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BACKGROUND: Postmenopausal osteoporosis significantly increases the risk of fracture, which seriously affects the quality of life of patients. Exercise therapy is an important non-drug means and prevention and treatment strategy for patients with osteoporosis, in which strength training is the best mode, but its specific biological mechanism has not been determined. OBJECTIVE: To investigate the effects of strength training on bone morphology, materials and biomechanics in ovariectomized rats and to explore the mechanism of extracellular matrix remodeling. METHODS: Forty-eight female Sprague-Dawley rats were divided into sham operation group, sham operation exercise group, ovariectomized group and ovariectomized exercise group according to the random number table method. The menopausal animal model was established by bilateral ovariectomy in the ovariectomized group and ovariectomized exercise group, while sham operation was performed in the sham operation group and sham operation exercise group. Four weeks after operation, the sham operation exercise group and the ovariectomized exercise group underwent 12-week tail weight-bearing ladder training, and the sham operation group and the ovariectomized group were raised quietly in the cage. The bilateral femur and tibia were separated after training. The right tibia was used for dual-energy X-ray densitometry and biomechanical, biophysical and biochemical analyses, the left tibia was detected using micro-computed tomography for bone microstructural examination, the right femur was subjected to hematoxylin-eosin staining for histological observation, and the left femur was used for western blot and gelatin zymography detection of protein expression and enzyme activity of extracellular matrix metabolismrelated factors, respectively. RESULTS AND CONCLUSION: Compared with the sham operation group, the maximal load and stiffness decreased (P < 0.05), bone density, bone mineral density, bone inorganic matter content, bone calcium content decreased (P < 0.05), bone water content increased (P < 0.05), trabecular bone volume fraction, trabecular connectivity density, and trabecular number decreased (P < 0.05), trabecular separation, structural model index increased (P < 0.05), bone adipocyte number and cross-sectional area increased (P < 0.05), matrix metalloproteinase-2 activity decreased (P < 0.05), and protein expression of tissue inhibitor of metalloproteinase-1 and osteoprotegerin increased (P < 0.05) in the ovariectomized group. Compared with the ovariectomized group, the maximal load, stiffness, fracture load and resilience increased (P < 0.05), bone mineral density, bone mineral content, bone mineral density, bone inorganic matter content, and bone calcium content increased (P < 0.05), bone water content decreased (P < 0.05), trabecular separation and bone marrow area decreased (P < 0.05), trabecular bone thickness, cortical bone volume fraction, cortical bone area fraction, cortical bone thickness, and cortical bone porosity increased (P < 0.05), bone adipocyte number and cross-sectional area reduced (P < 0.05), matrix metalloproteinase-2 activity increased (P < 0.05), and protein expression of tissue inhibitor of metalloproteinase-1, Runt-related transcription factor 2 and osteoprotegerin decreased (P < 0.05) in the ovariectomized exercise group. To conclude, strength training can protect against bone injury caused by estrogen deficiency, which is characterized by improvement of bone biomechanical properties, bone tissue composition and bone microstructure, and its mechanism is related to the regulation of extracellular matrix remodeling. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exercise is an effective method for preventing and treating osteoporosis, but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE: To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats, and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS: A rat model of postmenopausal osteoporosis was established, and a 24-week moderate-intensity exercise was used for intervention. After the experiment, serum estradiol levels were measured by ELISA, and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT. The biomechanical indicators of the tibia were tested by a three-point bending test. Autophagosomes were observed by transmission electron microscopy. The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION: The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group (P < 0.01). The body mass of rats in each group increased, and the order was the ovariectomized group > the ovariectomized+exercise group > the sham-operation group > the sham-operation+exercise group. The bone mineral density and bone mass of rats in all groups significantly increased (P < 0.01), but the increase in the ovariectomized group was significantly lower than that of the other groups, and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group. Compared with the sham-operation group, the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased (P < 0.01), while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased (P < 0.01). Compared with the ovariectomized+exercise group, the ovariectomized group showed significantly lower bone volume fraction, number of trabeculae, and bone mineral density of cancellous bone (P < 0.05), extremely significantly lower trabecular thickness (P < 0.01), and significantly higher mean trabecular pattern factor, trabecular separation, and structural model index (P < 0.01). Compared with the ovariectomized group, the LC3-II/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group (P < 0.05). Compared with the sham-operation and ovariectomized groups, the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups, respectively. To conclude, moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels. [ABSTRACT FROM AUTHOR]

Background: Microgravity, a condition experienced in a spatial environment, poses unique challenges to the skeletal system, particularly in juvenile organisms. This study aimed to investigate alterations in bone biomechanics of juvenile mice due to unloading – that simulates microgravity in the laboratory—and the effects of a bone-loading intervention. We compared bone compositional and mechanical properties between 21-six-week-old C57Bl/6 from a control group (wild type) and a group that underwent a tail-suspension unloading protocol to mimic microgravity (MG). The second group (MG) experienced additional in vivo loading protocol (MG + LDG) on the right hind leg, where dynamic compressive loading was applied to the right knee using a custom-built loading device. Results: Our results show that after two weeks, we successfully induced bone alterations by (i) decreasing the energy dissipated before fracture and (ii) decreasing the yield and maximum stress. In addition, we showed that Mineral to matrix component [ν1PO4/Amide I], Carbonate to Amide [CO3/Amide I], and Crystallinity [1/FWHM(ν1PO4)] are strongly linked in physiological bone but not in microgravity even after loading intervention. While Crystallinity is very sensitive to bone deformation (strain) alterations coming from simulated microgravity, we show that Carbonate to Amide [CO3/Amide I] – a common marker of turnover rate/remodeling activity—is a specific predictor of bone deformation for bone after simulated microgravity. Our results also invalidate the current parameters of the loading intervention to prevent bone alterations entirely in juvenile mice. Conclusions: Our study successfully induced bone alterations in juvenile mice by using an unloading protocol to simulate microgravity, and we provided a new Raman Spectroscopy (RS) dataset of juvenile mice that contributes to the prediction of cortical bone mechanical properties, where the degree of interrelationship for RS data for physiological bone is improved compared to the most recent evidence. [ABSTRACT FROM AUTHOR]

• Syndecan 4 null mice show vertebral osteopenia, reduced bone stiffness, and functionally altered bone biomechanics. • Osteopenic phenotype in Sdc4 null mice is driven by elevated osteoclast numbers. • Syndecan 4 fine-tunes collagen maturity and ECM composition in the intervertebral disc during early adult life. • Transcriptomic analysis shows dysregulation in heparan sulfate biosynthesis, UPR, and degradation along with decreased mitochondria metabolism. Syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan, is known to regulate matrix catabolism by nucleus pulposus cells in an inflammatory milieu. However, the role of SDC4 in the aging spine has never been explored. Here we analyzed the spinal phenotype of Sdc4 global knockout (KO) mice as a function of age. Micro-computed tomography showed that Sdc4 deletion severely reduced vertebral trabecular and cortical bone mass, and biomechanical properties of vertebrae were significantly altered in Sdc4 KO mice. These changes in vertebral bone were likely due to elevated osteoclastic activity. The histological assessment showed subtle phenotypic changes in the intervertebral disc. Imaging-Fourier transform-infrared analyses showed a reduced relative ratio of mature collagen crosslinks in young adult nucleus pulposus (NP) and annulus fibrosus (AF) of KO compared to wildtype discs. Additionally, relative chondroitin sulfate levels increased in the NP compartment of the KO mice. Transcriptomic analysis of NP tissue using CompBio, an AI-based tool showed biological themes associated with prominent dysregulation of heparan sulfate GAG degradation, mitochondria metabolism, autophagy, endoplasmic reticulum (ER)-associated misfolded protein processes and ER to Golgi protein processing. Overall, this study highlights the important role of SDC4 in fine-tuning vertebral bone homeostasis and extracellular matrix homeostasis in the mouse intervertebral disc. [ABSTRACT FROM AUTHOR]

O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D--binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system. [ABSTRACT FROM AUTHOR]

