The physiology and ontogeny of daily oral behaviors

In the masticatory system, activities of muscles are the main source of force. The daily activity of the jaw muscle is a measure of the total daily loading of the tissues involved. This article gives an overview on the recent assessments of the physiology and ontogeny of the daily use of the jaw muscles. Variations in the characteristics of daily activity could be linked to differences in the types of fibers composing the muscles as well as to the properties of the underlying bone, although these relationships are not absolute. Experimental decrease of the hardness of foods eaten by rats and rabbits showed a significant decrease in the number of daily bursts of feeding. These reductions in daily muscular activity were accompanied by higher mineralization of bone and by a transition toward "faster" fiber types in the muscles. It was revealed in rabbits that the characteristics of the daily activities of muscles (total duration of activity, number and lengths of bursts) were not altered during the transition from suckling to chewing and remained largely unaffected during further postnatal development. These results suggest that, despite large anatomical and functional changes, the average daily load on the jaw muscles by the masticatory system appears to be established before chewing develops and remains largely unchanged all the way through development. Whenever the daily muscular activity changes, this seems to have a significant effect on the properties of the tissues involved.     

Influence of mastication and edentulism on mandibular bone density

The aim of this study was to demonstrate that external loading due to daily activities, including mastication, speech and involuntary open–close cycles of the jaw contributes to the internal architecture of the mandible. A bone remodelling algorithm that regulates the bone density as a function of stress and loading cycles is incorporated into finite element analysis. A three-dimensional computational model is constructed on the basis of computerised tomography (CT) images of a human mandible. Masticatory muscle activation involved during clenching is modelled by static analysis using linear optimisation. Other loading conditions are approximated by imposing mandibular flexure. The simulations predict that mandibular bone density distribution results in a tubular structure similar to what is observed in the CT images. Such bone architecture is known to provide the bone optimum strength to resist bending and torsion during mastication while reducing the bone mass. The remodelling algorithm is used to simulate the influence of edentulism on mandibular bone loss. It is shown that depending on the location and number of missing teeth, up to one-third of the mandibular bone mass can be lost due to lack of adequate mechanical stimulation.     

Three-dimensional micro-level computational study of Wolff's law via trabecular bone remodeling in the human proximal femur using design space topology optimization

The law of bone remodeling, commonly referred to as Wolff's Law, asserts that the internal trabecular bone adapts to external loadings, reorienting with the principal stress trajectories to maximize mechanical efficiency creating a naturally optimum structure. The goal of the current study was to utilize an advanced structural optimization algorithm, called design space optimization (DSO), to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur and analyse the results to determine the validity of Wolff's hypothesis. DSO optimizes the layout of material by iteratively distributing it into the areas of highest loading, while simultaneously changing the design domain to increase computational efficiency. The result is a "fully stressed" structure with minimized compliance and increased stiffness. The large-scale computational simulation utilized a 175 μm mesh resolution and the routine daily loading activities of walking and stair climbing. The resulting anisotropic trabecular architecture was compared to both Wolff's trajectory hypothesis and natural femur samples from literature using a variety of visualization techniques, including radiography and computed tomography (CT). The results qualitatively revealed several anisotropic trabecular regions, that were comparable to the natural human femurs. Quantitatively, the various regional bone volume fractions from the computational results were consistent with quantitative CT analyses. The global strain energy proceeded to become more uniform during optimization; implying increased mechanical efficiency was achieved. The realistic simulated trabecular geometry suggests that the DSO method can accurately predict bone adaptation due to mechanical loading and that the proximal femur is an optimum structure as the Wolff hypothesized.     

European Society of Biomechanics S.M. Perren Award 2014: Safety factor of the proximal femur during gait: A population-based finite element study

It has been suggested that the mechanical competence of the proximal femur is preserved with respect to physiological loading conditions rather than accidental overloading, but the consequences of this adaptation for fracture risk in the elderly remain unclear. The goal of the present study was to analyse the safety factor of the human femur in the two most frequent daily activities, level walking and stair climbing, and to understand the dependence, if any, of this safety factor on age, volumetric bone mineral density (vBMD), and gender.     

