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Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and/or long‐term safety concerns. Proteoglycan‐4 (PRG4, also known as lubricin) is a mucin‐like glycoprotein best known for its boundary lubricating function of articular cartilage. In more recent years, it has been shown that PRG4 has anti‐inflammatory properties, contributes to the maintenance of subchondral bone integrity, and patients with PRG4 mutations are osteopenic. However, it remains unknown how PRG4 impacts mechanical and material properties of bone. Therefore, our objective was to perform a phenotyping study of bone in a Prg4 gene trap (GT) mouse (PRG4 deficient). We found that femurs of Prg4 GT mice have altered mechanical, structural, and material properties relative to wildtype littermates. Additionally, Prg4 GT mice have a greater number of calvarial osteoclasts than wildtype mice, but do not have a notable inflammatory serum profile. Finally, Prg4 GT mice do not have an altered rate of bone formation, and exogenous recombinant human PRG4 (rhPRG4) administration inhibited osteoclastogenesis in vitro, suggesting that the skeletal phenotype may be due to changes in bone resorption. Overall, this work demonstrates that PRG4 deficiency affects several integral properties of bone structure, mechanics, and skeletal cell activity, and provides the foundation and insight toward future work evaluating PRG4 as a potential therapeutic target in treating bone loss. [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]

The elemental composition of chemical elements can vary between healthy and diseased tissues, providing essential insights into metabolic processes in physiological and diseased states. This study aimed to evaluate the calcium (Ca) and phosphorus (P) levels in the bones of rats with/without streptozotocin-induced diabetes and/or exposure to infrasound. X-ray fluorescence spectroscopy was used to determine the concentrations of Ca and P in Wistar rat tibiae samples. The results showed a significant decrease in bone P concentration in streptozotocin-induced diabetic rats compared to untreated animals. Similarly, the Ca/P ratio was higher in the streptozotocin-induced diabetic group. No significant differences were observed in bone Ca concentration between the studied groups or between animals exposed and not exposed to infrasound. Moreover, streptozotocin-induced diabetic rats had lower bone P concentration but unaltered bone Ca concentration compared to untreated rats. Infrasound exposure did not impact bone Ca or P levels. The reduced bone P concentration may be associated with an increased risk of bone fractures in diabetes. [ABSTRACT FROM AUTHOR]

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL–TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL–TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion. [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]

Trabecular bone architecture in the developing skeleton is a widely researched area of bone biomechanics; however, despite its significance in weight‐bearing locomotion, the developing talus has received limited examination. This study investigates the talus with the purpose of identifying ontogenetic phases and developmental patterns that contribute to the growing understanding of the developing juvenile skeleton. Colour gradient mapping and radiographic absorptiometry were utilised to investigate 62 human tali from 38 individuals, ranging in age‐at‐death from 28 weeks intrauterine to 20 years of age. The perinatal talus exhibited a rudimentary pattern comparable to the structural organisation observed within the late adolescent talus. This early internal organisation is hypothesised to be related to the vascular pattern of the talus. After 2 years of age, the talus demonstrated refinement, where radiographic trajectories progressively developed into patterns consistent with adult trabecular organisation, which are linked to the forces associated with the bipedal gait, suggesting a strong influence of biomechanical forces on the development of the talus. [ABSTRACT FROM AUTHOR]

Objective: The class II transactivator (CIITA), encoded by the CIITA gene, controls expression of immune response regulators, which affect bone homeostasis. Previously, we investigated a functional CIITA polymorphism in elderly women. Women carrying the allele associated with lower CIITA levels displayed higher bone mineral density (BMD), but also higher bone loss. The present exploratory study in a rat model sought to investigate effects of differential expression of Ciita on bone structural integrity and strength. Two strains DA (normal-to-high expression) and DA.VRA4 (lower expression) underwent ovariectomy (OVX) or sham-surgery at ~ 14-weeks of age (DA OVX n = 8, sham n = 4; DA.VRA4 OVX n = 10, sham n = 2). After 16-weeks, femoral BMD and bone mineral content (BMC) were measured and morphometry and biomechanical testing performed. Results: In DA.VRA4 rats, BMD/BMC, cross-sectional area and biomechanical properties were lower. Ciita expression was accompanied by OVX-induced changes to cross-sectional area and femoral shaft strength; DA rats had lower maximum load-to-fracture. Thus, while lower Ciita expression associated with lower bone mass, OVX induced changes to structural and mechanical bone properties were less pronounced. Conclusion: The data tentatively suggests association between Ciita expression and structural and mechanical bone properties, and a possible role in bone changes resulting from estrogen deficiency. [ABSTRACT FROM AUTHOR]

It is well known that the bone loss which may lead to bone fracture risk occurs under microgravity and disuse. Besides bone mineral density (BMD), the role of collagen as the main component of bone in the mechanism has unknown. In addition, myofascia, which is also mainly composed of collagen, plays an important role in the force transmission in musculoskeletal system. In this study, the collagen alternations of hindlimb tibia and myofascia in tail-suspension rats, which hindlimb unloading as a model to simulate microgravity and/or disuse, were investigated and further the correlations with the mechanical properties were analyzed. The collagen fiber orientations were observed by second-harmonic generation (SHG) microscopy and quantitatively analyzed in MATLAB. Bone mechanical properties were measured by three-point-bending test and nanoindentation. Myofascial mechanical properties were explored by tensile test. The results showed: 1) the collagen fibers orientation both in bone and myofascia were dispersed, as standard deviation of collagen fiber orientation increased.2) the mechanical properties of tibia were decreased by unloading both at macro level (maximum load, breaking load and stiffness, etc.) and micro level (hardness). In myofascia, the yield strain and ultimate strain were significantly decreased. 3) correlation analysis showed bone collagen orientation was related to bone hardness/elastic modulus, and myofascial collagen orientation was related to myofascial elastic modulus and yield limit. Additionally, myofascial mechanical properties were related to bone mechanical properties. These suggested disordered collagen orientation may be related to the deterioration of mechanical properties in both bone and myofascia under simulated microgravity. The alternation of myofascial mechanical property may have a certain impact on the deterioration of bone mechanical properties through affecting the force transmission from muscle to bone. • The collagen fibers orientation both in bone and myofascia were dispersed under microgravity • The bone collagen orientation was related to bone hardness and elastic modulus • The myofascial collagen orientation was related to myofascial elastic modulus and yield limit • The myofascial mechanical properties were related to bone mechanical properties • The alternation of myofascial mechanical property may have a certain impact on the deterioration of bone mechanical properties through affecting the force transmission from muscle to bone [ABSTRACT FROM AUTHOR]