Bone loss in lower limbs under space microgravity condition can persist even after the astronauts return to Earth's gravitational environment. It is crucial to determine the extent and timing of bone recovery after spaceflight, especially for long-term flights. However, there is a lack of comprehensive descriptions of the recovery of various aspects of bone quality, particularly in terms of compositional characteristics that reflect changes in bone quality. Therefore, the objective of this study is to investigate the alterations in bone mineral density, composition characteristics, and mechanical properties of rat lower limbs during unloading (tail suspension) and the subsequent recovery loading period. Rats were subjected to tail suspension for four weeks (TS4) followed by reloading for an additional four weeks. Bone mineral density (BMD) was measured by μ-CT and analyzed. The mechanical properties of the tibia were assessed by a three-point bending test, and the composition characteristics of bone tissue were evaluated using Raman spectroscopy. Regression analysis was performed to identify main component related to mechanical property. In the metaphysis, BMD of the tibia significant decreased, particularly in trabecular bone. Upon reloading, only the cortical bone showed recovery. In the diaphysis, cortical bone remained unchanged during unloading but demonstrated delayed bone loss during the reloading period. Simultaneously, the mechanical properties of tibia experienced a substantial reduction after four weeks of unloading, The stiffness and maximum strength did not fully recover, though the elastic modulus and the ultimate strength were restored following the reloading process. Raman spectroscopy characterization found an increase in the carbonate substitution and crystal crystallinity of the diaphysis after 4 weeks of unloading. There was an intriguing alteration in the mineralized collagen ratio, that an increase was observed in the diaphysis while a decrease was observed in the metaphysis. During 4 weeks of reloading, the compositional characteristics of the diaphysis recovered earlier than those of the metaphysis, with the exception of crystallinity which remained unrecovered. Regression analysis indicated that carbonate replacement has a strong correlation to bone mechanical properties during the 4 weeks of unloading and subsequent 4 weeks of reloading. The data obtained in this study highlight the incomplete recovery of bone mineral density, mechanical properties, and compositional characteristics during reloading in tail-suspended rats. These findings deepen our understanding of microgravity-induced bone loss and provide valuable information to develop interventions not only for astronauts but also for persons on earth during and after prolonged periods of unloading. • Cortical and cancellous bone exhibit distinct responses to gravitational forces. • The components of load-bearing bone do not immediately recover after recovery from gravity. • The substitution of carbonate during periods of reloading is highly associated with the mechanical properties of bone. [ABSTRACT FROM AUTHOR]

We present a reduced order model for efficient nonlinear homogenization of bones, accounting for strength difference effects and containing some well‐known plasticity models (like von Mises or Drucker‐Prager) as special cases. The reduced order homogenization is done by using a cluster‐based model order reduction technique, called cluster‐based nonuniform transformation field analysis. For an offline phase, a space–time decomposition is performed on the mesoscopic plastic strain fields, while a clustering analysis is employed for a spatial decomposition of the mesoscale RVE model. A volumetric‐deviatoric split is additionally introduced to capture the enriched characteristics of the mesoscopic plastic strain fields. For an online analysis, the reduced order model is formulated in a unified minimization problem, which is compatible with a large variety of material models. Both cortical and trabecular bones are considered for numerical experiments. Compared to conventional FE‐based RVE computations, the developed reduced order model renders a considerable acceleration rate beyond 103, while maintaining a sufficient accuracy level. [ABSTRACT FROM AUTHOR]

A comprehensive study of deformation and destruction of compact bone tissue was carried out. Deformation of cylindrical samples was carried out in the mode of constant feed rate of the press plunger. During the experiments, deformation, changes in photon radiation on the surface of the samples and acoustic emission were recorded. It is shown that the initial accumulation of stresses on the relative axis of deformation for the occurrence of a crack on the lateral surface of the sample is the first link in the chain of formation of the micro-cut plane and an indicator of its orientation relative to the axis of the cylinder. The incipient plane of a macro-crack is a zone of increased local stresses, which stimulates the appearance of new microcracks in it. In this case, the exit of the microcrack to the lateral surface of the sample of compact bone tissue (human tibia) coincides in time with the registration of photoluminescence. [ABSTRACT FROM AUTHOR]

The determination of bone mechanical properties remains crucial, especially to feed up numerical models. An original methodology of inverse analysis has been developed to determine the longitudinal elastic modulus of femoral cortical bone. The method is based on a numerical twin of a specific three-point bending test. It has been designed to be reproducible on each test result. In addition, the biofidelity of the geometric acquisition method has been quantified. As the assessment is performed at the scale of a bone shaft segment, the Young's modulus values obtained (between 9518.29 MPa and 14181.15 MPa) are considered average values for the whole tissue, highlighting some intersubject variability. The material microstructure has also been studied through histological analysis, and bone-to-bone comparisons highlighted discrepancies in quadrants microstructures. Furthermore, significant intrasubject variability exists since differences between the bone's medial-lateral and anterior-posterior quadrants have been observed. Thus, the study of microstructures can largely explain the differences between the elastic modulus values obtained. However, a more in-depth study of bone mineral density would also be necessary and would provide some additional information. This study is currently being setup, alongside an investigation of the local variations of the elastic modulus. [ABSTRACT FROM AUTHOR]

This article studies the convolutional kernel function of fractal operators in bone fibers. On the basis of the micro-nano composite structure of compact bone, we abstracted the physical fractal space of bone fibers and derived the fractal operators. The article aims to construct the convolutional analytical expression of bone fractal operators and proves that the error function is the core component of the convolution kernel function in the fractal operators. In other words, bone mechanics is the fractional mechanics controlled by error function. [ABSTRACT FROM AUTHOR]

Background: Running with the appropriate intensity may produce a positive influence on the mechanical properties of cortical bone structure. However, few studies have discussed the effects of different running intensities on the mechanical properties at different levels, especially at the micro-level, because the micromechanical parameters are difficult to measure experimentally. Methods: An approach that combines finite element analysis and experimental data was proposed to predict a micromechanical parameter in the rat femoral cortical bone structure, namely, the micro-level failure strain. Based on the previous three-point bending experimental information, fracture simulations were performed on the femur finite element models to predict their failure process under the same bending load, and the micro-level failure strains in tension and compression of these models were back-calculated by fitting the experimental load–displacement curves. Then, the effects of different running intensities on the micro-level failure strain of rat femoral cortical bone structure were investigated. Results: The micro-level failure strains of the cortical bone structures expressed statistical variations under different running intensities, which indicated that different mechanical stimuli of running had significant influences on the micromechanical properties. The greatest failure strain occurred in the cortical bone structure under low-intensity running, and the lowest failure strain occurred in the structure under high-intensity running. Conclusions: Moderate and low-intensity running were effective in enhancing the micromechanical properties, whereas high-intensity running led to the weakening of the micromechanical properties of cortical bone. Based on these, the changing trends in the micromechanical properties were exhibited, and the effects of different running intensities on the fracture performance of rat cortical bone structures could be discussed in combination with the known mechanical parameters at the macro- and nano-levels, which provided the theoretical basis for reducing fracture incidence through running exercise. [ABSTRACT FROM AUTHOR]

Bone remodeling is an extraordinarily complex process involving a variety of factors, such as genetic, metabolic, and environmental components. Although genetic factors play a particularly important role, many have not been identified. In this study, we investigated the role of transmembrane 161a (Tmem161a) in bone structure and function using wild-type (WT) and Tmem161a-depleted (Tmem161aGT/GT) mice. Mice femurs were examined by histological, morphological, and bone strength analyses. Osteoblast differentiation and mineral deposition were examined in Tmem161a-overexpressed, -knockdown and -knockout MC3T3-e1 cells. In WT mice, Tmem161a was expressed in osteoblasts of femurs; however, it was depleted in Tmem161aGT/GT mice. Cortical bone mineral density, thickness, and bone strength were significantly increased in Tmem161aGT/GT mice femurs. In MC3T3-e1 cells, decreased expression of alkaline phosphatase (ALP) and Osterix were found in Tmem161a overexpression, and these findings were reversed in Tmem161a-knockdown or -knockout cells. Microarray and western blot analyses revealed upregulation of the P38 MAPK pathway in Tmem161a-knockout cells, which referred as stress-activated protein kinases. ALP and flow cytometry analyses revealed that Tmem161a-knockout cells were resistant to oxidative stress. In summary, Tmem161a is an important regulator of P38 MAPK signaling, and depletion of Tmem161a induces thicker and stronger bones in mice. [ABSTRACT FROM AUTHOR]

Enzymatic cross-linking of the bone collagen is important to resist to crack growth and to increased flexural strength. In the present study, we proposed a new method for assessment of enzymatic cross-link based on Fourier transform infrared (FTIR) microspectroscopy that takes into account secondary structure of type I collagen. Briefly, femurs were collected from sham or ovariectomized mice and subjected either to high-performance liquid chromatography—mass spectrometry or embedded in polymethylmethacrylate, cut and analyzed by FTIR microspectroscopy. FTIR acquisition was recorded before and after ultraviolet (UV) exposure or acid treatment. In addition, femurs from a second animal study were used to compare gene expression of Plod2 and Lox enzymes and enzymatic cross-links determined by FTIR microspectroscopy. We evidenced here that intensities and areas of subbands located at ~1660, ~1680, and ~1690 cm−1 were positively and significantly associated with the concentration of pyridinoline (PYD), deoxypyridinoline, or immature dihydroxylysinonorleucine/hydroxylysinonorleucine cross-links. Seventy-two hours exposure to UV light significantly reduced by ~86% and ~89% the intensity and area of the ~1660 cm−1 subband. Similarly, 24 h of acid treatment significantly reduced by 78% and 76% the intensity and area of the ~1690 cm−1 subband. Plod2 and Lox expression were also positively associated to the signal of the ~1660 and ~1690 cm−1 subbands. In conclusion, our study provided a new method for decomposing the amide I envelope of bone section that positively correlates with PYD and immature collagen cross-links. This method allows for investigation of tissue distribution of enzymatic cross-links in bone section. [ABSTRACT FROM AUTHOR]

