Bone Mechanical Properties Research Articles

Evaluation of the Effect of Ciprofloxacin and Vancomycin on Mechanical Properties of PMMA Cement; a Preliminary Study on Molecular Weight

Antibiotic-loaded bone cement (ALBC) is commonly used in joint replacement therapy for prevention and treatment of bone infection and mechanical properties of the cement is still an important issue. The effects of ciprofloxacin and vancomycin was investigated on mechanical characterization of PMMA bone cement. Different properties of cement containing (0, 2.5, 5 and 10% W/W) antibiotics, including compressive and bending properties, microstructural, porosity and density were evaluated. Both antibiotics significantly reduced the density values and mechanical properties (compressive and flexural strength and modulus) in all groups in comparison to control over first two weeks (p < 0.05). This reduction was due to increased porosity upon antibiotic addition (3.05 and 3.67% for ciprofloxacin and vancomycin, respectively) in comparison to control (2.08%) (p < 0.001) and exposure to aqueous medium. Vancomycin as antibiotic with higher molecular weight (MW = 1485) had significant effect on compressive strength reduction of the cement at high amount compared to ciprofloxacin (MW = 367) (P < 0.01), there was no difference between two antibiotics at lower concentrations (P > 0.05). The effect of antibiotic loading is both molecular weight and drug content dependent. The time is also an important parameter and the second week is the probably optimum time to study mechanical behavior of ALBC.

The consequences of dehydration-hydration on bone anisotropy and implications on the sublamellar organization of mineralized collagen fibrils

In this study, the effect of dehydration-hydration based sublamellar dimensional change on bone anisotropy was used as a tool to understand sublamellar organization of mineralized collagen fibrils. Bone consists of hydroxyapatite, Type I Collagen, mucopolysaccharides and bone fluid, which associates with bone constituents and improves the mechanical properties of bone. Knowing that dehydration causes dimensional changes comparable to those observed in the mechanical testing of a bone sample, here, the dehydrated organic component of lamellar bone was modelled to contract towards the mineral, forming a contraction vector as the surface normal of the mineral plate. The amount of dehydration based contraction in rotated collagen fibrils was calculated for two models of sublamellar arrangements, namely A and B, where the mineral plate of the 0° (axial, [0 0 1]) sublamellar collagen fibril was oriented respectively along either (0 1 0) or (0 0 1) planes. Projections of sublamellar contraction vectors were denoted as u, v and w displacements at 10°–20°–30° angles and summed to give the lamellar total. Using the total displacements, anisotropy ratios of properties in directions parallel (W) versus perpendicular (U or V) to the osteonal axis were calculated. With dehydration, the osteonal lamellae in Model A (behaving as positive Poisson’s ratio material) may display maximal planar expansion (at 1.4%) and peraxial contraction (−0.24%), which may even cause sample warping. The large variation in the wet and dry bone anisotropy ratios of the models demonstrates the effect of collagen orientation on bone mechanics.

An inspiration from the microstructure of the cortical bone in goat tibia

When vigorous goats are running and jumping, their leg bones play a crucial role in dynamic loading. The hierarchical structure of diverse tissues at different length scales is commonly used to account for the superior mechanical properties of bone. Yet, how the goat tibia achieves its remarkable function remains mostly unknown. Scanning electron microscopy was employed to image the multi-scale microstructure of the cortical bone in goat tibia. A new processing method was utilized during the preparation of one of the three kinds of samples. The transverse and longitudinal sections of the cortical bone were observed thoroughly, and high-quality images of the internal organizations are acquired. Some interesting findings, including the two-layered character of cortical bone and the microstructure near osteocyte lacunae, are discussed. A three-dimensional three-level hierarchical structure is found accordingly. Then, the cushioning mechanisms are discussed by analyzing the structure–function relationships of the bone tissues. Finally, a structural model of biomimetic composite is proposed based on the authors’ insights into the constitution of cortical bone, which is expected to inspire engineers to design load-bearing structures with excellent mechanical performance.

