia between groups of 83 male athletes (running, hockey, swimming, cricket) and sedentary controls using Bayesian multilevel models. We quantify midshaft cortical bone rigidity and area (J, CA), midshaft shape index (Imax/Imin), and mean trabecular bone mineral density (BMD) in the distal tibia., Results: All groups show unique combinations of biomechanical properties. Cortical bone rigidity is high in sports that involve impact loading (cricket, running, hockey) and low in nonimpact loaded swimmers and controls. Runners have more anteroposteriorly elliptical midshafts compared to other groups. Interestingly, all athletes have greater trabecular BMD compared to controls, but do not differ credibly among each other., Discussion: Results suggest that cortical midshaft hypertrophy is associated with impact loading while trabecular BMD is positively associated with both impact and nonimpact loading. Midshaft shape is associated with directionality of loading. Individuals from the different categories overlap substantially, but group means differ credibly, suggesting that nuanced group-level inferences of habitual behavior are possible when combinations of trabecular and cortical bone are analyzed., (© 2020 Wiley Periodicals LLC.)

The data-driven approach was formally introduced in the field of computational mechanics just a few years ago, but it has gained increasing interest and application as disruptive technology in many other fields of physics and engineering. Although the fundamental bases of the method have been already settled, there are still many challenges to solve, which are often inherently linked to the problem at hand. In this paper, the data-driven methodology is applied to a particular problem in tissue biomechanics, a context where this approach is particularly suitable due to the difficulty in establishing accurate and general constitutive models, due to the intrinsic intra and inter-individual variability of the microstructure and associated mechanical properties of biological tissues. The problem addressed here corresponds to the characterization and mechanical simulation of a piece of cortical bone tissue. Cortical horse bone tissue was mechanically tested using a biaxial machine. The displacement field was obtained by means of digital image correlation and then transformed into strains by approximating the displacement derivatives in the bone virtual geometric image. These results, together with the approximated stress state, assumed as uniform in the small pieces tested, were used as input in the flowchart of the data-driven methodology to solve several numerical examples, which were compared with the corresponding classical model-based fitted solution. From these results, we conclude that the data-driven methodology is a useful tool to directly simulate problems of biomechanical interest without the imposition (model-free) of complex spatial and individually-varying constitutive laws. The presented data-driven approach recovers the natural spatial variation of the solution, resulting from the complex structure of bone tissue, i.e. heterogeneity, microstructural hierarchy and multifactorial architecture, making it possible to add the intrinsic stochasticity of biological tissues into the data set and into the numerical approach.

Metabolic activities are closely correlated with bone remodeling and long-term anti-resorptive bisphosphonate treatment frequently causes atypical femoral fractures through unclear mechanisms. To explore whether metabolic alterations affect bone remodeling in femurs and lumbar vertebrae and whether anti-osteoporotic bisphosphonates perturb their reconstruction, we studied three mouse strains with different fat and lean body masses (BALB/c, C57BL6, and C3H mice). These mice displayed variable physical activity, food and drink intake, energy expenditure, and respiratory quotients. Following intraperitoneal calcein injection, double calcein labeling of the femoral diaphysis, as well as serum levels of the bone-formation marker procollagen type-I N-terminal propeptide and the bone-resorption marker C-terminal telopeptide of type-I collagen, revealed increased bone turnover in mice in the following order: C3H > BALB/c ≥ C57BL6 mice. In addition, bone reconstitution in femurs was distinct from that in lumbar vertebrae in both healthy control and estrogen-deficient osteoporotic mice with metabolic perturbation, particularly in terms of femoral trabecular and cortical bone remodeling in CH3 mice. Interestingly, subcutaneous administration of bisphosphonate risedronate to C3H mice with normal femoral bone density led to enlarged femoral cortical bones with a low bone mineral density, resulting in bone fragility; however, this phenomenon was not observed in mice with ovariectomy-induced femoral cortical bone loss. Together, these results suggest that diverse metabolic activities support various forms of bone remodeling and that femur remodeling differs from lumbar vertebra remodeling. Moreover, our findings imply that the adverse effect of bisphosphonate agents on femoral cortical bone remodeling should be considered when prescribing them to osteoporotic patients.