Compact, mineralized cortical bone tissues are often concealed on magnetic resonance (MR) images. Recent development of MR instruments and pulse techniques has yielded significant advances in acquiring anatomical and physiological information from cortical bone despite its poor 1H signals. This work demonstrates the first MR research on cortical bones under an ultrahigh magnetic field of 14 T. The 1H signals of different mammalian species exhibit multi‐exponential decays of three characteristic T2 or T2* values: 0.1–0.5 ms, 1–4 ms, and 4–8 ms. Systematic sample comparisons attribute these T2/T2* value ranges to collagen‐bound water, pore water, and lipids, respectively. Ultrashort echo time (UTE) imaging under 14 T yielded spatial resolutions of 20–80 microns, which resolves the 3D anatomy of the Haversian canals. The T2* relaxation characteristics further allow spatial classifications of collagen, pore water and lipids in human specimens. The study achieves a record of the spatial resolution for MR imaging in bone and shows that ultrahigh‐field MR has the unique ability to differentiate the soft and organic compartments in bone tissues. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

For biomechanical simulations of orthopaedic interventions, it is imperative to implement a material model that can realistically reproduce the nonlinear behavior of the bone structure. However, a proper material model that adequately combines the trabecular and cortical bone response is not yet widely identified. The current paper aims to investigate the possibility of using an isotropic crushable foam (ICF) model dependent on local bone mineral density (BMD) for simulating the femoral fracture risk. The elastoplastic properties of fifty-nine human femoral trabecular cadaveric bone samples were determined and combined with existing cortical bone properties to characterize two forms of the ICF model, a continuous and discontinuous model. Subsequently, the appropriateness of this combined material model was evaluated by simulating femoral fracture experiments, and a comparison with earlier published results of a softening Von-Mises (sVM) material model was made. The obtained mechanical properties of the trabecular bone specimens were comparable to previous findings. Furthermore, the ultimate failure load predicted by the simulations of femoral fractures was on average 79% and 90% for the continuous and discontinuous forms of the ICF model and 82% of the experimental value for the sVM material model. Also, the fracture locations predicted by ICF models were comparable to the experiments. In conclusion, a nonlinear material model dependent on BMD was characterized for human femoral bone. Our findings indicate that the ICF model could predict the femoral bone strength and reproduce the variable fracture locations in the experiments. [ABSTRACT FROM AUTHOR]

β-Arrestin 2 (β-arr2) binds activated parathyroid hormone (PTH) receptors stimulating internalization. PTH stimulates both anabolic and catabolic effect on bone depending on the way it is administered. Intermittent PTH stimulation increases trabecular bone formation in mice, but this is decreased in mice lacking β-arr 2, suggesting a role for β-arr 2 in the anabolic effects of PTH. The role of β-arr 2 in the catabolic effects of continuous PTH (cPTH) treatment is not known. To assess the effects of cPTH administration on bone in mice lacking β-arr 2 compared to wild-type (WT). Groups of male and female WT or β-arr2 knockout (KO) mice were administered either PTH or phosphate-buffered saline by osmotic pumps for 2 weeks. Following treatment, serum calcium and phosphate levels were measured, bone structure and mineral density were measured by microcomputed tomography, and bone cells measured by static and dynamic histomorphometry. β-arr2 KO had no effects on skeletal development in mice of either sex. PTH treatment caused hypercalcemia and hypophosphatemia and decreased trabecular and cortical bone only in male WT mice. β-arr2 KO in male mice completely abrogated the effects of PTH on bone, while in female β-arr2 KO mice, PTH treatment increased trabecular bone with no effects on cortical bone. These results demonstrate a profound sex effect on skeletal responses to cPTH treatment, suggesting a protective effect of estrogen on bone loss. β-arr2 plays a role in restraining the anabolic effects of PTH in both male and female mice. [ABSTRACT FROM AUTHOR]

In cases where human remains are unidentified because there is no initial identification hypothesis, limited contextual information, and/or poor preservation, radiocarbon (14C) dating may be a useful tool to further assist with identification. Through measuring the amount of 14C remaining in organic material, such as bone, teeth, nail, or hair, radiocarbon dating may provide an estimated year of birth and year of death for a deceased person. This information, may assist in, establishing whether a case of unidentified human remains (UHR) is actually of medicolegal significance and therefore, requires forensic investigation and identification. This case series highlights the application of 14C dating to seven of the 132 UHR cases in Victoria, Australia. Cortical bone was sampled from each case and the level of 14C was measured to provide an estimated year of death. Four of the seven cases analyzed contained the levels of 14C consistent with an archeological timeframe, one contained a level of 14C consistent with a modern (i.e., of medicolegal significance) timeframe, and the results for the remaining two samples were inconclusive. Applying this technique not only reduced the number of UHR cases in Victoria but also has investigative, cultural, and practical implications for medicolegal casework in general. [ABSTRACT FROM AUTHOR]

Bone undergoes constant remodeling by osteoclast bone resorption coupled with osteoblast bone formation at the bone surface. A third major cell type in the bone is osteocytes, which are embedded in the matrix, are well‐connected to the lacunar network, and are believed to act as mechanical sensors. Here, it is reported that sympathetic innervation directly regulates lacunar osteocyte‐mediated bone resorption inside cortical bone. It is found that sympathetic activity is elevated in different mouse models of bone loss, including lactation, ovariectomy, and glucocorticoid treatment. Further, during lactation elevated sympathetic outflow induces netrin‐1 expression by osteocytes to further promote sympathetic nerve sprouting in the cortical bone endosteum in a feed‐forward loop. Depletion of tyrosine hydroxylase‐positive (TH+) sympathetic nerves ameliorated osteocyte‐mediated perilacunar bone resorption in lactating mice. Moreover, norepinephrine activates β‐adrenergic receptor 2 (Adrb2) signaling to promote secretion of extracellular vesicles (EVs) containing bone‐degrading enzymes for perilacunar bone resorption and inhibit osteoblast differentiation. Importantly, osteocyte‐specific deletion of Adrb2 or treatment with a β‐blocker results in lower bone resorption in lactating mice. Together, these findings show that the sympathetic nervous system promotes osteocyte‐driven bone loss during lactation, likely as an adaptive response to the increased energy and mineral demands of the nursing mother. [ABSTRACT FROM AUTHOR]

Background: Femoral neck fractures are a common injury in older adults and their management presents a significant challenge for orthopedic surgeons. The Femoral Neck System (FNS) was recently introduced for the fixation of femur neck fractures. Although neck shortening was reduced with the FNS, the complication rates were not reduced. Thus, improvements to enhance fixation stability should be made for the FNS. We hypothesized that (1) the pre-sliding technique and (2) the use of longer anti-rotation screw would increase fracture stability. This study aimed to determine the change in fracture stability using the pre-sliding technique and long anti-rotation screw in the FNS for fixation of Pauwels type III femoral neck fractures. Methods: Finite element models of Pauwels type III femoral neck fracture fixed with pre-sliding FNS and 5-mm longer anti-rotation screw were established. The models were subjected to normal walking load. The material properties of the elements belonging to the bone were mapped by assigning the formulation with the computed tomography Hounsfield unit. Results: Pauwels type III femoral neck fractures fixed with pre-slided FNS showed better fracture stability, decreasing fracture gap and sliding by 14% and 12%, respectively, under normal walking load. No element of cortical bone in any of the models had an absolute value of principal strain that exceeded 1%. The peak von Mises stress (VMS) of the implants ranged from 260 to 289 MPa, and the highest peak VMS value was 50% lower than the yield strength of the titanium alloy (800 MPa). The longer anti-rotation screw did not affect fracture stability. Conclusions: The pre-sliding technique using the FNS showed higher fracture stability than the standard fixation technique for a Pauwels type III femoral neck fracture. The longer anti-rotation screw did not contribute significantly to fixation stability. As this finite element analysis considered the inhomogeneous mechanical property of the bone, it offered equivalent mechanical conditions to investigate the components of interest. [ABSTRACT FROM AUTHOR]

