How Artificial Intelligence and Machine Learning Is Assisting Us to Extract Meaning from Data on Bone Mechanics?

Dramatic advancements in interdisciplinary research with the fourth paradigm of science, especially the implementation of computer science, nourish the potential for artificial intelligence (AI), machine learning (ML), and artificial neural network (ANN) algorithms to be applied to studies concerning mechanics of bones. Despite recent enormous advancement in techniques, gaining deep knowledge to find correlations between bone shape, material, mechanical, and physical responses as well as properties is a daunting task. This is due to both complexity of the material itself and the convoluted shapes that this complex material forms. Moreover, many uncertainties and ambiguities exist concerning the use of traditional computational techniques that hinders gaining a full comprehension of this advanced biological material. This book chapter offers a review of literature on the use of AI, ML, and ANN in the study of bone mechanics research. A main question as to why to implement AI and ML in the mechanics of bones is fully addressed and explained. This chapter also introduces AI and ML and elaborates on the main features of ML algorithms such as learning paradigms, subtypes, main ideas with examples, performance metrics, training algorithms, and training datasets. As a frequently employed ML algorithm in bone mechanics, feedforward ANNs are discussed to make their taxonomy and working principles more readily comprehensible to researchers. A summary as well as detailed review of papers that employed ANNs to learn from collected data on bone mechanics are presented. Reviewing literature on the use of these data-driven tools is essential since their wider application has the potential to: improve clinical assessments enabling real-time simulations; avoid and/or minimize injuries; and, encourage early detection of such injuries in the first place.

Correlations of cortical bone microstructural and mechanical properties with water proton fractions obtained from ultrashort echo time (UTE) MRI tricomponent T2* model.

Mechanical and microstructural evaluations of cortical bone using ultrashort echo time magnetic resonance imaging (UTE-MRI) have been performed increasingly in recent years. UTE-MRI acquires considerable signal from cortical bone and enables quantitative bone evaluations. Fitting bone apparent transverse magnetization (T2*) decay using a bicomponent model has been regularly performed to estimate bound water (BW) and pore water (PW) in the quantification of bone matrix and porosity, respectively. Human cortical bone possesses a considerable amount of fat, which appears as MRI T2* signal oscillation and can subsequently lead to BW overestimation when using a bicomponent model. Tricomponent T2* fitting model has been developed to improve BW and PW estimations by accounting for fat contribution in the MRI signal. This study aimed to investigate the correlations of microstructural and mechanical properties of human cortical bone with water pool fractions obtained from a tricomponent T2* model. 135 cortical bone strips (~4 × 2 × 40 mm3 ) from tibial and femoral midshafts of 37 donors (61 ± 24 years old) were scanned using ten sets of dual-echo 3D-UTE-Cones sequences (TE = 0.032-24.0 ms) on a 3 T MRI scanner for T2* fitting analyses. Average bone porosity and pore size were measured using microcomputed tomography (µCT) at 9 µm voxel size. Bone mechanical properties were measured using 4-point bending tests. Using a tricomponent model, bound water fraction (FracBW ) showed significant strong (R = 0.70, P < 0.01) and moderate (R = 0.58-0.62, P < 0.01) correlations with porosity and mechanical properties, respectively. Correlations of bone microstructural and mechanical properties with water pool fractions were higher for tricomponent model results compared with the bicomponent model. The tricomponent T2* fitting model is suggested as a useful technique for cortical bone evaluation where the MRI contribution of bone fat is accounted for.

In Vivo Assessment of Cortical Bone Fragility.

