Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis

The objective of the present study was to explore the bone protective role of blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After 100 days of treatment, rats were euthanized, and blood and tissues were collected. Bone mineral density (BMD) and content of whole body, right tibia, right femur and fourth lumbar vertebra were assessed via dual-energy X-ray absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral, and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent the loss of whole-body BMD and had an intermediary effect on prevention of tibial and femoral BMD when compared to either Sham or Ovx controls. The bone-protective effects of blueberry may be due to suppression of Ovx-induced increase in bone turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase, collagen type I and tartrate-resistant acid phosphatase to the Sham levels. Similarly, serum osteocalcein levels were also lower in the blueberry group when compared to the Ovx control group, albeit not significantly. In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in BMD and favorable changes in biomarkers of bone metabolism.     

Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading

Osteocyte apoptosis is known to trigger targeted bone resorption. In the present study, we developed an osteocyte-viability-based trabecular bone remodeling (OVBR) model. This novel remodeling model, combined with recent advanced simulation methods and analysis techniques, such as the element-by-element 3D finite element method and the ITS technique, was used to quantitatively study the dynamic evolution of bone mass and trabecular microstructure in response to various loading and unloading conditions. Different levels of unloading simulated the disuse condition of bed rest or microgravity in space. The amount of bone loss and microstructural deterioration correlated with the magnitude of unloading. The restoration of bone mass upon the reloading condition was achieved by thickening the remaining trabecular architecture, while the lost trabecular plates and rods could not be recovered by reloading. Compared to previous models, the predictions of bone resorption of the OVBR model are more consistent with physiological values reported from previous experiments. Whereas osteocytes suffer a lack of loading during disuse, they may suffer overloading during the reloading phase, which hampers recovery. The OVBR model is promising for quantitative studies of trabecular bone loss and microstructural deterioration of patients or astronauts during long-term bed rest or space flight and thereafter bone recovery.     

A bone remodelling model including the directional activity of BMUs

Bone is able to adapt itself to the mechanical and biological environment by changing its porosity and/or orientation of its internal microstructure in a process known as bone remodelling. As a consequence, a change of bone mechanical properties is produced leading to an optimum structure, able to bear the external loads with the minimum weight. This adaptation is carried out by a temporal association of cells known as BMUs (basic multicellular units) that resorb old bone and sometimes produce new organic extracellular matrix (osteoid) that is later mineralized. This involves changes in porosity, damage level (density of microcracks accumulated by cyclic loads) and mineral content. All of these features were taken into account in a previous model, but the whole process and therefore the resulting bone constitutive behaviour was considered isotropic. The model proposed herein, recognizing that bone is actually anisotropic, tries to explain how BMUs modify the anisotropy by changing their progressing direction. We check the potential of the model to predict the alignment of the bone microstructure with the external loads in different situations. Then, the model is also applied to obtain the anisotropy and mechanical properties of the human proximal femur under physiological loads with initial conditions corresponding to a heterogeneous, but otherwise isotropic bone.     

Effect of trabecular bone loss on cortical strain rate during impact in an in vitro model of avian femur

Background  

Osteoporotic hip fractures occur due to loss of cortical and trabecular bone mass and consequent degradation in whole bone strength. The direct cause of most fractures is a fall, and hence, characterizing the mechanical behavior of a whole osteopenic bone under impact is important. However, very little is known about the mechanical interactions between cortical and trabecular bone during impact, and it is specifically unclear to what extent epiphyseal trabecular bone contributes to impact resistance of whole bones. We hypothesized that trabecular bone serves as a structural support to the cortex during impact, and hence, loss of a critical mass of trabecular bone reduces internal constraining of the cortex, and, thereby, decreases the impact tolerance of the whole bone.     

