Bone Tissue Material Properties Research Articles

Biomechanical, Microstructural and Material Properties of Tendon and Bone in the Young Oim Mice Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by low bone mass and spontaneous fractures, as well as extra-skeletal manifestations, such as dental abnormalities, blue sclera, hearing loss and joint hypermobility. Tendon ruptures have been reported in OI patients. Here, we characterized the biomechanical, structural and tissue material properties of bone and tendon in 5-week-old female osteogenesis imperfecta mice (oim), a validated model of severe type III OI, and compared these data with age- and sex-matched WT littermates. Oim tendons were less rigid and less resistant than those of WT mice. They also presented a significantly higher rate of pentosidine, without significant modification of enzymatic crosslinking. The oim bones were less resistant and avulsion fractures were evident at high tendinous stress areas. Alterations of trabecular and cortical bone microarchitectures were noticed in young female oim. Bone tissue material properties were also modified, with a less mature and more mineralized matrix in association with lower collagen maturity. Our data suggest that the tendon-to-bone unit is affected in young oim mice, which could explain tendon ruptures and bone fragility observed in OI patients.

Does a suspensory lifestyle result in increased tensile strength? Organ-level material properties of sloth limb bones.

The material composition of vertebrate connective tissue is highly conserved across taxa. Existing data suggest that the compressive and tensile strength of limb bones are very similar despite marked variation in limb posture and locomotor patterns. However, the material properties of limb bone tissue from suspensory taxa have not been formally evaluated. Sloths are nearly obligatory in their use of below-branch suspensory locomotion and posture, thus placing their limb bones and associated soft tissue structures under routine tensile loading. It is possible that sloth limb bones are modified for enhanced tensile strength, perhaps at the expense of compressive strength. Forelimb and hindlimb bones of two-toed (Choloepus hoffmanni) and three-toed (Bradypus variegatus) sloths were tested in compression and bending to evaluate this hypothesis. Strength and elastic (Young's) modulus were similarly lower in sloth limb bones during both compression and bending, as compared with pronograde taxa. Ratios of peak bending strength to compressive strength additionally were elevated (sloths: 1.4-1.7; upright taxa: 0.6-1.2) for sloth limb bones. Overall, the material properties measured from the limb bones of tree sloths support our hypothesis of predicted function in a tensile limb system. Future studies should aim to directly test bones in tension to confirm indications of elevated axial tensile strength. Nevertheless, the results herein expand understanding of functional adaptation in mammalian tissue for a range of locomotor/postural behaviors that were previously unexplored.

Retrospective Evaluation and Framework Development of Bone Anisotropic Material Behavior Compared with Elastic, Elastic-Plastic, and Hyper-Elastic Properties.

The main motivation for studying damage in bone tissue is to better understand how damage develops in the bone tissue and how it progresses. Such knowledge may help in the surgical aspects of joint replacement, fracture fixation or establishing the fracture tolerance of bones to prevent injury. Currently, there are no standards that create a realistic bone model with anisotropic material properties, although several protocols have been suggested. This study seeks to retrospectively evaluate the damage of bone tissue with respect to patient demography including age, gender, race, body mass index (BMI), height, and weight, and their role in causing fracture. Investigators believe that properties derived from CT imaging data to estimate the material properties of bone tissue provides more realistic models. Quantifying and associating damage with in vivo conditions will provide the required information to develop mathematical equations and procedures to predict the premature failure and potentially mitigate problems before they begin. Creating a realistic model for bone tissue can predict the premature failure(s), provide preliminary results before getting the surgery, and optimize the design of orthopaedic implants. A comparison was performed between the proposed model and previous efforts, where they used elastic, hyper- elastic, or elastic-plastic properties. Results showed that there was a significant difference between the anisotropic material properties of bone when compared with unrealistic previous methods. The results showed that the density is 50% higher in male subjects than female subjects. Additionally, the results showed that the density is 47.91% higher in Black subjects than Mixed subjects, 53.27% higher than Caucasian subjects and 57.41% higher than Asian. In general, race should be considered during modeling implants or suggesting therapeutic techniques.