Qu Feng Zhi Tong capsule increases mechanical properties of cortical bone in ovariectomised rats

Abstract Backgroud/objective Qu Feng Zhi Tong capsule (QF, Buchang Pharma, Xi'an, Shanxi, China) is officially approved Fufang formula in China for the treatment of rheumatoid arthritis (RA). As a Traditional Chinese Medicine formula, it consists of seven herbs, among which Erodium stephanianum, Dipsacus asper, and Viscum Coloratum were reported to be able to prevent bone loss and promote bone healing. Moreover, osthole from Angelica pubescens exerted anabolic effect on cortical bone by activating β-catenin-bone morphogenetic protein (BMP) signalling. So, we hypothesise that the formula QF has beneficial potential on preventing osteoporosis. Method In this study, high-performance liquid chromatography (HPLC) was used to identify the main constituents in QF, and SD female rats were ovariectomised (OVX) to examine antiosteoporotic efficacy. Thirty OVX rats were orally administrated with QF (162 and 648 ​mg/kg/day, L-QF, and H-QF) or estradiol (1 ​mg/kg/day, E2) for 12 weeks. Sham and OVX control group were treated with vehicle. Results Eleven compounds in QF extract were identified using HPLC, and the sum of their peak areas was covered 44.2% of total peak area of QF extract. As to in vivo results, compared to OVX group, H-QF had significantly higher ultimate load (P ​ Conclusion QF promoted cortical mechanical properties because of its positive effects on cortical thickness, porosity, and skeletal muscle. H-QF increased cortical thickness by promoting bone formation of periosteum and inhibiting bone absorption of endosteum in OVX rats. The translational potential of this article This study provided theoretical basis for QF as a conventional drug in osteoporosis to enhance cortical bone mechanical and avoid long bone fracture. As cortical diaphyseal bone is an important target of RA, this study also provides a possibility that QF is beneficial to RA by its positive effects on cortical bone to prevent bone erosions in RA patients.

Initiation and emerging complexity of the collagen network during prenatal skeletal development.

The establishment of a complex collagen network is critical for the architecture and mechanical properties of cartilage and bone. However, when and how the key collagens in cartilage and bone develop has not been characterised in detail. The study provides a detailed qualitative characterisation of the spatial localisations of collagens I-III, V-VI and IX-XI in the mouse and their regional architecture variation over three developmentally significant time points: when the rudiment starts to form at E13.5 [Theiler stage (TS) 22], when mineralisation is present at E16.5 (TS25) and during the latest prenatal stage at E18.5 (TS27). Dynamic changes in collagen distribution between stages with the progression of the growth plate and mineralisation (particularly collagens I, II, V, X and XI) and dramatic changes in collagen structural organisation and complexity with maturation, especially for collagens II and XI, were observed. The future articular cartilage region was demarcated by pronounced collagens II and VI expression at TS27 and the emergence of collagens I, III, V, IX and XI in the tendon and its insertion site was observed. The present study revealed, for the first time, the emergence and maturation of key cartilage and bone collagens, in high resolution, at multiple locations across the entire rudiment, including the joint regions, at three of the most developmentally significant stages of skeletogenesis, furthering the understanding of disease and regeneration of skeletal tissues.

In vitro and in vivo studies using non-traditional bisphosphonates.