A gravitational impulse model predicts collision impulse and mechanical work during a step-to-step transition

The simplest walking model, which assumes an instantaneous collision with negligible gravity effect, is limited in its representation of the collision mechanics of human gaits because the actual step-to-step transition occurs over a finite duration of time with finite impulsive ground reaction forces (GRFs) that have the same order of magnitude as the gravitational force. In this study, we propose a new collision model that includes the contribution of the gravitational impulse to the momentum change of the center of mass (COM) during a step-to-step transition. To validate the model, we measured the GRFs of six subjects' over-ground walking at five different gait speeds and calculated the collision impulses and mechanical work. The data showed a significant contribution of the gravitational impulse to the momentum change during collision. To compensate for the gravity, the magnitudes of collision impulse and COM work were estimated to be much greater than in previous predictions. Consistent with the model prediction, push-off propulsion fully compensated for the collision loss, implying the step-to-step transition occurred in an energetically optimal manner. The new model predicted a moderate change in the collision mechanics with gait speed, which seems to be physiologically achievable. The gravitational collision model enables us to better understand collision dynamics during a step-to-step transition.     

The effect of muscle loading on the simulation of bone remodelling in the proximal femur

A large number of finite element analyses of the proximal femur rely on a simplified set of muscle and joint contact loads to represent the boundary conditions of the model. In the context of bone remodelling analysis around hip implants, muscle loading affects directly the spatial distribution of the remodelling signal. In the present study we performed a sensitivity analysis on the effect of different muscle loading configurations on the outcome of the bone remodelling simulation. An anatomical model of the femur with the implanted stem in place was constructed using the CT data of the Visible Human Project dataset of the National Institute of Health. The model was loaded with three muscle force configurations with increasing level of complexity. A strain adaptive remodelling rule was employed to simulate the post-operative bone changes around the implant stem and the results of the simulation were assessed quantitatively in terms of the bone mineral content changes in 18 periprosthetic regions of interest. The results showed considerable differences in the amount of bone loss predicted between the three cases. The simplified models generally predicted more pronounced bone loss. Although the overall remodelling patterns observed were similar, the bone conserving effect of additional muscle forces in the vicinity of their areas of attachment was clear. The results of this study suggest that the loading configuration of the FE model does play an important role in the outcome of the remodelling simulation.     

A mechanobiological model of endothelial cell migration and proliferation

How angiogenesis is regulated by local environmental cues is still not fully understood despite its importance to many regenerative events. Although mechanics is known to influence angiogenesis, the specific cellular mechanisms influenced by mechanical loading are poorly understood. This study adopts a lattice-based modelling approach to simulate endothelial cell (EC) migration and proliferation in order to explore how mechanical stretch regulates their behaviour. The approach enables the explicit modelling of ECs and, in particular, their migration/proliferation (specifically, rate and directionality) in response to such mechanical cues. The model was first used to simulate previously reported experiments of EC migration and proliferation in an unloaded environment. Next, three potential effects (increased cell migration, increased cell proliferation and biased cellular migration) of mechanical stretch on EC behaviour were simulated using the model and the observed changes in cell population characteristics were compared to experimental findings. Combinations of these three potential drivers were also investigated. The model demonstrates that only by incorporating all three changes in cellular physiology (increased EC migration, increased EC proliferation and biased EC migration in the direction perpendicular to the applied strain) in response to dynamic loading, it is possible to successfully predict experimental findings. This provides support for the underlying model hypotheses for how mechanics regulates EC behaviour.     

Mammalian hibernation as a model of disuse osteoporosis: the effects of physical inactivity on bone metabolism, structure, and strength

Reduced skeletal loading typically leads to bone loss because bone formation and bone resorption become unbalanced. Hibernation is a natural model of musculoskeletal disuse because hibernating animals greatly reduce weight-bearing activity, and therefore, they would be expected to lose bone. Some evidence suggests that small mammals like ground squirrels, bats, and hamsters do lose bone during hibernation, but the mechanism of bone loss is unclear. In contrast, hibernating bears maintain balanced bone remodeling and preserve bone structure and strength. Differences in the skeletal responses of bears and smaller mammals to hibernation may be due to differences in their hibernation patterns; smaller mammals may excrete calcium liberated from bone during periodic arousals throughout hibernation, leading to progressive bone loss over time, whereas bears may have evolved more sophisticated physiological processes to recycle calcium, prevent hypercalcemia, and maintain bone integrity. Investigating the roles of neural and hormonal control of bear bone metabolism could give valuable insight into translating the mechanisms that prevent disuse-induced bone loss in bears into novel therapies for treating osteoporosis.     

