Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.

Advancing age is the strongest risk factor for osteoporosis and skeletal fragility. Rapamycin is an FDA-approved immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) complex, extends lifespan, and protects against aging-related diseases in multiple species; however, the impact of rapamycin on skeletal tissue is incompletely understood. We evaluated the effects of a short-term, low-dosage, interval rapamycin treatment on bone microarchitecture and strength in young-adult (3 mo old) and aged female (20 mo old) C57BL/6 mice. Rapamycin (2 mg/kg body mass) was administered via intraperitoneal injection 1×/5 d for a duration of 8 wk; this treatment regimen has been shown to induce geroprotective effects while minimizing the side effects associated with higher rapamycin dosages and/or more frequent or prolonged delivery schedules. Aged femurs exhibited lower cancellous bone mineral density, volume, trabecular connectivity density and number, higher trabecular thickness and spacing, and lower cortical thickness compared to young-adult mice. Rapamycin had no impact on assessed microCT parameters. Flexural testing of the femur revealed that both yield strength and ultimate strength were lower in aged mice compared to young-adult mice. There were no effects of rapamycin on these or other measures of bone biomechanics. Age, but not rapamycin, altered local and global measures of bone turnover. These data demonstrate that short-term, low-dosage interval rapamycin treatment does not negatively or positively impact the skeleton of young-adult and aged mice.

Open the pores - Polydimethylsiloxane influences the porous structure of cancellous bone surrogates for biomechanical testing of osteosyntheses.

Synthetic materials used for valid and reliable implant testing and design should reflect the mechanical and morphometric properties of human bone. Such bone models are already available on the market, but they do not reflect the population variability of human bone, nor are they open-celled porous as human bone is. Biomechanical studies aimed at cementing the fracture or an implant cannot be conducted with them. The aim of this study was to investigate the influence of a cell stabilizer on polyurethane-based cancellous synthetic bone in terms of morphology, compressive mechanics, and opening of the cancellous bone structure for bone cement application. Mechanical properties of cylindrical specimens of the bone surrogates were determined by static compression tests to failure. Furthermore, a morphometric analysis was performed using microcomputed tomography. To prove the open-cell nature of the bone surrogates, an attempt was made to apply bone cement. Effects on the mechanical properties of the polyurethane-based bone surrogates were observed by the addition of polydimethylsiloxane. All mechanical parameters like Young's modulus, ultimate stress and yield stress increased statistically significantly with increasing amounts of cell stabilizer (all p > 0.001), except for yield stress. The analysis of morphometric parameters showed a decrease in trabecular thickness, spacing and connectivity density, which was accompanied by an increase in trabecular number and an increase in pore size. The open-cell nature was proven by the application and distribution of bone cement in specimens with stabilizer, which was visualized by X-ray. In conclusion, the results show that by adding a cell stabilizer, polyurethane-based cancellous bone substrates can be produced that have an open-cell structure similar to human bone. This makes these bone surrogates suitable for biomechanical testing of osteosyntheses and for osteosynthesis cementation issues.

Environmental enrichment in finishing pigs: does it promote any changes in bone biomechanics?

The resistance of pigs' bone structure was evaluated for the first time, reared with and without environmental enrichment (EE) in the finishing phase using techniques in bone biomechanics; 432 swine from the Hampshire breed, being males and females, with initial body weight between 22 and 27 kg and final body weight between 110 and 125 kg were evaluated for 112 days. The experimental design was in randomized blocks, with 6 treatments, distributed in a 2 × 3 factorial scheme (sex × conditions in creation), with 12 repetitions/treatment, totaling 72 pens. The treatments were as follows: branched chain for males (T1), sisal branched string for males (T2), males without EE (T3), branched chain for females (T4), sisal branched string for females (T5), and females without EE (T6). At the end of the experimental period, all animals were slaughtered in an industrial slaughterhouse, having their femur bones collected for bone biomechanics analysis. There was no effect (P > 0.05) of the interaction (enrichment × sex) and individual factors for bone weight. There was a tendency (P = 0.08) of the interaction for flexion force, being higher in males enriched with branched ropes and chains. For breaking stress, there was an interaction effect (P = 0.04), being the females without EE the ones showing the lowest breaking stress, favoring bone fragility. The use of branched ropes and chains strengthens the bone structure in swine in the termination phase (110-125 kg BW - 183-190 days in age), being an important strategy used to meet the animal welfare requirements.