Editorial introductions.

Current Opinion in Endocrinology and Diabetes was launched in 1994, with Obesity added to the title in 2007. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of endocrinology and diabetes are divided into 12 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Viral N. ShahViral N. ShahDr Shah is a Board-Certified Adult Endocrinologist and an Associate Professor at the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, USA. His research is focused on improving glycemic control and reducing complications, with special interest in fracture prevention, in people with type 1 diabetes. Dr Shah has extensive experience in conducting clinical trials in field of diabetes. He has been the PI for many multicenter industry-sponsored, investigator-initiated, and nonprofit-funded clinical trials of diabetes technologies and therapeutics. He has been a part of landmark research such as REPLACE-BG, WISDM, Artificial pancreas Cambridge (ApCam), OP5 HCL, and Dexcom G6 pivotal that led to FDA approval of newer devices and changed the type 1 diabetes management. Moreover, his interest in understanding the effect of diabetes on bone fragility had led to two NIH-funded studies investigating effect of long-standing T1D on bone tissue material properties (AR075099) and factors affecting bone density (vBMD), bone mechanical properties in adults with type 1 diabetes (DK122554). Dr Shah has served on many leadership positions such as steering committee member for T1D Exchange Clinic Registry (2016–2017), Communication director for diabetes technology interest group at the American Diabetes Association (2019–2020), Ad hoc member of 79th AD annual meeting planning subcommittee for Diabetes Technology, and American College of Endocrinology Self-Assessment Program writing committee member (2020–2021). He is a recipient of prestigious AACE Rising Start in Endocrinology award (2021). He is well published with over 100 research publications including original article, invited reviews, editorials, and book chapters. He is reviewer for many peer-reviewed indexed journals and grant reviewer for JDRF, ADA and NIH. Peter GottliebPeter GottliebDr Peter Gottlieb was born in Havana, Cuba, but at age 2 moved to New Jersey, USA, where he grew up. After receiving his undergraduate degree from the University of Pennsylvania, USA, he attended UMDNJ-Robert Wood Johnson Medical School, USA from which he graduated in 1984. Dr Gottlieb completed his internship and residency in internal medicine at the University of Massachusetts Medical School, USA and then continued his fellowship training in endocrinology and metabolism there as well. In 1990, after completing his fellowship, he moved to the Weizmann Institute in Israel to do post-doctoral training in T cell immunology. After surviving Gulf War I, he returned to UMass, USA and joined the staff as Clinical Director of Diabetes. He subsequently joined the Barbara Davis Center for Childhood Diabetes in 1995, USA where he is a Professor of Pediatrics and Medicine and the Director of the Translational Research Unit at the Barbara Davis Center. He has authored, co-authored and collaborated on more than 155 publications in peer-reviewed journals, as well as several book chapters and served as section editor for several journal editions. His research areas of interest include the immunology of type 1 diabetes, intervention trials to prevent or reverse type 1 diabetes, islet transplantation and the genetics of autoimmune disease. He had led several multi-center trials in new onset type 1 diabetes and is an active member of the Steering Committee for Type 1 Diabetes TrialNet. Most recently, he has co-founded a biotech company to develop a small molecule therapy for Type 1 diabetes.

Modifying the Gut Microbiome Through Diet or Antibiotics Alters Bone Phenotypes in Older Mice