PURPOSE OF REVIEW: This review updates readers on recent developments in the assessment of cortical bone fragility in vivo. The review explains the clinical need that motivated the development of Cortical Bone Mechanics Technology™ (CBMT) as a scientific instrument, its unique capabilities, and its necessary further development as a medical device. RECENT FINDINGS: Clinical experience with dual-energy X-ray absorptiometry has led to calls for new clinical methods for assessing bone health. CBMT is a noninvasive, dynamic 3-point bending test that makes direct, functional measurements of the mechanical properties of cortical bone in ulnas of living people. Its technical validity in accurate measurements of ulna flexural rigidity and its clinical validity in accurate estimations of quasistatic ulna bending strength have been demonstrated. Because CBMT is a whole bone test, its measurements reflect the influences of bone quantity and bone quality at all hierarchical levels.

Advanced Modeling Methods-Applications to Bone Fracture Mechanics.

PURPOSE OF REVIEW: The goal of this review is to summarize recent advances in modeling of bone fracture using fracture mechanics-based approaches at multiple length scales spanning nano- to macroscale. RECENT FINDINGS: Despite the additional information that fracture mechanics-based models provide over strength-based ones, the application of this approach to assessing bone fracture is still somewhat limited. Macroscale fracture models of bone have demonstrated the potential of this approach in uncovering the contributions of geometry, material property variation, as well as loading mode and rate on whole bone fracture response. Cortical and cancellous microscale models of bone have advanced the understanding of individual contributions of microstructure, microarchitecture, local material properties, and material distribution on microscale fracture resistance of bone. Nano/submicroscale models have provided additional insight into the effect of specific changes in mineral, collagen, and non-collagenous proteins as well as their interaction on energy dissipation and fracture resistance at small length scales. Advanced modeling approaches based on fracture mechanics provide unique information about the underlying multiscale fracture mechanisms in bone and how these mechanisms are influenced by the structural and material constituents of bone at different length scales. Fracture mechanics-based modeling provides a powerful approach that complements experimental evaluations and advances the understanding of critical determinants of fracture risk.

Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation.

PURPOSE OF REVIEW: This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an effort to elucidate how the balance between the structural and metabolic functions of the skeleton is achieved during these physiological processes. RECENT FINDINGS: While pregnancy and lactation induce significant changes in bone density and structure to provide calcium for fetal/infant growth, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity. Both clinical and animal studies suggest that pregnancy and lactation lead to adaptations in cortical bone structure to allow for rapid calcium release from the trabecular compartment while maintaining whole bone stiffness and strength. Moreover, extents of lactation-induced bone loss and weaning-induced recovery are highly dependent on a given bone's load-bearing function, resulting in better protection of the mechanical integrity at critical load-bearing sites. The recent discovery of lactation-induced osteocytic perilacunar/canalicular remodeling (PLR) indicates a new means for osteocytes to modulate mineral homeostasis and tissue-level mechanical properties of the maternal skeleton. Furthermore, lactation-induced PLR may also play an important role in maintaining the maternal skeleton's load-bearing capacity by altering osteocyte's microenvironment and modulating the transmission of anabolic mechanical signals to osteocytes. Both clinical and animal studies show that parity and lactation have no adverse, or a positive effect on bone strength later in life. The skeletal effects during pregnancy and lactation reflect an optimized balance between the mechanical and metabolic functions of the skeleton.

What Animal Models Have Taught Us About the Safety and Efficacy of Bisphosphonates in Chronic Kidney Disease.

PURPOSE OF REVIEW: Bisphosphonates (BPs) have long been the gold-standard anti-remodeling treatment for numerous metabolic bone diseases. Since these drugs are excreted unmetabolized through the kidney, they are not recommended for individuals with compromised kidney function due to concerns of kidney and bone toxicity. The goal of this paper is to summarize the preclinical BP work in models of kidney disease with particular focus on the bone, kidney, and vasculature. RECENT FINDINGS: Summative data exists showing positive effects on bone and vascular calcifications with minimal evidence for bone or kidney toxicity in animal models. Preclinical data suggest it may be worthwhile to take a step back and reconsider the use of bisphosphonates to lessen skeletal/vascular complications associated with compromised kidney function.

Response to "Clinical Evaluation of Bone Strength and Fracture Risk".