Effects of blood flow restriction training on bone turnover markers, microstructure, and biomechanics in rats.

Objective: The present study aimed to investigate the effects of blood flow restriction training on muscle strength, bone tissue structure material, and biomechanical properties in rats applying various exercise interventions and to analyze the process by identifying the bone turnover markers, it provides a theoretical basis for the application of BFRT in clinical rehabilitation. Methods: A total of 24, 3-month-old male SD (Sprague Dawley) rats were randomly divided into pressurized control group (CON, n=6), low-intensity training group (LIRT, n=6), high-intensity training group (HIRT, n=6), and blood flow restriction training group (LIBFR, n=6) for 8-week ladder-climbing exercises. The pressured control group were given only ischemia treatments and did not undertake any burden. The low-intensity training group was allowed to climb the ladder with 30% of the maximum voluntary carrying capacity (MVCC). The rats in the high-intensity training group were allowed to climb the ladder with 70% MVCC. The blood flow restriction training group climbed the ladder with 30% MVCC while imposing blood flow restriction. Before sampling, the final MVCC was measured using a ladder-climbing protocol with progressively increasing weight loading. The serum, muscle, and bone were removed for sampling. The concentrations of the bone turnover markers PINP, BGP, and CTX in the serum were measured using ELISA. The bone mineral density and microstructure of femur bones were measured using micro-CT. Three-point bending and torsion tests were performed by a universal testing machine to measure the material mechanics and structural mechanics indexes of the femur bone. Results: The results of maximum strength test showed that the MVCC in LIRT, HIRT, and LIBFR groups was significantly greater than in the CON group, while the MVCC in the HIRT group was significantly higher than that in the LIRT group (P<0.05). According to the results of the bone turnover marker test, the concentrations of bone formation indexes PINP (amino-terminal extension peptide of type I procollagen) and BGP (bone gla protein) were significantly lower in the CON group than in the HIRT group (P<0.01), while those were significantly higher in the LIRT group compared to the HIRT group (P<0.01). In terms of bone resorption indexes, significant differences were identified only between the HIRT and other groups (P<0.05). The micro-CT examination revealed that the HIRT group had significantly greater bone density index values than the CON and LIRT groups (P<0.05). The results of three-point bending and torsion test by the universal material testing machine showed that the elastic modulus and maximum load indexes of the HIRT group were significantly smaller than those of the LIBFR group (P<0.05). The fracture load indexes in the HIRT group were significantly smaller than in the LIBFR group (P<0.05). Conclusion: 1. LIRT, HIRT, LIBFR, and CON all have significant differences, and this training helps to improve maximum strength, with HIRT being the most effective. 2. Blood flow restriction training can improve the expression of bone turnover markers, such as PINP and BGP, which promote bone tissue formation. 3. Blood flow restriction training can improve muscle strength and increase the positive development of bone turnover markers, thereby improving bone biomechanical properties such as bone elastic modulus and maximum load.

The influence of different shaped osteocyte lacunae on microcrack initiation and propagation.

BACKGROUND: The morphology of osteocyte lacunae varies in bones of different ages and bone pathologies. Osteocyte lacunae can cause stress concentration and initiate microcracks. However, the influence of changes in osteocyte lacunar shape on microcrack is unknown. Therefore, the aim of this study was to determine the effects of osteocyte lacunae with different shapes on microcrack initiation and propagation. METHODS: Osteon models containing osteocyte lacunae with different shapes were established. The progressive damage analysis method, based on computer simulations, was used to study the evolution of microdamage within the osteon, including the processes of intralaminar and interlaminar microdamage. FINDINGS: Models with larger DoE values can effectively delay or prevent the formation of linear microcracks, which ensures high fracture toughness of cortical bone. It is subjected to stronger mechanical stimulation, making it more sensitive to loads. Models with smaller DoE values increase the load threshold for microdamage generation and reduces its impact on bone mechanical performance, making it less susceptible to microdamage than models with larger DoE values. INTERPRETATION: These findings enhance the limited knowledge of the influence of the lacunar shape on microdamage and contribute to a better understanding of bone biomechanics.