Objective: In this study effects of three types of beddings on broiler leg health and bone biomechanics were evaluated. Methods: A total of 504 male chicks (Ross 308) were randomly placed on three beddings (4 replicates/group; 42 birds/pen), zeolite-added litter (ZL), plastic-grid flooring (PF), and wood shavings (WS). On day 42, chickens were weighed, slaughtered, and samples (bone, muscle, and drumstick) were collected. Bones were subjected to leg health tests, morphometric measurements, biomechanical testing, and ash analysis. Results: Broilers in PF and WS groups showed higher live weight than the ZL group (p<0.001), and the incidence of tibial dyschondroplasia (TD) and varus valgus deformity due to distal bending was significantly higher in PF (p<0.001). Multinomial logistic regression showed that bedding has a significant (p = 0.038) contribution toward the development of TD. Tibial strength (p = 0.040), drumstick width (p = 0.001), and total femur and epiphyseal ash contents (p = 0.044, 0.016) were higher in the ZL group. Chicken live weight was correlated with tibial length and weight (r = 0.762, 0.725). Conclusion: Flooring and the type of bedding material directly affect broiler bone length, strength and leg health. Plastic bedding improves the slaughter weight of chickens on the expense of leg deformities, and zeolite litter improves leg health and bone strength. [ABSTRACT FROM AUTHOR]

In recent years, the concept of physical fractal space has been abstracted from muscle/ligament fibers, nerve fibers and blood flows. In the physical fractal space, bio-fractal mechanics may be set up. Surprisingly, the concepts and methods developed in the above bio-fractal mechanics are of universalities, i.e., the physical fractal spaces, fractal operators and fractional-order mechanics universally exist in various biological systems such as bones. This paper will focus on the bones in which the physical fractal space is abstracted, the fractal operators are derived and the fractional-order mechanics is established. [ABSTRACT FROM AUTHOR]

Simple Summary: To understand the developmental changes in hare femora, this study aimed to examine the mechanical properties, mineralization, and general geometric properties of the thigh bone (femur) throughout the growth and maturation process. The study involved analyzing the strength, stiffness, bone mineral density, and structure of the femur in both young and adult hares. Additionally, the study sought to establish a connection between bone properties and the ecological functions of hares in their natural habitats. Understanding the changes in hare femora as they grow and mature is crucial for many reasons as it provides valuable insights into the effects of aging on wild hares, shedding light on their adaptability and survival strategies. Lagomorphs, which include hares, rabbits, and pikas, are herbivorous animals renowned for their exceptional running abilities. The femur, the largest and strongest bone in their bodies, plays a crucial role in supporting their weight and facilitating movement. This study aimed to investigate the structural and functional changes in the femora of hares during their development in a sex-dependent manner, and the influence of aging on femur structure and function. Various mechanical properties, including stiffness and strength, as well as densitometry and morphology, were evaluated. The study was conducted on n = 24 hares collected from a hunting district in the Lublin region of Poland and divided into four groups: young females, adult females, young males and adult males (n = 6 animals each). Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral content (BMC) and bone mineral density (BMD), and a three-point bending test was performed to assess mechanical properties. The findings revealed age-related differences in bone properties, with adult males exhibiting increased BMC, and BMD compared to young males. Geometrical properties of the femora mid-diaphysis, such as cortical index and cross-sectional area, remained relatively unchanged during maturation. Regarding mechanical properties, the femora of young males exhibited higher elastic work compared to those of young females, while the femora of adult males exhibited higher elastic and breaking work than those of adult females. The stiffness of femora was higher in adult females compared to young females. The results provide insights into the development and aging of hare femora and contribute to our understanding of the relationship between bone mechanical properties, musculoskeletal system, and aging in the wild. This knowledge can inform animal husbandry practices in captivity and enhance our broader understanding of the ecological functions of lagomorphs. [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]

The use of a phase‐retrieval technique for propagation‐based phase‐contrast neutron imaging with a polychromatic beam is demonstrated. This enables imaging of samples with low absorption contrast and/or improving the signal‐to‐noise ratio to facilitate e.g. time‐resolved measurements. A metal sample, designed to be close to a phase pure object, and a bone sample with canals partially filled with D2O were used for demonstrating the technique. These samples were imaged with a polychromatic neutron beam followed by phase retrieval. For both samples the signal‐to‐noise ratios were significantly improved and, in the case of the bone sample, the phase retrieval allowed for separation of bone and D2O, which is important for example for in situ flow experiments. The use of deuteration contrast avoids the use of chemical contrast enhancement and makes neutron imaging an interesting complementary method to X‐ray imaging of bone. [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]

In 1892, J.L. Wolff proposed that bone could respond to mechanical and biophysical stimuli as a dynamic organ. This theory presents a unique opportunity for investigations on bone and its potential to aid in tissue repair. Routine activities such as exercise or machinery application can exert mechanical loads on bone. Previous research has demonstrated that mechanical loading can affect the differentiation and development of mesenchymal tissue. However, the extent to which mechanical stimulation can help repair or generate bone tissue and the related mechanisms remain unclear. Four key cell types in bone tissue, including osteoblasts, osteoclasts, bone lining cells, and osteocytes, play critical roles in responding to mechanical stimuli, while other cell lineages such as myocytes, platelets, fibroblasts, endothelial cells, and chondrocytes also exhibit mechanosensitivity. Mechanical loading can regulate the biological functions of bone tissue through the mechanosensor of bone cells intraosseously, making it a potential target for fracture healing and bone regeneration. This review aims to clarify these issues and explain bone remodeling, structure dynamics, and mechano-transduction processes in response to mechanical loading. Loading of different magnitudes, frequencies, and types, such as dynamic versus static loads, are analyzed to determine the effects of mechanical stimulation on bone tissue structure and cellular function. Finally, the importance of vascularization in nutrient supply for bone healing and regeneration was further discussed. [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]

Cryopreserved bone allografts(CBA) are susceptible to infection, nonunion, and late stress fracture. Although surgical revascularization by intramedullary implantation of an arteriovenous bundle (AV bundle) generates a neoangiogenic blood supply, there is potential for vascular ingrowth‐mediated bone resorption to weaken the graft. For this reason, we have evaluated changes in CBA mechanical properties of structural tibial allografts with and without surgically induced angiogenesis. Cryopreserved tibia bone allografts were transplanted to reconstruct a 3.5 cm segmental tibial defect in 16 Yucatan mini pigs. Surgical revascularization was performed in half by implantation of a cranial tibial AV bundle, (revascularization group). A control group of identical size had a ligated AV bundle implanted, (ligated group). At 20 weeks micro‐computed tomography (CT) measured bone mineral density (BMD) as well as bone union. Reference point indentation (RPI) compared cortex material properties, and axial compression determined the allotransplant compressive modulus. Seven of eight tibiae in the angiogenesis group were healed at both junction points at 20 weeks. Only four of eight tibiae healed in the ligated control group. There was no significant difference between the revascularization and ligated control groups in BMD and axial compression test. Similarly, RPI parameters were statistically equal. In paired comparisons with contralateral tibias, however, some RPI values were significantly worse in the ligated control group tibiae. This study demonstrates no adverse effect of surgical angiogenesis on cryopreserved structural bone allograft biomechanical properties in a large animal orthotopic segmental tibial defect model. These data suggest the potential value of surgical angiogenesis in clinical limb‐sparing reconstructive surgery. [ABSTRACT FROM AUTHOR]

