Bone Mechanical Properties Research Articles

Temporal and spatial changes in bone mineral content and mechanical properties during breast-cancer bone metastases

Cancer cells favour migration and metastasis to bone tissue for 70–80 % of advanced breast cancer patients and it has been proposed that bone tissue provides attractive physical properties that facilitate tumour invasion, resulting in osteolytic and or osteoblastic metastasis. However, it is not yet known how specific bone tissue composition is associated with tumour invasion. In particular, how compositional and nano-mechanical properties of bone tissue evolve during metastasis, and where in the bone they arise, may affect the overall aggressiveness of tumour invasion, but this is not well understood. The objective of this study is to develop an advanced understanding of temporal and spatial changes in nano-mechanical properties and composition of bone tissue during metastasis. Primary mammary tumours were induced by inoculation of immune-competent BALB/c mice with 4T1 breast cancer cells in the mammary fat pad local to the right femur. Microcomputed tomography and nanoindentation were conducted to quantify cortical and trabecular bone matrix mineralisation and nano-mechanical properties. Analysis was performed in proximal and distal femur regions (spatial analysis) of tumour-adjacent (ipsilateral) and contralateral femurs after 3 weeks and 6 weeks of tumour and metastasis development (temporal analysis). By 3 weeks post-inoculation there was no significant difference in bone volume fraction or nano-mechanical properties of bone tissue between the metastatic femora and healthy controls. However, early osteolysis was indicated by trabecular thinning in the distal and proximal trabecular compartment of tumour-bearing femora. Moreover, cortical thickness was significantly increased in the distal region, and the mean mineral density was significantly higher in cortical and trabecular bone tissue in both proximal and distal regions, of ipsilateral (tumour-bearing) femurs compared to healthy controls. By 6 weeks post-inoculation, overt osteolytic lesions were identified in all ipsilateral metastatic femora, but also in two of four contralateral femora of tumour-bearing mice. Bone volume fraction, cortical area, cortical and trabecular thickness were all significantly decreased in metastatic femora (both ipsilateral and contralateral). Trabecular bone tissue stiffness in the proximal femur decreased in the ipsilateral femurs compared to contralateral and control sites. Temporal and spatial analysis of bone nano-mechanical properties and mineralisation during breast cancer invasion reveals changes in bone tissue composition prior to and following overt metastatic osteolysis, local and distant from the primary tumour site. These changes may alter the mechanical environment of both the bone and tumour cells, and thereby play a role in perpetuating the cancer vicious cycle during breast cancer metastasis to bone tissue.

Laser Sintering Approaches for Bone Tissue Engineering.

The adoption of additive manufacturing (AM) techniques into the medical space has revolutionised tissue engineering. Depending upon the tissue type, specific AM approaches are capable of closely matching the physical and biological tissue attributes, to guide tissue regeneration. For hard tissue such as bone, powder bed fusion (PBF) techniques have significant potential, as they are capable of fabricating materials that can match the mechanical requirements necessary to maintain bone functionality and support regeneration. This review focuses on the PBF techniques that utilize laser sintering for creating scaffolds for bone tissue engineering (BTE) applications. Optimal scaffold requirements are explained, ranging from material biocompatibility and bioactivity, to generating specific architectures to recapitulate the porosity, interconnectivity, and mechanical properties of native human bone. The main objective of the review is to outline the most common materials processed using PBF in the context of BTE; initially outlining the most common polymers, including polyamide, polycaprolactone, polyethylene, and polyetheretherketone. Subsequent sections investigate the use of metals and ceramics in similar systems for BTE applications. The last section explores how composite materials can be used. Within each material section, the benefits and shortcomings are outlined, including their mechanical and biological performance, as well as associated printing parameters. The framework provided can be applied to the development of new, novel materials or laser-based approaches to ultimately generate bone tissue analogues or for guiding bone regeneration.

Does the bone mineral density measured on a preoperative CT scan before total hip arthroplasty reflect the bone's mechanical properties?