Precision of bone mechanoregulation assessment in humans using longitudinal high-resolution peripheral quantitative computed tomography in vivo.

Local mechanical stimuli in the bone microenvironment are essential for the homeostasis and adaptation of the skeleton, with evidence suggesting that disruption of the mechanically-driven bone remodelling process may lead to bone loss. Longitudinal clinical studies have shown the combined use of high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis can be used to measure load-driven bone remodelling in vivo; however, quantitative markers of bone mechanoregulation and the precision of these analyses methods have not been validated in human subjects. Therefore, this study utilised participants from two cohorts. A same-day cohort (n = 33) was used to develop a filtering strategy to minimise false detections of bone remodelling sites caused by noise and motion artefacts present in HR-pQCT scans. A longitudinal cohort (n = 19) was used to develop bone imaging markers of trabecular bone mechanoregulation and characterise the precision for detecting longitudinal changes in subjects. Specifically, we described local load-driven formation and resorption sites independently using patient-specific odds ratios (OR) and 99 % confidence intervals. Conditional probability curves were computed to link the mechanical environment to the remodelling events detected on the bone surface. To quantify overall mechanoregulation, we calculated a correct classification rate measuring the fraction of remodelling events correctly identified by the mechanical signal. Precision was calculated as root-mean-squared averages of the coefficient of variation (RMS-SD) of repeated measurements using scan-rescan pairs at baseline combined with a one-year follow-up scan. We found no significant mean difference (p < 0.01) between scan-rescan conditional probabilities. RMS-SD was 10.5 % for resorption odds, 6.3 % for formation odds, and 1.3 % for correct classification rates. Bone was most likely to be formed in high-strain and resorbed in low-strain regions for all participants, indicating a consistent, regulated response to mechanical stimuli. For each percent increase in strain, the likelihood of bone resorption decreased by 2.0 ± 0.2 %, and the likelihood of bone formation increased by 1.9 ± 0.2 %, totalling 38.3 ± 1.1 % of strain-driven remodelling events across the entire trabecular compartment. This work provides novel robust bone mechanoregulation markers and their precision for designing future clinical studies.

A coarse-grained molecular dynamics investigation of the role of mineral arrangement on the mechanical properties of mineralized collagen fibrils.

Mineralized collagen fibrils (MCFs) comprise collagen molecules and hydroxyapatite (HAp) crystals and are considered universal building blocks of bone tissue, across different bone types and species. In this study, we developed a coarse-grained molecular dynamics (CGMD) framework to investigate the role of mineral arrangement on the load-deformation behaviour of MCFs. Despite the common belief that the collagen molecules are responsible for flexibility and HAp minerals are responsible for stiffness, our results showed that the mineral phase was responsible for limiting collagen sliding in the large deformation regime, which helped the collagen molecules themselves undergo high tensile loading, providing a substantial contribution to the ultimate tensile strength of MCFs. This study also highlights different roles for the mineralized and non-mineralized protofibrils within the MCF, with the mineralized groups being primarily responsible for load carrying due to the presence of the mineral phase, while the non-mineralized groups are responsible for crack deflection. These results provide novel insight into the load-deformation behaviour of MCFs and highlight the intricate role that both collagen and mineral components have in dictating higher scale bone biomechanics.

Longitudinal alterations in bone morphometry, mechanical integrity and composition in Type-2 diabetes in a Zucker diabetic fatty (ZDF) rat.

Individuals with Type-2 Diabetes (T2D) have an increased risk of bone fracture, without a reduction in bone mineral density. It is hypothesised that the hyperglycaemic state caused by T2D forms an excess of Advanced Glycated End-products (AGEs) in the organic matrix of bone, which are thought to stiffen the collagen network and lead to impaired mechanical properties. However, the mechanisms are not well understood. This study aimed to investigate the geometrical, structural and material properties of diabetic cortical bone during the development and progression of T2D in ZDF (fa/fa) rats at 12-, 26- and 46-weeks of age. Longitudinal bone growth was impaired as early as 12-weeks of age and by 46-weeks bone size was significantly reduced in ZDF (fa/fa) rats versus controls (fa/+). Diabetic rats had significant structural deficits, such as bending rigidity, ultimate moment and energy-to-failure measured via three-point bend testing. Tissue material properties, measured by taking bone geometry into account, were altered as the disease progressed, with significant reductions in yield and ultimate strength for ZDF (fa/fa) rats at 46-weeks. FTIR analysis on cortical bone powder demonstrated that the tissue material deficits coincided with changes in tissue composition, in ZDF (fa/fa) rats with long-term diabetes having a reduced carbonate:phosphate ratio and increased acid phosphate content when compared to age-matched controls, indicative of an altered bone turnover process. AGE accumulation, measured via fluorescent assays, was higher in the skin of ZDF (fa/fa) rats with long-term T2D, bone AGEs did not differ between strains and neither AGEs correlated with bone strength. In conclusion, bone fragility in the diabetic ZDF (fa/fa) rats likely occurs through a multifactorial mechanism influenced initially by impaired bone growth and development and proceeding to an altered bone turnover process that reduces bone quality and impairs biomechanical properties as the disease progresses.