Significant effort continues to be made to understand whether differences exist in the structural, compositional, and mechanical properties of cortical bone subjected to different strain modes or magnitudes. We evaluated juvenile sheep femora (age = 4 months) from the anterior and posterior quadrants at three points along the diaphysis as a model system for variability in loading. Micro-CT scans (50 micron) were used to measure cortical thickness and mineral density. Three point bending tests were performed to measure the flexural modulus, strength, and post-yield displacement. There was no difference in cortical thickness or density between anterior or posterior quadrants; however, density was consistently higher in the middle diaphysis. Interestingly, bending modulus and strength were higher in anterior quadrants compared to posterior quadrants. Together, our results suggest that there is a differential spatial response of bone in terms of elastic bending modulus and mechanical strength. The origins of this difference may lie within the variation in ongoing mineralization, in combination with the collagen-rich plexiform structure, and whether this is related to strain mode remains to be explored. These data suggest that in young ovine cortical bone, modulation of strength occurs via potentially complex interactions of both mineral and collagen-components that may be different in regions of bone exposed to variable amounts of strain. Further work is needed to confirm the physiological load state of bone during growth to better elucidate the degree to which these variations are a function of the local mechanical environment. [ABSTRACT FROM AUTHOR]

Ultrashort echo time (UTE) MRI techniques can be used to image the concentration of water in bones. Particularly, quantitative MRI imaging of collagen-bound water concentration (Cbw) and pore water concentration (Cpw) in cortical bone have been shown as potential biomarkers for bone fracture risk. To investigate the effect of Cbw and Cpw on the evaluation of bone mechanical properties, MRI-based finite element models of cadaver radii were generated with tissue material properties derived from 3 D maps of Cbw and Cpw measurements. Three-point bending tests were simulated by means of the finite element method to predict bending properties of the bone and the results were compared with those from direct mechanical testing. The study results demonstrate that these MRI-derived measures of Cbw and Cpw improve the prediction of bone mechanical properties in cadaver radii and have the potential to be useful in assessing patient-specific bone fragility risk. [ABSTRACT FROM AUTHOR]

As we age, our bones undergo a process of loss, often accompanied by muscle weakness and reduced physical activity. This is exacerbated by decreased responsiveness to mechanical stimulation in aged skeleton, leading to the hypothesis that decreased mechanical stimulation plays an important role in age‐related bone loss. Piezo1, a mechanosensitive ion channel, is critical for bone homeostasis and mechanotransduction. Here, we observed a decrease in Piezo1 expression with age in both murine and human cortical bone. Furthermore, loss of Piezo1 in osteoblasts and osteocytes resulted in an increase in age‐associated cortical bone loss compared to control mice. The loss of cortical bone was due to an expansion of the endosteal perimeter resulting from increased endocortical resorption. In addition, expression of Tnfrsf11b, encoding anti‐osteoclastogenic protein OPG, decreases with Piezo1 in vitro and in vivo in bone cells, suggesting that Piezo1 suppresses osteoclast formation by promoting Tnfrsf11b expression. Our results highlight the importance of Piezo1‐mediated mechanical signaling in protecting against age‐associated cortical bone loss by inhibiting bone resorption in mice. [ABSTRACT FROM AUTHOR]

Cortical bone allograft sterilized with a standard γ‐radiation dose of 25–35kGy has demonstrated reduced static and cyclic fracture resistance compared with unirradiated bone. To mitigate radiation damage, we recently observed a dose‐dependent response of high‐cycle fatigue behavior of human cortical bone from 0 to 25 kGy, with lower doses exhibiting logarithmically longer fatigue lives. The objectives of this study were as follows: (1) to determine whether fracture toughness, work‐to‐fracture, and fatigue crack propagation resistance of human cortical bone are also radiation dose‐dependent, and (2) to determine the associations of radiation dose and a Raman biomarker for collagen disorder with fracture properties. Compact tension specimens were machined from two donor femoral pairs and allocated to four treatment groups: 0 (unirradiated control), 10, 17.5, and 25 kGy. Fracture toughness specimens were monotonically loaded to failure and the critical stress intensity factor (KC) was determined. Work‐to‐fracture was calculated from the load versus displacement integral up to fracture. Fatigue crack propagation specimens were cyclically loaded under constant room‐temperature irrigation and fatigue crack growth rate (da/dN) and cyclic stress intensity (∆K) were calculated. Fracture toughness, work‐to‐fracture, and fatigue crack propagation resistance decreased 18%, 33%, and 15‐fold from 0 to 25 kGy, respectively (p < 0.05). Radiation dose was more predictive of fracture properties than collagen disorder. These findings support that quasi‐static and fatigue fracture properties of cortical bone are radiation dose‐dependent within this dose range. The structural alterations arising from irradiation that cause these losses in fracture resistance remain to be elucidated. [ABSTRACT FROM AUTHOR]

Skeletal pneumaticity is a key feature of extant avian structure and biology, which first evolved among the non-flying archosaurian ancestors of birds. The widespread presence of air-filled bones across the postcranial skeleton is unique to birds among living vertebrates, but the true extent of skeletal pneumaticity has never been quantitatively investigated—hindering fundamental insights into the evolution of this key avian feature. Here, we use microCT scans of fresh, frozen birds to directly quantify the fraction of humerus volume occupied by air across a phylogenetically diverse taxon sample to test longstanding hypotheses regarding the evolution and function of avian skeletal pneumatization. Among other insights, we document weak positive allometry of internal air volume with humeral size among pneumatized humeri and provide strong support that humeral size, body mass, aquatic diving, and the presence or absence of pneumaticity all have independent effects on cortical bone thickness. Our quantitative evaluation of humeral pneumaticity across extant avian phylogeny sheds new light on the evolution and ontogenetic progression of an important aspect of avian skeletal architecture, and suggests that the last common ancestor of crown birds possessed a highly pneumatized humerus. [ABSTRACT FROM AUTHOR]

BACKGROUND: Implant fixation has become a more satisfactory repair method for patients. All-on-Four and pterygomaxillary implants can meet the implant requirements under certain conditions. At present, there is no biomechanical comparative analysis of the two schemes under different bone quality conditions. OBJECTIVE: To explore the appropriate implant scheme, three-dimensional finite element analysis was used to compare the stress distribution of All-on-Four and pterygomaxillary implant under different bone conditions. METHODS: The cone beam CT data of an edentulous patient with severe maxillary bone deficiency were selected, in order to set up physical models with three kinds of cortical bone thickness (1.0, 1.5, 2.0 mm) and two cancellous bone densities (high density, low density). For each model, All-on-Four and pterygomaxillary implant schemes were designed respectively. A total of 12 models were established and 200 N vertical static forces were applied to the bilateral posterior teeth to calculate the von Mises stress values of implants and cortical bone, together with the deformation of titanium framework. RESULTS AND CONCLUSION: (1) The von Mises stress values of implants and cortical bone were at the most distal site and the deformation of titanium framework was at the distal end of the stent in All-on-Four and pterygomaxillary implant designs. (2) Under the same cancellous bone density, the von Mises stress values of implants and cortical bone and the deformation of titanium framework were the highest in 1 mm cortical bone, and decreased with the increase of cortical bone thickness in All-on-Four and pterygomaxillary implant designs. (3) Under the same implant design, the von Mises stress values of implant, cortical bone and the deformation of titanium framework were larger in low-density cancellous bone than those of high-density cancellous bone. (4) Under the condition of the same bone, the von Mises stress values of implant, cortical bone and titanium framework deformation in pterygomaxillary implant group were lower than those in All-on-Four group (P < 0.05). (5) The results showed that the increase of cortical bone thickness and cancellous bone density could reduce the stress concentration of implants and cortical bone and the deformation of titanium framework. From the perspective of biomechanics, the pterygomaxillary implant was more favorable for long-term prognosis than All-on-Four [ABSTRACT FROM AUTHOR]

Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE−xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu. [ABSTRACT FROM AUTHOR]

The zygapophyseal joints of the spine, also known as the facet joints, are paired diarthrodial joints posterior to the intervertebral disc and neural elements. The pathophysiology of facet osteoarthritis (OA), as well as crosstalk between the disc and facets, remains largely understudied compared to disc degeneration. The purpose of this study was to characterize alterations to human facet cartilage and subchondral bone across a spectrum of degeneration and to investigate correlations between disc and facet degeneration. Human lumbar facet articular surfaces from six independent donors were subject to creep indentation mechanical testing to quantify cartilage mechanical properties, followed by microcomputed tomography (µCT) analyses for subchondral bone morphometry. The degenerative state of each articular surface was assessed via macroscopic scoring and via Osteoarthritis Research Society International histopathology scoring. Our data suggest reduced facet cartilage compressive and tensile moduli and increased permeability with increasing degenerative grade, particularly at the lower levels of the spine. µCT analyses revealed spinal level‐dependent alterations to the subchondral bone, with an increase in trabecular bone at the L4−L5 level, but a decrease at the upper levels of the lumbar spine with increasing degenerative grade. Cortical bone volume fraction was generally decreased with increasing degenerative grade across spinal levels. Correlation analysis revealed several associations between quantitative measures of disc degeneration and facet OA. This study showed that alterations in the mechanical properties of facet cartilage and in the structural properties of facet subchondral bone correlated with aspects of disc degeneration and were highly dependent on spinal level. [ABSTRACT FROM AUTHOR]