ObjectivesGut microbiota have been shown to influence bone quality and quantity, both risk determinants for osteoporosis. Previous research in young mice showed oral antibiotic treatment during rapid bone gain impaired bone tissue quality. We sought to determine if modifying the gut microbiome of aged mice through diet or antibiotic treatment affects bone geometry and/or strength. MethodsA high (HG) or low glycemic (LG) diet was fed in equal amounts to 12-mo. male mice. The diets differed only by starch composition, which was 100% rapidly digested amylopectin in the HG diet or 30% amylopectin/70% amylose in the LG diet. A third group received the LG diet containing antibiotics (ampicillin and neomycin; LGAbx). Feces were collected at baseline and after 10 months of treatment and 16s rRNA sequencing was performed followed by ecological diversity and differential abundance analysis. Femora were harvested after 12 months of treatment for analysis of bone geometry and strength via mechanical testing and imaging. ResultsAntibiotic treatment reduced alpha diversity, including an average 92% reduction in observed OTUs from baseline compared with 30% reduction in the other groups. Both diet and antibiotic treatment significantly altered taxonomic composition, including an expansion of Proteobacteria in response to antibiotics.Whole bone strength is determined by a combination of the section modulus (the measure of geometry most closely related to bending strength) and the mechanical properties of the bone tissue itself. In HG-fed mice the section modulus was greater than that of the other groups and the bone showed a correspondingly greater strength. However, in LGAbx-fed mice the whole bone strength was 22% lower than bones with similar section modulus in the LG and HG-fed groups, indicating impaired bone tissue material properties. ConclusionsAltering diet resulted in significant changes to bone geometry and strength, while changes in the gut microbiota associated with antibiotic treatment resulted in a reduction to bone strength which could not be explained by bone geometry. Our study indicates that dietary or antibiotics treatments applied to mice later in life can alter bone properties, which suggests that interventions to improve bone strength may be effective in older adults. Funding SourcesNIH/NIAMS, BrightFocus Foundation, Stanley N. Gershoff Scholarship.

Osteogenesis imperfecta in children.

Osteogenesis imperfecta (OI) is a disease characterised by altered bone tissue material properties together with abnormal micro and macro-architecture and thus bone fragility, increased bone turnover and hyperosteocytosis. Increasingly appreciated are the soft tissue changes, sarcopenia in particular. Approaches to treatment are now multidisciplinary, with bisphosphonates having been the primary pharmacological intervention over the last 20years. Whilst meta-analyses suggest that anti-fracture efficacy across the life course is equivocal, there is good evidence that for children bisphosphonates reduce fracture risk, increase vertebral size and improve vertebral shape, as well as improving motor function and mobility. The genetics of OI continues to provide insights into the molecular pathogenesis of the disease, although the pathophysiology is less clear. The complexity of the multi-scale interactions of bone tissue with cellular function are gradually being disentangled, but the fundamental question of why increased tissue brittleness should be associated with so many other changes is unclear; ER stress, pro-inflammatory cytokines, accelerated senesence and altered matrix component release might all contribute, but a unifying hypothesis remains elusive. New approaches to therapy are focussed on increasing bone mass, following the paradigm established by the treatment of postmenopausal osteoporosis. For adults, this brings the prospect of restoring previously lost bone - for children, particularly at the severe end of the spectrum, the possibility of further reducing fracture frequency and possibly altering growth and long term function are attractive. The alternatives that might affect tissue brittleness are autophagy enhancement (through the removal of abnormal type I collagen aggregates) and stem cell transplantation - both still at the preclinical stage of assessment. Preclinical assessment is not supportive of targeting inflammatory pathways, although understanding why TGFb signalling is increased, and whether that presents a treatment target in OI, remains to be established.

Musculoskeletal microbiology: The utility of the microbiome in orthopedics.

The past 15 years have witnessed a renaissance in the study of the microbes that colonize the human body. The vast majority of the human microbiome resides within the gut. Alterations to the gut microbiome have been associated with the pathogenesis and progression of wide-ranging diseases throughout the body-including atherosclerosis, depression, and obesity. Our understanding of the effects of the gut microbiome on the musculoskeletal system remains in its infancy, but preclinical work has demonstrated an effect of the gut microbiome on the success of orthopedic surgical procedures, osteoporosis, osteoarthritis, and muscle mass. In this perspective I review preclinical findings demonstrating that an impaired presurgical gut microbiome can increase the likelihood of developing periprosthetic joint infection and how alterations in the gut microbiome can reduce bone strength by impairing bone tissue material properties. In addition to discussing these examples, I review the hypothesis that many chronic non-communicable diseases have become more prevalent in modern industrialized societies as a result of changes in the composition of the gut microbiome resulting from changes in environment/lifestyle (diet, sanitation, antibiotic use). The most burdensome musculoskeletal disorders are chronic and non-communicable and may therefore be related to generational shifts in the composition of the gut microbiome, a possibility I illustrate by reviewing changes in the prevalence of osteoarthritis over the last century. Microbiome-based therapeutics are potentially innocuous, inexpensive, and have the potential to be effective with only occasional use, making them attractive for addressing the needs of chronic and/or slowly progressing musculoskeletal disorders.