Effects of Incretin Pathway Elements on Bone Properties.

Introduction The effects of incretin-based drugs, such as receptor agonists of glucagon-like peptide-1 and inhibitors of dipeptidyl peptidase-4, on bone metabolism are not completely clear yet. The aim of this study is to compare the effects of glucagon-like peptide-1 and inhibitors of dipeptidyl peptidase-4 on the bone to see how different elements of the incretin pathway affect bone quality in terms of biomechanical properties, bone turnover, and mineral properties. Materials and methods Forty 10-week-old Wistar rats were divided into four groups: a control group, a control diabetic group, a diabetic group treated with sitagliptin, and a diabetic group treated with exenatide. Type 2 diabetes was simulated by dietary manipulation in addition to low-dose streptozotocin, and then two different incretin-based drugs were administered. The rats were sacrificed after five weeks of therapeutic treatment. Their serum was analyzed with the enzyme-linked immunosorbent assay (ELISA) method for basic bone turnover markers, and their right femur was subjected to a three-point bending test. Finally, Hematoxylin & Eosin staining, in addition to Raman spectroscopy, were employed to access the collagen and mineral properties of the bone. Results Both incretin-based drugs reduced osteoclast function; however, they were not able to restore osteoblastic function to normal. The net effect on bone strength was surprising: bone elasticity was restored by the antidiabetic treatment, but bone strength deteriorated. Exenatide had a slightly more pronounced effect, which, although not significant, points to the direction that dipeptidyl peptidase-4 (DPP4) may be a linking factor between reduced osteoclastic function and reduced bone formation, as suggested by the literature. Conclusion DPP4 receptors seem to be one of the links between reduced osteoclast function and reduced bone remodeling, so DPP4 inhibition can be more detrimental to the bone than glucagon-like peptide-1 (GLP-1) receptor agonists.

Assessment of fracture healing in orthopaedic trauma.

Fracture healing is a complex physiologic process, relying on the crucial interplay between biological and mechanical factors. It is generally assessed using imaging modalities, including conventional radiology, CT, MRI and ultrasound (US), based on the fracture and patient features. Although these techniques are routinely used in orthopaedic clinical practice, unfortunately, they do not provide any information about the biomechanical status of the fracture site. Therefore, in recent years, several non-invasive techniques have been proposed to assess bone healing using ultrasonic wave propagation, changes in electrical properties of bones and callus stiffness measurement. Moreover, different research groups are currently developing smart orthopaedic implants (plates, intramedullary nails and external fixators), able to provide information about the fracture healing process. These devices could significantly improve orthopaedic and trauma clinical practice in the future and, at the same time, reduce patients' exposure to X-rays. This study aims to define the role of traditional imaging techniques and emerging technologies in the assessment of the fracture healing process.

Statistical Properties of a Virtual Cohort for In Silico Trials Generated with a Statistical Anatomy Atlas.

