An integrated experimental-computational framework to assess the influence of microstructure and material properties on fracture toughness in clinical specimens of human femoral cortical bone.

Microstructural and compositional changes that occur due to aging, pathological conditions, or pharmacological treatments alter cortical bone fracture resistance. However, the relative importance of these changes to the fracture resistance of cortical bone has not been quantified in detail. In this technical note, we developed an integrated experimental-computational framework utilizing human femoral cortical bone biopsies to advance the understanding of how fracture resistance of cortical bone is modulated due to modifications in its microstructure and material properties.

Influence of Osteocyte Lacunar-Canalicular Morphology and Network Architecture on Osteocyte Mechanosensitivity.

Purpose Of Review: The goal of this review is to summarize recent findings related to modifications in osteocyte lacunar and canalicular morphology due to physiological and pathological conditions. In addition, this review aims to outline how these modifications may influence the local mechanical environment of osteocytes and their mechanosensitivity.

Recent Findings: Reduction in lacunar density with age and increasing lacunar size with lactation are confirmed in multiple studies in human and murine bone.

Evaluating the Role of Canalicular Morphology and Perilacunar Region Properties on Local Mechanical Environment of Lacunar-Canalicular Network Using Finite Element Modeling.

Physiological and pathological processes such as aging, diseases, treatments, and lactation can alter lacunar-canalicular network (LCN) morphology and perilacunar region properties. These modifications can impact the mechanical environment of osteocytes which in turn can influence osteocyte mechanosensitivity and the remodeling process. In this study, we aim to evaluate how the modifications in the canalicular morphology, lacunar density, and the perilacunar region properties influence the local mechanical environment of LCN and the apparent bone properties using three-dimensional finite element (FE) modeling.

Quantifying how altered lacunar morphology and perilacunar tissue properties influence local mechanical environment of osteocyte lacunae using finite element modeling.

Previous studies have demonstrated that osteocyte lacunar morphology and perilacunar bone tissue properties undergo alterations due to physiological and pathological processes such as aging, lactation, diseases, and treatments. However, the influence of these alterations on the apparent mechanical properties of the bone and the local mechanical environment of osteocyte lacunae has not been evaluated in detail. The goal of this study is to quantify the influence of osteocyte lacunar morphology and perilacunar tissue properties on local mechanical environment around lacunae and the apparent mechanical properties of the bone using three-dimensional FE models of lacunae networks with varying lacunar morphology and perilacunar properties based on previously reported experimental data.

Structural role of osteocyte lacunae on mechanical properties of bone matrix: A cohesive finite element study.

Despite the extensive studies on biological function of osteocytes, there are limited studies that evaluated the structural role of osteocyte lacunae on local mechanical properties of the bone matrix. As a result, the goal of this study was to elucidate the independent contribution of osteocyte lacunae structure on mechanical properties and fracture behavior of the bone matrix uncoupled from its biological effects and bone tissue composition variation. This study combined cohesive finite element modeling with experimental data from a lactation rat model to evaluate the influence of osteocyte lacunar area porosity, density, size, axis ratio, and orientation on the elastic modulus, ultimate strength, and ultimate strain of the bone matrix as well as on local crack formation and propagation.

Biomechanical mechanisms of atypical femoral fracture.

Antiresorptives such as bisphosphonates (BP) and denosumab are commonly used osteoporosis treatments that are effective in preventing osteoporotic fractures by suppressing bone turnover. Although these treatments reduce fracture risk, their long-term use has been associated with atypical femoral fracture (AFF), a rare potential side effect. Despite its rare occurrence, AFF has had a disproportionately significant adverse impact on society due to its severe outcomes such as loss of function and delayed healing.

A three-dimensional multiscale finite element model of bone coupling mineralized collagen fibril networks and lamellae.

Despite evidence of contribution of mineralized collagen fibrils (MCF) to both the microscale elastic and fracture response of bone, the extent of influence of MCF orientation and material property variation on the lamellar scale mechanical properties is still not well quantified. To this end, in this study, we developed a three-dimensional multiscale finite element model that linked submicroscale models of MCF networks to microscale models of several lamellae. The developed models evaluated the individual and relative influence of MCF orientation as well as material property variation due to MCF mineral distribution and interaction on the lamellar scale mechanical response of bone.