A two-layer elasto-visco-plastic rheological model for the material parameter identification of bone tissue

The ability to measure bone tissue material properties plays a major role in diagnosis of diseases and material modeling. Bone’s response to loading is complex and shows a viscous contribution to stiffness, yield and failure. It is also ductile and damaging and exhibits plastic hardening until failure. When performing mechanical tests on bone tissue, these constitutive effects are difficult to quantify, as only their combination is visible in resulting stress–strain data. In this study, a methodology for the identification of stiffness, damping, yield stress and hardening coefficients of bone from a single cyclic tensile test is proposed. The method is based on a two-layer elasto-visco-plastic rheological model that is capable of reproducing the specimens’ pre- and postyield response. The model’s structure enables for capturing the viscously induced increase in stiffness, yield, and ultimate stress and for a direct computation of the loss tangent. Material parameters are obtained in an inverse approach by optimizing the model response to fit the experimental data. The proposed approach is demonstrated by identifying material properties of individual bone trabeculae that were tested under wet conditions. The mechanical tests were conducted according to an already published methodology for tensile experiments on single trabeculae. As a result, long-term and instantaneous Young’s moduli were obtained, which were on average 3.64 GPa and 5.61 GPa, respectively. The found yield stress of 16.89 MPa was lower than previous studies suggest, while the loss tangent of 0.04 is in good agreement. In general, the two-layer model was able to reproduce the cyclic mechanical test data of single trabeculae with an root-mean-square error of 2.91 ± 1.77 MPa. The results show that inverse rheological modeling can be of great advantage when multiple constitutive contributions shall be quantified based on a single mechanical measurement.

The GLP-1 Receptor Agonist Exenatide Ameliorates Bone Composition and Tissue Material Properties in High Fat Fed Diabetic Mice.

Type 2 diabetes mellitus (T2DM) has recently been recognized as a significant risk factor for bone fragility. Careful investigations of bone mechanical properties in human studies suggested possible alterations of bone composition, although this axis has poorly been investigated. The main aim of this study was to evaluate the impact of high fat diet-induced diabetes and therapy using the clinically approved GLP-1 receptor agonist, exenatide, on tissue bone mechanical properties and compositional parameters. Male mice had free access to high fat diet for 16 weeks to induce diabetes prior to commencement of the study. Exenatide was administered twice daily by i.p. injection at a dose of 25 nmol/kg for 52 days. Normal and high fat diet fed (HFD) mice injected with saline were used as controls. Bone mechanical properties was assessed at the organ level by 3-point bending and at the tissue level by nanoindentation. Bone microarchitecture was investigated by microcomputed tomography and bone composition was evaluated by Fourier transform infrared imaging. HFD mice exhibited profound alterations of bone mechanical properties at both the organ and tissue level. Collagen maturity as well as trabecular and cortical bone microarchitectures were abnormal. Administration of exenatide, led to clear ameliorations in bone mechanical properties at the organ and tissue levels by modifications of both cortical microarchitecture and bone compositional parameters (collagen maturity, mineral crystallinity, carbonate/phosphate ratio, acid phosphate content). These results bring new light on the mode of action of exenatide in bone physiology and demonstrate the value of GLP-1 mimetics in the treatment of fragility fractures in diabetes.

The Effect of Formalin Preservation Time and Temperature on the Material Properties of Bovine Femoral Cortical Bone Tissue.