Osteoporosis-related hip fragility fractures are a catastrophic event for patient lives but are not frequently observed in prospective studies, and therefore phase III clinical trials using fractures as primary clinical endpoint require thousands of patients enrolled for several years to reach statistical significance. A novel answer to the large number of subjects needed to reach the desired evidence level is offered by In Silico Trials, that is, the simulation of a clinical trial on a large cohort of virtual patients, monitoring the biomarkers of interest. In this work we investigated if statistical aliasing from a custom anatomy atlas could be used to expand the patient cohort while retaining the original biomechanical characteristics. We used a pair-matched cohort of 94 post-menopausal women (at the time of the CT scan, 47 fractured and 47 not fractured) to create a statistical anatomy atlas through principal component analysis, and up-sampled the atlas in order to obtain over 1000 synthetic patient models. We applied the biomechanical computed tomography pipeline to the resulting virtual cohort and compared its fracture risk distribution with that of the original physical cohort. While the distribution of femoral strength values in the non-fractured sub-group was nearly identical to that of the original physical cohort, that of the fractured sub-group was lower than in the physical cohort. Nonetheless, by using the classification threshold used for the original population, the synthetic population was still divided into two parts of approximatively equal number.

The effects on type 2 diabetes mellitus mouse femoral bone achieved by anti-osteoporosis exercise interventions.

Purpose: Exercise therapy and key regulators of bone quality exert anti-hyperglycemic effects on type 2 diabetes mellitus (T2DM) mice. A number of programs have been reported to have an effect on bone disease in T2DM. Major unanswered questions concern the potential correlation of exercise with the improvement of bone quality in T2DM mice and how the nonlinear optical properties of bone are correlated with changes to its crystal structure. Methods: Subjects were randomly divided into six groups: 1) control (C) group, which was fed a normal diet (n = 8); 2) T2DM quiet group, which was given a high-fat diet and quiet (n = 8); 3) T2DM plus swimming (T2DM+S) group, which received T2DM and swim training (n = 8); 4) T2DM plus resistance exercise (T2DM+RE) group, which was given T2DM and resistance exercise (n = 8); 5) T2DM plus aerobic exercise (T2DM+AE) group, with T2DM and medium-intensity treadmill exercise (n = 8); and 6) T2DM plus high-intensity interval training (T2DM+HIIT), with T2DM and high-intensity variable-speed intervention (n = 8). The levels of runt-related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase (ALP), as well as the bone microstructure and morphometry, were measured at the end of the 8-week exercise intervention. Results: Compared with the C group, the bone microstructure indexes [bone mineral density (BMD), bone volume/tissue volume (BV/TV), cortical thickness (Ct.Th), and connectivity density (Conn.D)], the bone biomechanical properties (maximum load, fracture load, yield stress, and elastic modulus), and the osteogenic differentiation factors (RUNX2, OSX, and BMP2) of the T2DM group were significantly decreased (all p < 0.05). Compared with the T2DM group, there were obvious improvements in the osteogenic differentiation factor (OSX) and Th.N, while the separation of trabecular bone (Tb.Sp) decreased in the T2DM+AE and T2DM+HIIT groups (all p < 0.05). In addition, the bone microstructure indicators BV/TV, tissue mineral density (TMD), Conn.D, and degree of anisotropy (DA) also increased in the T2DM+HIIT group, but the yield stress and Ct.Th deteriorated compared with the T2DM group (all p < 0.05). Compared with the T2DM+S and T2DM+RE groups, the BV/TV, trabecular number (Tb.N), Tb.Sp, and Conn.D in the T2DM+AE and T2DM+HIIT groups were significantly improved, but no significant changes in the above indicators were found between the T2DM+S and T2DM+RE groups (all p < 0.05). In addition, the BMD and the expression of ALP in the T2DM+AE group were significantly higher than those in the T2DM+HIIT group (all p < 0.05). Conclusion: There was a significant deterioration in femur bone mass, trabecular bone microarchitecture, cortical bone geometry, and bone mechanical strength in diabetic mice. However, such deterioration was obviously attenuated in diabetic mice given aerobic and high-intensity interval training, which would be induced mainly by suppressing the development of T2DM. Regular physical exercise may be an effective strategy for the prevention of not only the development of diabetes but also the deterioration of bone properties in patients with chronic T2DM.

Prebiotics improve osteoporosis indicators in a preclinical model: systematic review with meta-analysis.