Objective: Mineral metabolism disorders are common in chronic kidney disease (CKD) and increase the risk of fractures. It has been confirmed by animal models that these changes in bone also cause negative results in the mechanical properties of bone. Although there are many available methods for diagnosing metabolic bone disorders and estimating fracture risk, it has been suggested that biomechanical tests that provide information about bone's structural and material properties are most appropriate, particularly in small rodents with CKD. Therefore, this study aimed to investigate the effects of trauma-induced kidney damage on bone biomechanical properties. Materials and Methods: In this study, we used 16 adult Wistar Albino rats, 200--300 g, 4-5 months old. The animals were examined under two groups: kidney control (n = 9) and healty kidney control group and kidney damage group (n = 7). In the control group, the rats were fixed by laparotomy, and the kidneys were closed without suturing. However, the kidney damage group was approached by suturing. Results: When the bone biomechanical properties of the control and kidney-damaged groups were compared, a statistically significant difference was found between the displacement at maximum load, duration, and young's modulus groups (P < 0.005). Conclusion: The study showed that the bone biomechanical properties of rats with trauma-induced kidney damage changed, and there was an increased fracture risk. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is widely used to examine the carbonate content within bone apatite, but Raman spectra are also sensitive to orientation effects between the polarisation of the incoming laser light and the sample orientation. This may lead to discrepancies when using Raman spectroscopy to evaluate the carbonate content as the extent of crystal organisation can change depending on the type of bone, age, and presence of mineralisation disorders in the organism. It is experimentally very challenging to evaluate the effect of orientation using individual bone crystals. Therefore, we have used density functional theory to examine the effect of orientation in apatitic materials. We examined hydroxyapatite and three different types of carbonated apatite: A‐type where the carbonate ion substitutes the two OH groups in the unit cell, B‐type where co‐substitution occurs between carbonate in a phosphate position and Na+ for Ca2+ to maintain charge balance, and AB‐type where carbonate sits in both A‐site and B‐site. Our simulations show that the OH group in hydroxyapatite has a strong orientation dependence, consistent with previous literature. In addition, the phosphate and carbonate bands of the apatitic structures are predicted to be orientation dependent, where the maximum scattering efficiency occurs in configurations in which the laser polarisation is parallel to the crystallographic axes of the material. The intensity changes of the phosphate and carbonate bands are not consistent upon changing orientations and thus may lead to an underestimation of carbonate contents if insufficient sampling points are used during bone analysis. [ABSTRACT FROM AUTHOR]

With the developments in wireless technologies, living beings are increasingly exposed to electromagnetic fields (EMFs). EMFs are known to affect bone metabolism and muscle tissue. However, their effects on bones and skeletal muscles are controversial, as some studies have reported positive effects while others have reported adverse effects. In this study, the effects of radiofrequency radiation (RFR) on bone biomechanics and skeletal muscle tissues were investigated in diabetic and healthy rats. Rats were exposed to 3.5 GHz RFR for 2 h per day for 30 days. Bone biomechanics measurements were taken to evaluate the effects of RFR on bone quality, flexibility and durability. The whole-body specific absorption rate (SAR) was found to be 37 mW/kg. The results showed that RFR exposure had adverse effects on bone biomechanics, including decreased elasticity coefficient and Young's modulus, increased maximum displacement and decreased maximum force. However, oxidative stress parameters in diabetics were also altered by 3.5 GHz RFR to a greater extent than in healthy rats. In conclusion, 3.5 GHz RFR may have potential to alter bone quality and structural integrity including muscle oxidative stress parameters in rats. It should be emphasized that the observed changes were more obvious in diabetic rats. In addition, the changes observed in healthy and diabetic rats exposed to RFR showed a statistically significant difference according to the sham groups. [ABSTRACT FROM AUTHOR]

Nutrition is a key determinant of bone health and attainment of peak bone mass. Excess oxidative stress induces bone loss while increasing antioxidant capacity promotes protective effects on bone. Nuts are rich in antioxidants; therefore, we tested the hypothesis that compared to a control diet high in fat (40 % energy) and cholesterol, diets containing isocaloric amounts of pistachios (8·1 % g/g) or mixed nuts (7·5 % g/g) for 8 weeks would result in greater bone health in male adolescent (3 weeks; a state of continued skeletal growth) Sprague-Dawley rats. We found no difference in bone mechanical properties among groups. Tibial apparent density was ∼5 % higher in the pistachio and mixed nuts groups v. control (P < 0·05) with no clear difference detected for the femur. Expressions of genes known to impact bone turnover and serum bone turnover biomarkers were unaffected by either diet relative to control. Serum antioxidant capacity was ∼2-fold higher in the pistachio and mixed nuts groups compared with control (P < 0·05) but were similar between groups. Therefore, pistachios and mixed nuts may increase tibial density, in part, due to increasing antioxidant capacity. Longer dietary interventions may be necessary to elicit detectable changes in other bones (e.g. femur) and to detect potential mechanisms for the possible bone protective effects of nuts. [ABSTRACT FROM AUTHOR]

Bone consists of organic (mostly collagen) and inorganic (mostly bioapatite mineral) components that are organized into hierarchical structures from nano-to macro-scales that provide load-bearing functions. The structures and properties of bone are affected by bone remodeling activities, which are affected by mechanotransduction, a process through which mechanical signals are converted to biochemical signals in cellular signaling. Atomic Force Microscopy (AFM) technique can be used to characterize the surface morphology and mechanical properties of the specimens and can achieve atomic resolution in the resulting images. Therefore, the AFM technique has been applied in bone research and has provided new understandings of the structures and properties of hierarchical structures in bone across multiple length scales. This review begins by introducing the tip-surface interactions and the operation modes of AFM, including the recently developed sub-resonance modes, including PeakForce Tapping mode. Then the contact adhesion theories used in analyzing AFM data are reviewed, followed by a systematic review of the applications of the AFM technique to bone and bone-related tissues and cells, including surface morphology imaging, contact indentation testing, and other mechanical tests. The applications of sub-resonance tapping mode to bone and other biological molecules, cells, and tissues are also reviewed. • Development and operation modes of Atomic Force Microscope (AFM). • Contact, adhesion, indentation theories and models related to AFM. • Application of AFM to research on bone and related tissues and cells. • Recent advances with PeakForce mapping AFM on bone research. [ABSTRACT FROM AUTHOR]