We read with great interest the recent review by de Bakker et al that summarized the state of several existing and emerging technologies for estimating bone strength and fracture risk in vivo. Much of their review focused on how well the measurements of selected technologies predicted experimental measurements of bone strength by ex vivo quasistatic mechanical testing (QMT) and on how well they tracked changes in mechanical properties of bone. The authors noted that the association of many common skeletal health measurements (e.g., DXA measures of trabecular bone score and areal and volumetric BMD) are only moderately associated with bone strength. The authors did not include mechanical response tissue analysis (MRTA) in their review. MRTA is a dynamic mechanical bending test that uses a vibration analysis technique to make immediate, direct, functional measurements of the mechanical properties (mass, stiffness, and damping) of long bones in humans in vivo. In this article we note our interest in the ability of MRTA to detect large changes in bone stiffness that go undetected by DXA. We also highlight results of our proprietary improvements to MRTA technology that have resulted in unmatched accuracy in QMT-validated measurements of the bending stiffness and estimates of the bending strength (both R2 = 0.99) of human ulna bones. To distinguish our improved technique from the legacy MRTA technology, we refer to it as Cortical Bone Mechanics Technology (CBMT). Further research will determine whether such CBMT measurements are clinically useful.

Relationship Between Ulnar Variance, Cortical Bone Density, and Load to Failure in the Distal Radius at the Typical Site of Fracture Initiation.

PURPOSE: Increased ulnar variance has been shown to lead to diminished load borne by the distal radius. The purpose of this study was to determine the correlations among ulnar variance, bone mineral density, and load to failure at the distal radius. METHODS: Posteroanterior radiographs and computed tomographic scans were taken of 12 cadaveric forearms in neutral rotation. Ulnar variance was measured for each wrist by the method of perpendiculars. Measurements of cortical, trabecular, and combined bone density were made at the distal radius. We performed linear regression analysis and correlation analysis to determine the relationship between bone densities and ulnar variance measurements. Next, we loaded the 12 cadaveric radii to failure under axial compression. Linear regression analysis and correlation analysis were then performed to determine the relationship between load to failure and both ulnar variance and cortical density. RESULTS: Increased ulnar variance was significantly correlated with decreased cortical bone density at the distal radius and both were correlated with decreased load to failure. We found no correlation between ulnar variance and trabecular density or combined trabecular and cortical bone density at the distal radius. CONCLUSIONS: Our study found that increased ulnar variance and decreased cortical bone mineral density correlates with decreased load to failure under axial compression. CLINICAL RELEVANCE: Ulnar variance is linked to both bone quality and load to failure at the distal radius.

Romosozumab rescues impaired bone mass and strength in a murine model of diabetic kidney disease.

As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 µL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at -20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.

An investigation of composition, morphology, mechanical properties, and microdamage accumulation of human type 2 diabetic bone.

This study investigates the biomechanics of type 2 diabetic bone fragility through a multiscale experimental strategy that considers structural, mechanical, and compositional components of ex vivo human trabecular and cortical bone. Human tissue samples were obtained from the femoral heads of patients undergoing total hip replacement. Mechanical testing was carried out on isolated trabecular cores using monotonic and cyclic compression loading and nanoindentation experiments, with bone microdamage analysed using micro-computed tomography (CT) imaging. Bone composition was evaluated using Raman spectroscopy, high-performance liquid chromatography, and fluorometric spectroscopy. It was found that human type 2 diabetic bone had altered mechanical, compositional, and morphological properties compared to non-type 2 diabetic bone. High-resolution micro-CT imaging showed that cores taken from the central trabecular region of the femoral head had higher bone mineral density (BMD), bone volume, trabecular thickness, and reduced trabecular separation. Type 2 diabetic bone also had enhanced macro-mechanical compressive properties under mechanical loading compared to non-diabetic controls, with significantly higher apparent modulus, yield stress, and pre-yield toughness evident, even when properties were normalised against the bone volume. Using nanoindentation, there were no significant differences in the tissue-level mechanical properties of cortical or trabecular bone in type 2 diabetic samples compared to controls. Through compositional analysis, higher levels of furosine were found in type 2 diabetic trabecular bone, and an increase in both furosine and carboxymethyl-lysine (an advanced glycation end-product) was found in cortical bone. Raman spectroscopy showed that type 2 diabetic bone had a higher mineral-to-matrix ratio, carbonate substitution, and reduced crystallinity compared to the controls. Together, this study shows that type 2 diabetes leads to distinct changes in both organic and mineral phases of the bone tissue matrix, but these changes did not coincide with any reduction in the micro- or macro-mechanical properties of the tissue under monotonic or cyclic loading.