Interstitial fluid velocity is decreased around cortical bone vascular pores and depends on osteocyte position in a rat model of disuse osteoporosis

Biomechanics and Modeling in Mechanobiology - Muscle paralysis induced with botulinum toxin (Botox) injection increases vascular porosity and reduces osteocyte lacunar density in the tibial...     

A novel mathematical model of bone remodelling cycles for trabecular bone at the cellular level

After an initial phase of growth and development, bone undergoes a continuous cycle of repair, renewal and optimisation by a process called remodelling. This paper describes a novel mathematical model of the trabecular bone remodelling cycle. It is essentially formulated to simulate a remodelling event at a fixed position in the bone, integrating bone removal by osteoclasts and formation by osteoblasts. The model is developed to construct the variation in bone thickness at a particular point during the remodelling event, derived from standard bone histomorphometric analyses. The novelties of the approach are the adoption of a predator-prey model to describe the dynamic interaction between osteoclasts and osteoblasts, using a genetic algorithm-based solution; quantitative reconstruction of the bone remodelling cycle; and the introduction of a feedback mechanism in the bone formation activity to co-regulate bone thickness. The application of the model is first demonstrated by using experimental data recorded for normal (healthy) bone remodelling to predict the temporal variation in the number of osteoblasts and osteoclasts. The simulated histomorphometric data and remodelling cycle characteristics compare well with the specified input data. Sensitivity studies then reveal how variations in the model's parameters affect its output; it is hoped that these parameters can be linked to specific biochemical factors in the future. Two sample pathological conditions, hypothyroidism and primary hyperparathyroidism, are examined to demonstrate how the model could be applied more broadly, and, for the first time, the osteoblast and osteoclast populations are predicted for these conditions. Further data are required to fully validate the model's predictive capacity, but this work shows it has potential, especially in the modelling of pathological conditions and the optimisation of the treatment of those conditions.     

Improving the damage accumulation in a biomechanical bone remodelling model

We extend, reformulate and analyse a phenomenological model for bone remodelling. The original macrobiomechanical model (MBM), proposed by Hazelwood et al. [J Biomech 2001; 34:299–308], couples a population equation for the cellular activities of the basic multicellular units (BMUs) in the bone and a rate equation to account for microdamage and repair. We propose to account for bone failure under severe overstressing by incorporating a Paris-like power-law damage accumulation term. The extended model agrees with the Hazelwood et al. predictions when the bone is under-stressed, and allows for suitably loaded bones to fail, in agreement with other MBM and experimental data regarding damage by fatigue. We numerically solve the extended model using a convergent algorithm and show that for unchanging loads, the stationary solution captures fully the model behaviour. We compute and analyse the stationary solutions. Our analysis helps guide additional extensions to this and other BMU activity based models.     

Numerical investigations on the strain-adaptive bone remodelling in the periprosthetic femur: Influence of the boundary conditions

Background  

There are several numerical investigations on bone remodelling after total hip arthroplasty (THA) on the basis of the finite element analysis (FEA). For such computations certain boundary conditions have to be defined. The authors chose a maximum of three static load situations, usually taken from the gait cycle because this is the most frequent dynamic activity of a patient after THA.     

A mechanistic model for internal bone remodeling exhibits different dynamic responses in disuse and overload

Bone is a dynamic tissue which, through the process of bone remodeling in the mature skeleton, renews itself during normal function and adapts to mechanical loads. It is, therefore, important to understand the effect of remodeling on the mechanical function of bone, as well as the effect of the inherent time lag in the remodeling process. In this study, we develop a constitutive model for bone remodeling which includes a number of relevant mechanical and biological processes and use this model to address differences in the remodeling behavior as a volume element of bone is placed in disuse or overload. The remodeling parameters exhibited damped oscillatory behavior as the element was placed in disuse, with the amplitude of the oscillations increasing as the severity of disuse increased. In overload situations, the remodeling parameters exhibited critically sensitive behavior for loads beyond a threshold value. These results bear some correspondence to experimental findings, suggesting that the model may be useful when examining the importance of transient responses for bone in disuse, and for investigating the role fatigue damage removal plays in preventing or causing stress fractures. In addition, the constitutive algorithm is currently being employed in finite element simulations of bone adaptation to predict important features of the internal structure of the normal femur, as well as to study bone diseases and their treatment.     