Vertical bone augmentation to create host bone prior to implant placement is one of the most challenging regenerative procedures. The objective of this study is to evaluate the capacity of a UV-photofunctionalized titanium microfiber scaffold to recruit osteoblasts, generate intra-scaffold bone, and integrate with host bone in a vertical augmentation model with unidirectional, limited blood supply. Scaffolds were fabricated by molding and sintering grade 1 commercially pure titanium microfibers (20 μm diameter) and treated with UVC light (200–280 nm wavelength) emitted from a low-pressure mercury lamp for 20 min immediately before experiments. The scaffolds had an even and dense fiber network with 87% porosity and 20–50 mm inter-fiber distance. Surface carbon reduced from 30% on untreated scaffold to 10% after UV treatment, which corresponded to hydro-repellent to superhydrophilic conversion. Vertical infiltration testing revealed that UV-treated scaffolds absorbed 4-, 14-, and 15-times more blood, water, and glycerol than untreated scaffolds, respectively. In vitro, four-times more osteoblasts attached to UV-treated scaffolds than untreated scaffolds three hours after seeding. On day 2, there were 70% more osteoblasts on UV-treated scaffolds. Fluorescent microscopy visualized confluent osteoblasts on UV-treated microfibers two days after seeding but sparse and separated cells on untreated microfibers. Alkaline phosphatase activity and osteocalcin gene expression were significantly greater in osteoblasts grown on UV-treated microfiber scaffolds. In an in vivo model of vertical augmentation on rat femoral cortical bone, the interfacial strength between innate cortical bone and UV-treated microfiber scaffold after two weeks of healing was double that observed between bone and untreated scaffold. Morphological and chemical analysis confirmed seamless integration of the innate cortical and regenerated bone within microfiber networks for UV-treated scaffolds. These results indicate synergy between titanium microfiber scaffolds and UV photofunctionalization to provide a novel and effective strategy for vertical bone augmentation. [ABSTRACT FROM AUTHOR]

Cortical bone is a complex hierarchical structure consisting of biological fiber composites with transversely isotropic constituents, whose microstructures deserve extensive study to understand the mechanism of living organisms and explore development of biomimetic materials. Based on this, we establish a three-level hierarchical structure from microscale to macroscale and propose a multiscale micromechanics model of cortical bone, which considers Haversian canal, osteonal lamellae, cement line and interstitial lamellae. In order to study the microstructural effect on the elastic behavior of hierarchical structures, the Mori–Tanaka model and locally exact homogenization theory are introduced for the homogenization of heterogeneous materials of microstructure at each level. Within sub-microscale, Haversian canal and Osteonal lamella are treated as fiber and matrix, whose homogenization is surrounded with cement line matrix in microstructure (or what we called "osteon") for the second homogenization; finally, osteon and interstitial lamella establish the meso-structure for the third homogenization, predicting the effective moduli of cortical bone. The correctness of the model in this paper is verified against the data in literature with good agreement. Finally, the dynamic viscoelastic response of cortical bones is investigated from a multiscale perspective, where the measured data are substituted into the present models to study the hydration and aging effect on bones' stiffness and viscoelasticity. It is demonstrated that the hydration is much more influential in affecting the storage and loss moduli of cortical bone than the aging effect. We also present a few numerical investigations on microstructural material and geometric parameters on the overall mechanical properties of cortical bone. [ABSTRACT FROM AUTHOR]

Background Anemia and chronic kidney disease–mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) versus intravenous (IV) iron on CKD-MBD and iron homeostasis in moderate CKD. Methods We tested the effects of 10 weeks of 2% FC versus IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates. Outcomes included a comprehensive assessment of CKD-MBD, iron homeostasis and oxidative stress. Results CKD rats had azotemia, elevated phosphorus, parathyroid hormone and fibroblast growth factor-23 (FGF23). Compared with untreated CKD rats, treatment with FC led to lower plasma phosphorus, intact FGF23 and a trend (P = 0.07) toward lower C-terminal FGF23. FC and IV iron equally reduced aorta and heart calcifications to levels similar to NL animals. Compared with NL animals, CKD animals had higher bone turnover, lower trabecular volume and no difference in mineralization; these were unaffected by either iron treatment. Rats treated with IV iron had cortical and bone mechanical properties similar to NL animals. FC increased the transferrin saturation rate compared with untreated CKD and NL rats. Neither iron treatment increased oxidative stress above that of untreated CKD. Conclusions Oral FC improved phosphorus homeostasis, some iron-related parameters and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate–advanced CKD. [ABSTRACT FROM AUTHOR]

The use of guided wave ultrasonography as a means to assess cortical bone quality has been a significant practice in bone quantitative ultrasound for more than 20 years. In this article, the key developments within the technology of ultrasonic guided waves (UGW) in long bones during the past decade are documented. The covered topics include data acquisition configurations available for measuring bone guided waveforms, signal processing techniques applied to bone UGW, numerical modeling of ultrasonic wave propagation in cortical long bones, formulation of inverse approaches to extract bone properties from observed ultrasonic signals, and clinical studies to establish the technology’s application and efficacy. The review concludes by highlighting specific challenging problems and future research directions. In general, the primary purpose of this work is to provide a comprehensive overview of bone guided-wave ultrasound, especially for newcomers to this scientific field. [ABSTRACT FROM AUTHOR]

Triply periodic minimum surfaces (TPMS), which outperform other structures in terms of bulk moduli and relative density, have been widely used to dramatically improve the mechanical strength of natural echinoderm skeletons and engineered scaffolds. Herein, TPMS‐structure‐based 3D‐printed hydroxyapatite (HAp) scaffolds to highly improve their limited mechanical strength and evaluate the underlying mechanism in terms of mechanical match and biological bone repair process as a bone regeneration scaffold are constructed. The results show that TPMS‐structure‐based HAp scaffolds have a greater compressive strength range that is sufficient to meet the strength requirements for human cortical and trabecular bone, and outperform traditional HAp scaffolds with Cross‐hatch structures in terms of compressive strength, cell density, and osteogenic differentiation. The reduction of stress concentration and open‐cell permeable structure of Split‐P scaffolds can benefit the generation and ingrowth of new bone after the in vivo implantation in the rabbit femur bone. Furthermore, RNA‐seq and immunochemistry staining results of in vivo samples unravel the bone repair mechanism in a time sequence. The optimized scaffolds with TPMS macrostructures and an in‐depth understanding of repair mechanisms will contribute to the development of bone regeneration materials that perform on par with load‐bearing bone. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at an alarming risk of fracture compared to age and sex-matched non-CKD individuals. Clinical and preclinical data highlight two key factors in CKD-induced skeletal fragility: cortical porosity and reduced matrix-level properties including bone hydration. Thus, strategies are needed to address these concerns to improve mechanical properties and ultimately lower fracture risk in CKD. We sought to evaluate the singular and combined effects of mechanical and pharmacological interventions on modulating porosity, bone hydration, and mechanical properties in CKD. Sixteen-week-old male C57BL/6J mice underwent a 10-week CKD induction period via a 0.2 % adenine-laced casein-based diet (n = 48) or remained as non-CKD littermate controls (Con, n = 48). Following disease induction (26 weeks of age), n = 7 CKD and n = 7 Con were sacrificed (baseline cohort) to confirm a steady-state CKD state was achieved prior to the initiation of treatment. At 27 weeks of age, all remaining mice underwent right tibial loading to a maximum tensile strain of 2050 μƐ 3× a week for five weeks with the contralateral limb as a non-loaded control. Half of the mice (equal number CKD and Con) received subcutaneous injections of 0.5 mg/kg raloxifene (RAL) 5× a week, and the other half remained untreated (UN). Mice were sacrificed at 31 weeks of age. Serum biochemistries were performed, and bi-lateral tibiae were assessed for microarchitecture, whole bone and tissue level mechanical properties, and composition including bone hydration. Regardless of intervention, BUN and PTH were higher in CKD animals throughout the study. In CKD, the combined effects of loading and RAL were quantified as lower cortical porosity and improved mechanical, material, and compositional properties, including higher matrix-bound water. Loading was generally responsible for positive impacts in cortical geometry and structural mechanical properties, while RAL treatment improved some trabecular outcomes and material-level mechanical properties and was responsible for improvements in several compositional parameters. While control animals responded positively to loading, their bones were less impacted by the RAL treatment, showing no deformation, toughness, or bound water improvements which were all evident in CKD. Serum PTH levels were negatively correlated with matrix-bound water. An effective treatment program to improve fracture risk in CKD ideally focuses on the cortical bone and considers both cortical porosity and matrix properties. Loading-induced bone formation and mechanical improvements were observed across groups, and in the CKD cohort, this included lower cortical porosity. This study highlights that RAL treatment superimposed on active bone formation may be ideal for reducing skeletal complications in CKD by forming new bone with enhanced matrix properties. • Raloxifene-treated CKD animals had higher bound water. • Loading in CKD resulted in improved cortical outcomes and mechanical properties. • Loading plus raloxifene resulted in even tougher, more ductile, and stronger bones. • Control animals responded positively to loading but were less impacted by raloxifene. [ABSTRACT FROM AUTHOR]

Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as intellectual disability and behavioral comorbidities, including autism and anxiety. Tatton-Brown-Rahman Syndrome is one type of overgrowth and intellectual disability disorder caused by heterozygous missense mutations in the DNA methyltransferase 3A (DNMT3A) gene. Numerous DNMT3A mutations have been identified in Tatton-Brown-Rahman Syndrome patients and may be associated with varying phenotype severities of clinical presentation. Two such mutations are the R882H and P904L mutations which result in severe and mild phenotypes, respectively. Mice with paralogous mutations (Dnmt3a P900L /+ and Dnmt3a R878H /+) exhibit overgrowth in their long bones (e.g., femur, humerus), but the mechanisms responsible for their skeletal overgrowth remain unknown. The goal of this study is to characterize skeletal phenotypes in mouse models of Tatton-Brown-Rahman Syndrome and identify potential cellular mechanisms involved in the skeletal overgrowth phenotype. We report that mature mice with the Dnmt3a P900L /+ or Dnmt3a R878H /+ mutation exhibit tibial overgrowth, cortical bone thinning, and weakened bone mechanical properties. Dnmt3a R878H /+ mutants also contain larger bone marrow adipocytes while Dnmt3a P900L /+ mutants show no adipocyte phenotype compared to control animals. To understand the potential cellular mechanisms regulating these phenotypes, growth plate chondrocytes, osteoblasts, and osteoclasts were assessed in juvenile mutant mice using quantitative static histomorphometry and dynamic histomorphometry. Tibial growth plates appeared thicker in mutant juvenile mice, but no changes were observed in osteoblast activity or osteoclast number in the femoral mid-diaphysis. These studies reveal new skeletal phenotypes associated with Tatton-Brown-Rahman Syndrome in mice and provide a rationale to extend clinical assessments of patients with this condition to include bone density and quality testing. These findings may be also informative for skeletal characterization of other mouse models presenting with overgrowth and intellectual disability phenotypes. • Genetic mouse models of Tatton-Brown-Rahman Syndrome recapitulate bone phenotypes. • Heterozygous mutations in Dnmt3a cause long bone overgrowth and cortical thinning. • Bone mechanical properties are compromised in Dnmt3a mutants. • Bone marrow adipose tissue is upregulated in mice with the Dnmt3a R878H /+ mutation. • Juvenile mice with mutations in Dnmt3a exhibit growth plate thickening. [ABSTRACT FROM AUTHOR]

This research focuses on the importance of understanding bone adaptation for gaining insights into diseases such as osteoporosis. The study investigates the role of fluid flow in cortical bone adaptation, with a specific focus on the network of osteocyte canaliculi and the chemical reactions involved in bone resorption. Prior studies have implemented methods such as poroelasticity theory and dual porosity, but these models did not account for mass exchange between the solid and fluid phases within the bone or the pressure exerted by arteries. The movement of interstitial fluid between the vascular porosity and lacuno-canalicular porosity in cortical bone, as well as the velocity of the fluid, are affected by both the pressure exerted by arteries and the exchange of mass between the solid and fluid components of the bone. To incorporate these effects in the model, the authors propose a dual porosity model based on the theory of porous media. The model considers the transfer of mass between vascular and lacunar-canalicular porosities, as well as between solid and fluid phases, while also accounting for blood pressure variations. To verify the proposed model, a numerical example is solved and compared with the results of previous studies. The model enables the measurement and analysis of the interstitial fluid velocity and the pressure in the respective porosities. The results reveal that accounting for blood pressure pulses and mass exchange between solid and fluid phases can alter the velocity and pressure fields of interstitial fluid within cortical bone. In addition, this study investigates transient examples and various scenarios of the bone remodeling. Overall, this research provides a more accurate understanding of the bone remodeling and the effects of blood pressure variation and mass exchange between solid and fluid phases of cortical bone. • Highlights bone adaptation mechanics' importance for osteoporosis insights. • Introduces porous media approach for fluid flow and chemical reactions in canaliculi. • Models mass exchange and arterial pressure in bone remodeling process. • Mass exchange & arterial pressure impact interstitial fluid velocity & pressure. • Proposed model verified via multiple scenarios and compared with prior studies. [ABSTRACT FROM AUTHOR]

The remodelling process in bones is closely related to electromechanical phenomena. In addition to streaming potentials and piezoelectricity, flexoelectricity has been found to serve as an initiator for remodelling in cortical bone. Since flexoelectricity is coupled to strain gradients, the effect is size-dependent and, accordingly, most relevant on small scales. This means that particularly microcracks which occur in the mechanically loaded bone under daily activity, are healed in response to flexoelectric initiation. More specifically speaking, flexoelectricity induces electric fields in the vicinity of such microcracks and thereby causes osteocyte apoptosis which is a pivotal event in the process of bone remodelling. Since experiments on such small scales are difficult to conduct, a numerical framework is established in this contribution which captures the flexoelectric initiation of bone remodelling as well as the remodelling process itself, including bone cell diffusion and progressive crack closure through surface growth. Due to the higher-order PDEs that result from the incorporation of flexoelectricity, a globally C 1 -continuous isogeometric analysis framework is adopted for the initiation process, whereas a classic finite element approach is proposed for the subsequent diffusion and growth processes. This framework is applied to a cortical bone sample with a narrow microcrack subject to mechanical loading. Growth is coupled to the activity of osteoblasts and incorporated numerically by a moving mesh algorithm. It is shown that the proposed framework can capture the entire process of cortical bone remodelling from its initiation until the successive healing of the microcrack. [ABSTRACT FROM AUTHOR]

Drilling is one of the most important surgical steps and bone fracture repair. In this step, the temperature may exceed 47 °C and thermal necrosis may occur, which has irreversible consequences. Knowing the amount of heat transferred to the bone and its changes can be effective in recognizing this heat damage and minimizing it. In this research, it was tried to estimate the amount of heat flux entering the bone during the drilling process using the inverse heat transfer method. Drilling tests were performed on cow bone samples and the temperature changes at the hole location were measured using the inverse heat conduction transfer method. The amount of heat input was estimated. The K-type thermocouple is used to measure temperature. The diaphysis fragment of the cow's thigh (middle part), which has a length of about 90 mm and the thickness of the cortical bone in this range is about 8–10 mm, was used. Also, to ease the tests, the beginning and end parts of the fresh femur were cut with a saw. The results show that the maximum heat flux occurs earlier than the maximum temperature. It was observed that the maximum heat flux and the maximum temperature rise with the increase of the rotational speed and the diameter of the tool. As the feed speed rises, first the maximum temperature and maximum heat flux decrease and then increase. By tripling the feed speed, the maximum heat flux decreases by about 20%. The highest percentage rise in temperature and heat flux occurs with a rise in rotational speed, which is around 130–140%. After the rotational speed, increasing the drill diameter increases the temperature up to about 66.7%. The results can be used to prevent thermal necrosis because the maximum heat flux is visible before the occurrence of the maximum temperature. [ABSTRACT FROM AUTHOR]

Bone fracture is an extremely dangerous health risk to human. Actually, cortical bone is often subjected to the complicated loading patterns. The mechanical properties and deformation mechanism under the complicated loading pattern could provide a more precise understanding for the bone fracture. For this purpose, the mechanical response and multi-scale deformation mechanism of cortical bone material were investigated by in-situ experimental research using the compression-torsion coupling loads as an example. It was found that the torsion strength and shear modulus all decreased under the compression-torsion coupling loads than single torsion load. This indicated bone would suffer greater risk of fracture under the compression-torsion coupling loads. Based on in-situ observation, it was found that the rapid reduction of the anisotropy of bone material under the compression load was the potential influencing factor. Because of the redistribution of the principal strain and the variations of cracks propagation, the comprehensive fracture pattern containing both transverse and longitudinal fracture was shown under the coupling loads, and finally resulted in the reduction of the torsion properties. This research could provide new references for researches on mechanical properties of cortical bone material under complicated loading patterns. [ABSTRACT FROM AUTHOR]