IntroductionNo method exists to quantify the bone quality and factors that will ensure osteointegration of total hip arthroplasty (THA) implants. A preoperative CT scan can be used to evaluate the bone mineral density (BMD) when planning a THA procedure. The aim of this study was to validate BMD measurement as a marker of bone quality based on a preoperative CT scan. HypothesisBMD reflects the bone's mechanical properties for the purposes of preoperative THA planning. MethodsPatients who underwent primary THA for hip osteoarthritis or dysplasia with cementless implants and 3D preoperative plan were enrolled prospectively. The cortical BMD was calculated on CT scans used in the preoperative planning process. During the surgical procedure, the femoral head and neck were collected. These bone samples were subsequently scanned with a calibrated micro-CT scanner. The BMD was derived from the micro-CT scan and used as input for a finite element model to determine the bone's mechanical properties. Correlations between BMD, apparent moduli of elasticity and porosity were calculated. ResultsThe values of cortical BMD measured on the micro-CT and CT scan were significantly correlated (cc=0.52). The mean angular cortical BMD measured with the micro-CT scan was 1472.33mg/cm3 (SD: 357.53mg/cm3, 980.64–2830.6mg/cm3). There was no significant correlation between cortical BMD and the various apparent moduli of elasticity, except for Eyy and Gzy. Cortical BMD and porosity were inversely correlated with a Spearman coefficient of −0.41 (CI95: [−0.71; −0.02], p=0.03). There was also an inverse correlation between the apparent moduli of elasticity (independent of their orientation) and porosity (p<0.01). DiscussionBMD provides information about porosity, which is a major factor when evaluating the bone's mechanical properties before THA. Level of evidenceIV.

Systematic Review on Multilevel Analysis of Radiation Effects on Bone Microarchitecture.

Introduction Modern radiation therapy has become an effective method to treat and monitor tumour growth in cancer patients. It has proved to be a successful way to minimise mortality rates. However, the adverse effects of radiation have been historical evidence in the clinical environment involving diminishing the quality and density of bone and causing fragility fracture to the bone in the long run. This systematic review was aimed at identifying and evaluating the effects of irradiation on morphology and mechanical properties of murine model bone in previous publications. Methods A systematic literature review was undertaken following the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search was performed using Scopus, Web of Science, and Science Direct databases (English only studies published between 2015 and 2020). The selected studies were evaluated according to three criteria: (1) criteria for study sample selection; (2) criteria for methodological procedures; and (3) criteria for detection and evaluation. Results The initial search strategy identified 1408 related studies, 8 of were included based on inclusion and exclusion criteria. This review revealed an association between bone destruction and the magnitude of time and dose postirradiation. We agreed that the effect of radiation on bone morphology and strength primarily is a later stage event but noticeable in both low (1 Gy) and high dose (30 Gy) radiation. Trabecular and cortical bone microstructures were significantly altered at irradiation and contralateral sites. Besides, the mechanical strength was significantly impacted in both shorter and longer periods. Conclusion Overall, the radiotherapy altered bone microstructures and substantially decreases bone mechanical properties. The alteration was related to quantity and the activity of the osteoblast and osteoclast. Early detection of those most at risk for radiation-induced bone alterations could lead to better prophylactic intervention decisions.

Effects of processing and gamma radiation on mechanical properties and organic composition of frozen, freeze-dried and demineralised human cortical bone allograft.

Bone processing and radiation were reported to influence mechanical properties of cortical bones due in part to structural changes and denaturation of collagen composition. This comparative study was to determine effects of bone processing on mechanical properties and organic composition, and to what extent the radiation damaging after each processing. Human femur cortical bones were processed by freezing, freeze-drying and demineralisation and then gamma irradiated at 5, 15, 20, 25 and 50kGy. In the compression test, freeze drying significantly decreased the Young's Modulus by 15%, while demineralisation reduced further by 90% (P < 0.05) when compared to the freezing. Only demineralisation significantly reduced ultimate strength of bone by 93% (P < 0.05). In the bending test, both freeze drying and demineralisation significantly reduced the ultimate strength and the work to failure. Radiation at 25kGy showed no effect on compression for ultimate strength in each processing group. However, high dose of 50kGy significantly reduced bending ultimate strength by 47% in demineralisation group. Alterations in collagen in bones irradiated at 25 and 50kGy showed by the highest peak of the amide I collagen in the Fourier Transfer Infra-Red spectra indicating more collagen was exposed after calcium was removed in the demineralised bone, however radiation showed no effect on the collagen crosslink. The study confirmed that demineralisation further reduced the ability to resist deformation in response to an applied force in freeze-dried bones due to calcium reduction and collagen composition. Sterilisation dose of 25kGy has no effect on mechanical properties and collagen composition of the processed human cortical bone.