The use of external fixators for distraction osteogenesis has revolutionized treatment options for segmental bone defects in the tibia. Following corticotomy, the latency phase allows the biologic environment to initiate healing, and optimized distraction rates produce regenerate. Regenerate consolidation can be improved with local and systemic biologic optimization. Consolidation time is often considered to be 3 to 4 times longer than distraction in adults. Soft tissue considerations are important during external fixation and distraction. Additionally, slow regenerate can be benefited by various techniques discussed in this article. Distraction osteogenesis is a beneficial tool for segmental bone defects., Competing Interests: Disclosures K. Millonig has nothing to disclose. B. Hutchinson has consulted for Orthofix., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Quantification of cortical bone mass and architecture using μCT is commonplace in osteoporosis and osteoarthritis research. Different groups often report substantially divergent mouse cortical bone responses to nominally comparable interventions. In the case of studies assessing bones' responses to externally applied loading, these differences are commonly associated with methodological differences in the loading regime. This chapter describes a widely published, standardized method of in vivo mouse tibia axial loading to produce lamellar bone formation. Despite uniform application of axial loading, changes in bone mass are highly site-specific within individual bones. For example, the mouse proximal tibia rapidly accrues new bone following axial loading, but this osteogenic response tapers to produce undetectable differences distally. Consequently, the bone sites selected for comparisons substantially influence the magnitude of differences observed. Application of the freely available Site Specificity software allows site-specific responses to be identified by rapidly quantifying cortical bone mass at each 1% site along the bone's length. This high-content screening tool has been informatively applied to study the local effects of changes in loading as well as systemic interventions including hormonal treatment and aging. Automated multisite analyses of cortical mass is increasingly identifying site-specific effects of "systemic" interventions such as global gene deletions. Biological mechanisms underlying this apparent regionalization of cortical responses are largely unknown but may start to be elucidated by increasingly widespread application of Site Specificity methods.

Porcine bone is often used as a substitute for human bone in forensic trauma studies, but little has been published on its comparative mechanical behavior. The factors affecting mechanical properties and therefore selection of bone models are complex and include the age of the animal at death, and physiological loading conditions, the latter being of particular relevance when using a quadrupedal animal as a human substitute. The regional variation in hardness of adult and infant porcine bones was investigated using Vickers' indentation tests and compared to published data for human limb bones to relate differences to inherent genetic effects and loading influences, and to examine the validity of the porcine-human model. Significant differences in hardness were observed both along and around the adult porcine humerus and femur, but no significant differences were found along the length of the infant bones. Significant differences were found between the forelimb and hindlimb, but only in the infant specimens. The hardness values for porcine adult cortical bone from the femur (52.23 ± 1.00 kg mm -2 ) were comparable to those reported in the literature for adult human cortical bone from the fibula, ilium, and calcaneus. These data will help inform subject selection in terms of both species and bone type for use in future trauma studies., (© 2020 American Academy of Forensic Sciences.)

Loss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.

Various tissue types, including fibrous connective tissue, bone marrow, cartilage, woven and lamellar bone, coexist in healing bone. Similar to most bone tissue type, healing bone contains a lacuno-canalicular network (LCN) housing osteocytes. These cells are known to orchestrate bone remodeling in healthy bone by sensing mechanical strains and translating them into biochemical signals. The structure of the LCN is hypothesized to influence mineralization processes. Hence, the aim of the present study was to visualize and match spatial variations in the LCN topology with mineral characteristics, within and at the interfaces of the different tissue types that comprise healing bone. We applied a correlative multi-method approach to visualize the LCN architecture and quantify mineral particle size and orientation within healing femoral bone in a mouse osteotomy model (26 weeks old C57BL/6 mice). This approach revealed structural differences across several length scales during endochondral ossification within the following regions: calcified cartilage, bony callus, cortical bone and a transition zone between the cortical and callus region analyzed 21 days after the osteotomy. In this transition zone, we observed a continuous convergence of mineral characteristics and osteocyte lacunae shape as well as discontinuities in the lacunae volume and LCN connectivity. The bony callus exhibits a 34% higher lacunae number density and 40% larger lacunar volume compared to cortical bone. The presented correlations between LCN architecture and mineral characteristics improves our understanding of how bone develops during healing and may indicate a contribution of osteocytes to bone (re)modeling., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Visualizing bone mineralization and collagen fibril organization at intermediate scales between the nanometer and the hundreds of microns range, is still an important challenge. Similarly, visualizing cellular components which locally affect the tissue structure requires a precision of a few tens of nanometers at maximum while spanning several tens of micrometers. In the last decade, gallium focused ion beam (FIB) equipped with a scanning electron microscope (SEM) proved to be an extremely valuable structural tool to meet those ends. In this study, we assess the capability of a recent plasma FIB-SEM technology which provides a potential increase in measurement speed over gallium FIB-SEM, thus paving the way to larger volume analysis. Nanometer-scale layers of demineralized and mineralized unstained human femoral lamellar bone were sequentially sectioned over volumes of 6-16,000 μm 3 . Analysis of mineralized tissue revealed prolate ellipsoidal mineral clusters measuring approximately 1.1 µm in length by 700 nm at their maximum diameter. Those features, suggested by others in high resolution studies, appear here as a ubiquitous motif in mineralized lamellar bone over thousands of microns cubed, suggesting a heterogeneous and yet regular pattern of mineral deposition past the single collagen fibril level. This large scale view retained sufficient resolution to visualize the collagen fibrils while also partly visualizing the lacuno-canalicular network in three-dimensions. These findings are strong evidence for suitability of PFIB as a bone analysis tool and the need to revisit bone mineralization over multi-length scales with mineralized tissue., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This paper is focused on specification of conditions at failure in bovine cortical bone. Both experimental and analytical studies are conducted. The experimental part includes a series of novel direct shear tests which examine the sensitivity of shear strength to the applied normal stress for different orientations of the sample microstructure. These experiments are supplemented by standard axial compression and tension tests in order to define and quantify a general form of failure criterion. The analytical part examines two different methodologies, viz. critical plane approach and microstructure tensor approach, for defining the anisotropic strength criterion. A procedure for identification of material parameters is outlined which is based on the results of the performed material tests.