Background: Accurate evaluation of the mechanical properties of trabecular bone is important, in which the internal bone marrow plays an important role. The aim of this systematic review is to investigate the roles of bone marrow on the mechanical properties of trabecular bone to better support clinical work and laboratory research.Methods: A systematic review of the literature published up to June 2022 regarding the role of bone marrow on the mechanical properties of trabecular bone was performed, using PubMed and Web of Science databases. The journal language was limited to English. A total of 431 articles were selected from PubMed (n = 186), Web of Science (n = 244) databases, and other sources (n = 1).Results: After checking, 38 articles were finally included in this study. Among them, 27 articles discussed the subject regarding the hydraulic stiffening of trabecular bone due to the presence of bone marrow. Nine of them investigated the effects of bone marrow on compression tests with different settings, i.e., in vitro experiments under unconfined and confined conditions, and computer model simulations. Relatively few controlled studies reported the influence of bone marrow on the shear properties of trabecular bone.Conclusion: Bone marrow plays a non-neglectable role in the mechanical properties of trabecular bone, its contribution varies depending on the different loading types and test settings. To obtain the mechanical properties of trabecular bone comprehensively and accurately, the solid matrix (trabeculae) and fluid-like component (bone marrow) should be considered in parallel rather than tested separately. [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 remodeling is mediated by several factors including strain. An increase in strain between 1% and 10% compared to homeostasis can trigger bone formation. We aim to create an orthopedic implant using clinically established imaging and manufacturing methods that induces this strain control in human bone. Titanium scaffolds were manufactured with multiaxial apparent modulus tailored to the mechanical properties of bone defined from computed tomography scans of cadaver human tibiae. Five bone cubes were tested with corresponding titanium scaffolds by loading under compression, which is similar to the implanted tibia loading condition. Bone strain was precisely controlled by varying the scaffold modulus, from 0% to 15% bone strain increase. This strain increase is the magnitude reported to invoke bone's positive remodeling. Axial modulus was closely matched between titanium scaffolds and bone, ranging from 48–728 and 81–800 MPa, respectively, whereby scaffold axial modulus was within 2% of nominal target values. Fine control of multiaxial moduli resulted in transverse modulus that matched bone well; ranging from 42–648 and 47–585 MPa in scaffolds and bone respectively. The scaffold manufacturing material and method are already used in the orthopedic industry. This study has significant clinical implications as it enables the design of implants which positively harness bone's natural mechanoresponse and respect bone's mechanical anisotropy and heterogeneity. [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]

The piezoelectric response of bone at the submicron scale is analyzed under mechanical loadings using the finite element (FE) method. A new algorithm is presented to virtually reconstruct realistic bone nanostructures, consisting of collagen fibrils embedded in a hydroxyapatite mineral network. This algorithm takes into account potential misalignments between fibrils, as well the porous structure of the mineral phase. A parallel non-iterative mesh generation algorithm is utilized to create high-fidelity FE models for several representative volume elements (RVEs) of the bone with various fibrils volume fractions and misalignments. The piezoelectric response of each RVE is simulated under three types of loading: the longitudinal compression, lateral compression, and shear. The resulting homogenized stress and electric field in RVEs with aligned fibrils showed a linear variation with the fibrils volume fraction under all loading conditions. For RVEs with misaligned fibrils, although more oscillations were observed in homogenized results, their difference with the results of RVEs with aligned fibrils subject to lateral compression and shear loadings were negligible. However, under longitudinal compression, the electric field associated with RVEs with misaligned fibrils was notably higher than that of RVEs with aligned fibrils for the same volume fraction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Existing animal experiments have shown that there are a certain number of osteoblasts and osteogenic growth factors in the fibrous tissue of the fractured bone end, and moreover, the number of blood vessels around the fractured end is not statistically different from that in the healed tissue. OBJECTIVE: To investigate the change of osteogenic growth factors, bone morphogenetic protein, vascular endothelial growth factor, transforming growth factor β1, in the broken end of bone nonunion under mechanical stress. METHODS: Sixty male Sprague-Dawley rats were selected to build the nonunion models. Nonunion models were established with self-made adjustable compressive external fixation. Then 40 rat models were selected for the experiment and were randomized into an experimental group and a control group. Then low-intensity high-frequency mechanical stress was applied to the experimental group, while nothing done to the control group. After 3 months, osteogenesis at the broken end of bone nonunion was assessed by radiological and histological observations. The changes of osteogenic growth factors, bone morphogenetic protein, vascular endothelial growth factor, transforming growth factor β1 at the broken end of bone nonunion were detected by immunochemistry and RT-PCR. RESULTS AND CONCLUSION: The consequences of radiography and histology showed that the broken end was sealed, with no bone bridge linking and connective tissue filled the broken gap between bone nonunion after 12 weeks. Then the gap became vague under mechanical stress after 4 weeks and was flocculent after 8 weeks. Unilateral osseous bridge connected the ends after 12 weeks. The radiographic score of the experimental group at the 12th week was significantly higher than that at the 4th and 8th weeks as well as that of the control group (P < 0.05). The results of RT-PCR and immunohistochemistry showed the expression of bone morphogenetic protein reached the peak at the 8th week. Gene amplification of vascular endothelial growth factor reached the peak at the 4th week and its expression peaked at the 8th week. The expression of transforming growth factor β1 kept smooth tendency. Compared with the control group, the expression of these osteogenic growth factors was significantly higher in the experimental group (P < 0.05). To conclude, the expression and gene amplification of bone morphogenetic protein, vascular endothelial growth factor, and transforming growth factor β1 could be obviously increased between the ends under mechanical stress, osteogenic tissue was found at the broken end. The consequences indicate that low-intensity mechanical stress has a positive relationship with osteogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, the standard method for clinical treatment of bone defects is autologous bone transplantation. However, the source of autologous bone is limited and it can cause new trauma and defects. Therefore, the development of ergonomic tissue-engineered bone has become the trend of repairing bone defects. OBJECTIVE: To summarize the characteristics and manufacturing techniques of collagen/inorganic materials to construct tissue-engineered bone. METHODS: PubMed, Web of Science (January 2000–January 2020) and CNKI (2010–2020) databases were used online to retrieve the relative articles regarding the application of collagen/inorganic composite scaffold. The key words were “collagen; inorganic materials; tissue-engineered bone; bone repair; geometry of bone scaffold” in English and Chinese, respectively. RESULTS AND CONCLUSION: Applying the principle of bionics, collagen composite inorganic materials were used to construct tissue-engineered bones by simulating the composition, structure, and characteristics of natural bones, which is an important direction in the field of bone graft materials. Collagen provides the extracellular matrix effect of the scaffold material, and promotes the migration, adhesion, and proliferation of cells on the scaffold, and accelerates the degradation of the scaffold in the body, and makes the composite scaffold has good biocompatibility and osteoinductivity. Choosing a suitable manufacturing technology to change the geometry of the collagen/inorganic material scaffold, and achieving the best three-dimensional porous nanoscale structure can promote cell adhesion and proliferation, and enhance the bone regeneration capacity of collagen/inorganic material scaffolds. Simultaneously, the surface of collagen/inorganic scaffolds is modified. Stem cells, biological factors, and polymers with osteogenic or angiogenic potential were compounded onto collagen/inorganic material scaffolds, which will improve the poor mechanical properties, insufficient structural stability, and limited bone regeneration capacity of collagen/inorganic material scaffolds. This provides a good idea for the option of tissue-engineered bone graft materials. [ABSTRACT FROM AUTHOR]