Non-traditional bisphosphonates, that is, bisphosphonates that do not inhibit osteoclast viability or function, were initially reported in the 1990s by Socrates Papapoulos' group. Originally designed to study the role of the R1 residue of aminobisphosphonates on bisphosphonate affinity for hydroxyapatite, these modified bisphosphonates retained similar affinity for mineralized bone as their parent compounds, but they lacked the potential to inhibit the mevalonate pathway or bone resorption. We found that, similar to classical bisphosphonates, these non-traditional compounds prevented osteoblast and osteocyte apoptosis in vitro through a pathway that requires the expression of the gap junction protein connexin 43, and the activation of the Src/MEK/ERK signaling pathway. Furthermore, one of those compounds named IG9402 (also known as amino-olpadronate or lidadronate), was able to inhibit osteoblast and osteocyte apoptosis, without affecting osteoclast number or bone resorption in vivo in a model of glucocorticoid-induced osteoporosis. IG9402 administration also ameliorated the decrease in bone mass and in bone mechanical properties induced by glucocorticoids. Similarly, IG9402 prevented apoptosis of osteoblastic cells in a model of immobilization due to hindlimb unloading. However, in this case, the bisphosphonate was not able to preserve the bone mass, and only partially prevented the decrease in bone mechanical properties induced by immobilization. The effect of IG9402 administration was also tested in a mouse model of masticatory hypofunction through the induction of masseter muscle atrophy by unilateral injection of botulinum toxin type A (BoNTA). IG9402 partially inhibited the loss of trabecular bone microstructure in the mandibular condyle, but not the decrease in masseter muscle mass induced by BoNTA administration. In summary, these non-traditional bisphosphonates that lack anti-resorptive activity but are able to preserve osteoblast and osteocyte viability could constitute useful tools to study the consequences of preventing apoptosis of osteoblastic cells in animal models. Furthermore, they could be used to treat conditions associated with reduced bone mass and increased bone fragility in which a reduction of bone remodeling is not desirable.

Experimental and numerical study on the mechanical properties of cortical and spongy cranial bone of 8-week-old porcines at different strain rates.

Pediatric porcines have widely been used as substitute for children in biomechanical research. Previous studies have used entire piglet cranium when testing their properties. Here, the piglet craniums from the frontal and parietal locations were carefully dissected into spongy and cortical part, and tensile tests at different strain rates were then conducted on these two bone types. It is found that the elastic modulus, yield stress, and ultimate stress of the cortical bone were all significantly higher than those of the spongy bone. The ultimate strains of the cortical and spongy bone were similar. Overall, the effect of the position on the mechanical properties did not reach significance. Cortical bone strength from the frontal location was slightly higher than that obtained from the parietal location; however, spongy bone did not show this location difference. The mechanical properties of both the cortical and spongy bone are significantly strain-rate dependent. Specifically, the elastic modulus, yield stress, and the ultimate stress of the cortical bone increased by approximately 123%, 63%, and 50%, respectively, with strain rates ranging from 0.001 to 10/s. For spongy bone, increases were approximately 128%, 73%, and 77%, respectively. Ultimate strain decreased by approximately 37% and 7% for cortical and spongy bone, respectively. An elastic-plastic constitutive model incorporating with strain rate based on a combined exponential and logarithmic function was proposed and implemented into LS-DYNA through user-defined material. The developed model and the subroutine code successfully simulated the strain-rate characteristics and the fracture process of the bone samples.

Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology

AbstractBone is a hard yet dynamic tissue with remarkable healing capacities. Research to date has greatly advanced the understanding of how bone heals and has led to marked success in the treatment of bone injuries. Nevertheless, the effective treatment of nonunions and large bone defects continues to present a challenge for orthopedic surgeons. Biomaterials provide researchers with a powerful instrument to potentially guide effective bone tissue regeneration in challenging healing environments. However, the most appropriate biomaterial for bone tissue engineering continues to be an area of intense debate. Indeed, the mechanical properties of real bone can be reproduced in vitro but the development of a functional bone substitute goes beyond the sole mechanical properties. The faithful reproduction of bone as a functional organ requires the combination of different cell types and temporal regulation of the molecular signaling involved during the different stages of bone formation and regeneration. This is not at all a trivial task. Herein, critical aspects of bone healing/regeneration including mechanical loading, inflammation, vascularization, and innervation are described. The success and the challenges behind the development of biomaterials, and the technologies used to functionalize them, in order to support the underlying cellular mechanisms are also highlighted.

Investigation of the mechanism of gamma irradiation effect on bovine bone.