Till now monocrotophos (MCP) has been addressed as a neurotoxic stressor. Limited studies investigate its aftermath on bone pathologies. Given the fact that MCP is a propensely used insecticide in developing countries, this study investigates its potential to mirror osteoporotic features and bone loss incurred in a rodent model. Briefly, Swiss albino mice were orally gavaged daily with varying doses of MCP for 8 weeks. Musculoskeletal changes were analyzed through micro-computed tomography and histology. A series of in vitro and ex vivo cell culture experiments were performed on MC3T3E-1 and primary osteoclast cultures. Results highlight that oral gavaging with MCP causes bone loss from the cortico-trabecular interface by decreasing the osteoblast and increasing the osteoclast number. Results from in vitro studies establish that MCP treatment increases the TRAP-positive multinucleated cell number during osteoclast differentiation. Ex-vivo experiments with MCP-treated animal sera further substantiate the in vivo claims with significant decreases seen in cell viability, proliferation, mineralization and differentiation studies. In conclusion MCP induces osteoclastogenesis (bone loss) on direct stimulation and alters the circulating factors in MCP-treated serum. Holistically, this work would be of potential significance to patients suffering from pesticide induced osteoporosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bone being a hierarchical composite material has a structure varying from macro- to nanoscale. The arrangement of the components of bone material and the bonding between fibers and matrix gives rise to its unique material properties. In this study, the micromechanisms of cortical bone failure were examined under different loading conditions using scanning electron microscopy. The experimental tests were conducted in longitudinal and transverse directions of bone diaphysis under tensile as well as compressive loading. The results show that bone material has maximum stiffness under longitudinal tensile loading, while the strength is higher under transverse compressive loading. A reverse trend of compressive mechanical properties of bone is observed for longitudinal and transverse loading as compared to trends reported in the previous studies. Therefore, micromechanisms of cortical bone failure were analyzed for different loading conditions to reveal such type of behavior of cortical bone and to correlate bone microstructure with mechanical response of bone., (Copyright © 2020 by ASME.)

Objectives: The femur is a major weight-bearing bone that is variably loaded throughout growth as children transition through locomotory states prior to the attainment of a mature bipedal gait. Here, we document ontogenetic trends in femoral cross-sectional geometry (CSG) and explore how changes in loading regime may impact the structural arrangement of cortical bone along the length of the developing diaphysis., Materials and Methods: Micro-CT scans of 110 immature femora were generated from a documented archaeological sample ranging in age from birth to 8.5 years old. CSG properties indicative of relative bone strength and bending rigidity were analyzed from cross-sections extracted at 35%, 50% and 65% of total intermetaphyseal length., Results: Infants experience a marked redistribution of cortical bone between birth and 7 months facilitating a more advantageous mechanical structure for early load bearing behaviors as bone is displaced further from the section centroid. Early walkers are characterized by a mediolaterally reinforced cross-section that becomes more circular as gait continues to develop., Discussion: During ontogeny the femur undergoes distinct morphological phases, which correspond with changes in loading regime. This study illustrates the importance of loading conditions in shaping immature bone morphology. Nonmechanical factors such as changes in hormonal environmental can also impact on this dynamic., (© 2020 Wiley Periodicals LLC.)