CONTEXT: Studies using experimental models have demonstrated that prebiotics are involved in antiosteoporotic mechanisms. OBJECTIVE: This study was conducted to determine the impact of supplementation with prebiotics in the basal diet of ovariectomized rats with induced osteoporosis as a preclinical model. METHODS: A comprehensive systematic search was carried out in the electronic databases PubMed, Science Direct, Web of Science, Scielo, and Google through March 2022 for studies that investigated the impact of prebiotics on bone mineral density (BMD), bone mineral content (BMC), and bone biomechanics. RESULTS: The search returned 844 complete articles, abstracts, or book chapters. After detailed screening, 8 studies met the inclusion criteria. Rats (n = 206), were randomly divided between control and treatment groups. Weighted mean differences (WMDs) with the 95%CIs were used to estimate the combined effect size. Compared with the control group, dietary intake of prebiotics significantly increased bone density in the BMD subgroups, with WMDs as follows: 0.03 g/cm3, 95%CI, 0.01-0.05, P < 0.00001, n = 46; and 0.00 g/cm2, 95%CI, 0.00-0.02, P < 0.00001, n = 81; total BMD: WMD, 0.01, 95%CI, 0.01-0.02, P < 0.00001, n = 127; bone content in BMC: WMD, 0.02 g, 95%CI, 0.00-0.04, P = 0.05, n = 107; and the 3-point-bend test: WMD, 15.20 N, 95%CI, 5.92-24.47, P = 0.00001, n = 120. CONCLUSION: Prebiotics improve indicators of osteoporosis, BMD, BMC, and bone biomechanics in ovariectomized rats. More studies are needed to increase the level of evidence. SYSTEMIC REVIEW REGISTRATION: Systematic Review Protocol for Animal Intervention Studies.

Aerobic training improves bone fragility by reducing the inflammatory microenvironment in bone tissue in type 2 diabetes.

Aerobic training (AT) is indicated in type 2 diabetes mellitus (T2DM) to control hyperglycaemia and inflammation. AT improves bone microarchitecture and resistance to fracture. The intensity of AT and the mechanisms that lead to the improvement in bone quality are still unknown. Using a mouse model of T2DM, we evaluated the effects of two intensities of forced AT. We divided mice into: sedentary (SED), T2DM-SED, low runners (LOW), T2DM-LOW, high runners (HIGH) and T2DM-HIGH. The AT for low was 8 m/minute (m/min); 5° slope or high 18 m/min; 15° slope for 2 months. We measured metabolic parameters, the serum cytokines concentration, lipocalin-2 (LCN-2) and adiponectin; and the tibial concentrations of LCN-2, tumour necrosis factor alpha (TNF-α) and protein carbonylation (CO). We evaluated femur morphometry and biomechanical properties. We performed multiple correlation analysis. The T2DM-LOW versus T2DM-SED group, shown an increase of interleukin (IL)-10 (417 ± 90 vs 102 ± 25 pg/mL) and improved trabecular bone (BV/TV: 31.8 ± 2.3 vs 19.25 ± 1.4%; Tb.Sp.: 1.62 ± 0.02 vs 2.0 ± 0.07 mm), by a decrease bone CO (3.4 ± 0.1 vs 6.0 ± 0.5 nmol/mg), bone TNF-α (84 ± 4 vs 239 ± 13 pg/mL) and LCN-2 (2887 ± 23 vs 3418 ± 105 pg/mL). The T2DM-HIGH versus T2DM-SED group showed a greater hypoglycaemic effect (228 ± 10 vs 408 ± 5 mg/dL), with improved cortical bone density (0.26 ± 0.012 vs 0.21 ± 0.007 mm) and fracture resistance (102 ± 8 vs 78 ± 5 MPa), by a reduction of bone TNF-α (77 ± 34 vs 239 ± 13 pg/mL); LCN-2 (2768 ± 20 vs 3418 ± 105 pg/mL) and CO (4.8 ± 0.5 vs 6.0 ± 0.5 nmol/mg). In conclusion, AT improves bone morphometry and biomechanical properties by reducing the bone inflammatory microenvironment.

3D Printing and Computer-Aided Design for Precision Osteotomy-Aided Modules in Bone Biomechanical Study.