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development. [Display omitted] • Osx-conditional deletion of YAP and TAZ impairs fetal bone development • YAP/TAZ mediate osteogenic/angiogenic coupling to regulate vascular morphogenesis • YAP and TAZ regulate Cxcl12 expression in Pdgfr+ VOPs • YAP and TAZ regulate load-induced osteogenesis during fetal bone development Collins et al. show that the mechanosensitive transcriptional regulators YAP and TAZ mediate the co-mobilization of osteoblast precursors with blood vessels, control growth plate remodeling through osteogenic-angiogenic crosstalk, and mediate mechanoregulation of fetal limb bone formation. Specifically, YAP and TAZ regulate a subset of vessel-associated osteoblast precursors (VOPs) that regulate angiogenesis, in part through Cxcl12 and collagen-integrin interactions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although extracellular signal-regulated kinase 5 (ERK5) is an essential transducer of external signals for osteoblasts growth, differentiation, and survival, the effects of ERK5 signaling on bone homeostasis in vivo have not yet been described. OBJECTIVE: To elucidate whether the inhibition of ERK5 activity and its downstream targets by XMD8-92 results in osteoporosis and aggravates dexamethasoneinduced osteoporosis. METHODS: In vivo experiment: A mouse model of osteoporosis was induced by dexamethasone. There were four groups: blank control group (PBS); XMD8-92 group (50 mg/kg); dexamethasone group (50 mg/kg); XMD8-92+dexamethasone group (50 mg/kg XMD8-92 plus 50 mg/kg dexamethasone). Administration was done for 5 continuous weeks. Cell experiment: There were four groups: blank control group; XMD8-92 group (5 μmol/L); dexamethasone group (10×10-6 mol/L); XMD8-92+dexamethasone group (treatment with 5 μmol/L XMD8-92 followed by 10×10-6 mol/L dexamethasone). Cells were incubated for 1 hour. In addition, ERK5 activation was induced using epidermal growth factor. ERK5 activity in mice and MC3T3-E1 cells were detected. We further detected bone mass, bone architecture and mechanical stress of the trabecular bone, measured the expression of receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) and observed the roles of XMD8-92 in osteoblast proliferation and apoptosis. The study protocol was approved by the Ethics Committee of the Second Hospital of Lanzhou University (No. 2016-D44). RESULTS AND CONCLUSION: XMD8-92 could block ERK5 phosphorylation, change the architecture of the trabecular bone, reduce bone mass and aggravate dexamethasone-induced osteoporosis. XMD8-92 could significantly reduce the biomechanical properties of bone tissues in mice. XMD8-92 could up-regulate RANKL/OPG rate, lower osteoblasts vitality by inhibiting Cyclin B1 and CDK1 expression, and promote osteoblast apoptosis by up-regulating the expression of FasL. The novel findings suggest that ERK5 activity plays an important role in maintenance of bone mass, and altered ERK5 activation in disease conditions such as osteoporosis or dexamethasone-induced osteoporosis should be considered as a potential mechanism for abnormal bone homeostasis. [ABSTRACT FROM AUTHOR]

The remodeling behavior of bone is influenced by its mechanical environment. By mapping bone's mechanical properties in detail, orthopedic implants with respect to its mechanical properties could stimulate and harness remodeling to improve patient outcomes. In this study, multiaxial apparent modulus and strength of cadaveric proximal tibial bone are mapped and predicted from computed tomography (CT) derived apparent density. Group differences are identified from testing order, subchondral depth, condyle, and sub‐meniscal bone with covariates; age and gender. Axial modulus is 50% greater than the transverse modulus. Medial axial modulus is 30% greater than the lateral side. On the lateral side, axial modulus decreases by 50% from proximal to 25 mm distal. On the medial side, axial modulus remains relatively constant. Differences are quantified for density and multiaxial modulus across all subchondral depths, and different power law relationships are provided for each location. Density explains 75% of variation when grouped by subchondral depth and condyle. Yield strength is well‐predicted across all test directions, with density predicting 81% of axial strength variation and no differences over subchondral depth. Quantified mapping of bone multiaxial modulus based on condyle and subchondral depth is shown for the first time in a clinically viable protocol using conventional CT. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, bone remodeling imbalance is considered as a core reason leading to osteoporosis. An effective early intervention is performed to regulate bone remodeling imbalance at initial stage that can reverse osteoporosis and improve prognosis to some extent. Antiresorptive and anabolic agents are two types of anti-osteoporosis drugs addressing bone remodeling imbalance. Therefore, investigating the mechanism of bone remodeling imbalance is essential to guide medical treatment in osteoporosis. In addition, clinical application and therapeutic effect between antiresorptive and anabolic agents urgently need to be systematically summarized and may serve as a guide for clinical medication. OBJECTIVE: To review mechanism of bone remodeling imbalance in osteoporosis, summarize action mechanism of antiresorptive and anabolic agents in regulating bone remodeling imbalance, and compare their clinical effects so as to give clinical medical guidance. METHODS: Related articles were searched in PubMed databases, Web of Science and CNKI from inception to February 2020. The key words were “osteoporosis, bone remodeling, antiresorptive, anabolic, bisphosphonate, RANKL inhibitor, PTH analogue, anti-sclerostin antibody” in English and Chinese. Initially, 144 articles were searched, and according to the inclusion and exclusion criteria, 84 eligible articles were included in final analysis. RESULTS AND CONCLUSION: (1) Bone remodeling is activated by bone damaging. Reversible and irreversible deficits are two bone reforming types followed by remodeling. (2) The reversible one goes through bone resorption, bone refilling and secondary mineralization process for 3 months and new forming bone exhibits high mechanical strength. (3) The irreversible deficit occurred after bone remodeling imbalance that bone forming rate is much lower than resorption rate. Although there is certain amount of new forming bone generated in breaking area but the bone quality is unsatisfied, which tends to break again. (4) Bisphosphonates and RANKL inhibitors belong to antiresorptive agents, and are capable to reduce bone resorption, but bone forming mass is also decreased accordingly. (5) In addition, anabolic agents including PTH analogues and anti-sclerostin antibodies are benefit for reconstructing damaged bone structure, especially haversian canal, and significantly promote bone quality and mechanical property as well. [ABSTRACT FROM AUTHOR]