Influence of physical activity on the regulation of bone density

Using a mathematical model which relates bone density to daily stress histories, the influence of physical activities on the apparent density of the calcaneal cancellous bone was investigated. Assuming that the mechanical bone maintenance stimulus is constant for all bone tissue, bone apparent density was calculated by a linear superposition of the mechanical stimulus provided by different daily physical activities. An empirical weighting factor, m, accounted for possible differences in the relative importance of load magnitude and number of cycles in each activity. By considering hypothetical variations in body weight and occupational activity levels, the range of probable m values was established. The model was then applied to the results of two previous running studies in which calcaneal density was measured to obtain an estimate of the stress exponent parameter, m. The results indicate that stress magnitudes (or joint forces) have a greater influence on bone mass than the number of loading cycles. We demonstrate that by carefully considering the magnitudes of imposed skeletal forces and the number of loading cycles, it may be possible to design exercise programs to achieve predictable changes in bone mass.     

Predicting the structural integrity of bone defects repaired using bone graft materials

Bone defects create stress concentrations which can cause fracture under impact or cyclic loading. Defects are often repaired by filling them with a bone graft material; this will reduce the stress concentration, but not completely, because these materials have lower stiffness than bone. The fracture risk decreases over time as the graft material is replaced by living bone. Many new bone graft materials are being developed, using tissue engineering and other techniques, but currently there is no rational way to compare these materials and predict their effectiveness in repairing a given defect. This paper describes, for the first time, a theoretical model which can be used to predict failure by brittle fracture or fatigue, initiating at the defect. Preliminary results are presented, concentrating on the prediction of stress fracture during the crucial post-operative period. It is shown that the likelihood of fracture is strongly influenced by the shape of the defect as well as its size, and also by the level of post-operative exercise. The most important finding is that bone graft materials can be successful in preventing fracture even when their mechanical properties are greatly inferior to those of bone. Future uses of this technique include pre-clinical assessment of bone replacement materials and pre-operative planning in orthopaedic surgery.     

Predicting the structural integrity of bone defects repaired using bone graft materials

Bone defects create stress concentrations which can cause fracture under impact or cyclic loading. Defects are often repaired by filling them with a bone graft material; this will reduce the stress concentration, but not completely, because these materials have lower stiffness than bone. The fracture risk decreases over time as the graft material is replaced by living bone. Many new bone graft materials are being developed, using tissue engineering and other techniques, but currently there is no rational way to compare these materials and predict their effectiveness in repairing a given defect. This paper describes, for the first time, a theoretical model which can be used to predict failure by brittle fracture or fatigue, initiating at the defect. Preliminary results are presented, concentrating on the prediction of stress fracture during the crucial post-operative period. It is shown that the likelihood of fracture is strongly influenced by the shape of the defect as well as its size, and also by the level of post-operative exercise. The most important finding is that bone graft materials can be successful in preventing fracture even when their mechanical properties are greatly inferior to those of bone. Future uses of this technique include pre-clinical assessment of bone replacement materials and pre-operative planning in orthopaedic surgery.     