Precise and shape-matching osteotomy models are determinants of the experimental homogeneity in the assessment of orthopedic biomechanical properties. At present, however, publications on detailed description of osteotomy in bone biomechanical study are scanty. The purposes of this study were to design a new method of osteotomy-aided module production for bone biomechanical study with the help of three-dimensional (3D) printing and computer-aided design (CAD) and to test the accuracy of osteotomy. Fourteen fourth-generation composite femurs were analyzed. The composite bone was scanned using computed tomography (CT) scanner and loaded in Mimics for reconstruction and, then, imported into 3-Matic software to design intertrochanteric region, distal femur, and rotation control lever models. 3D printer was used to print each component. After assembling Sawbones and osteotomy modules, a horizontal band-saw was used to create fracture models. The volume and mass of intermediate fragments were calculated and analyzed. Satisfactory osteotomies of all composite Sawbones were achieved. The mean volume and mass of intermediate fragments were 21.0 ± 1.5 mm3 and 19.0 ± 1.2 g, respectively. Range of deviation from average of volumes was -1.9 - 2.8 mm3 and most of these deviations fall within the range of -1.4 - 2.1 mm3. Range of deviation from average of mass was -2.0 - 1.6 g and most of these deviations fall within the range of -1.4 - 1.6 g. One-dimensional histogram of deviation from average shows the precise and stable osteotomy performed based on the modules accordingly. A new method of osteotomy-aided module production for bone biomechanical study with the help of 3D printing and CAD was designed and the accuracy of osteotomy was verified. This method is expected to achieve homogeneity and standardization of osteotomy in bone biomechanical study.

Percutaneous-Reinforced Osteoplasty: A Review of Emerging Treatment Strategies for Bone Interventions.

Percutaneous-reinforced osteoplasty is currently being investigated as a possible therapeutic procedure for fracture stabilization in high-risk patients, primarily in patients with bone metastases or osteoporosis. For these patients, a percutaneous approach, if structurally sound, can provide a viable method for treating bone fractures without the physiologic stress of anesthesia and open surgery. However, the low strength of fixation is a common limitation that requires further refinement in scaffold design and selection of materials, and may potentially benefit from tissue-engineering-based regenerative approaches. Scaffolds that have tissue regenerative properties and low inflammatory response promote rapid healing at the fracture site and are ideal for percutaneous applications. On the other hand, preclinical mechanical tests of fracture-repaired specimens provide key information on restoration strength and long-term stability and enable further design optimization. This review presents an overview of percutaneous-reinforced osteoplasty, emerging treatment strategies for bone repair, and basic concepts of in vitro mechanical characterization.

Experimental Exposure to Bisphenol A Has Minimal Effects on Bone Tissue in Growing Rams-A Preliminary Study.

Bisphenol A (BPA) is a well-known synthetic compound that belongs to the group of endocrine-disrupting chemicals. Although bone tissue is a target for these compounds, studies on BPA-related effects on bone morphology in farm animals are limited. In this preliminary study, we investigated the effects of short-term dietary BPA exposure on femoral morphology, metabolism, mineral content, and biomechanical behavior in rams aged 9-12 months. Fourteen rams of the Istrian Pramenka breed were randomly divided into a BPA group and a control group (seven rams/group) and exposed to 25 µg BPA/kg bw for 64 days in feed. Blood was collected for determination of bone turnover markers (procollagen N-terminal propeptide, C-terminal telopeptide), and femurs were assessed via computed tomography, histomorphometry, three-point bending test, and mineral analysis. BPA had no significant effects on most of the parameters studied. Only mineral analysis showed decreased manganese (50%; p ≤ 0.05) and increased copper content (25%; p ≤ 0.05) in the femurs of BPA-exposed rams. These results suggest that a 2-month, low-dose exposure to BPA in growing rams did not affect the histomorphology, metabolism, and biomechanical behavior of femurs; however, it affected the composition of microelements, which could affect the histometric and biophysical properties of bone in the long term.

Does anti-IgE therapy prevent chronic allergic asthma-related bone deterioration in asthmatic mice?