Analysis of different geometrical features to achieve close-to-bone stiffness material properties in medical device: A feasibility numerical study

Background and objectiveIn orthopedic medical devices, elasto-plastic behavior differences between bone and metallic materials could lead to mechanical issues at the bone-implant interface, as stress shielding. Those issue are mainly related to knee and hip arthroplasty, and they could be responsible for implant failure. To reduce mismatching-related adverse events between bone and prosthesis mechanical properties, modifying the implant's internal geometry varying the bulk stiffness and density could be the right approach. Therefore, this feasibility study aims to assess which in-body gap geometry improves, by reducing, the bulk stiffness. MethodsUsing five finite element models, a uniaxial compression test in five cubes with a 20 mm thickness was simulated and analyzed. The displacements, strain and Young Modulus were calculated in four cubes, each containing internal prismatic gaps with different transversal sections (squared, hexagonal, octagonal, and circular). Those were compared with a fifth full-volume cube used as control. ResultsThe most significant difference have been achieved in displacement values, in cubes containing internal gaps with hexagonal and circular transversal sections (82 µm and 82.5 µm, respectively), when compared to the full-volume cube (69.3 µm). ConclusionsThis study suggests that hexagonal and circular shape of the gaps allows obtaining the lower rigidity in a size range of 4 mm, offering a starting approach to achieve a “close-to-bone” material, with a potential use in prosthetic devices with limited thickness.

Additively Manufactured Multilevel Voronoi-Lattice Scaffolds with Bonelike Mechanical Properties.

Irregular porous scaffold through Voronoi tessellation based on global modeling demonstrated randomness to a certain degree and susceptibility to producing large processing deviations. A modeling method for new types of scaffolds based on periodic arrays of Voronoi unit cell was proposed in this study. These porous scaffolds presented controllable local cells and satisfactory mechanical properties. The topological structure of the Voronoi unit cell was controlled using three independent cell design factors (Voronoi polyhedron volume V, face-centered scaled factor F1, and body-centered scaled factor F2), and multilevel Voronoi-lattice scaffolds were constructed on the basis of periodic arrays of the Voronoi unit cell. Compressive test and simulation were combined to quantify the mechanical properties of scaffolds. The regression equations were established using the response surface method (RSM) to determine relationships between Voronoi unit cell design factors and structural characteristic parameters and mechanical properties. The same trends were observed in stress-strain curves of the compressive test and simulation. The mechanical properties of scaffolds can be appropriately quantified via simulation. Regression equations based on RSM can properly predict the structural characteristic parameters and mechanical properties of the scaffold. Compared with V, F1 and F2 exerted a stronger influence on the structural characteristic parameters and mechanical properties of the scaffold. The modeling method of the multilevel Voronoi-lattice scaffold based on the Voronoi unit cell was proposed in this study to design the porous scaffold and meet the requirements of human bone morphology, mechanical properties, and actual manufacturing by adjusting factors V, F1, and F2. The proposed method can provide a feasible strategy for designing implants with suitable and similar morphologies and mechanical properties to cancellous bone.