Literature has reported controversial findings on whether formalin affected bone properties, or not, especially when different preservation time durations and temperatures were involved. Hence, accurately and systematically quantifying the effect of formalin on the mechanical properties of bone using a large dataset is crucial for assessing biomechanical responses based on fixed specimens. A total of 154 longitudinal and 149 transverse cuboid-shaped (12mm × 2mm × 0.5mm) specimens from themidsection of 12 bovine femora from six bovines were prepared and assigned to ten groups, including fresh-frozen, formalin-preserved at 25°C for 4weeks and 8weeks, and formalin-preserved at 4°C for 4weeks and 8weeks. All specimens underwent quasi-static three-point bending tests with a loading rate of 0.02mm/s. The Young's modulus, yield stress, yield strain, tangent modulus, effective plastic strain, ultimate stress, and toughness were calculated by optimizing the material parameters to make the force-displacement curve of the finite element prediction consistent with the experimental curve, combined with specimen-specific finite element models. Preservation time and temperature both had significant effects on the Young's modulus, yield stress, effective plastic strain, yield strain and ultimate stress of cortical bone (p < 0.05). The Young's modulus, yield stress, and ultimate stress of longitudinal specimens decreased significantly with the increase of preservation time, and the yield strain increased significantly. As the preservation temperature increases, the Young's modulus of the transverse sample decreased significantly, and the yield strain increased significantly. The preservation time mainly affects the longitudinal specimens, while the preservation temperature mainly affects the transverse specimens. Formalin preservation of bovine femoral cortical bones at alower temperature and less than 4weeks is recommended for biomechanical testing.

Diabetes pharmacotherapy and effects on the musculoskeletal system.

Persons with type 1 or type 2 diabetes have a significantly higher fracture risk than age-matched persons without diabetes, attributed to disease-specific deficits in the microarchitecture and material properties of bone tissue. Therefore, independent effects of diabetes drugs on skeletal integrity are vitally important. Studies of incretin-based therapies have shown divergent effects of different agents on fracture risk, including detrimental, beneficial, and neutral effects. The sulfonylurea class of drugs, owing to its hypoglycemic potential, is thought to amplify the risk of fall-related fractures, particularly in the elderly. Other agents such as the biguanides may, in fact, be osteo-anabolic. In contrast, despite similarly expected anabolic properties of insulin, data suggests that insulin pharmacotherapy itself, particularly in type 2 diabetes, may be a risk factor for fracture, negatively associated with determinants of bone quality and bone strength. Finally, sodium-dependent glucose co-transporter 2 inhibitors have been associated with an increased risk of atypical fractures in select populations, and possibly with an increase in lower extremity amputation with specific SGLT2I drugs. The role of skeletal muscle, as a potential mediator and determinant of bone quality, is also a relevant area of exploration. Currently, data regarding the impact of glucose lowering medications on diabetes-related muscle atrophy is more limited, although preclinical studies suggest that various hypoglycemic agents may have either aggravating (sulfonylureas, glinides) or repairing (thiazolidinediones, biguanides, incretins) effects on skeletal muscle atrophy, thereby influencing bone quality. Hence, the therapeutic efficacy of each hypoglycemic agent must also be evaluated in light of its impact, alone or in combination, on musculoskeletal health, when determining an individualized treatment approach. Moreover, the effect of newer medications (potentially seeking expanded clinical indication into the pediatric age range) on the growing skeleton is largely unknown. Herein, we review the available literature regarding effects of diabetes pharmacotherapy, by drug class and/or by clinical indication, on the musculoskeletal health of persons with diabetes.

Clinical measurements of bone tissue mechanical behavior using reference point indentation.