Comprehensive knowledge of strain rate-dependent viscoelastic properties of bony materials is necessary to understand the mechanisms of bone fracture under impact loading conditions (e.g., falls, traffic accidents, and military environments). Although the mechanical properties of bones have been studied for several decades, the high strain rate data and corresponding material parameters of the rate-dependent constitutive models are still limited. In this study, split Hopkinson pressure bar technique was used to test bovine cortical bones, to obtain the rate-dependent stress-strain curves in two directions (along and perpendicular to the bone fibers). A constitutive relationship comprising two terms was then applied to identify the material constants with strain rate effect and viscoelastic properties. In this model, the linear elasticity was combined with nonlinear viscoelasticity components to describe the overall nonlinear strain rate dependence. The presented data give strong experimental evidence and basis for further development of numerical biomechanical models to simulate human cortical bone fracture., (Copyright © 2020 by ASME.)

Calcination and decalcification are basic procedures useful to a morphological approach of a biological, composite material like cortical bone. The study was carried out on a whole human femur conserved in liquid (from an educational collection). Cortical fracturing and SEM observation of vascular canals surface collagen texture was used to study bone deproteination at scalar temperatures (400-1,200°C) and acid bone decalcification at crescent time intervals. Heating burned and vaporized the organic matrix with shrinkage of the bone specimens as documented by the weight loss and transverse surface morphometry. SEM showed a pattern of aligned spherulites at 400°C which maintained the collagen fibrils layout (like a mineral cast), followed by a spherulites fusion progression with the temperature increments. At 1200°C a crystalline-like structure of tightly-packed trapezohendron units. XRD analysis supported the SEM morphology displaying the complete Debey rings of hydroxyapatite and spotted Debey rings of withlockite. Surface Ca and P elution was documented after 12 hr of exposition to the acid solution by dissolution of spherulites and the whole canal surface decalcified in depth after 15 days by SEM-EDAX analysis. The periodic pattern of collagen fibrils was still evident up to 15 days of decalcification together with fine granular deposits of a not-collagenic proteic material, while after 30 days no period was observed in the decalcified fibrils. Collagen mineral cast at 400°C calcination. Complete crystalline transformation at 1200°C. Up to 15 days of decalcification fibrils period maintained., (© 2020 Wiley Periodicals, Inc.)

We review evidence supporting an updated mechanostat model in bone that highlights the central role of osteocytes within bone's four mechanoadaptive pathways: 1) formation modeling and 2) targeted remodeling, which occur with heightened mechanical loading, 3) resorption modeling, and 4) disuse-mediated remodeling, which occur with disuse. These four pathways regulate whole-bone stiffness in response to changing mechanical demands.

Purpose: To determine the effectiveness of a synthetic bone insert on improving medial opening wedge high tibial osteotomy integrity in response to post-surgical cyclical loading., Materials and Methods: A medial opening wedge high tibial osteotomy, secured with a compression fixation plate, was performed on 12 cadaveric knee specimens that were randomised to either: (1) a synthetic insert condition (n = 6), in which a 9 mm bio-absorbable wedge was inserted into the gap space; or (2) a plate-only condition (n = 6). Uniaxial strain gauges, placed on the lateral cortex and fixation plate, measured the strain response as the specimens were subjected to a staircase cyclical loading protocol; a sinusoidal waveform between 100 and 800 N was applied and increased by increments of 200 N every 5000 cycles until failure. Peak strains at failure were compared between conditions using a one-tailed independent samples t test., Results: The strains from the fixation plate were significantly different between the insert and plate only conditions (p = 0.02), transitioning from a compressive strain with the wedge (mean [SD] = - 8.6 [- 3.6] µε) to a tensile strain without the wedge (mean [SD] = 12.9 [23] µε). The strains measured at the lateral cortex were also significantly affected by the inclusion of a synthetic bone insert (p = 0.016), increasing from - 55.6 (- 54.3) µε when the insert was utilised to 23.7 (55.7) µε when only the plate was used., Conclusions: The addition of a synthetic insert limited the tensile strains at the plate and lateral cortex, suggesting that this may protect these regions from fracture during prolonged loading.