Radiation sterilization is an effective method of bone sterilization prior to bone graft transplantation. Gamma irradiation affects the biological and mechanical properties of bone; depending on the dose of radiation. The effect of gamma irradiation on bone mechanical properties is an unwanted phenomenon. However the mechanism of the effect of irradiation on bone mechanical properties is not properly understood. In this research paper the mechanism of the effect of gamma irradiation on bovine bone is investigated using scanning electron microscopy, energy-dispersive X-rays spectroscopy and Fourier transform infrared spectroscopy techniques. Gamma irradiation affects the mineral and fiber composition of bovine bone. The mineral content of bone especially calcium, magnesium and phosphorus decrease with increasing dose of gamma radiation. At Nano-level gamma irradiation alter amide I, amide II and amide III collagen contents. High dose gamma irradiation induces collagen cross-linking reaction in bone and degrades bone properties.

3D printing of acellular scaffolds for bone defect regeneration: A review

Bone injuries can be treated using tissue engineering scaffolds, but the conventional constructs have a big challenge in supplying requirements of native tissue, i.e., bioactivity potential, mechanical stability, controllable biodegradability, and proper cellular interaction. In this regard, 3D printing technology with the possibility of controlling the internal microstructure and geometry of synthesized matrixes was introduced as a promising approach for bone defect regeneration. Although a variety of novel materials, which have shown initial potential for bone repair, can be used for preparing the biocompatible matrixes, the 3D printer type and selecting an innovated technology depend on the properties of applied biomaterials. In all the used methods, tunable, controllable, and interconnected porous microstructure can be fabricated even though identification of suitable porosity and microstructure, which can supply required mechanical properties of natural bone and support cellular adhesion, proliferation, and differentiation, need to evaluate. Therefore, this mini-review explains current advances in acellular 3D printed scaffolds, proper microporous structure and geometry for bone repair, and suitable materials for 3D printing the regenerative bone substitutes. Herein, the novel and recent studies were focused and probable limitations, and existing strategies were discussed.

Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour.

The extent to which load transfer in a diseased mandible with odontogenic tumour might influence the potential risk of pathological fracture has scarcely been investigated. The study sought to investigate the quantitative deviations in load transfer across healthy and cancer-affected (diseased) mandibles having odontogenic tumours. The effect of size of the tumours (small: 9 mm diameter, large: 19 mm diameter), and variation in bone mechanical (elastic) properties of the mandible on load transfer in cancer-affected mandibles during a mastication cycle have been investigated. Based on patient-specific computed tomography-scan datasets, detailed three-dimensional finite element models of healthy and diseased mandibles were developed. High stresses of 25-30 MPa and strains ∼700 µε were observed in the healthy mandible during the right molar bite. However, marginal deviations were observed in principal stress distributions in the diseased mandibles with small- and large-sized tumours, as compared to the healthy mandible. Maximum principal strains of ∼1474 µε were found in the body region adjacent to the symphysis region for small-sized tumour. Whereas for large-sized tumour, maximum strains of ∼2700 µε were observed in the right buccal regions. Reduction in Young's modulus due to different stages of odontogenic tumours had a localised effect on the principal stress distributions, but triggered an abrupt increase in the principal tensile strains. It appears that there is a potential risk of pathological fracture for large-sized odontogenic tumour, owing to high tensile stresses and strains.

A novel three-dimensional structure model of biomimetic staggered composites

The staggered structure is considered to be one of the key factors for the excellent mechanical properties of bone. In order to solve the problem of non-uniform stress distribution in the hard component of the original biomimetic staggered composites, a novel three-dimensional structure model with pores is proposed in this paper. By generalizing the shear lag theory model of the original staggered structure to the new model, the constitutive relation of the porous structure is established. On this basis, the stress distribution with respect to the aspect ratio of the hard prisms is studied. Finally, the two composite models are simulated by finite element method. The results show that stress in the novel structure tends to be uniformly distributed under external force. So it has higher stiffness and strength to mass ratio, and maintains stronger toughness. It is illustrated that pores in staggered structure can help to fully exploit the mechanical potential of each phase in the composites, providing an explanation for the existing of large number of voids in bone. This study may have an important inspiration for designing lightweight load-bearing composites with high efficiency of vibration isolation and cushioning.