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

Mechanotransduction is pivotal in the maintenance of homeostasis in different tissues and involves multiple cell signaling pathways. In bone, mechanical stimuli regulate the balance between bone formation and resorption; osteocytes play a central role in this regulation. Dysfunctions in mechanotransduction signaling or in osteocytes response lead to an imbalance in bone homeostasis. This alteration is very relevant in some conditions such as osteoporosis and aging. Both are characterized by increased bone weakness due to different causes, for example, the increase of osteocyte apoptosis that cause an alteration of fluid space, or the alteration of molecular pathways. There are intertwined yet very different mechanisms involved among the cell-intrinsic effects of aging on bone, the cell-intrinsic and tissue-level effects of estrogen/androgen withdrawal on bone, and the effects of reduced mechanical loading on bone, which are all involved to some degree in how aged bone fails to respond properly to stress/strain compared to younger bone. This review aims at clarifying how the cellular and molecular pathways regulated and induced in bone by mechanical stimulation are altered with aging and in osteoporosis, to highlight new possible targets for antiresorptive or anabolic bone therapeutic approaches. [ABSTRACT FROM AUTHOR]

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

The heat generated during orthopedic surgery can cause thermal damage to bone cells, leading to cell necrosis, death, and bone resorption. In this study, the drill-exit surface in cortical bone drilling was firstly investigated by infrared thermography to understand the thermal characteristics of bone cutting. In order to mimic the short-term thermal condition of high temperature during surgical cutting, the osteoblasts were exposed to heat shock for short periods of time to investigate the effect of cutting heat on the bone. Necrosis and apoptosis were investigated immediately after heat shock for 2 s, 5 s, and 15 s at 50 °C, 60 °C, 70 °C, and 80 °C, respectively. The cells were then incubated for 4 days at 37 °C and analyzed by fluorescein annexin V-FITC/PI double staining. The temperature and heat-duration were precisely controlled by a novel heating approach. In comparison to the control group (37 °C), immediate necrotic and apoptotic response to heat shock was found in cells exposed to 50 °C for 5 s (11.8%, p<0.05); however, the response was negligible in cells exposed to 50 °C for 2 s. In addition, recovery was found in the group exposed to 50 °C and 60 °C for 2 s (p ≤ 0.05) after incubation for 4 days. Cell damage depends on the magnitude and duration of heat exposure. These findings provide fundamental knowledge for future developments of surgical tool design and cutting methods. [ABSTRACT FROM AUTHOR]

Piezoelectricity in bone is thought to be a mechanism by which ultrasound promotes the healing of bone fractures. However, a few studies have been conducted in the more clinically relevant megahertz range. To understand the piezoelectricity in bone, we fabricated ultrasound transducers using bone samples as piezoelectric materials and identified the longitudinal ultrasound radiation and reception in the megahertz range. The maximum transmitting sensitivity of the bone transducer was 140 mPa/V, which was nearly 1/1000 of a polyvinylidene difluoride (PVDF) transducer that has better electrical properties and piezoelectricity. The resonance frequencies of the transducer depend on the plate thickness and angle between the bone axis (alignment direction of the hydroxyapatite crystallites) and ultrasound propagation direction, reflecting the anisotropic character of the bone. The reception and transmission sensitivities of the bone transducers also depend on the plate thickness and angle, showing maximum values at off-axis angles. These results indicate the existence of both piezoelectricity and inverse piezoelectricity in bone, which may be key factors in understanding the bone healing by low-intensity biophysical (electrical or mechanical) stimulation. [ABSTRACT FROM AUTHOR]

Bone as such displays an intrinsic regenerative potential following fracture; however, this capacity is limited with large bone defects that cannot heal spontaneously. The management of critical‐sized bone defects remains a major clinical and socioeconomic need with osteoregenerative biomaterials constantly under development aiming at promoting and enhancing bone healing. X‐ray computed tomography (XCT) has become a standard and essential tool for quantifying structure–function relationships in bone and biomaterials, facilitating the development of novel bone tissue engineering strategies. This paper presents recent advancements in XCT analysis of biomaterial‐mediated bone regeneration. As a noninvasive and nondestructive technique, XCT allows for qualitative and quantitative evaluation of three‐dimensional (3D) scaffolds and biomaterial microarchitecture, bone growth into the scaffold as well as the 3D characterisation of biomaterial degradation and bone regeneration in vitro and in vivo. Furthermore, in combination with in situ mechanical testing and digital volume correlation (DVC), XCT demonstrated its potential to better understand the bone–biomaterial interactions and local mechanics of bone regeneration during the healing process in relation to the regeneration achieved in vivo, which will likely provide valuable knowledge for the development and optimisation of novel osteoregenerative biomaterials. Lay Description: Bone, being a dynamically adaptable material, displays excellent regenerative properties following fracture. However, the self‐healing capacity of bone becomes more difficult with large bone defects. Those defects are common and occur in many clinical situations; hence, biomaterials are mostly used to restore both bone structure and function in the defect site. X‐ray computed tomography (XCT) is a powerful tool to evaluate bone regeneration in critical‐sized defects after the implantation of biomaterials, allowing to an improved understanding of the regeneration process following different bone tissue engineering approaches. This paper focuses on recent advancements in XCT analysis to characterise biomaterial‐mediated bone regeneration in critical‐sized defects. XCT supports three‐dimensional (3D) analysis of biomaterials, scaffolds and regenerated bone microarchitecture, as well as bone ingrowth into the scaffold. As a nondestructive technique, XCT allows for a 3D characterisation of biomaterial degradation and bone regeneration over time. In addition, XCT combined with in situ mechanical experiments and digital volume correlation (DVC) provides a 3D evaluation and quantification of bone–biomaterial interactions and deformation mechanisms during the regeneration process. This remains essential for the development and enhancement of novel biomaterials able to produce bone that is comparable with the native tissue they aim to replace. [ABSTRACT FROM AUTHOR]