Purpose: The study aimed to evaluate the optimal timing for plate removal after open-wedge high tibial osteotomy (OWHTO) without loss of correction and to investigate risk factors for loss of correction after plate removal. The study presents the hypothesis that plate removal without loss of correction was possible when gap filling reached zone 2 (25-50%) on anteroposterior radiographs., Methods: Ninety-one patients (101 knees) who underwent OWHTO using the TomoFix ® plate were enrolled. Plate removal was performed at an average 16.4 ± 5.4 months after OWHTO. Clinical evaluation included plate-related symptoms, the Japanese Orthopedic Association Knee Score (JOA score), and Oxford Knee Score (OKS). Radiological outcomes, including the hip-knee-ankle angle (HKA), weight-bearing line ratio (WBLR), medial proximal tibial angle (MPTA), and posterior tibial slope (PTS), were evaluated preoperatively, at plate removal and at 1 year after plate removal. Computed tomography (CT) was performed at plate removal to evaluate the flange bone union, progression rates of gap filling, and posterior cortex bone union. In addition, the risk factors for loss of correction after plate removal were evaluated., Results: At plate removal, 63 (62.4%) knees had plate-related symptoms (mild, 56 knees; moderate, 7 knees; severe, 0). After plate removal, the JOA score did not change, whereas OKS further improved; six knees developed loss of correction. On CT evaluation at plate removal, the flange bone union was achieved in all cases; the progression rates of gap filling and posterior cortex bone union were 47.0% ± 16.6% and 62.8% ± 16.5%, respectively. A posterior cortex union rate of < 43.3% was the only predictor for loss of correction after plate removal (odds ratio: 1.38, P < 0.01)., Conclusions: Plate removal without loss of correction after OWHTO was possible when bone union of the posterior cortex reached the center of the osteotomy gap even in incompletely filled gaps., Level of Evidence: Therapeutic case series, Level IV.

Water is an important component of bone and plays a key role in its mechanical and structural integrity. Water molecules in bone are present in different locations, including loosely or tightly bound to the matrix and/or mineral (biological apatite) phases. Identification of water location and interactions with matrix components impact bone function but have been challenging to assess. Here, we used near infrared (NIR) spectroscopy to identify loosely and tightly bound water present in cortical bone. In hydrated samples, NIR spectra have two primary water absorption bands at frequencies of ∼5200 and 7000 cm -1 . Using lyophilization and hydrogen-deuterium exchange assays, we showed that these absorption bands are primarily associated with loosely bound bone water. Using further demineralization assays, thermal denaturation, and comparison to standards, we found that these absorption bands have underlying components associated with water molecules tightly bound to bone. In dehydrated samples, the peak at ∼5200 cm -1 was assigned to a combination of water tightly bound to collagen and to mineral, whereas the peak at 7000 cm -1 was exclusively associated with tightly bound mineral water. We also found significant positive correlations between the NIR mineral absorption bands and the mineral content as determined by an established mid infrared spectroscopic parameter, phosphate/amide I. Moreover, the NIR water data showed correlation trends with tissue mineral density (TMD) in cortical bone tissues. These observations reveal the ability of NIR spectroscopy to non-destructively identify loosely and tightly bound water in bone, which could have further applications in biomineralization and biomedical studies.

Background: What is the right surface for an implant to achieve biological fixation? Surface technologies can play important roles in encouraging interactions between the implant surface and the host bone to achieve osseointegration. Preclinical animal models provide important insight into in vivo performance related to bone ongrowth and implant fixation., Methods: A large animal model was used to compare the in vivo response of HA and plasma-sprayed titanium coatings in a well-reported adult ovine model to evaluate bone ongrowth in terms of mechanical properties in cortical sites, and histology and histomorphometry in cortical and cancellous sites at 4 and 12 weeks., Results: Titanium plasma-sprayed surfaces outperformed the HA-coated samples in push-out testing in cortical sites while both surfaces supported new bone ongrowth and remodeling in cortical and cancellous sites., Conclusions: While both HA and Ti plasma provided an osteoconductive surface for bone ongrowth, the Ti plasma provided a more robust bone-implant interface that ideally would be required for load transfer and implant stability in the longer term.

The early diagnosis of osteoporosis through bone quality assessment is a major public health challenge. Research in axial transmission using ultrasonic guided waves has shown the method to be sensitive to the geometrical and mechanical properties of the cortical layer in long bones. However, because of the asymmetric nature of cortical bone, the introduction of a more elaborate numerical model than the analytical plate and cylinder models, as well as its inversion, continues to be challenging. The aim of this article is, therefore, to implement a bone-like geometry using semianalytical finite-element (SAFE) modeling to perform the inverse characterization of ex vivo radii at low frequencies (< 60 kHz). Five cadaveric radiuses were taken from donors aged between 53 and 88 and tested using a typical axial transmission configuration at the middle of the diaphysis. The dispersion curves of the propagating modes were measured experimentally and then systematically compared with the solutions obtained with the SAFE method. For each sample, four parameters were estimated using a parameter identification procedure: 1) the bulk density; 2) the thickness; 3) the outer diameter; and 4) a shape factor (SF). The results showed a moderate agreement between the predicted bulk density and the average voxel value calculated from X-ray computed tomography images. Furthermore, a good agreement was observed between the geometrical parameters (thickness, outer diameter, and SF) and the reference images.