Mechanical impact of regional structural deterioration and tissue-level compensation on proximal femur trabecular bone.

Introduction: Osteoporosis-induced changes in bone structure and composition significantly reduce bone strength, particularly in the human proximal femur. This study examines how these changes affect the mechanical performance of trabecular bone to enhance diagnosis, prevention, and treatment strategies. Methods: A proximal femur sample was scanned using micro-CT at 40 µm resolution. Five regions of interest were selected within the femoral head, femoral neck, and greater trochanter. Structural models simulating various stages of osteoporosis were created using image processing software. Micro-finite element analysis evaluated the mechanical properties of trabecular bone under different conditions of structural deterioration and tissue-level elastic modulus variations. The combined effects of structural deterioration and tissue-level mechanical properties on trabecular bone mechanical performance were further analyzed. Results: The mechanical performance of trabecular bone generally follows a power-law relationship with its microstructural characteristics. However, in any specific region, the apparent mechanical properties linearly decrease with structural deterioration. The femoral neck and greater trochanter are more sensitive to structural deterioration than the femoral head. A 5% bone mass loss in the femoral head led to a 7% reduction in mechanical performance, while the femoral neck experienced a 12% loss. Increasing tissue-level elastic modulus improved mechanical performance, partially offsetting bone mass reduction effects. Conclusion: Trabecular bone in low bone mass regions is more affected by bone mass loss. Structural deterioration primarily reduces bone strength, but improvements in tissue-level properties can mitigate this effect, especially in early osteoporosis. Targeted assessments and interventions are crucial for effective management. Future research should explore heterogeneous deterioration models to better understand osteoporosis progression.

Total body irradiation is associated with long-term deficits in femoral bone structure but not mechanical properties in male rhesus macaques.

Exposure to ionizing radiation for oncological therapy increases the risk for late-onset fractures in survivors. However, the effects of total body irradiation (TBI) on adult bone are not well-characterized. The primary aim of this study was to quantify the long-term effects of TBI on bone microstructure, material composition, and mechanical behavior in skeletally mature rhesus macaque (Macaca mulatta) non-human primates. Femora were obtained post-mortem from animals exposed to an acute dose of TBI (6.0-6.75 Gy) nearly a decade earlier, age-matched non-irradiated controls, and non-irradiated young animals. The microstructure of femoral trabecular and cortical bone was assessed via micro-computed tomography. Material composition was evaluated by measuring total fluorescent advanced glycation end products (fAGEs). Cortical bone mechanical behavior was quantified via four-point bending and cyclic reference point indentation (cRPI). Animals exposed to TBI had slightly worse cortical microstructure, including lower cortical thickness (-11%, p = 0.037) and cortical area (-24%, p = 0.049), but similar fAGE content and mechanical properties as age-matched controls. Aging did not influence cortical microstructure, fAGE content, or cRPI measures but diminished femoral cortical post-yield properties, including toughness to fracture (-32%, p = 0.032). Because TBI was administered after the acquisition of peak bone mass, these results suggest that the skeletons of long-term survivors of adulthood TBI may be resilient, retaining or recovering their mechanical integrity during the post-treatment period, despite radiation-induced architectural deficits. Further investigation is necessary to better understand radiation-induced skeletal fragility in mature and immature bone to improve care for radiation patients of all ages.