Size, structure and gender: lessons about fracture risk

The differences in age-related fracture risks among men and women must reflect gender differences in the relevant variables. We are concerned here with gender differences in structural variables that relate to the size and shape of bones. As children grow, their bones grow in diameter through periosteal modeling. Studies show that radial growth is driven by mechanical forces and is not just "genetically programmed". Moving bone mass farther from the center of the diaphysis makes it more effective in resisting bending and twisting forces, and disproportionately so in comparison to changes in bone mass. Gender differences in long bone structure appear to arise because the bone cells of males and females function in different hormonal environments which affect their responses to mechanical loading. In girls, bone formation on the metacarpal periosteal surface essentially stops at puberty, and is replaced by formation on the endosteal surface, reducing endosteal diameter until about age 20. Bone strength is 60% greater in male metacarpals than in those of females because bone is added periosteally in boys and endosteally in girls. At menopause endosteal resorption resumes, accompanied by slow periosteal apposition, weakening cortical structure. Similar phenomena occur in such critical regions as the femoral neck. Another fundamental gender difference in skeletal development is that whole body bone mineral content increases in linear proportion to lean body mass throughout skeletal maturation in boys, but in girls there is a distinct increase in the slope of this relationship at puberty, when estrogen rises. Frost's hypothesis is that this reflects an effect of estrogen on bone's mechanostat set point, and this is increasingly supported by data showing that estrogen and mechanical strain act through a common pathway in osteoblast-like cells. If Frost's hypothesis is correct, the mechanostat is set for maximal effect of mechanical loading on bone gain during the 2-3 years preceding menarche. During the childbearing years, the set point is at an intermediate level, and at menopause, it shifts again to place the skeleton into the metabolic equivalent of a disuse state. The most direct approach to resolving this problem would be to simulate the putative effect of estrogen on the set point itself.     

Is skeletal mechanotransduction under genetic control?

Studies of twins have established that peak bone mass is about 70% heritable. The skeletal response to exercise contributes to peak bone mass, as mechanical loading increases skeletal mass during growth and development. It is possible that the skeletal responsiveness to mechanical loading is under genetic control, so that some individuals will build stronger bones with exercise. This appears to be the case in mice. Long bones in mice of the C3H/He strain are largely unresponsive to mechanical loading. Ironically, this strain of mice has very high bone density. Perhaps the genes that regulate BMD are not the same as those that regulate mechanical loading response. Studies of recombinant inbred and congenic strains derived from C3H mice will help to identify genes influencing bone size, density and responsiveness to mechanical loading.     

Relationships between femoral fracture loads for two load configurations

Studies of proximal femoral strength usually involve one of two types of loading conditions, loading similar to joint loading during single-limb stance or loading simulating impact from a fall. When interpreting the results of studies involving only one of these load configurations, the question arises as to their applicability to the other configuration. In addition, it is desirable to know whether, for an individual bone, fracture load for one load configuration is indicative of fracture load for the other configuration. In this study, the relationship between proximal femoral fracture loads for single-limb stance loading and loading simulating impact from a type of fall was determined from mechanical testing of 17 matched pairs of human proximal femora. Fracture loads for these two configurations were found to be linearly related (r = 0.901, p < 0.001). However, the correlation between fracture loads is not notably stronger than correlations currently available between fracture load and measures of bone density and geometry. In addition, the regression results indicate that 81% of the variance in fracture load for one loading condition is accounted for by fracture load for the other loading condition. Thus, 19% of the variance remains unexplained, indicating that the results of studies involving only one load configuration are not necessarily indicative of those that would be found for another configuration.     

Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk

There is mounting evidence suggesting that the commonly used analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), may inhibit new bone formation with physical training and increase risk of stress fractures in physically active populations. Stress fractures are thought to occur when bones are subjected to repetitive mechanical loading, which can lead to a cycle of tissue microdamage, repair, and continued mechanical loading until fracture. Adaptive bone formation, particularly on the periosteal surface of long bones, is a concurrent adaptive response of bone to heightened mechanical loading that can improve the fatigue resistance of the skeletal structure, and therefore may play a critical role in offsetting the risk of stress fracture. Reports from animal studies suggest that NSAID administration may suppress this important adaptive response to mechanical loading. These observations have implications for populations such as endurance athletes and military recruits who are at risk of stress fracture and whose use of NSAIDs is widespread. However, results from human trials evaluating exercise and bone adaptation with NSAID consumption have been less conclusive. In this review, we identify knowledge gaps that must be addressed to further support NSAID-related guidelines intended for at-risk populations and individuals.     