Over the last thirty years, it has become increasingly clear the amount of bone (e.g. 'bone quantity') and the quality of the bone matrix (e.g. 'bone quality') both critically contribute to bone's tissue-level mechanical behavior and the subsequent ability of bone to resist fracture. Although determining the tissue-level mechanical behavior of bone through mechanical testing is relatively straightforward in the laboratory, the destructive nature of such testing is unfeasible in humans and in animal models requiring longitudinal observation. Therefore, surrogate measurements are necessary for quantifying tissue-level mechanical behavior for the pre-clinical and clinical evaluation of bone strength and fracture risk in vivo. A specific implementation of indentation known as reference point indentation (RPI) enables the mechanical testing of bone tissue without the need to excise and prepare the bone surface. However, this compromises the ability to carefully control the specimen geometry that is required to define the bone tissue material properties. Yet the versatility of such measurements in clinical populations is provocative, and to date there are a number of promising studies that have utilized this tool to discern bone pathologies and to monitor the effects of therapeutics on bone quality. Concurrently, on-going efforts continue to investigate the aspects of bone material behavior measured by RPI, and the compositional factors that contribute to these measurements. There are currently two variants, cyclic- and impact- RPI, that have been utilized in pre-clinical and clinical studies. This review surveys clinical studies that utilize RPI, with particular emphasis on the clinical instrument, as well as the endeavors to understand the fundamental mechanisms of such measurements. Ultimately, an improved awareness in the tradeoffs and limitations of in vivo RPI is critical towards the effective and successful utilization of this tool for the overall improvement of fragility determination in the clinic.

Determinants of bone damage: An ex-vivo study on porcine vertebrae.

Bone’s resistance to fracture depends on several factors, such as bone mass, microarchitecture, and tissue material properties. The clinical assessment of bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA), measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it is considered the major predictor of bone strength, BMD only accounts for about 70% of fragility fractures, while the remaining 30% could be described by bone “quality” impairment parameters, mainly related to tissue microarchitecture. The assessment of bone microarchitecture generally requires more invasive techniques, which are not applicable in routine clinical practice, or X-Ray based imaging techniques, requiring a longer post-processing. Another important aspect is the presence of local damage in the bony tissue that may also affect the prediction of bone strength and fracture risk. To provide a more comprehensive analysis of bone quality and quantity, and to assess the effect of damage, here we adopt a framework that includes clinical, morphological, and mechanical analyses, carried out by means of DXA, μCT and mechanical compressive testing, respectively. This study has been carried out on trabecular bones, taken from porcine trabecular vertebrae, for the similarity with human lumbar spine. This study confirms that no single method can provide a complete characterization of bone tissue, and the combination of complementary characterization techniques is required for an accurate and exhaustive description of bone status. BMD and TBS have shown to be complementary parameters to assess bone strength, the former assessing the bone quantity and resistance to damage, and the latter the bone quality and the presence of damage accumulation without being able to predict the risk of fracture.

The effect of storage time in saline solution on the material properties of cortical bone tissue

BackgroundThe use of saline in preserving bone specimens may affect the mechanical properties of specimens. Yet, the reported effects varied and contradicted to each other, with a lack of investigating constitutive material parameters. Therefore, we quantified the effects of preservation time on the constitutive properties of cortical bone. MethodsWe collected 120 specimens from the mid-diaphysis of six male bovine femora, which were assigned to five groups, including fresh-frozen for 60 days (−20 °C), storage in saline for 3, 10, 36 and 60 days (25 °C). All specimens underwent quasi-static three-point bending tests with a loading rate of 0.02 mm/s. Using the optimization method combined with specimen-specific finite element models, the Young's modulus, tangent modulus, yield stress, effective plastic strain, yield strain, ultimate stress, and toughness were calculated. FindingsSaline preservation resulted in a significant decrease of Young's modulus, yield stress, ultimate stress and pre-yield toughness (P < 0.001), and a significant increase of effective plastic strain (P = 0.034). After 10 days of preservation, yield stress and pre-yield toughness decreased −14.9% and −21.4%, respectively, and they continued to decrease with longer preservation time. After 36 days of preservation, Young's modulus and ultimate stress decreased −19.2% and −17.3%, respectively, and continued to decrease with longer preservation time. Our data also showed changes of material properties collected after 3-day saline preservation, while the low statistical power must be considered for this group. InterpretationSaline preservation impacts on mechanical properties of cortical bone tissue and the effect is already observable after 3 days.