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.

Assessment of the multifactorial causes of atypical femoral fractures using a novel multiscale finite element approach.

Atypical femoral fracture (AFF), which is a low energy fracture in the subtrochanteric or diaphysis region of the femur, has multifactorial causes that span macro- to microscale mechanisms including femoral geometry, cortical bone composition and structure. However, the extent of individual and combined influence of these factors on AFF is still not well understood. As a result, the aim of this study is to develop a multiscale fracture mechanics-based finite element modeling framework that is capable of quantifying the individual and combined influence of macroscale femoral geometrical properties as well as cortical bone microscale material properties and structure on AFF.

A finite element study evaluating the influence of mineralization distribution and content on the tensile mechanical response of mineralized collagen fibril networks.

One of the key length scales of interest in bone's hierarchical structure is the submicroscale which has been shown to influence the fracture behavior of bone at larger length scales. At the submicroscale, the building block of bone is mineralized collagen fibrils (MCF). The mineral distribution and content of MCFs as well as the interaction between MCFs influence the mechanical response of bone at the submicroscale.

Material heterogeneity, microstructure, and microcracks demonstrate differential influence on crack initiation and propagation in cortical bone.

The recent studies have shown that long-term bisphosphonate use may result in a number of mechanical alterations in the bone tissue including a reduction in compositional heterogeneity and an increase in microcrack density. There are limited number of experimental and computational studies in the literature that evaluated how these modifications affect crack initiation and propagation in cortical bone. Therefore, in this study, the entire crack growth process including initiation and propagation was simulated at the microscale by using the cohesive extended finite element method.

Interaction of Microcracks and Tissue Compositional Heterogeneity in Determining Fracture Resistance of Human Cortical Bone.

Recent studies demonstrated an association between atypical femoral fracture (AFF) and long-term bisphosphonate (BP) use for osteoporosis treatment. Due to BP treatment, bone undergoes alterations including increased microcrack density and reduced tissue compositional heterogeneity. However, the effect of these changes on the fracture response of bone is not well understood.

Effect of modifications in mineralized collagen fibril and extra-fibrillar matrix material properties on submicroscale mechanical behavior of cortical bone.

A key length scale of interest in assessing the fracture resistance of bone is the submicroscale which is composed of mineralized collagen fibrils (MCF) and extra-fibrillar matrix (EFM). Although the processes through which the submicroscale constituents of bone contribute to the fracture resistance in bone have been identified, the extent of the modifications in submicroscale mechanical response due to the changes in individual properties of MCFs and EFM has not been determined. As a result, this study aims to quantify the influence of individual MCF and EFM material property modifications on the mechanical behavior (elastic modulus, ultimate strength, and resistance to failure) of bone at the submicroscale using a novel finite element modeling approach that incorporate 3D networks of MCFs with three different orientations as well as explicit representation of EFM.

Mineralized collagen fibril network spatial arrangement influences cortical bone fracture behavior.

Bone is a hierarchical material exhibiting different fracture mechanisms at each length scale. At the submicroscale, the bone is composed of mineralized collagen fibrils (MCF). At this scale, the fracture processes in cortical bone have not been extensively studied in the literature.

Assessment of the effect of reduced compositional heterogeneity on fracture resistance of human cortical bone using finite element modeling.

The recent reports of atypical femoral fracture (AFF) and its possible association with prolonged bisphosphonate (BP) use highlighted the importance of a thorough understanding of mechanical modifications in bone due to bisphosphonate treatment. The reduced compositional heterogeneity is one of the modifications in bone due to extensive suppression of bone turnover. Although experimental evaluations suggested that compositional changes lead to a reduction in the heterogeneity of elastic properties, there is limited information on the extent of influence of reduced heterogeneity on fracture resistance of cortical bone.

A direct role of collagen glycation in bone fracture.