The outer cortical table of the parietal bone has been commonly used as a calvarial bone graft site for the craniofacial reconstruction. However, little is known about how removing the outer table may affect the function and structure of the inner table, and how the knowledge of the biomechanics and material properties of cortical bones will help the calvarial graft to better integrate into the biological and mechanical functions of its surrounding native tissues. In this study, it was hypothesized that there were significant differences in both density and material properties between inner and outer cortical plates in cranial bones. Twelve cylindrical specimens, including inner-outer layers, of cortical parietal bone of a female baboon were collected. Cortical thicknesses and densities were measured, and elastic properties were assessed using an ultrasonic technique. Results demonstrated remarkable difference in both thickness (t = 8.248, p ≤0.05) and density (t = 4.926, p≤0.05) between inner and outer cortical paired samples. Orthotropic characteristics of the cortical plates were detected as well, these findings suggest that there are differences in biomechanical properties between two surfaces of cranial bones at both tissue and organ levels. How these differences are linked to the stress environments of the inner and outer cranial cortical layers awaits further studies. Further study will greatly enhance our ability to address questions derived from both morphological and craniofacial medicine fields about the development and biomechanics of craniofacial skeletons., Competing Interests: The authors also declared that no competing interests exist.

Objectives: Small-bodied vertical clinging and leaping primates have elongated calcanei which enhance leap performance by optimizing leap velocity, distance, and acceleration, but at the expense of experiencing relatively large forces during takeoff and landing. This study tests the hypothesis that the elongated calcaneus of leaping galagids is adapted to resist larger and more stereotyped bending loads compared to more quadrupedal galagids., Materials and Methods: The calcanei of 14 individuals of Otolemur and 14 individuals of Galago (three species of each genus) were μCT scanned. Calcaneal cross-sectional properties (maximum and minimum second moments of area and polar section modulus) were obtained from a slice representing the 50% position of bone segment length and dimensionless ratios were created for each variable using calcaneal cuboid facet area as a proxy for body mass., Results: There were no significant differences in size-adjusted bending strength between Galago and Otolemur. Galago exhibited more elliptically shaped calcaneal cross sections, however, suggesting that its calcanei are more adapted to stereotyped loading regimes than those of Otolemur., Discussion: The results suggest that the calcaneus of specialized leapers is adapted to more stereotyped loading patterns. The lack of predicted bone strength differences between Galago and Otolemur may be related to body size differences between these taxa, or it may indicate that loads encountered by Galago during naturalistic leaping are not reflected in the available experimental force data., (© 2019 Wiley Periodicals, Inc.)

Durophagous fish consume a diet based primarily on hard-shelled animals, mainly mollusks. In order to successfully perform this task, they are equipped with an extra set of jaws located in their throat called pharyngeal jaws. Here we present the results of a study of the structure of the bony material of the exceptionally powerful lower pharyngeal jaws (LPJs) of the black drum Pogonias cromis which generate the highest biting forces documented in bony fishes. In particular, we studied the two long and slender struts that support the entire dental plate and teeth of the LPJ, in order to determine how this structure withstands the huge stresses it encounters repetitively and for long periods of time. We describe the hierarchical structure of the struts of lower pharyngeal jaw of P. cromis at a wide range of length scales, and show how it is adapted to successfully achieve its high mechanical performance. In particular, we show that the bone material of the strut is neither cortical nor cancellous, and although it is highly porous, its complex and layered three-dimensional arrangement of thick lamellae sheets, which are inter-connected by thin plates, is perfectly tailored to withstand extremely large but directionally-consistent forces. STATEMENT OF SIGNIFICANCE: The diet of some fish consists of hard food, like mollusks and shells. In order to accomplish the task of cracking this type of food, they have an extra set of bony jaws located in their throat, called pharyngeal jaws. Here we describe the hierarchical structural elements of these jaws which allow them to withstand huge forces repeatedly over long periods of time. Surprisingly, the structure is very porous, but its architectural design is superbly adapted to handle consistently-oriented forces. This structural motif defines a new bony material which is neither cortical nor cancellous., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Most bone loss during the development of osteoporosis occurs in cortical bone at the peripheral skeleton. Decreased cortical thickness (Ct.Th) and the prevalence of large pores at the tibia are associated with reduced bone strength at the hip. Ct.Th and cortical sound velocity, i.e., a surrogate marker for changes of cortical porosity (Ct.Po), are key biomarkers for the identification of patients at high fracture risk. In this study, we have developed a method using a conventional ultrasound array transducer to determine thickness (Ct.Th) and the compressional sound velocity propagating in the radial bone direction (Ct. ν 11 ) using a refraction-corrected multifocus imaging approach. The method was validated in-silico on porous bone plate models using a 2-D finite-difference time-domain method and ex vivo on plate-shaped plastic reference materials and on plate-shaped cortical bovine tibia samples. Plane-wave pulse-echo measurements provided reference values to assess precision and accuracy of our method. In-silico results revealed the necessity to account for inclination-dependent transmission losses at the bone surface. Moreover, the dependence of Ct. ν 11 on both porosity and pore density was observed. Ct.Th and Ct. ν 11 obtained ex vivo showed a high correlation ) with reference values. The ex-vivo accuracy and precision for Ct. ν 11 were 29.9 m/s and 0.94%, respectively, and those for Ct.Th were 0.04 mm and 1.09%, respectively. In conclusion, this numerical and experimental study demonstrates an accurate and precise estimation of Ct.Th and Ct. ν 11 . The developed multifocus technique may have high clinical potential to improve fracture risk prediction using noninvasive and nonionizing conventional ultrasound technology with image guidance.