Consideration of multiple load cases is critical in modelling orthotropic bone adaptation in the femur

Functional adaptation of the femur has been investigated in several studies by embedding bone remodelling algorithms in finite element (FE) models, with simplifications often made to the representation of bone’s material symmetry and mechanical environment. An orthotropic strain-driven adaptation algorithm is proposed in order to predict the femur’s volumetric material property distribution and directionality of its internal structures within a continuum. The algorithm was applied to a FE model of the femur, with muscles, ligaments and joints included explicitly. Multiple load cases representing distinct frames of two activities of daily living (walking and stair climbing) were considered. It is hypothesised that low shear moduli occur in areas of bone that are simply loaded and high shear moduli in areas subjected to complex loading conditions. In addition, it is investigated whether material properties of different femoral regions are stimulated by different activities. The loading and boundary conditions were considered to provide a physiological mechanical environment. The resulting volumetric material property distribution and directionalities agreed with ex vivo imaging data for the whole femur. Regions where non-orthogonal trabecular crossing has been documented coincided with higher values of predicted shear moduli. The topological influence of the different activities modelled was analysed. The influence of stair climbing on the properties of the femoral neck region is highlighted. It is recommended that multiple load cases should be considered when modelling bone adaptation. The orthotropic model of the complete femur is released with this study.     

The benefit of combining non-mechanical agents with mechanical loading: a perspective based on the Utah Paradigm of Skeletal Physiology

The Utah Paradigm of Skeletal Physiology with its key component, the mechanostat hypothesis, suggest plausible explanations of some of the tissue-level changes occurring from combining selected non-mechanical agents (anabolic and anti-resorptive/( re)modeling agents) with mechanical loading (osteogenic exercise) to increase bone mass and strength. The evidence for combining selected anabolic agents like parathyroid hormone, prostaglandin E(2), growth hormone, etc. with mechanical loading can increase bone mass is strong. Anabolic agents influence loading-related bone formation changes in a permissive manner and modulate (increase) the responsiveness of bone tissue to mechanical loading by changing thresholds for bone formation and resorption. However, any beneficial effect of combining selected anti-resorptive/(re)modeling agents like estrogen with loading is marginal, especially in adult skeletons. Postulated changes in modeling and remodeling thresholds (set points) and known direct effects on bone cells by non-mechanical agents may explain the observed tissue-level changes associated with large and minor increases in bone mass. Although the pharmaceutical industry has avoided considering osteogenic loading in the treatment of osteoporosis, a methodical dose-response study of anabolic agents combined with loading should: (1) provide opportunities for therapeutic intervention to imitate or enhance the osteogenic response to loading in order to correct osteopenias; (2) provide the potential to diminish the dosage of drugs required to induce bone formation in ways that enhanced efficacy and reduced any side effects; and (3) improve the quality of life and reduce the risk of falls by improving balance, gait speed and muscle strength with a non-mechanical agent like GH that could improve both muscle and bone mass and strength. Lastly, more studies are needed which determine bone strength instead of only "mass" in aged skeletons so one can assess how effective such treatments would reduce the risk of fracture in the clinic.     

Influence of gait loads on implant integration in rat tibiae: Experimental and numerical analysis

Implanted rat bones play a key role in studies involving fracture healing, bone diseases or drugs delivery among other themes. In most of these studies the implants integration also depends on the animal daily activity and musculoskeletal loads, which affect the implants mechanical environment. However, the tissue adaption to the physiological loads is often filtered through control groups or not inspected. This work aims to investigate experimentally and numerically the effects of the daily activity on the integration of implants inserted in the rat tibia, and to establish a physiological loading condition to analyse the peri-implant bone stresses during gait. Two titanium implants, single and double cortex crossing, are inserted in the rat tibia. The animals are caged under standard conditions and divided in three groups undergoing progressive integration periods. The results highlight a time-dependent increase of bone samples with significant cortical bone loss. The phenomenon is analysed through specimen-specific Finite Element models involving purpose-built musculoskeletal loads. Different boundary conditions replicating the post-surgery bone–implant interaction are adopted. The effects of the gait loads on the implants integration are quantified and agree with the results of the experiments. The observed cortical bone loss can be considered as a transient state of integration due to bone disuse atrophy, initially triggered by a loss of bone–implant adhesion and subsequently by a cyclic opening of the interface.     