Introduction: Ashing is widely used to determine weight fraction of water-free bone that is mineral, but no standard procedure exists and the range of techniques used spans a range of temperatures and times over which the amount of weight loss is variable. We show that variability is largely due to progressive loss of CO2 from CO32− ions in the apatite crystal lattice, beginning at 600 ℃, typically used for ashing. We test the effect of varying temperature, time, and weight of sample and develop a reliable method, using small samples. Materials and methods: Replicate samples of bovine cortical bone were tested at 500 ℃, 600 ℃, and 700 ℃ for times ranging up to 24 h. We also tested samples of multiple humans at what we concluded to be the optimal conditions. Results: Varying conditions of ashing resulted in variations in apparent ash weight % by up to 7%. Samples between 5 and 20 mg heated to 600 ℃ for 1 h gave results agreeing with generally accepted values, but with much smaller variability. Ash wt% values for multiple human bone samples differed by up to 4.8%, but replicate data for individuals agree to ± 1 wt%. Discussion: In conclusion, a satisfactory method is given for ash weight determination using small samples, and yielding highly reproducible data. If accepted widely, ash weight values between laboratories could be used to study variations due to diet, age, drug treatment, and disease. [ABSTRACT FROM AUTHOR]

Bone is an extraordinary biological material that continuously adapts its hierarchical microstructure to respond to static and dynamic loads for offering optimal mechanical features, in terms of stiffness and toughness, across different scales, from the sub-microscopic constituents within osteons—where the cyclic activity of osteoblasts, osteoclasts, and osteocytes redesigns shape and percentage of mineral crystals and collagen fibers—up to the macroscopic level, with growth and remodeling processes that modify the architecture of both compact and porous bone districts. Despite the intrinsic complexity of the bone mechanobiology, involving coupling phenomena of micro-damage, nutrients supply driven by fluid flowing throughout hierarchical networks, and cells turnover, successful models and numerical algorithms have been presented in the literature to predict, at the macroscale, how bone remodels under mechanical stimuli, a fundamental issue in many medical applications such as optimization of femur prostheses and diagnosis of the risk fracture. Within this framework, one of the most classical strategies employed in the studies is the so-called Stanford's law, which allows uploading the effect of the time-dependent load-induced stress stimulus into a biomechanical model to guess the bone structure evolution. In the present work, we generalize this approach by introducing the bone poroelasticity, thus incorporating in the model the role of the fluid content that, by driving nutrients and contributing to the removal of wastes of bone tissue cells, synergistically interacts with the classical stress fields to change homeostasis states, local saturation conditions, and reorients the bone density rate, in this way affecting growth and remodeling. Through two paradigmatic example applications, i.e. a cylindrical slice with internal prescribed displacements idealizing a tract of femoral diaphysis pushed out by the pressure exerted by a femur prosthesis and a bone element in a form of a bent beam, it is highlighted that the present model is capable to catch more realistically both the transition between spongy and cortical regions and the expected non-symmetrical evolution of bone tissue density in the medium–long term, unpredictable with the standard approach. A real study case of a femur is also considered at the end in order to show the effectiveness of the proposed remodeling algorithm. [ABSTRACT FROM AUTHOR]

Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130-136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130-136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2 secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2 administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of acetabular fractures due to low-energy falls is increasing among the geriatric population. Studies have shown that several biomechanical factors such as body configuration, impact velocity, and trochanteric soft-tissue thickness contribute to the severity and type of acetabular fracture. The effect of reduction in apparent density and elastic modulus of bone as well as other bone mechanical properties due to osteoporosis on low-energy acetabular fractures has not been investigated. Methods: The current comprehensive finite element study aimed to study the effect of reduction in bone mechanical properties (trabecular, cortical, and trabecular + cortical) on the risk and type of acetabular fracture. Also, the effect of reduction in the mechanical properties of bone on the load-transferring mechanism within the pelvic girdle was examined. Results: We observed that while the reduction in the mechanical properties of trabecular bone considerably affects the severity and area of trabecular bone failure, reduction in mechanical properties of cortical bone moderately influences both cortical and trabecular bone failure. The results also indicated that by reducing bone mechanical properties, the type of acetabular fracture turns from elementary to associated, which requires a more extensive intervention and rehabilitation period. Finally, we observed that the cortical bone plays a substantial role in load transfer, and by increasing reduction in the mechanical properties of cortical bone, a greater share of load is transmitted toward the pubic symphysis. Conclusion: This study increases our understanding of the effect of osteoporosis progression on the incidence of low-energy acetabular fractures. The osteoporosis-related reduction in the mechanical properties of cortical bone appears to affect both the cortical and trabecular bones. Also, during the extreme reduction in the mechanical properties of bone, the acetabular fracture type will be more complicated. Finally, during the final stages of osteoporosis (high reduction in mechanical properties of bone) a smaller share of impact load is transferred by impact-side hemipelvis to the sacrum, therefore, an osteoporotic pelvis might mitigate the risk of sacral fracture. [ABSTRACT FROM AUTHOR]

Background: Gamma irradiation, which minimizes the risk of infectious disease transmission when human bone allograft is used, has been found to negatively affect its biomechanical properties. However, in those studies, the deep-freezing temperature during irradiation was not necessarily maintained during transportation and sterilization, which may have affected the findings. Prior reports have also suggested that controlled deep freezing may mitigate the detrimental effects of irradiation on the mechanical properties of bone allograft.Question/purpose: Does a controlled deep-freezing temperature during irradiation help preserve the compressive mechanical properties of human femoral cortical bone allografts?Methods: Cortical bone cube samples, each measuring 64 mm3, were cut from the mid-diaphyseal midshaft of five fresh-frozen cadaver femurs (four male donors, mean [range] age at procurement 42 years [42 to 43]) and were allocated via block randomization into one of three experimental groups (with equal numbers of samples from each donor allocated into each group). Each experimental group consisted of 20 bone cube samples. Samples irradiated in dry ice were subjected to irradiation doses ranging from 26.7 kGy to 27.1 kGy (mean 26.9 kGy) at a deep-freezing temperature below -40°C (the recommended long-term storage temperature for allografts). Samples irradiated in gel ice underwent irradiation doses ranging from 26.2 kGy and 26.4 kGy (mean 26.3 kGy) in a freezing temperature range between -40°C and 0°C. Acting as controls, samples in a third group were not subjected to gamma irradiation. The mechanical properties (0.2% offset yield stress, ultimate compression stress, toughness, and the Young modulus) of samples from each group were subsequently evaluated via axial compression loading to failure along the long axis of the bone. The investigators were blinded to sample group during compression testing.Results: The mean ultimate compression stress (84 ± 27 MPa versus 119 ± 31 MPa, mean difference 35 [95% CI 9 to 60]; p = 0.005) and toughness (3622 ± 1720 kJ/m3 versus 5854 ± 2900 kJ/m3, mean difference 2232 [95% CI 70 to 4394]; p = 0.009) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than in those irradiated at deep-freezing temperatures (below -40°C). The mean 0.2% offset yield stress (73 ± 28 MPa versus 109 ± 38 MPa, mean difference 36 [95% CI 11 to 60]; p = 0.002) and ultimate compression stress (84 ± 27 MPa versus 128 ± 40 MPa, mean difference 44 [95% CI 17 to 69]; p < 0.001) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than the nonirradiated control group samples. The mean 0.2% offset yield stress (73 ± 28 MPa versus 101 ± 28 MPa, mean difference 28 [95% CI 3 to 52]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to those irradiated at deep-freezing temperature. The mean toughness (3622 ± 1720 kJ/m3 versus 6231 ± 3410 kJ/m3, mean difference 2609 [95% CI 447 to 4771]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to the non-irradiated control group samples. The mean 0.2% offset yield stress, ultimate compression stress, and toughness of samples irradiated in deep-freezing temperatures (below -40°C) were not different with the numbers available to the non-irradiated control group samples. The Young modulus was not different with the numbers available among the three groups.Conclusion: In this study, maintenance of a deep-freezing temperature below -40°C, using dry ice as a cooling agent, consistently mitigated the adverse effects of irradiation on the monotonic-compression mechanical properties of human cortical bone tissue. Preserving the mechanical properties of a cortical allograft, when irradiated in a deep-freezing temperature, may have resulted from attenuation of the deleterious, indirect effects of gamma radiation on its collagen architecture in a frozen state. Immobilization of water molecules in this state prevents radiolysis and the subsequent generation of free radicals. This hypothesis was supported by an apparent loss of the protective effect when a range of higher freezing temperatures was used during irradiation.Clinical Relevance: Deep-freezing temperatures below -40°C during gamma irradiation may be a promising approach to better retain the native mechanical properties of cortical bone allografts. A further study of the effect of deep-freezing during gamma radiation sterilization on sterility and other important biomechanical properties of cortical bone (such as, tensile strength, fracture toughness, and fatigue) is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The Bayesian inference with prior knowledge has been proposed recently to solve the inverse problem in resonant ultrasound spectroscopy. It allows inferring the elastic properties of high damping materials, such as cortical bone with less dependence on the initial guessed values. In this method, the estimation of the stiffness coefficients is expressed as a probabilistic solution to the inverse problem, which can be achieved by sampling or optimization methods. However, the detailed performance comparison of these two strategies applied to high damping materials has not been fully studied. In this work, the full stiffness tensor of 52 transversely isotropic cortical bone specimens was obtained using Markov chain Monte Carlo (MCMC) sampling and particle swarm optimization (PSO), respectively. Results showed that the local probability distributions of stiffness coefficients estimated by the two methods are consistent. Compared with MCMC, the average calculation speed of PSO is ten times faster [614 s ± 59 s (MCMC) versus 53 s ± 22 s (PSO)]. The mean standard error between theoretical and experimental resonant frequencies was slightly smaller for PSO compared with MCMC. In conclusion, PSO, a global optimization strategy, is suitable to solve the inverse problem for high damping materials. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis, marked by estrogen deficiency, is a major contributor to osteoporotic fractures, yet early prediction of fractures in this population remains challenging. Our goal was to explore the temporal changes in bone-specific inflammation, oxidative stress, bone turnover, and bone-matrix water, and their relationship with estrogen deficiency-induced modifications in bone structure and mechanical properties. Additionally, we sought to determine if emerging clinically translatable imaging techniques could capture early bone modifications prior to standard clinical imaging. Two-month-old female Sprague Dawley rats (n = 48) underwent ovariectomy (OVX, n = 24) or sham operations (n = 24). A subgroup of n = 8 rats per group was sacrificed at 2-, 5-, and 10-weeks post-surgery to assess the temporal relationships of inflammation, oxidative stress, bone turnover, bone matrix water, mechanics, and imaging outcomes. OVX rats exhibited higher body weight compared to sham rats at all time points. By 5-weeks, OVX animals showed elevated markers of inflammation and oxidative stress in cortical bone, which persisted throughout the study, while cortical bone formation rate did not differ from sham until 10-weeks. DXA outcomes did not reveal differences between OVX and sham at any time point. Bound water, assessed using ultrashort echo time magnetic resonance imaging (UTE MRI), was lower in OVX at the earliest time point (2-weeks) and reduced again at 10-weeks with no difference at 5-weeks. These data demonstrate that bound water assessment using novel UTE MRI technology was lower at the earliest time point following OVX. However, no temporal relationship with bone turnover, inflammation, or oxidative stress was observed at the time points assessed in this study. These findings underscore both the increased need to understand bone hydration changes and highlight the usefulness of UTE MRI for non-invasive bone hydration measurements. • Bone hydration measured via UTE MRI showed early changes following ovariectomy. • Bone hydration did not closely correspond with changes in bone cellular changes. • Temporal progressive changes in bone hydration were not detected post-OVX. [ABSTRACT FROM AUTHOR]