Non-enzymatic glycation (NEG) is an age-related process accelerated by diseases like diabetes, and causes the accumulation of advanced glycation end-products (AGEs). NEG-mediated modification of bone's organic matrix, principally collagen type-I, has been implicated in impairing skeletal physiology and mechanics. Here, we present evidence, from in vitro and in vivo models, and establish a causal relationship between collagen glycation and alterations in bone fracture at multiple length scales.

Analysis of toughening mechanisms in the Strombus gigas shell.

A finite element analysis of the fracture mechanisms in the Strombus gigas conch shell is presented in this work. The S. gigas shell has a complex microarchitecture that consists of three main macroscopic layers of calcium carbonate: the inner, middle, and outer layers.

Association between non-enzymatic glycation, resorption, and microdamage in human tibial cortices.

Unlabelled: To better understand the association between different components of bone quality, we investigated the relationship among in vivo generated non-enzymatic glycation, resorption, and microdamage. The results showed negative correlation between advanced glycation end-products (AGEs) and resorption independent of age highlighting the interaction between these parameters that may lead to bone fragility.

Introduction: Changes in the quality of bone material contribute significantly to bone fragility.

A new fracture assessment approach coupling HR-pQCT imaging and fracture mechanics-based finite element modeling.

A new fracture assessment approach that combines HR-pQCT imaging with fracture mechanics-based finite element modeling was developed to evaluate distal radius fracture load. Twenty distal radius images obtained from postmenopausal women (fracture, n=10; nonfracture, n=10) were processed to obtain a cortical and a whole bone model for each subject. The geometrical properties of each model were evaluated and the corresponding fracture load was determined under realistic fall conditions using cohesive finite element modeling.

Dilatational band formation in bone.

Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone's nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands.

Evaluation of the influence of strain rate on Colles' fracture load.

Colles' fracture, a transverse fracture of the distal radius bone, is one of the most frequently observed osteoporotic fractures resulting from low energy or traumatic events, associated with low and high strain rates, respectively. Although experimental studies on Colles' fracture were carried out at various loading rates ranging from static to impact loadings, there is no systematic study in the literature that isolates the influence of strain rate on Colles' fracture load. In order to provide a better understanding of fracture risk, the current study combines experimental material property measurements under varying strain rates with computational modeling and presents new information on the effect of strain rate on Colles' fracture.

Interaction of microstructure and microcrack growth in cortical bone: a finite element study.

Microstructural features including osteons and cement lines are considered to play an important role in determining the crack growth behaviour in cortical bone. This study aims to develop a computational mechanics approach to evaluate microscale fracture mechanisms in bone. In this study, finite element models based on actual human cortical bone images that allow for arbitrary crack growth were utilised to determine the crack propagation behaviour.

The effect of strain rate on fracture toughness of human cortical bone: a finite element study.

Evaluating the mechanical response of bone under high loading rates is crucial to understanding fractures in traumatic accidents or falls. In the current study, a computational approach based on cohesive finite element modeling was employed to evaluate the effect of strain rate on fracture toughness of human cortical bone. Two-dimensional compact tension specimen models were simulated to evaluate the change in initiation and propagation fracture toughness with increasing strain rate (range: 0.

Finite element modeling of the influence of hand position and bone properties on the Colles' fracture load during a fall.

Distal forearm fracture is one of the most frequently observed osteoporotic fractures, which may occur as a result of low energy falls such as falls from a standing height and may be linked to the osteoporotic nature of the bone, especially in the elderly. In order to prevent the occurrence of radius fractures and their adverse outcomes, understanding the effect of both extrinsic and intrinsic contributors to fracture risk is essential. In this study, a nonlinear fracture mechanics-based finite element model is applied to human radius to assess the influence of extrinsic factors (load orientation and load distribution between scaphoid and lunate) and intrinsic bone properties (age-related changes in fracture properties and bone geometry) on the Colles' fracture load.

Prediction of Colles' fracture load in human radius using cohesive finite element modeling.

Osteoporotic and age-related fractures are a significant public health problem. One of the most common osteoporotic fracture sites in the aging population is distal radius. There is evidence in the literature that distal radius fractures (Colles' fracture) are an indicative of increased risk of future spine and hip fractures.