Production And Characterization Of Ti-10Cr-3,33Co-3,33Egg Shelter Composite Materials Using By Powder Metallurgy

Titanium-based intermetallic compounds are frequently used in the production of biomaterials. The behavior of titanium similar to bone mechanical properties causes the use of titanium as a biomaterial and preferred among the materials. It also makes its use attractive in industrial applications at high temperatures. TiCrCo intermetallics are known to be used together with Ti matrix materials to improve the properties of the group in addition to elements such as Cr, especially Ti, Co, Mo and Fe in various application areas. This information is used frequently in the sintering process. In this study, Ti-10Cr-3,33Co-3,33 egg shelter powders were prepared as a sample mixture. When the properties of the samples produced after sintering are examined, it shows the effects of Co on TiCr. 3.33% Co additive was used in the composition of the composition and mechanical properties were determined in the produced samples. By looking at metallographic analysis, structural features were tried to be determined. The density of the produced samples was calculated, hardness and shear strength were determined. According to the results of the analysis, 3.33% Co composition and 3.71 gr / cm3 density, and 285.5 HV hardness values at 1200 ° C were obtained. In this study, Ti-10Cr-3,33Co-3,33 egg shelter powders were prepared as a sample mixture. When the properties of the samples produced after sintering are examined, it shows the effects of Co on TiCr. 3.33% Co additive was used in the composition of the composition and mechanical properties were determined in the produced samples. By looking at metallographic analysis, structural features were tried to be determined. The density of the produced samples was calculated, hardness and shear strength were determined. According to the results of the analysis, 3.33% Co composition and 3.71 gr / cm3 density, and 285.5 HV hardness values at 1200 ° C were obtained..

Age-Related Trends in the Trabecular Micro-Architecture of the Medial Clavicle: Is It of Use in Forensic Science?

The mechanical and structural properties of bone are known to change significantly with age. Within forensic and archaeological investigations, the medial end of the clavicle is typically used for estimating the age-at-death of an unknown individual. Although, this region of the skeleton is of interest to forensic and clinical domains, alterations beyond the macro-scale have not been fully explored. For this study, non-destructive micro-computed tomography (μ-CT) was employed to characterize structural alterations to the cancellous bone of the medial clavicle. Fresh human cadaveric specimens (12-59 years) obtained at autopsy were utilized for this study, and were scanned with a voxel size of ~83 μm. Morphometric properties were quantified and indicated that the bone volume, connectivity density, mineral density, and number of trabeculae decreased with age, while the spacing between the trabeculae increased with age. In contrast to other sub-regions of the skeleton, trabecular thickness, and degree of anisotropy did not correlate with age. Collectively, this could suggest that the network is becoming increasingly perforated with age rather than exhibiting trabecular thinning. These results are used in the context of deriving a potential protocol for forensic investigations by using this particular and largely unexplored region of the skeleton, and provide inspiration for future experiments concerning micro-architectural and small scale changes in other regions of the human skeleton.

Finite element analysis of bone strength in osteogenesis imperfecta.

As a dedicated experimentalist, John Currey praised the high potential of finite element (FE) analysis but also recognized its critical limitations. The application of the FE methodology to bone tissue is reviewed in the light of his enthusiastic and colorful statements. In the past decades, FE analysis contributed substantially to the understanding of structure-function properties in the hierarchical organization of bone and to the simulation of bone adaptation. The systematic experimental validation of FE analysis of bone strength in anatomical locations at risk of fracture led to its application in clinical studies to evaluate efficacy of antiresorptive or anabolic treatment of bone fragility. Beyond the successful analyses of healthy or osteoporotic bone, FE analysis becomes increasingly involved in the investigation of other fragility-related bone diseases. The case of osteogenesis imperfecta (OI) is exposed, the multiscale alterations of the bone tissue and the effect of treatment summarized. A few FE analyses attempting to answer open questions in OI are then reported. An original study is finally presented that explored the structural properties of the Brtl/+ murine model of OI type IV subjected to sclerostin neutralizing antibody treatment using microFE analysis. The use of identical material properties in the four-point bending FE simulations of the femora reproduced not only the experimental values but also the statistical comparisons examining the effect of disease and treatment. Further efforts are needed to build upon the extraordinary legacy of John Currey and clarify the impact of different bone diseases on the hierarchical mechanical properties of bone.