Current evidence on the association between allergic diseases and bone metabolism indicates asthma may be a potential risk factor for bone health. Using anti-IgE has been proven effective in allergic asthma treatment with a good safety profile; however, its effects on bone health are unknown. Thus, we aimed to investigate whether: (i) chronic allergic asthma (CAA) causes any meaningful changes in bone, and if any, (ii) anti-IgE therapy prevents any CAA-induced adverse alteration. A murine model was used to study CAA. Thirty-two BALB/c male-mice were assigned into four groups (eight-mice/group): Control, CAA (treated with saline), CAA + 100 µg of anti-IgE (CAA + 100AIgE), and CAA + 200 µg of anti-IgE (CAA + 200AIgE) groups. After immunization, saline or anti-IgE was performed intraperitoneally for 8-weeks (in five-sessions at 15-days interval). Three-point bending test was used for the mechanical analysis. Bone calcium (Ca2+) and phosphorus (P3-) as well as Ca/P ratio were evaluated using inductively-coupled plasma-mass-spectrometer (ICP-MS). Compared to control, reductions observed in yield and ultimate moments, rigidity, energy-to-failure, yield and ultimate stresses, elastic modulus, toughness, and post-yield toughness parameters of the CAA group were found significant (P < 0.05). Similar declines were also detected regarding bone Ca2+, P3- and Ca/P ratio (P < 0.05). Compared to control, we observed that 200 µg administration of anti-IgE in CAA + 200AIgE group hindered CAA-related impairments in mineral and mechanical characteristics of bone, while 100 µg in CAA + 100AIgE failed to do so. Our results showed CAA may cause bone loss, leading to a decrease in bone strength, and anti-IgE administration may dose-dependently inhibit these impairments in bone.

Mechanical and morphometric characterization of custom-made trabecular bone surrogates.

Synthetic bones for biomechanical testing and surgeon training have become more important due to their numerous advantages compared to human bones. Several bone models are already available on the market, but most of them do not reflect the full range of versatile properties that characterize human bone like population-level influences, size, stiffness, bone-implant-interface or morphometry. Thus, the objectives of this study were to develop synthetic trabecular bone surrogates from polyurethane and varying additives and to determine their elastic and plastic mechanical compressive and additionally morphometric properties. Another aim was to investigate the influence of varying additives on aforementioned properties and finally compare the results with published data from human trabecular bone. Additives used were blowing agents to create a porous structure, mineral fillers to manipulate the basic polyurethane resin, and cell stabilizers to achieve an open porous composition. Mechanical properties were obtained from static compression tests until failure while morphometric analysis was carried out using microcomputed tomography. Thereby, the blowing agent showed the strongest influence on mechanical and morphometric properties with mean Young's moduli ranging from 627 ± 37 MPa (0% blowing agent) to 154 ± 15 MPa (0.25% blowing agent) while the variation of mineral filler content resulted in small standard deviations of approximately 10-20 MPa with a constant proportion of blowing agent. The achieved mechanical properties of the developed synthetic bones, such as the Young's modulus, ultimate stress and yield stress were in accordance with human trabecular bone, while yield strain for all groups was noticeably higher compared to human trabecular bone. Additionally, morphometric analysis showed results indicating similar morphometry of the custom-made synthetic bone and human cancellous bone. Although recreating bone structures in physiological conditions is not simple, the results of the current study show the possibility of developing synthetic bone materials with characteristics like human trabecular bone.

3D pull-out finite element simulation of the pedicle screw-trabecular bone interface at strain rates.

Biomedical experimental studies such as pull-out (PO), screw loosening experience variability mechanical properties of fresh bone, legal procedures of cadaver bone samples and time-consuming problems. Finite Element Method (FEM) could overcome experimental problems in biomechanics. However, material modelling of bone is quite difficult, which has viscoelastic and viscoplastic properties. The study presents a bone material model which is constructed at the strain rates with the Johnson-Cook (JC) material model, one of the robust constitutive material models. The JC material constants of trabecular bone are determined by the curve fitting method at strain rates for the 3D PO finite element simulation, which defines the screw-bone interface relationship. The PO simulation is performed using the Abaqus/CAE software program. Bone fracture mechanisms are simulated with dynamic/explicit solutions during the PO phenomenon. The paper exposes whether the strain rate has effects on the PO performance. Moreover, simulation reveals the relationship between pedicle screw diameter and PO performance. The results obtained that the maximum pull-out force (POF) improves as both the screw diameter and the strain rate increase. For 5.5 mm diameter pedicle screw POFs were 487, 517 and 1708 N at strain rate 0.00015, 0.015 and 0.015 s-1, respectively. The FOFs obtained from the simulation of the other screw were 730, 802 and 2008 N at strain rates 0.00015, 0.0015 and 0.015, respectively. PO phenomenon was also simulated realistically in the finite element analysis (FEA).