The Role of the Size and Location of the Tumors and of the Vertebral Anatomy in Determining the Structural Stability of the Metastatically Involved Spine: a Finite Element Study

Vertebral fractures associated with the loss of structural integrity of neoplastic vertebrae are common, and determined to the deterioration of the bone quality in the lesion area. The prediction of the fracture risk in metastatically involved spines can guide in deciding if preventive solutions, such as medical prophylaxis, bracing, or surgery are indicated for the patient. In this study, finite element models of 22 thoracolumbar vertebrae were built based on CT scans of three spines, covering a wide spectrum of possible clinical scenarios in terms of age, bone quality and degenerative features, taking into account the local material properties of bone tissue. Simulations were performed in order to investigate the effect of the size and location of the tumoral lesion, the bone quality and the vertebral level in determining the structural stability of the neoplastic vertebrae. Tumors with random size and positions were added to the models, for a total of 660 simulations in which a compressive load was simulated. Results highlighted the fundamental role of the tumor size, whereas the other parameters had a lower, but non-negligible impact on the axial collapse of the vertebra, the vertebral bulge in the transverse plane and the canal narrowing under the application of the load. All the considered parameters are radiologically measurable, and can therefore be translated in a straightforward way to the clinical practice to support decisions about preventive treatment of metastatic fractures.

The Microbiome and Bone and Joint Disease.

Changes in the constituents and activity of the microbiome have been associated with a number of conditions linked to bone and joint disease. This review concentrates on ways in which the microbiome is known to influence osteoarthritis and osteoporosis. Animal studies have demonstrated that changes in the microbiome can mediate the effects of obesity on cartilage degeneration. Additionally, the microbiome influences the amount of the bone (bone quantity), as well as bone tissue material properties (bone quality). Early clinical findings support the effects of the microbiome on osteoporosis and osteoarthritis. Although animal studies implicate the microbiome in the development of bone and joint disease, available results are limited and can be conflicting. Further investigation of the mechanisms linking from changes in the microbiome to alterations in the bones and joints are necessary.

In vivo bone strain and finite element modeling of a rhesus macaque mandible during mastication

Finite element analysis (FEA) is a commonly used tool in musculoskeletal biomechanics and vertebrate paleontology. The accuracy and precision of finite element models (FEMs) are reliant on accurate data on bone geometry, muscle forces, boundary conditions and tissue material properties. Simplified modeling assumptions, due to lack of in vivo experimental data on material properties and muscle activation patterns, may introduce analytical errors in analyses where quantitative accuracy is critical for obtaining rigorous results. A subject-specific FEM of a rhesus macaque mandible was constructed, loaded and validated using in vivo data from the same animal. In developing the model, we assessed the impact on model behavior of variation in (i) material properties of the mandibular trabecular bone tissue and teeth; (ii) constraints at the temporomandibular joint and bite point; and (iii) the timing of the muscle activity used to estimate the external forces acting on the model. The best match between the FEA simulation and the in vivo experimental data resulted from modeling the trabecular tissue with an isotropic and homogeneous Young’s modulus and Poisson’s value of 10GPa and 0.3, respectively; constraining translations along X,Y, Z axes in the chewing (left) side temporomandibular joint, the premolars and the m1; constraining the balancing (right) side temporomandibular joint in the anterior-posterior and superior-inferior axes, and using the muscle force estimated at time of maximum strain magnitude in the lower lateral gauge. The relative strain magnitudes in this model were similar to those recorded in vivo for all strain locations. More detailed analyses of mandibular strain patterns during the power stroke at different times in the chewing cycle are needed.

Alterations to the Gut Microbiome Impair Bone Strength and Tissue Material Properties.