Bone quality following peripubertal growth in a mouse model of transmasculine gender-affirming hormone therapy.

During peri-puberty, bone growth and the attainment peak bone mass is driven predominantly by sex steroids. This is important when treating transgender and gender diverse youth, who have become increasingly present at pediatric clinics. Analogues of gonadotropin-releasing hormone (GnRH) are commonly prescribed to transgender and gender diverse youth prior to starting gender-affirming hormone therapy (GAHT). However, the impact of GnRH agonists on long bones with the addition of GAHT is relatively unknown. To explore this, we developed a trans-masculine model by introducing either GnRHa or vehicle treatment to female-born mice at a pre-pubertal age. This treatment was followed by male GAHT (testosterone, T) or control treatment three weeks later. Six weeks after T therapy, bone quality was compared between four treatment groups: Control (vehicle only), GnRHa-only, GnRHa + T, and T-only. Bone length/size, bone shape, mechanical properties, and trabecular morphology were modulated by GAHT. Independent of GnRHa administration, mice treated with T had shorter femurs, larger trabecular volume and increased trabecular number, higher trabecular bone mineral density, and wider superstructures on the surface of bone (e.g., third trochanters) when compared to control or GnRHa-only mice. In conclusion, prolonged treatment of GnRHa with subsequent GAHT treatment directly affect the composition, parameters, and morphology of the developing long bone. These findings provide insight to help guide clinical approaches to care for transgender and gender diverse youth.

The Morphology of the Femur Influences the Fracture Risk during Stumbling and Falls on the Hip-A Computational Biomechanical Study.

Proximal femur fracture risk depends on subject-specific factors such as bone mineral density and morphological parameters. Here, we aim to analyze the dependency of the femoral strength on sixteen morphological parameters. Therefore, finite-element analyses of 20 human femurs during stumbling and lateral falls on the hip were conducted. Pearson correlation coefficients were calculated and morphological parameters with significant correlations were examined in principal component analysis and linear regression analysis. The dependency of the fracture strength on morphological parameters was more pronounced during lateral falls on the hip compared to stumbling. Significant correlations were observed between the neck shaft angle (r = -0.474), neck diameter (r = 0.507), the true distance between the femoral head center and femoral shaft axis (r = 0.459), and its projected distance on the frontal plane (r = 0.511), greater trochanter height (r = 0.497), and distance between the femoral head center and a plane parallel to the frontal plane containing the projection of the femoral head center to the femoral neck axis (r = 0.669). Principal component analysis was strongly weighted by parameters defining the lever arm during a lateral fall as well as the loaded cross-section in the femoral neck.

Effect of different constraining boundary conditions on simulated femoral stresses and strains during gait.

Finite element analysis (FEA) is commonly used in orthopaedic research to estimate localised tissue stresses and strains. A variety of boundary conditions have been proposed for isolated femur analysis, but it remains unclear how these assumed constraints influence FEA predictions of bone biomechanics. This study compared the femoral head deflection (FHD), stresses, and strains elicited under four commonly used boundary conditions (fixed knee, mid-shaft constraint, springs, and isostatic methods) and benchmarked these mechanics against the gold standard inertia relief method for normal and pathological femurs (extreme anteversion and retroversion, coxa vara, and coxa valga). Simulations were performed for the stance phase of walking with the applied femoral loading determined from patient-specific neuromusculoskeletal models. Due to unrealistic biomechanics observed for the commonly used boundary conditions, we propose a novel biomechanical constraint method to generate physiological femur biomechanics. The biomechanical method yielded FHD (< 1 mm), strains (approaching 1000 µÎµ), and stresses (< 60 MPa), which were consistent with physiological observations and similar to predictions from the inertia relief method (average coefficient of determination = 0.97, average normalized root mean square error = 0.17). Our results highlight the superior performance of the biomechanical method compared to current methods of constraint for  both healthy and pathological femurs.