Mechanical Properties of Embryonic Mouse Cartilage and Bone

Differences in material characteristics of cartilage and bone are primarily known through investigation of postnatal specimens but the mechanical properties of these tissue during embryogenesis are less well studied. Importantly, embryonic cartilage and bone have not been tested extensively in aqueous environments, limiting the validity of previous investigations. The purpose of this project is to characterize the stiffness and strength of embryonic cranial bone and cartilage using atomic force microscopy (AFM). We test the hypothesis that embryonic cartilage is stronger than embryonic bone against the null hypothesis that embryonic tissue response will be comparable to adult tissue in which bone is the stronger of the two tissues. In vivo conditions are simulated by immersing tissues in room‐temperature phosphate‐buffered saline before and during testing. Data are acquired using calibrated AFM probes which yield quantitative and qualitative data. Force‐distance curves include data on topography, adhesion, and DMTModulus, the latter of which can be transformed into Young’s Modulus through models which approximate the shape of the AFM probe, including the Sneddon model. Calcified tissue intended for testing is verified on the micro scale using AFM topography and on the macro scale using calcein dye. Each 2 square micron topographical image is accompanied by 16,384 force versus distance curves which yield a value for modulus of elasticity. Data show DMTModulus values ranging from approximately 200 kPa to 7.7 MPa for embryonic cartilage and 120 kPa to 3.0 MPa for embryonic bone providing preliminary data indicating that cartilage varies more than bone and may be significantly stronger than bone in mouse embryos.

Craniofacial Bone Mineral Density at Muscle Attachment Sites in Mice with Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic disease commonly caused by mutations in the COL1A1 or COL1A2 gene affecting the production of type I collagen, a major component of bone that determines the toughness of bone, or its resistance to fracture. Thus, patients with OI present with brittle bones and higher rates of skeletal fractures. Additionally, defects in the collagen framework of developing bones impair their biomineralization, further compromising bone mechanical properties. Previous work in our lab investigated BMD at cranial locations which experience compressive forces during feeding (e.g. joints). Muscles also contribute to cranial growth through tensile forces exerted on bone during contraction, but the relationship between muscle function and bone quality in OI is unclear. The aim of this study is to quantify the BMD in a mouse model of OI, with a focus on skeletal sites associated with cranial musculature. We hypothesize that the mice with OI will have lower BMD in skeletal areas associated with muscle attachment compared to their unaffected littermates.To test our hypothesis, we used the homozygous recessive OI murine (OIM) mouse (B6C3Fe a/a‐Col1a2oim/J), a model for the severe type III OI seen in humans. Adult (16 weeks old) OIM mice (n=11) and wildtype (WT, n=13) littermates were CT scanned, and BMD was measured using the Bruker CTAnalyzer software in 7 regions of interest encompassing muscle attachment sites on the mandible, zygomatic arch, and parietal bone. For each region, BMD values were compared between genotypes by a Kruskal‐Wallis test.OI mice had significantly lower BMD at the coronoid process (p=0.007), parietal bone (p=0.031), and posterior mylohyoid line (p=0.007) compared to WT mice. No significant differences were found in BMD at the gonial angle or zygomatic arch. This suggests a disproportionate weakness of the temporalis and mylohyoid muscles in mice with OI, but not in the masseter muscle. While type I collagen defects impact the structural organization of skeletal muscle, it is possible that masseter muscle function is preserved in OIM mice because of its key roles in rodent feeding and postural control of the jaw. The imbalance between temporalis and masseter muscles may contribute to the prevalence of dental malocclusions in human patients with type III OI.The findings of this study support further exploration of specific muscle groups (e.g. jaw adductors/temporalis, hyoid muscles/mylohyoid) and efforts to improve their functions during feeding, as a way of recovering facial growth and preventing dental malocclusions in OI. A better appreciation of muscle‐bone interactions in the skull and their effect on bone quality can potentially be used to inform oro‐motor therapies to improve feeding function, muscle strength, and facial bone quality for patients with OI.

Effects of ferric citrate and intravenous iron sucrose on markers of mineral, bone, and iron homeostasis in a rat model of CKD-MBD.