Alterations in the gut microbiome have been associated with changes in bone mass and microstructure, but the effects of the microbiome on bone biomechanical properties are not known. Here we examined bone strength under two conditions of altered microbiota: (1) an inbred mouse strain known to develop an altered gut microbiome due to deficits in the immune system (the Toll-like receptor 5-deficient mouse [TLR5KO]); and (2) disruption of the gut microbiota (ΔMicrobiota) through chronic treatment with selected antibiotics (ampicillin and neomycin). The bone phenotypes of TLR5KO and WT (C57Bl/6) mice were examined after disruption of the microbiota from 4 weeks to 16 weeks of age as well as without treatment (n = 7 to 16/group, 39 animals total). Femur bending strength was less in ΔMicrobiota mice than in untreated animals and the reduction in strength was not fully explained by differences in bone cross-sectional geometry, implicating impaired bone tissue material properties. Small differences in whole-bone bending strength were observed between WT and TLR5KO mice after accounting for differences in bone morphology. No differences in trabecular bone volume fraction were associated with genotype or disruption of gut microbiota. Treatment altered the gut microbiota by depleting organisms from the phyla Bacteroidetes and enriching for Proteobacteria, as determined from sequencing of fecal 16S rRNA genes. Differences in splenic immune cell populations were also observed; B and T cell populations were depleted in TLR5KO mice and in ΔMicrobiota mice (p < 0.001), suggesting an association between alterations in bone tissue material properties and immune cell populations. We conclude that alterations in the gut microbiota for extended periods during growth may lead to impaired whole-bone mechanical properties in ways that are not explained by bone geometry. © 2017 American Society for Bone and Mineral Research.

Development, Evaluation, and Sensitivity Analysis of Parametric Finite Element Whole-Body Human Models in Side Impacts.

Occupant stature and body shape may have significant effects on injury risks in motor vehicle crashes, but the current finite element (FE) human body models (HBMs) only represent occupants with a few sizes and shapes. Our recent studies have demonstrated that, by using a mesh morphing method, parametric FE HBMs can be rapidly developed for representing a diverse population. However, the biofidelity of those models across a wide range of human attributes has not been established. Therefore, the objectives of this study are 1) to evaluate the accuracy of HBMs considering subject-specific geometry information, and 2) to apply the parametric HBMs in a sensitivity analysis for identifying the specific parameters affecting body responses in side impact conditions. Four side-impact tests with two male post-mortem human subjects (PMHSs) were selected to evaluate the accuracy of the geometry and impact responses of the morphed HBMs. For each PMHS test, three HBMs were simulated to compare with the test results: the original Total Human Model for Safety (THUMS) v4.01 (O-THUMS), a parametric THUMS (P-THUMS), and a subject-specific THUMS (S-THUMS). The P-THUMS geometry was predicted from only age, sex, stature, and BMI using our statistical geometry models of skeleton and body shape, while the S-THUMS geometry was based on each PMHS's CT data. The simulation results showed a preliminary trend that the correlations between the PTHUMS- predicted impact responses and the four PMHS tests (mean-CORA: 0.84, 0.78, 0.69, 0.70) were better than those between the O-THUMS and the normalized PMHS responses (mean-CORA: 0.74, 0.72, 0.55, 0.63), while they are similar to the correlations between S-THUMS and the PMHS tests (mean-CORA: 0.85, 0.85, 0.67, 0.72). The sensitivity analysis using the PTHUMS showed that, in side impact conditions, the HBM skeleton and body shape geometries as well as the body posture were more important in modeling the occupant impact responses than the bone and soft tissue material properties and the padding stiffness with the given parameter ranges. More investigations are needed to further support these findings.

Finite Element-Based Mechanical Assessment of Bone Quality on the Basis of In Vivo Images

Beyond bone mineral density (BMD), bone quality designates the mechanical integrity of bone tissue. In vivo images based on X-ray attenuation, such as CT reconstructions, provide size, shape, and local BMD distribution and may be exploited as input for finite element analysis (FEA) to assess bone fragility. Further key input parameters of FEA are the material properties of bone tissue. This review discusses the main determinants of bone mechanical properties and emphasizes the added value, as well as the important assumptions underlying finite element analysis. Bone tissue is a sophisticated, multiscale composite material that undergoes remodeling but exhibits a rather narrow band of tissue mineralization. Mechanically, bone tissue behaves elastically under physiologic loads and yields by cracking beyond critical strain levels. Through adequate cell-orchestrated modeling, trabecular bone tunes its mechanical properties by volume fraction and fabric. With proper calibration, these mechanical properties may be incorporated in quantitative CT-based finite element analysis that has been validated extensively with ex vivo experiments and has been applied increasingly in clinical trials to assess treatment efficacy against osteoporosis.