Ultrasound attenuation of cortical bone correlates with biomechanical, microstructural, and compositional properties.

BACKGROUND: We investigated the relationship of two commonly used quantitative ultrasound (QUS) parameters, speed of sound (SoS) and attenuation coefficient (α), with water and macromolecular contents of bovine cortical bone strips as measured with ultrashort echo time (UTE) magnetic resonance imaging (MRI). METHODS: SoS and α were measured in 36 bovine cortical bone strips utilizing a single-element transducer with nominal 5 MHz center frequency based on the time of flight principles after accommodating for reflection losses. Specimens were then scanned using UTE MRI to measure total, bound, and pore water proton density (TWPD, BWPD, and PWPD) as well as macromolecular proton fraction and macromolecular transverse relaxation time (T2-MM). Specimens were also scanned using microcomputed tomography (µCT) at 9-µm isometric voxel size to measure bone mineral density (BMD), porosity, and pore size. The elastic modulus (E) of each specimen was measured using a 4-point bending test. RESULTS: α demonstrated significant positive Spearman correlations with E (R = 0.69) and BMD (R = 0.44) while showing significant negative correlations with porosity (R = -0.41), T2-MM (R = -0.47), TWPD (R = -0.68), BWPD (R = -0.67), and PWPD (R = -0.45). CONCLUSIONS: The negative correlation between α and T2-MM is likely indicating the relationship between QUS and collagen matrix organization. The higher correlations of α with BWPD than with PWPD may indicate that water organized in finer structure (bound to matrix) provides lower acoustic impedance than water in larger pores, which is yet to be investigated thoroughly. RELEVANCE STATEMENT: This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone, including the collagenous matrix and water. Investigating the full potential of QUS and its validation facilitates a more affordable and accessible tool for bone health monitoring in clinics. KEY POINTS: • Ultrasound attenuation demonstrated significant positive correlations with bone mechanics and mineral density. • Ultrasound attenuation demonstrated significant negative correlations with porosity and bone water contents. • This study highlights the importance of future investigations exploring the relationship between QUS measures and all major components of the bone.

Mechanical loading of ex vivo bovine trabecular bone in 3D printed bioreactor chambers.

Previous ex vivo bone culture methods have successfully implemented polycarbonate (PC) bioreactors to investigate bone adaptation to mechanical load; however, they are difficult to fabricate and have been limited to a 5 mm maximum specimen height. The objective of this study was to validate a custom-made 3D printed MED610TM bioreactor system that addresses the limitations of the PC bioreactor and assess its efficacy in ex vivo bone culture. Twenty-three viable trabecular bone cores (10 mm height by 10 mm diameter) from an 18-month-old bovine sternum were cultured in MED610TM bioreactors with culture medium at 37 °C and 5% CO2 for 21-days. Bone cores were ranked based on their day 0 apparent elastic modulus (Eapp) and evenly separated into a "Load" group (n = 12) and a control group (n = 11). The Load group was loaded five times per week with a sinusoidal strain waveform between -1000 and -5000 µÎµ for 120 cycles at 2 Hz. Eapp was assessed on day 0, 8, and 21 using quasi-static tests with a -4000 µÎµ applied strain. Over 21-days, the Eapp of Load group samples tended to increase by more than double the control group (53.4% versus 20.9%) and no visual culture contamination was observed. This study demonstrated that bone organ culture in 3D printed MED610TM bioreactors replicated Eapp trends found in previous studies with PC bioreactors. However, further studies are warranted with a larger sample size to increase statistical power and histology to assess cell viability and bone mineral apposition rate.

IL-1RI participates in normal growth plate development and bone modeling.