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

Effects of type 2 diabetes on the viscoelastic behavior of human trabecular bone

SummaryType 2 diabetes (T2D) is a well-known disease that impaired bone mechanical properties and increases the risk of fragility fracture. The bone tissue is a viscoelastic material that means the loading rate determines its mechanical properties. This study investigates the impact of T2D on the viscoelastic properties of human bone and its association with microstructure and biochemical properties. IntroductionViscoelasticity is an important mechanical property of bone and for this the interaction of individual constituents of bone plays an important role. The viscoelastic nature of bone can be affected by aging and diseases, which can further influence its deformation and damage behavior. MethodsThe present study investigated the effects of T2D on the viscoelastic behavior of trabecular bone. The femoral heads of T2D (n = 26) and non-T2D (n = 40) individuals with hip fragility fractures were collected for this investigation. Following the micro-CT scanning of all bone samples, the stress relaxation and dynamic mechanical analysis (DMA) tests were performed to quantify the viscoelasticity of bone. Further, a correlation analysis was performed to investigate the effects of alteration in bone microstructural and biochemical parameters on viscoelasticity. ResultsThe stress relaxation and frequency sweep responses of T2D and non-T2D trabecular bone specimens were not found significantly different. However, the storage modulus, initial stiffness, and initial stress were found lower in T2D bone. The significant correlation of percentage stress relaxed is obtained between the mineral content (r= - 0.52, p-value = 0.003), organic content (r = 0.40, p-value = 0.02), and mineral-to-matrix ratio (r = - 0.43, p-value = 0.009). Further, storage and loss modulus were correlated with bone volume fraction (BV/TV) for both groups. The stress relaxation and frequency sweep characteristics were not found significantly connected with the other chemical, structural, or clinical parameters. ConclusionThis study suggests that T2D does not affect the time-dependent response of human femoral trabecular bone. The viscoelastic properties are positively correlated with organic content and negatively correlated with mineral content.

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

BackgroundVerapamil was mainly used to treat hypertension, cardiovascular disease, inflammation and improve blood glucose in patients with diabetes, but its effects on bone mass, microstructure and mechanical properties were unclear. This study described the effects of verapamil on bone mass, microstructure, macro and nano mechanical properties in type 2 diabetic rats.MethodsRat models of type 2 diabetes were treated with verapamil at doses of 4, 12, 24 and 48 mg/kg/day by gavage respectively, twice a day. After 12 weeks, all rats were sacrificed under general anesthesia. Blood glucose, blood lipid, renal function and biochemical markers of bone metabolism were obtained by serum analysis, Micro-CT scanning was used to assess the microstructure parameters of cancellous bone of femoral head, three-point bending test was used to measure maximum load and elastic modulus of femoral shaft, and nano-indentation tests were used to measure indentation moduli and hardnesses of longitudinal cortical bone in femoral shaft, longitudinal and transverse cancellous bones in femoral head.ResultsCompared with T2DM group, transverse indentation moduli of cancellous bones in VER 24 group, longitudinal and transverse indentation moduli and hardnesses of cancellous bones in VER 48 group were significantly increased (p < 0.05). Furthermore, the effects of verapamil on blood glucoses, microstructures and mechanical properties in type 2 diabetic rats were dependent on drug dose. Starting from verapamil dose of 12 mg/kg/day, with dose increasing, the concentrations of P1NP, BMD, BV/TV, Tb. Th, Tb. N, maximum loads, elastic moduli, indentation moduli and hardnesses of femurs in rats in treatment group increased gradually, the concentrations of CTX-1 decreased gradually, but these parameters did not return to the level of the corresponding parameters of normal rats. Verapamil (48 mg/kg/day) had the best therapeutic effect.ConclusionVerapamil treatment (24, 48 mg/kg/day) significantly affected nano mechanical properties of the femurs, and tended to improve bone microstructures and macro mechanical properties of the femurs, which provided guidance for the selection of verapamil dose in the treatment of type 2 diabetic patients.