Osteocytes play a critical role in mediating cell–cell communication and regulating bone homeostasis, and osteocyte apoptosis is associated with increased bone resorption. miR21, an oncogenic microRNA, regulates bone metabolism by acting directly on osteoblasts and osteoclasts, but its role in osteocytes is not clear. Here, we show that osteocytic miR21 deletion has sex‐divergent effects in bone. In females, miR21 deletion reduces osteocyte viability, but suppresses bone turnover. Conversely, in males, miR21 deletion increases osteocyte viability, but stimulates bone turnover and enhances bone structure. Further, miR21 deletion differentially alters osteocyte cytokine production in the two sexes. Interestingly, despite these changes, miR21 deletion increases bone mechanical properties in both sexes, albeit to a greater extent in males. Collectively, our findings suggest that miR21 exerts both sex‐divergent and sex‐equivalent roles in osteocytes, regulating osteocyte viability and altering bone metabolism through paracrine actions on osteoblasts and osteoclasts differentially in males vs females, whereas, influencing bone mechanical properties independent of sex. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is characterized by morphological changes that alter bone structure and mechanical properties. This study compared bone morphometric parameters and apparent modulus between humeral heads excised from end‐stage OA patients undergoing total shoulder arthroplasty (n = 28) and non‐pathologic normal cadavers (n = 28). Morphometric parameters were determined in central cores, with regional variations compared in four medial to lateral regions. Linear regression compared apparent modulus, morphometric parameters, and age. Micro finite element models estimated trabecular apparent modulus and derived density–modulus relationships. Significant differences were found for bone volume fraction (p < 0.001) and trabecular thickness (p < 0.001) in the most medial regions. No significant differences occurred between morphometric parameters and apparent modulus or age, except in slope between groups for apparent modulus versus trabecular number (p = 0.021), and in intercept for trabecular thickness versus age (p = 0.040). Significant differences occurred in both slope and intercept between density–modulus regression fits for each group (p ≤ 0.001). The normal group showed high correlations in the power‐fit (r2 = 0.87), with a lower correlation (r2 = 0.61) and a more linear relationship, in the OA group. This study suggests that alterations in structure and apparent modulus persist mainly in subchondral regions of end‐stage OA bone. As such, if pathologic regions are removed during joint replacement, computational models that utilize modeling parameters from non‐pathologic normal bone may be applied to end‐stage OA bone. An improved understanding of humeral trabecular bone variations has potential to improve the surgical management of end‐stage OA patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:503–509, 2020 [ABSTRACT FROM AUTHOR]

The damage to normal bone tissue following therapeutic irradiation increases the risk of fracture and bone osteoporosis. Bioactive glasses have been synthesized with improved properties exhibiting promising prospects to restore bone defects and to reduce bone alterations. This study aims in evaluating the performance therapy of nano-bioglass (NBG). In vivo, after rat 60Co y-radiation, the tissue wound healing process was studied by grafting NBG material in rat femoral condyle tissue. An improved mechanical property was noticed (31.11 ± 5.0 HV) when compared with that of BG-implanted group (24.16 ± 4.9 HV). On the other hand, a rise in Ca and P ion concentrations in the implanted microenvironment was shown to lead to the formation/deposition of Ca–P phases. Trace elements, such as Mg and Zn, were detected in the newly formed bone and involved in bone healing. Serum alanine aminotransferase (ALT), aspartate transaminase (AST), and gamma-glutamyl-transpeptidases (GTT) in groups implanted with NBG show no significant variation for all time of implantation. Serum creatinine maintains their normal levels in the implanted groups in different time of implantation. The histomorphometric parameters of bone tissue showed amelioration in NBG-treated rats. Moreover, no hepatocyte or renal necrosis was noticed. Additionally, no remarkable change in the tissue morphology was shown. Our findings suggested that NBG might have promising potential applications for wound healing. [ABSTRACT FROM AUTHOR]

This study focused on analyzing the effects of inclusion of modern hybrid rye to corn-wheat diet on mechanical properties of bones and tendons. A total of 224 broiler chickens were fed a diet without rye inclusion or a diet containing 15% of hybrid rye cv. Brasetto. The diets were either unsupplemented or supplemented with xylanase (minimum activity 1000 FXU/g, dose 200 mg/kg of feed). Each dietary group consisted of 56 birds. On day 42, selected chickens (n = 7 from each group) were slaughtered. Tibia were analyzed for mineralization, geometry, and biomechanical characteristics of bone mid-diaphysis. The mechanical properties of digital flexor III tendon were also assessed. Bone mineral density and bone ash percentage did not differ when both diets were given without xylanase. Enzyme supplementation increased bone mineral density (P < 0.01) in both dietary groups, whereas bone ash percentage (P < 0.01) increased only for corn-wheat diet. Rye inclusion had no effect on bone mid-shaft geometrical traits related to tibia weight-bearing capacity (cross-sectional area, cortical index, and mean relative wall thickness). Performed bending test showed no effect of hybrid rye inclusion on bone mechanical endurance. When xylanase was supplemented, bone length (P < 0.01) and weight (P < 0.05) decreased, whereas yield load (P < 0.01), stiffness (P < 0.05), Young modulus (P < 0.05), elastics stress (P < 0.01), and ultimate stress (P < 0.01) increased, irrespective of rye presence. The tendon tensile strain test showed that in corn-wheat diet enzyme supplementation positively influenced rupture force (P < 0.05) and tendon stiffness (P < 0.01). Xylanase supplementation increased the value of energy required to tendon rupture, irrespective of rye inclusion (P < 0.05). Study showed that modern hybrid rye varieties can be introduced to corn-wheat diets of broiler chickens in the aspect of animal welfare related to the development and homeostasis of musculoskeletal system, irrespective of xylanase supplementation. The enzyme addition positively affected biomechanical properties of bones and tendons. [ABSTRACT FROM AUTHOR]

Development of effective and cost-efficient bone tissue engineering grafts has been the key area of research for regenerative medicine, yet an ideal grafting material has remained elusive due in large part to the highly dynamic nature of bone. A wide array of materials, both natural and synthetic, have been implemented as potential candidates for commercially available products, yet the gold standard for grafting material still remains autogenous bone. We review currently commercially available bone graft materials and relevant graft characteristics that impact the effectiveness of tissue repair, emphasizing the advantages and disadvantages of materials based on composition and origin. Examined materials were selected through a web-based search for readily accessible and clinically applicable graft materials. Grafts were then categorized according to material source to examine advantages and disadvantages associated with allogenic, xenogeneic, synthetic materials. Lastly, the application of bioactive molecules onto these basal grafts is explored to illustrate the enhancement and regulative capacity of these additives on traditional osteobiologic materials. [ABSTRACT FROM AUTHOR]