Computational study of Wolff's law with trabecular architecture in the human proximal femur using topology optimization

In the field of bone adaptation, it is believed that the morphology of bone is affected by its mechanical loads, and bone has self-optimizing capability; this phenomenon is well known as Wolff's law of the transformation of bone. In this paper, we simulated trabecular bone adaptation in the human proximal femur using topology optimization and quantitatively investigated the validity of Wolff's law. Topology optimization iteratively distributes material in a design domain producing optimal layout or configuration, and it has been widely and successfully used in many engineering fields. We used a two-dimensional micro-FE model with 50 microm pixel resolution to represent the full trabecular architecture in the proximal femur, and performed topology optimization to study the trabecular morphological changes under three loading cases in daily activities. The simulation results were compared to the actual trabecular architecture in previous experimental studies. We discovered that there are strong similarities in trabecular patterns between the computational results and observed data in the literature. The results showed that the strain energy distribution of the trabecular architecture became more uniform during the optimization; from the viewpoint of structural topology optimization, this bone morphology may be considered as an optimal structure. We also showed that the non-orthogonal intersections were constructed to support daily activity loadings in the sense of optimization, as opposed to Wolff's drawing.     

Foot forces during typical days on the international space station

Decreased bone mineral density (BMD) in astronauts returning from long-duration spaceflight missions has been well documented, but the altered mechanical loading environment experienced by the musculoskeletal system, which may contribute to these changes, has not been well characterized. The current study describes the loading environment of the lower extremity (LE) during typical days on the International Space Station (ISS) compared to similar data for the same individuals living on Earth. Data from in-shoe force measurements are also used as input to the enhanced daily load stimulus (EDLS) model to determine the mechanical “dose” experienced by the musculoskeletal system and to associate this dose with changes in BMD.Four male astronauts on approximately 6-month missions to the ISS participated in this study. In-shoe forces were recorded using capacitance-based insoles during entire typical working days both on Earth and on-orbit. BMD estimates from the hip and spine regions were obtained from dual energy X-ray absorptiometry (DXA) pre- and post-flight.Measurable loading was recorded for only 30% of the time assigned for exercise. In-shoe forces during treadmill walking and running on the ISS were reduced by 25% and 46%, respectively, compared to similar activities on Earth. Mean on-orbit LE loads varied from 0.20 to 1.3 body weight (BW) during resistance exercise and were ～0.10 BW during bicycle ergometry. Application of the EDLS model showed a mean decrease of 25% in the daily load experienced by the LE. BMD decreased by 0.71% and 0.83% per month during their missions in the femoral neck and lumbar spine, respectively.Our findings support the conclusion that the measured ISS exercise durations and/or loading were insufficient to provide the loading stimulus required to prevent bone loss. Future trials with EDLS values closer to 100% of Earth values will offer a true test of exercise as a countermeasure to on-orbit bone loss.     

Fracture toughness and fatigue crack propagation rate of short fiber reinforced epoxy composites for analogue cortical bone