Mechanical and microstructural evaluations of cortical bone using ultrashort echo time magnetic resonance imaging (UTE-MRI) have been performed increasingly in recent years. UTE-MRI acquires considerable signal from cortical bone and enables quantitative bone evaluations. Fitting bone apparent transverse magnetization (T2*) decay using a bicomponent model has been regularly performed to estimate bound water (BW) and pore water (PW) in the quantification of bone matrix and porosity, respectively. Human cortical bone possesses a considerable amount of fat, which appears as MRI T2* signal oscillation and can subsequently lead to BW overestimation when using a bicomponent model. Tricomponent T2* fitting model has been developed to improve BW and PW estimations by accounting for fat contribution in the MRI signal. This study aimed to investigate the correlations of microstructural and mechanical properties of human cortical bone with water pool fractions obtained from a tricomponent T2* model. 135 cortical bone strips (~4 × 2 × 40 mm 3 ) from tibial and femoral midshafts of 37 donors (61 ± 24 years old) were scanned using ten sets of dual-echo 3D-UTE-Cones sequences (TE = 0.032-24.0 ms) on a 3 T MRI scanner for T2* fitting analyses. Average bone porosity and pore size were measured using microcomputed tomography (μCT) at 9 μm voxel size. Bone mechanical properties were measured using 4-point bending tests. Using a tricomponent model, bound water fraction (Frac BW ) showed significant strong (R = 0.70, P < 0.01) and moderate (R = 0.58-0.62, P < 0.01) correlations with porosity and mechanical properties, respectively. Correlations of bone microstructural and mechanical properties with water pool fractions were higher for tricomponent model results compared with the bicomponent model. The tricomponent T2* fitting model is suggested as a useful technique for cortical bone evaluation where the MRI contribution of bone fat is accounted for., (© 2019 John Wiley & Sons, Ltd.)

Cortical bone fracture mechanisms are well studied under quasi-static loading. The influence of strain rate on crack propagation mechanisms needs to be better understood, however. We have previously shown that several aspects of the bone micro-structure are involved in crack propagation, such as the complete porosity network, including the Haversian system and the lacunar network, as well as biochemical aspects, such as the maturity of collagen cross-links. The aim of this study is to investigate the influence of strain rate on the toughness of human cortical bone with respect to its microstructure and organic non-collagenous composition. Two strain rates will be considered: quasi-static loading (10 -4  s -1 ), a standard condition, and a higher loading rate (10 -1  s -1 ), representative of a fall. Cortical bone samples were extracted from eight female donors (age 50-91 years). Three-point bending tests were performed until failure. Synchrotron radiation micro-computed tomography imaging was performed to assess bone microstructure including the Haversian system and the lacunar system. Collagen enzymatic cross-link maturation was measured using a high performance liquid chromatography column. Results showed that that under quasi-static loading, the elastic contribution of the fracture process is correlated to both the collagen cross-links maturation and the microstructure, while the plastic contribution is correlated only to the porosity network. Under fall-like loading, bone organization appears to be less linked to crack propagation.