The proinflammatory cytokine interleukin-1 (IL-1) signals through IL-1 receptor type I (IL-1RI) and induces osteoclastogenesis and bone resorption mainly during pathological conditions. Little is known about the effect of excess or absence of IL-1 signaling on the physiological development of the growth plate and bone. In this study, we examine growth plate morphology, bone structure, and mechanical properties as well as osteoclast number in IL-1RI knockout mice to evaluate the role of IL-1RI in the normal development of the growth plate and bone. We show for the first time that IL-1RI knockout mice have narrower growth plates due to a smaller hypertrophic zone, suggesting a role for this cytokine in hypertrophic differentiation, together with higher proteoglycan content. The bones of theses mice exhibit higher trabecular and cortical mass, increased mineral density, and superior mechanical properties. In addition, IL-1RI knockout mice have significantly reduced osteoclast numbers in the chondro-osseous junction, trabecular bone, and cortical bone. These results suggest that IL-1RI is involved in normal growth plate development and ECM homeostasis and that it is significant in the physiological process of bone modeling.

Fatigue crack propagation and fracture toughness of cortical bone are radiation dose-dependent.

Cortical bone allograft sterilized with a standard γ-radiation dose of 25-35kGy has demonstrated reduced static and cyclic fracture resistance compared with unirradiated bone. To mitigate radiation damage, we recently observed a dose-dependent response of high-cycle fatigue behavior of human cortical bone from 0 to 25 kGy, with lower doses exhibiting logarithmically longer fatigue lives. The objectives of this study were as follows: (1) to determine whether fracture toughness, work-to-fracture, and fatigue crack propagation resistance of human cortical bone are also radiation dose-dependent, and (2) to determine the associations of radiation dose and a Raman biomarker for collagen disorder with fracture properties. Compact tension specimens were machined from two donor femoral pairs and allocated to four treatment groups: 0 (unirradiated control), 10, 17.5, and 25 kGy. Fracture toughness specimens were monotonically loaded to failure and the critical stress intensity factor (KC ) was determined. Work-to-fracture was calculated from the load versus displacement integral up to fracture. Fatigue crack propagation specimens were cyclically loaded under constant room-temperature irrigation and fatigue crack growth rate (da/dN) and cyclic stress intensity (∆K) were calculated. Fracture toughness, work-to-fracture, and fatigue crack propagation resistance decreased 18%, 33%, and 15-fold from 0 to 25 kGy, respectively (p < 0.05). Radiation dose was more predictive of fracture properties than collagen disorder. These findings support that quasi-static and fatigue fracture properties of cortical bone are radiation dose-dependent within this dose range. The structural alterations arising from irradiation that cause these losses in fracture resistance remain to be elucidated.

In Vivo Assessment of Skin Surface Pattern: Exploring Its Potential as an Indicator of Bone Biomechanical Properties.

The mechanical properties of bone tissue are the result of a complex process involving collagen-crystal interactions. The mineral density of the bone tissue is correlated with bone strength, whereas the characteristics of collagen are often associated with the ductility and toughness of the bone. From a clinical perspective, bone mineral density alone does not satisfactorily explain skeletal fragility. However, reliable in vivo markers of collagen quality that can be easily used in clinical practice are not available. Hence, the objective of the present study is to examine the relationship between skin surface morphology and changes in the mechanical properties of the bone. An experimental study was conducted on healthy children (n = 11), children with osteogenesis imperfecta (n = 13), and women over 60 years of age (n = 22). For each patient, the skin characteristic length (SCL) of the forearm skin surface was measured. The SCL quantifies the geometric patterns formed by wrinkles on the skin's surface, both in terms of size and elongation. The greater the SCL, the more deficient was the organic collagen matrix. In addition, the bone volume fraction and mechanical properties of the explanted femoral head were determined for the elderly female group. The mean SCL values of the healthy children group were significantly lower than those of the elderly women and osteogenesis imperfecta groups. For the aged women group, no significant differences were indicated in the elastic mechanical parameters, whereas bone toughness and ductility decreased significantly as the SCL increased. In conclusion, in bone collagen pathology or bone aging, the SCL is significantly impaired. This in vivo skin surface parameter can be a non-invasive tool to improve the estimation of bone matrix quality and to identify subjects at high risk of bone fracture.