Additively Manufactured Porous Ti6Al4V for Bone Implants: A Review

Ti-6Al-4V (Ti64) alloy is one of the most widely used orthopedic implant materials due to its mechanical properties, corrosion resistance, and biocompatibility nature. Porous Ti64 structures are gaining more research interest as bone implants as they can help in reducing the stress-shielding effect when compared to their solid counterpart. The literature shows that porous Ti64 implants fabricated using different additive manufacturing (AM) process routes, such as laser powder bed fusion (L-PBF) and electron beam melting (EBM) can be tailored to mimic the mechanical properties of natural bone. This review paper categorizes porous implant designs into non-gradient (uniform) and gradient (non-uniform) porous structures. Gradient porous design appears to be more promising for orthopedic applications due to its closeness towards natural bone morphology and improved mechanical properties. In addition, this paper outlines the details on bone structure and its properties, mechanical properties, fatigue behavior, multifunctional porous implant designs, current challenges, and literature gaps in the research studies on porous Ti64 bone implants.

A novel bone cement injector augments Chinese osteoporotic lumbar pedicle screw channel: a biomechanical investigation

BackgroundThe study aimed to (1) create a series of pedicle injectors with different number of holes on the sheath especially for the Chinese elderly patients and (2) further investigate the effects of the injectors on the augmentation of pedicle screw among osteoporotic lumbar pedicle channel.MethodsThis study used the biomechanical test module of polyurethane (Pacific Research Laboratory Corp, USA) to simulate the mechanical properties of human osteoporotic cancellous bone. The bone cement injectors were invented based on anatomical parameters of lumbar pedicle in Chinese elderly patients. Mechanical test experiments were performed on the bone cement injectors according to the three groups, namely, a local augmentation group, a full-length augmentation group, and a control group. The local augmentation group included three subgroups including 4-hole group, 6-hole group, and 8-hole group. All holes were laterally placed. The full-length augmentation group was a straight-hole injector. The control group was defined that pedicle screws were inserted without any cement augmentation. Six screws were inserted in each group and the maximum insertion torque was recorded. After 24 h of injecting acrylic bone cement, routine X-ray and CT examinations were performed to evaluate the distribution of bone cement. The axial pull-out force of screws was tested with the help of the material testing system 858 (MTS-858) mechanical tester.ResultsThe bone cement injectors were consisted of the sheaths and the steel rods and the sheaths had different number of lateral holes. The control group had the lowest maximum insertion torque as compared with the 4-hole, 6-hole, 8-hole, and straight pore groups (P < 0.01), but the differences between the 4-hole, 6-hole, 8-hole, and straight pore groups were no statistical significance. The control group had the lowest maximum axial pull-out force as compared with the other four groups (P < 0.01). Subgroup analysis showed the 8-hole group (161.35 ± 27.17 N) had the lower maximum axial pull-out force as compared with the 4-hole group (217.29 ± 49.68 N), 6-hole group (228.39 ± 57.83 N), and straight pore group (237.55 ± 35.96 N) (P < 0.01). Bone cement was mainly distributed in 1/3 of the distal end of the screw among the 4-hole group, in the middle 1/3 and distal end of the screw among the 6-hole group, in the proximal 1/3 of the screw among the 8-hole group, and along the long axis of the whole screw body in the straight pore group. It might indicate that the 8-hole and straight-hole groups were more vulnerable to spinal canal cement leakage. After pullout, bone cement was also closely connected with the screw without any looseness or fragmentation.ConclusionsThe bone cement injectors with different number of holes can be used to augment the pedicle screw channel. The pedicle screw augmented by the 4-hole or 6-hole sheath may have similar effects to the straight pore injector. However, the 8-hole injector may result in relatively lower pull-out strength and the straight pore injector has the risks of cement leakage as well as cement solidarization near the screw head.

Mild-intensity physical activity prevents cardiac and osseous iron deposition without affecting bone mechanical property or porosity in thalassemic mice