Disorders of the spine are among the most common indications for neurosurgical and orthopedic surgical interventions. Spinal fixation in the form of pedicle screw placement is a common form of instrumentation method in the lower cervical, thoracic, and lumbar spine. A vital principle to understand for the safe and accurate placement of pedicle screws is the palpable difference between the cortical and cancellous bone, both of which have different material properties and compositions. Probing and palpation of the hard cortical bone, also known as the "ventral lamina", covering the neural elements of the spinal canal during screw placement provides manual feedback to the surgeon, indicating an impending breach if continued directional force is applied. Generally, this practice is learned at the expense of patients in live operating room scenarios. Currently, there is a paucity of human vertebra simulation designs that have been validated based on the in vivo ultrastructure and physical properties of human cortical and cancellous bone. In this study, we examined the feasibility of combining three-dimensionally printed thermoplastic polymers with polymeric foam to replicate both the vertebral corticocancellous interface and surface anatomy for procedural education.

Quantitative ultrasound is used to characterize osseointegration at the bone-implant interface (BII). However, the interaction between an ultrasonic wave and the implant remains poorly understood. Hériveaux, Nguyen, and Haiat [(2018). J. Acoust. Soc. Am. 144, 488-499] recently employed a two-dimensional (2D) model of a rough BII to investigate the sensitivity of the ultrasonic response to osseointegration. The present letter aimed at assessing the validity of the 2D assumption. The values of the reflection coefficient of the BII obtained with two and three-dimensional models were found not to be significantly different for implant roughness lower than 20 μm. 2D modeling is sufficient to describe the interaction between ultrasound and the BII.

An in silico model for the estimation of volumetric bone mineral density (vBMD) changes at a cortical bone site subjected to mechanobiological bone remodeling is proposed in this manuscript. Mechanisms of cell differentiation, receptor-ligand binding, mechanical signaling, and resorption or deposition of bone matrix were considered, therefore providing a comprehensive description of mechanobiological bone remodeling in the bone microenvironment and enabling the analysis of temporal evolution of disease or therapy scenarios. The proposed model is composed by five modules, namely, bone cells populations, mechanobiology, volume fractions and porosity, mineral density, and structural stiffness. The model is an extension of other models found in the literature because equations for the obtaining of cortical vBMD and the binding of parathyroid hormone (PTH) to parathyroid hormone 1 receptor are included. The proposed model showed a satisfactory agreement with the solutions of other in silico models found in the literature. Simulations of walking and running exercise routines were performed for the evaluation of model capability regarding the control of the numerical error and prediction of vBMD. The computational method used to solve the case study controlled the relative numerical error by less than 1 × 10-7 for approximately 1.7 × 106 time steps. The predicted values correlate with the concept of increasing BMD by vigorous physical activity; however, they contrast with the specific effect of physical activities on cortical vBMD., (Copyright © 2020 by ASME.)

Quantitative computed tomography-based finite element (QCT-FE) modeling has potential to clarify the role of altered subchondral bone stiffness in osteoarthritis. The objective of this research was to evaluate different QCT-FE modeling and thresholding approaches to identify the method which best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. Our results showed that separate modeling of proximal tibial cortical and trabecular bone offered little improvement in QCT-FE-predicted stiffness (0% to +3% improvement in explained variance) when compared to modeling the proximal tibia as a single structure. Based on the results of this study, we do not recommend separate modeling of cortical bone and trabecular bone when developing QCT-FE models of the proximal tibia for predicting subchondral bone stiffness.

Purpose of Review: This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an effort to elucidate how the balance between the structural and metabolic functions of the skeleton is achieved during these physiological processes., Recent Findings: While pregnancy and lactation induce significant changes in bone density and structure to provide calcium for fetal/infant growth, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity. Both clinical and animal studies suggest that pregnancy and lactation lead to adaptations in cortical bone structure to allow for rapid calcium release from the trabecular compartment while maintaining whole bone stiffness and strength. Moreover, extents of lactation-induced bone loss and weaning-induced recovery are highly dependent on a given bone's load-bearing function, resulting in better protection of the mechanical integrity at critical load-bearing sites. The recent discovery of lactation-induced osteocytic perilacunar/canalicular remodeling (PLR) indicates a new means for osteocytes to modulate mineral homeostasis and tissue-level mechanical properties of the maternal skeleton. Furthermore, lactation-induced PLR may also play an important role in maintaining the maternal skeleton's load-bearing capacity by altering osteocyte's microenvironment and modulating the transmission of anabolic mechanical signals to osteocytes. Both clinical and animal studies show that parity and lactation have no adverse, or a positive effect on bone strength later in life. The skeletal effects during pregnancy and lactation reflect an optimized balance between the mechanical and metabolic functions of the skeleton.