Chronic heavy alcohol consumption may influence the skeleton by suppressing intracortical bone remodeling which may impact the quality of bone and its mechanical properties. However, this aspect has not been thoroughly assessed in either humans or animal models whose cortical bone microstructure resembles the microstructure of human cortical bone. The current study is the first to investigate the effects of chronic heavy alcohol consumption on various mechanical properties of bone in a non-human primate model with intracortical remodeling. Male rhesus macaques (5.3 years old at the initiation of treatment) were induced to drink alcohol and then gi v en the choice to voluntarily self-administer water or ethanol (4 % w / v) for approximately 14 months, followed by three abstinence phases (lasting 34, 41, and 39–46 days) with approximately 3 months of ethanol access in between. During the initial 14 months of open-access, monkeys in the alcohol group consumed an average of 2.9 ± 0.8 g/kg/d ethanol (mean ± SD) resulting in a blood ethanol concentration of 89 ± 47 mg/dl in longitudinal samples taken at 7 h after the daily sessions began. To understand the impact of alcohol consumption on material properties, various mechanical tests were conducted on the distal tibia diaphysis of 2–5 monkeys per test group, including dynamic mechanical analysis (DMA) testing, nano-indentation, microhardness testing, compression testing, and fracture resistance curve (R -curve) testing. Additionally, compositional analyses were performed using Fourier-transform infrared (FTIR) spectroscopy. Significant differences in microhardness, compressive stress-strain response, and composition were not observed with alcohol consumption, and only minor differences were detected in hardness and elastic modulus of the matrix and osteons from nanoindentation. Furthermore, the R -curves of both groups overlapped, with similar crack initiation toughness, despite a significant decrease in crack growth toughness (p = 0.032) with alcohol consumption. However, storage modulus (p = 0.029) and loss factor (p = 0.015) from DMA testing were significantly increased in the alcohol group compared to the control group, while loss modulus remained unchanged. These results indicate that heavy alcohol consumption may have only a minor influence on the material properties and the composition of cortical bone in young adult male rhesus macaques. • First alcohol study investigating bone mechanical properties using rhesus macaques • DMA testing revealed increase in storage modulus and decrease in loss factor • Hardness, compressive stress-strain response, and bone composition were not affected • Crack initiation toughness was unchanged but growth toughness decreased [ABSTRACT FROM AUTHOR]

Femur bone fracture is mainly caused by sports injuries or accidents and has become serious attention in orthopedic trauma. The unique cortical bone microstructures and features contribute to complex fracture behavior. This paper presents the investigation of Type 2 and Type 3 arch-shaped microcrack penetration based on von Mises stress and stress intensity factor (SIF) parameters around the microcrack tips penetration in Haversian system cortical bones. The fracture model was constructed based on bone continuum mechanics theory named Kachanov theory of elastic interaction. It aims to determine the level of stress amplification and stress shielding for the transition of Type 2 to Type 3 for heterogeneous cortical bone fracture model. A total of eight microcrack extension points (CP1–8) were constructed based on 1-mm2 Haversian system model, subjected to the force of 10 N in Mode I and Mode II loading. Finite element (FE) analysis was then performed to evaluate the von Mises stress around the crack end tips and SIF under the assumption of bone damage, D < 1. The study found that the greatest von Mises stress value was observed at the CP4 (175.766 MPa) and CP8 (213.264 MPa) for Mode I loading and CP4 (106.037 MPa) for Mode II loading. In terms of fracture parameter, the critical SIF magnitude was peaked at CP4 (1272.8 MPa*m1/2) and CP8 (1369.0 MPa*m1/2) for Mode I loading and CP5 (402.29 MPa*m1/2) for Mode II loading. The results show that the transition of Type 2 (straight crack) to Type 3 (arch crack) microcrack penetration in Haversian system experienced the multilevel of stress amplification (CP1–CP4, CP6–8) and stress shielding (CP4–CP6) to represent the bone micro-damage level. [ABSTRACT FROM AUTHOR]

This two-part paper is aimed at developing a microstructure-based mechanistic modeling framework to predict the cutting forces and acoustic emissions (AEs) generated during bone sawing. The modeling framework is aimed at the sub-radius cutting condition that dominates chip-formation mechanics during the bone sawing process. Part 1 of this paper deals specifically with the sawing experiments and modeling of the cutting/thrust forces. The model explicitly accounts for key microstructural constituents of the bovine bone (viz., osteon, interstitial matrix, lamellar bone, and woven bone). The cutting and thrust forces are decomposed into their shearing and ploughing components. Microstructure-specific shear stress values critical to the model calculations are estimated using micro-scale orthogonal cutting tests. This approach of estimating the microstructure-specific shear stress overcomes a critical shortcoming in the literature related to high-strain rate characterization of natural composites, where the separation of the individual constituents is difficult. The six model coefficients are calibrated over a range of clinically relevant depth-of-cuts (DOCs) using pure haversian regions (comprising of osteon and interstitial matrix), and pure plexiform regions (comprising of lamellar bone and woven bone). The calibrated model is then used to make predictions in the transition region between the Haversian and plexiform bone, which is characterized by gradient structures involving varying percentages of osteon, interstitial matrix, lamellar bone, and woven bone. The mean absolute percentage error in the force predictions is under 10% for both the cutting and thrust forces. The reality of spatially varied properties in the cortical bone limits the universal use of microstructure-specific shear stress values reported here. Fundamental advancements in the literature associated with both high-strain rate bone mechanics and machining are needed to address this critical limitation. [ABSTRACT FROM AUTHOR]