Thalassemia causes anemia, ineffective erythropoiesis, bone loss and iron accumulation in several tissues, e.g., liver, bone and heart, the last of which leads to lethal cardiomyopathy and arrhythmia. Although exercise reportedly improves bone density in thalassemic mice, exercise performance is compromised and might pose risk of cardiovascular accident in thalassemic patients. Therefore, we sought to explore whether mild-intensity physical activity (MPA) with 30–50% of maximal oxygen consumption was sufficient to benefit the heart and bone. Herein, male hemizygous β-globin knockout (BKO) mice and wild-type littermates were subjected to voluntary wheel running 1 h/day, 5 days/week for 3 months (MPA group) or kept sedentary (SDN; control). As determined by atomic absorption spectroscopy, BKO-MPA mice had less iron accumulation in heart and bone tissues compared with BKO-SDN mice. Meanwhile, the circulating level of fibroblast growth factor-23—a factor known to reduce serum iron and intestinal calcium absorption—was increased early in young BKO-MPA mice. Nevertheless, MPA did not affect duodenal calcium transport or body calcium retention. Although MPA restored the aberrant bone calcium-phosphorus ratio to normal range, it did not change vertebral calcium content or femoral mechanical properties. Microstructural porosity in tibia of BKO-MPA mice remained unaltered as determined by synchrotron radiation X-ray tomographic microscopy. In conclusion, MPA prevents cardiac and bone iron accumulation, which is beneficial to thalassemic patients with limited physical fitness or deteriorated cardiac performance. However, in contrast to moderate-intensity exercise, MPA does not improve bone mechanical properties or reduce bone porosity.

Bioinspired laminated bioceramics with high toughness for bone tissue engineering.

For the research of biomaterials in bone tissue engineering, it is still a challenge to fabricate bioceramics that overcome brittleness while maintaining the great biological performance. Here, inspired by the toughness of natural materials with hierarchical laminated structure, we presented a directional assembly-sintering approach to fabricate laminated MXene/calcium silicate-based (L-M/CS) bioceramics. Benefiting from the orderly laminated structure, the L-M/CS bioceramics exhibited significantly enhanced toughness (2.23 MPa·m1/2) and high flexural strength (145 MPa), which were close to the mechanical properties of cortical bone. Furthermore, the L-M/CS bioceramics possessed more suitable degradability than traditional CaSiO3 bioceramics due to the newly formed CaTiSiO5 after sintering. Moreover, the L-M/CS bioceramics showed good biocompatibility and could stimulate the expression of osteogenesis-related genes. The mechanism of promoting osteogenic differentiation had been shown to be related to the Wnt signaling pathway. This work not only fabricated calcium silicate-based bioceramics with excellent mechanical and biological properties for bone tissue engineering but also provided a strategy for the combination of bionics and bioceramics.

Early effects of ovariectomy on bone microstructure, bone turnover markers and mechanical properties in rats

BackgroundFragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of postmenopausal osteoporosis (PMOP) is very important for elderly women.Methods and materialsForty 12-week-old female rats were divided into two groups including the ovariectomy (OVX) group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bones and femurs were dissected completely for micro-Computed Tomography (micro-CT) scanning, biological modulus detection and histomorphological observation.ResultsIn OVX group, bone volume/total volume (BV/TV), bone trabecular connection density (Conn.D) and trabecular bone number (Tb.N) decreased significantly with time (P < 0.05). The elastic modulus of femur in OVX group was lower than that in control group, but there was no significant difference between them (P > 0.05). Over time, the tartrate resistant acid phosphatase (TRAP), osteocalcin (BGP), type I procollagen amino terminal propeptide (PINP) and type I collagen carboxy terminal peptide (CTX-I) in OVX group increased significantly (P < 0.05). The micrographs of the OVX group showed sparse loss of the trabecular interconnectivity and widening intertrabecular spaces with time.ConclusionThe bone loss patterns of vertebral body and femur were different in the early stage of estrogen deficiency. The bone turnover rate of OVX rats increased, however the changes of biomechanical properties weren’t obvious.

Selenium nanoparticles stimulate osteoblast differentiation via BMP-2/MAPKs/β-catenin pathway in diabetic osteoporosis.

Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cells were used for in vitro studies and female Sprague-Dawley rats were used for type 2 diabetes-associated osteoporosis in vivo study. Results:In vitro studies show that SeNPs promote osteoblast differentiation via modulating alkaline phosphatase (ALP) activity, andpromoting calcium nodule formation and collagen content. The authorsalso provide evidence regarding the involvement of the BMP-2/MAPKs/β-catenin pathway in preventing diabetic osteoporosis. Further, in vivo and ex vivo studies suggested that SeNPs can preserve mechanical and microstructural properties of bone. Conclusion: To the best of our knowledge, thisstudy provides the first evidence regarding the therapeutic benefits of SeNPs in preventing diabetes-associated bone fragility.