Dietary Calcium to Digestible Phosphorus Ratio for Optimal Growth Performance and Bone Mineralization in Growing and Finishing Pigs.

Simple SummaryMinimizing the use of dietary non-renewable mineral phosphates improves the sustainability of phosphorus use in growing-finishing pigs. As the phosphorus metabolism is closely linked to calcium, this experiment compared three dietary calcium to digestible phosphorus ratios within two phosphorus levels to determine the optimum levels for growth performance and bone mineralization. The lowest calcium level was insufficient for an efficient metabolic use of P, the medium level was sufficient to maximize growth performance and highest level further improved bone mineralization. The low digestible phosphorus level enabled a complete removal of supplemented mineral phosphates in the finisher period, which resulted, per pig, in a decrease of its use by 65% and a decrease of the calculated P excretion by 41%, without impaired growth performance. However, a reduced bone mineralization was observed. This study shows that there is potential to reduce the digestible phosphorus compared to practiced levels in grower–finisher pigs and shows that the optimal calcium to digestible phosphorus ratio needs to be maintained at the upper range of the actually available recommendations.Within the context of maximizing the use of dietary phosphorus, a growing-finishing pig study was conducted to determine the optimal total dietary calcium (Ca) to digestible phosphorus (dP) ratio and to verify the possibility of mineral phosphate removal during the finishing period on growth performance and mineral status. The potential for replacing chemical and mechanical bone properties by dual energy X-ray absorptiometry (DXA) measures on non-dissected feet was also verified. Three Ca to dP ratios (2.2:1, 2.5:1 and 2.8:1) within two dP levels (P+, P–) were fed during 91 days to 84 pigs. The grower and finisher P+ diets contained 3.0 and 2.4 and P– diets contained 2.5 and 1.7 g dP/kg, respectively. Growth performance and blood serum mineral content were independent of treatments, except that 2.2:1 impaired finisher feed conversion ratio compared to 2.5:1 and 2.8:1. Urinary P concentration increased by 37% in 2.2:1 compared to 2.5:1 and 2.8:1. Maximal load on bone and DXA mineral density were reduced in 2.2:1 compared to 2.8:1. Bone ash and volumetric density were reduced in 2.2:1 and 2.5:1 compared to 2.8:1. Diet P– reduced bone ash, maximal load, volumetric density and DXA bone mineral content and density. No interaction was observed between Ca and dP level. Therefore, 2.2:1 was insufficient for an efficient metabolic use of P, 2.5:1 was sufficient to maximize growth performance and 2.8:1 further improved bone mineralization. Increasing dietary Ca did not impair bone zinc content. Diets P– without supplemented mineral phosphates during the finisher period resulted, per pig, in a decrease of its use by 65% and of the calculated P excretion by 41%, without impaired growth performance. Finally, DXA data responded to dietary treatments as did labor intensive chemical and mechanical bone properties.

Numerical modeling of the effects hydration and number of hydrogen bonds on the mechanical properties of the tropocollagen molecule.