• Study developed a method for automated FE analyses from clinical hip CT images. • FE model includes distinguished cortical bone with corrected partial volume effect. • Segmentation accuracy verified against clinical CT and ground-truth uCT. • FE model analyzed against experimental strains recorded with high-speed DIC. Finite element (FE) models based on quantitative computed tomography (CT) images are better predictors of bone strength than conventional areal bone mineral density measurements. However, FE models require manual segmentation of the femur, which is not clinically applicable. This study developed a method for automated FE analyses from clinical CT images. Clinical in-vivo CT images of 13 elderly female subjects were collected to evaluate the method. Secondly, proximal cadaver femurs were harvested and imaged with clinical CT (N = 17). Of these femurs, 14 were imaged with µCT and three had earlier been tested experimentally in stance-loading, while collecting surface deformations with digital image correlation. Femurs were segmented from clinical CT images using an automated method, based on the segmentation tool Stradwin. The method automatically distinguishes trabecular and cortical bone, corrects partial volume effect and generates input for FE analysis. The manual and automatic segmentations agreed within about one voxel for in-vivo subjects (0.99 ± 0.23 mm) and cadaver femurs (0.21 ± 0.07 mm). The strains from the FE predictions closely matched with the experimentally measured strains (R2 = 0.89). The method can automatically generate meshes suitable for FE analysis. The method may bring us one step closer to enable clinical usage of patient-specific FE analyses. [ABSTRACT FROM AUTHOR]

Aim. Is to evaluate the influence of glucovance therapy on biomechanical properties of bone in streptozotocin - induced diabetes mellitus (DM) in rats. Materials and Methods. A total of 28 male Wistar-Albino rats (12-week-old; 210-300 g) were divided into 4 groups including control (C; no treatment; n=7), sham [Sh; distilled water (gavage, for 8 weeks); n=7], diabetes [DM; streptozotocin (45 mg/kg, single i.p injection); n=7] and diabetes+ Glucovance treatment [DM+G; streptozotocin (45 mg/kg, single i.p injection) + Glucovance (Glucovance, 500/5 mg/kg/day/rat, gavage, for 8 weeks); n=7] groups. Body weight, blood glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical properties of bone tissue were evaluated. BGLs in diabetic rats were significantly increased compared to non-diabetic rats, while the body weights were decreased (p<0.05). Results. A significant difference was not detected between groups with regard to cross-sectional area of diaphyseal femur (p>0.05). Maximum load, energy absorption capacity, ultimate stress, ultimate strain, toughness and displacement were shown to decrease and stiffness was shown to increase in DM rats (p<0.05). Ultimate stress and maximum load were significantly increased in DM+G groups compared to DM groups (p<0.05). Conclusion. Glucovance treatment seems to be effective in restoration of biomechanical deterioration of bone specific to STZ-induced DM. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effects of radiotherapy on biomechanical, histomorphometric, and microstructural characteristics of bone, in diverse periods, compared with intact bone tissue. Materials and methods: Eighteen adult male New Zealand rabbits were treated with a single radiation dose of 30 Gy. The animals were randomly divided into six groups: NoIr, control group, no radiation, and five irradiated groups sacrificed after 24 h (Ir24h), 7 (Ir7d), 14 (Ir14d), 21 (Ir21d), and 28 (Ir28d) days. After these periods, the animals were sacrificed and their tibias (n = 6) evaluated using three-point bending test to calculate the ultimate force, work to failure, and bone stiffness. Dynamic indentation test was used to quantify Vickers hardness and elasticity modulus of bone tissue. Micro-CT was used to analyze the cortical volume (CtV), cortical thickness (CtTh), and porosity (Ct.Po). Histomorphometric assessment was based on the lacunarity of bone tissue. Data were analyzed using one-way ANOVA and Kruskal−Wallis tests followed by Tukey, Dunnet, and Dunn's post-tests (P < 0.05). Results: The ultimate force, work to failure, stiffness, elastic modulus, and Vickers hardness values of irradiated bone were significantly lower that non-irradiated bone. Irradiated bone showed significantly lower CtTh and CtV values and higher CtPo than non-irradiated bone. No significant difference was found for lacunarity between non-irradiated bone and irradiated bone. Conclusions: Ionizing radiation decreases normal anisotropy on microarchitecture of cortical bone, and increases bone fragility compared with non-irradiated bone. Further, these changes were seen after longer periods (e.g., 14 and 21 days), and not immediately after radiation therapy. Clinical relevance: The radiotherapy reduces bone mechanical properties and the normal structure of organic and inorganic bone matrix. For studying the protocols to protect the radiotherapy effect using rabbit model, the use of the sacrificing period between 14 and 21 days is recommended. [ABSTRACT FROM AUTHOR]

Patients with cancer can present with bone metastases (BM), which are frequently complicated by different types of fractures necessitating prompt management to avoid serious impairment in terms of quality of life and survival. Percutaneous image-guided bone consolidation has rapidly emerged as an alternative to surgical fixation and is mainly reserved for patients who are deemed unfit for surgical management. Two percutaneous techniques, osteoplasty and osteosynthesis, are available and are selected based on the biomechanics of the target bones as well as the fracture types. The aim of this narrative review is to present the different types of BM-related fractures and the interventional strategies and techniques underpinning their minimally invasive percutaneous fixation. [ABSTRACT FROM AUTHOR]

Abstract Hindlimb suspension is the most used model for inducing bone loss from unloading but requires a separate ground control group. This control group cannot be used for genetic studies involving outbred mice. In this study, we evaluated a single limb immobilization (SLI) model for inducing bone loss from unloading, with the contralateral limb from the same animal used as a control. Male 10-week old C57Bl/6J mice had one limb immobilized for one, two, or three weeks. Subsequently, an additional group of male 16-week old C57Bl/6J mice had one limb immobilized for three weeks. SLI resulted in decreased tibial trabecular BV/TV, Tb Th, and Tb N compared to contralateral limbs in young mice. Femoral trabecular BV/TV, Tb Th, Tb N, and femoral cortical area fraction were also decreased. Mechanical properties were not affected after three weeks. In adult mice, femoral trabecular BV/TV, Tb Th, and Tb N were decreased. Femoral stiffness, ultimate stress, and Young's modulus were decreased. Bone properties decreased by SLI were also decreased by hindlimb suspension previously. The results suggest SLI can be an effective model for inducing bone loss in growing and adult mice after three weeks of immobilization. [ABSTRACT FROM AUTHOR]