Cortical porosity development and progression is mitigated after etelcalcetide treatment in an animal model of chronic kidney disease.

Chronic kidney disease (CKD) leads to increased bone fragility and risk of fracture. Cortical deteriorations, including cortical porosity, are key factors in fracture susceptibility in CKD. Since secondary hyperparathyroidism is common in CKD individuals and contributes to cortical deterioration, we hypothesized that reducing parathyroid hormone (PTH) may modulate CKD-induced cortical porosity. The goal of this pilot study was to assess the effects of lowering PTH, via the preclinical analogue of the FDA-approved calcimimetic etelcalcetide (KP-2326), on the development and progression of cortical pores in the setting of CKD. Male Cy/+ Sprague Dawley rats with clinical biochemistries consistent with CKD (N=8) were assigned to the study. At 30-32weeks of age, cortical bone was assessed via In vivo μCT and blood collected for biochemistries to create baseline measures. Calcimimetic treatment with KP-2326 (KP) was then administered 3× weekly for 2-4weeks. Cortical bone and biochemical parameters were repeated at study endpoint (33-37 wks of age). A group of age- and cohort-matched CKD rats (N=4) were utilized as untreated controls. Untreated CKD rats had significantly increased cortical porosity over time, while porosity in KP-treated CKD rats was not significantly changed over time. Individual pore analysis revealed that pore area was significantly higher for expanding pores in untreated CKD rats compared to KP-treated CKD rats. Mechanical properties of KP-treated animal femora were similar to historical values of age-matched CKD animals and lower than those of age-matched non-diseased animals. Our pilot preclinical study demonstrates that etelcalcetide treatment can mitigate the progression of cortical bone changes in an animal model of CKD through suppression of pre-existing cortical pore expansion and limiting the size of new pore development. While stabilization of porosity is beneficial it remains likely that infilling of porosity will be needed to positively affect mechanical properties of bones in the setting of CKD.

Effect of bone morphogenic protein-2 and desferoxamine on distraction osteogenesis

BackgroundAngiogenesis is crucial for formation of a stable regenerate during distraction osteogenesis (DO). This experimental study evaluates if bone morphogenic protein-2 (BMP-2) and desferrioxamine (DFO), two agents which are known to induce neoangiogenesis in vivo, would increase angiogenesis and osteogenesis, and improve mechanical properties of bone regenerate in DO model. MethodsTwenty-four tibias of 24 New Zealand rabbits were osteotomized and fixed with semi-circular fixators. Three groups of 8 animals were formed. BMP-2 soaked scaffolds were used in the first group, whereas daily local DFO injections were made in the second group. Subjects in the control group did not receive any agents during the surgery or in the distraction period. The rabbits in all three groups underwent distraction at a rate of 0.6 mm/day for 15 days following the 7-day latent period. Animals were sacrificed on day 38, and the tibia were harvested for histological and mechanical examination of the regenerate. ResultsAll 24 rabbits survived the surgical procedure, and there were no side effects against the BMP-2 and local DFO. Three-point bending tests revealed a higher force (361 ± 267 N.) required for fracture in Group 1 (p: 0.018). Similarly, the bending moment in Group 1 (5.4 ± 4.0 Nmm) was significantly higher than the other groups (p: 0.021). There was no significant difference between the groups in terms of deflection and stiffness (p ˃ 0.05). Histologically, there was no statistical difference between the groups in terms of endochondral, periosteal, and intramembranous ossification and VEGF activity (p ˃ 0.05). ConclusionBMP-2 and DFO stimulate angiogenesis by increasing VEGF activity. Angiogenesis is one of the most important mechanisms for the initiation and maintenance of new bone formation. Stimulation of angiogenesis in unfavorable biomechanical conditions may not be sufficient for ideal bone formation.