Bone aging involves structural and molecular modifications, especially at the level of type I tropocollagen. This macromolecule shows two main age-related alterations, which are the decrease of both molecular diameter (due to the loss of hydration) and number of hydrogen bonds. In this work, it is proposed to investigate the influence of these two parameters (molecular diameter and number of hydrogen bonds) on the mechanical behavior of tropocollagen using finite element method. To this end, a novel three-dimensional finite element model of collagen molecule accounting for hydrogen bonds was developed. Then, a numerical design of experiments for the diameter of tropocollagen and variations in the number of hydrogen bonds has been established. The mechanical properties ("load-strain" curve and apparent Young's modulus) of the collagen molecule were obtained by employing the proposed model to uniaxial tensile tests. The parametric study demonstrates that the mechanical properties of tropocollagen are slightly affected by the rate of hydration but considerably affected by variation of the number of hydrogen bonds. Finally, a fitted analytical function was deduced from the above results showing effects of the two parameters (hydration rate and hydrogen bonds) on the apparent Young's modulus of tropocollagen. This study could be useful to understand the influence of structural age modifications of tropocollagen on the macroscopic mechanical properties of bone.

6′-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders. It has recently been demonstrated that RAL can have significant positive effects on overall bone mechanical properties by binding to collagen and increasing bone tissue hydration in a cell-independent manner. A Raloxifene-Analog (RAL-A) was synthesized by replacing the 6-hydroxyl substituent with 6-methoxy in effort to reduce the compound's binding affinity for estrogen receptors (ER) while maintaining its collagen-binding ability. It was hypothesized that RAL-A would improve the mechanical integrity of bone in a manner similar to RAL, but with reduced estrogen receptor binding. Molecular assessment showed that while RAL-A did reduce ER binding, downstream ER signaling was not completely abolished. In-vitro, RAL-A performed similarly to RAL and had an identical concentration threshold on osteocyte cell proliferation, differentiation, and function. To assess treatment effect in-vivo, wildtype (WT) and heterozygous (OIM+/−) female mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL or RAL-A from 8 weeks to 16 weeks of age. There was an untreated control group for each genotype as well. Bone microarchitecture was assessed using microCT, and mechanical behavior was assessed using 3-point bending. Results indicate that both compounds produced analogous gains in tibial trabecular and cortical microarchitecture. While WT mechanical properties were not drastically altered with either treatment, OIM+/− mechanical properties were significantly enhanced, most notably, in post-yield properties including bone toughness. This proof-of-concept study shows promising results and warrants the exploration of additional analog iterations to further reduce ER binding and improve fracture resistance.

Secondary osteon structural heterogeneity between the cranial and caudal cortices of the proximal humerus in white-tailed deer.

Cortical bone remodeling is an ongoing process triggered by microdamage, where osteoclasts resorb existing bone and osteoblasts deposit new bone in the form of secondary osteons (Haversian systems). Previous studies revealed regional variance in Haversian systems structure and possibly material, between opposite cortices of the same bone. As bone mechanical properties depend on tissue structure and material, it is predicted that bone mechanical properties will vary in accordance with structural and material regional heterogeneity. To test this hypothesis, we analysed the structure, mineral content and compressive stiffness of secondary bone from the cranial and caudal cortices of the white-tailed deer proximal humerus. We found significantly larger Haversian systems and canals in the cranial cortex but no significant difference in mineral content between the two cortices. Accordingly, we found no difference in compressive stiffness between the two cortices and thus our working hypothesis was rejected. As the deer humerus is curved and thus likely subjected to bending during habitual locomotion, we expect that similar to other curved long bones, the cranial cortex of the deer humerus is likely subjected primarily to tensile strains and the caudal cortex is subject primarily to compressive strains. Consequently, our results suggest that strain magnitude (larger in compression) and sign (compression versus tension) affect the osteoclasts and osteoblasts differently in the basic multicellular unit. Our results further suggest that osteoclasts are inhibited in regions of high compressive strains (creating smaller Haversian systems) while the osteoid deposition and mineralization by osteoblasts is not affected by strain magnitude and sign.

Mechanical Properties of Bovine Femoral Cortical Bone in Local Demineralization Process with Voltage Application

Mechanical Properties of Bovine Femoral Cortical Bone in Local Demineralization Process with Voltage Application