Third-generation mechanical analogue bone models and synthetic analogue cortical bone materials manufactured by Pacific Research Laboratories, Inc. (PRL) are popular tools for use in mechanical testing of various orthopedic implants and biomaterials. A major issue with these models is that the current third-generation epoxy-short fiberglass based composite used as the cortical bone substitute is prone to crack formation and failure in fatigue or repeated quasistatic loading of the model. The purpose of the present study was to compare the tensile and fracture mechanics properties of the current baseline (established PRL "third-generation" E-glass-fiber-epoxy) composite analogue for cortical bone to a new composite material formulation proposed for use as an enhanced fourth-generation cortical bone analogue material. Standard tensile, plane strain fracture toughness, and fatigue crack propagation rate tests were performed on both the third- and fourth-generation composite material formulations using standard ASTM test techniques. Injection molding techniques were used to create random fiber orientation in all test specimens. Standard dog-bone style tensile specimens were tested to obtain ultimate tensile strength and stiffness. Compact tension fracture toughness specimens were utilized to determine plane strain fracture toughness values. Reduced thickness compact tension specimens were also used to determine fatigue crack propagation rate behavior for the two material groups. Literature values for the same parameters for human cortical bone were compared to results from the third- and fourth-generation cortical analogue bone materials. Tensile properties of the fourth-generation material were closer to that of average human cortical bone than the third-generation material. Fracture toughness was significantly increased by 48% in the fourth-generation composite as compared to the third-generation analogue bone. The threshold stress intensity to propagate the crack was much higher for the fourth-generation material than for the third-generation composite. Even at the higher stress intensity threshold, the fatigue crack propagation rate was significantly decreased in the fourth-generation composite compared to the third-generation composite. These results indicate that the bone analogue models made from the fourth-generation analogue cortical bone material may exhibit better performance in fracture and longer fatigue lives than similar models made of third-generation analogue cortical bone material. Further fatigue testing of the new composite material in clinically relevant use of bone models is still required for verification of these results. Biomechanical test models using the superior fourth-generation cortical analogue material are currently in development.     

A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading

Bone has a capability to repair itself when it is fractured. Repair involves the generation of intermediate tissues, such as fibrous connective tissue, cartilage and woven bone, before final bone healing can occur. The intermediate tissues serve to stabilise the mechanical environment and provide a scaffold for differentiation of new tissues. The repair process is fundamentally affected by mechanical loading and by the geometric configuration of the fracture fragments. Biomechanical analyses of fracture healing have previously computed the stress distribution within the callus and identified the components of the stress tensor favouring or inhibiting differentiation of particular tissue phenotypes. In this paper, a biphasic poroelastic finite element model of a fracture callus is used to simulate the time-course of tissue differentiation during fracture healing. The simulation begins with granulation tissue (post-inflammation phase) and finishes with bone resorption. The biomechanical regulatory model assumes that tissue differentiation is controlled by a combination of shear strain and fluid flow acting within the tissue. High shear strain and fluid flows are assumed to deform the precursor cells stimulating formation of fibrous connective tissue, lower levels stimulate formation of cartilage, and lower again allows ossification. This mechano-regulatory scheme was tested by simulating healing in fractures with different gap sizes and loading magnitudes. The appearance and disappearance of the various tissues found in a callus was similar to histological observation. The effect of gap size and loading magnitude on the rate of reduction of the interfragmentary strain was sufficiently close to confirm the hypothesis that tissue differentiation phenomena could be governed by the proposed mechano-regulation model.     

Who's afraid of the big bad Wolff?: “Wolff's law” and bone functional adaptation

"Wolff's law" is a concept that has sometimes been misrepresented, and frequently misunderstood, in the anthropological literature. Although it was originally formulated in a strict mathematical sense that has since been discredited, the more general concept of "bone functional adaptation" to mechanical loading (a designation that should probably replace "Wolff's law") is supported by much experimental and observational data. Objections raised to earlier studies of bone functional adaptation have largely been addressed by more recent and better-controlled studies. While the bone morphological response to mechanical strains is reduced in adults relative to juveniles, claims that adult morphology reflects only juvenile loadings are greatly exaggerated. Similarly, while there are important genetic influences on bone development and on the nature of bone's response to mechanical loading, variations in loadings themselves are equally if not more important in determining variations in morphology, especially in comparisons between closely related individuals or species. The correspondence between bone strain patterns and bone structure is variable, depending on skeletal location and the general mechanical environment (e.g., distal vs. proximal limb elements, cursorial vs. noncursorial animals), so that mechanical/behavioral inferences based on structure alone should be limited to corresponding skeletal regions and animals with similar basic mechanical designs. Within such comparisons, traditional geometric parameters (such as second moments of area and section moduli) still give the best available estimates of in vivo mechanical competence. Thus, when employed with appropriate caution, these features may be used to reconstruct mechanical loadings and behavioral differences within and between past populations.