Influence of the change in stem length on the load transfer and bone remodelling for a cemented resurfaced femur

The effect of a short-stem femoral resurfacing component on load transfer and potential failure mechanisms has rarely been studied. The stem length has been reduced by approximately 50% as compared to the current long-stem design. Using 3-D FE models of natural and resurfaced femurs, the study is aimed at investigating the influence of a short-stem resurfacing component on load transfer and bone remodelling. Applied loading conditions include normal walking and stair climbing. The mechanical role of the stem along with implant–cement and stem–bone contact conditions was observed to be crucial. Shortening the stem length to half of the current length (long-stem) led to several favourable effects, even though the stress distributions in the implant and the cement were similar in both the cases. The short-stem implant led not only to a more physiological stress distribution but also to bone apposition (increase of 20–70% bone density) in the superior resurfaced head, when the stem–bone contact prevailed. This also led to a reduction in strain concentration in the cancellous bone around the femoral neck–component junction. The normalised peak strain in this region was lower for the short-stem design as compared to that of the long-stem one, thereby reducing the initial risk of neck fracture. The effect of strain shielding (50–75% reduction) was restricted to a small bone volume underlying the cement, which was approximately half of that of the long-stem design. Consequently, bone resorption was considerably less for the short-stem design. The short-stem design offers better prospects than the long-stem resurfacing component.     

A bone remodelling model coupling microdamage growth and repair by 3D BMU-activity

Bone as most of living tissues is able, during its entire lifetime, to adapt its internal microstructure and subsequently its associated mechanical properties to its specific mechanical and physiological environment in a process commonly known as bone remodelling. Bone is therefore continuously renewed and microdamage, accumulated by fatigue or creep, is removed minimizing the risk of fracture. Nevertheless, bone is not always able to repair itself completely. Actually, if bone repairing function is slower than microdamage accumulation, a type of bone fracture, usually known as stress fracture, can finally evolve. In this paper, we propose a bone remodelling continuous model able to simulate microdamage growth and repair in a coupled way and able therefore to predict the occurrence of stress fractures. The biological bone remodelling process is modelled in terms of equations that describe the activity of basic multicellular units. The predicted results show a good correspondence with experimental and clinical data. For example, in disuse, bone porosity increases until an equilibrium situation is achieved. In overloading, bone porosity decreases unless the damage rate is so high that causes resorption or stress fracture.Research partially supported by Diputación General de Aragón project P–008/2001) and National Network IM3 (Molecular and Multimodal Medical Imaging, Spanish Ministry of Health, Associated Partner, 300++, 2003-2005)     

Icariin reduces bone loss in a Rankl-induced transgenic medaka (Oryzias latipes) model for osteoporosis

Given the limitations and side effects of many synthetic drugs, natural products are an important alternative source for drugs and medications for many diseases. Icariin (ICA), one of the main flavonoids from plants of the Epimedium genus, has been shown to ameliorate osteoporosis and improve bone health in preclinical studies. Those studies have used different in vivo models, mostly rodents, but the underlying mechanisms remain unclear. The present study shows, for the first time, that ICA reduces bone damage in a Rankl-induced medaka fish (Oryzias latipes), a non-rodent osteoporosis model. Live imaging was previously performed in this model to characterize antiresorptive and bone-anabolic properties of drugs. Here, a new quantification method (I_M) was established based on the length of mineralized neural arches to quantify levels of bone mineralization damage and protection in early post-embryonic fish. This method was validated by quantification of three levels of bone damage in three independent Rankl fish lines, and by the determination of different degrees of severity of osteoporosis-like phenotypes in one Rankl line exposed to variable Rankl induction schemes. I_M was also used to quantify the efficacy of alendronate and etidronate, two common anti-osteoporotic bisphosphonates, and revealed comparable bone protective effects for ICA and alendronate in this fish osteoporosis model. This study's data support the value of the medaka fish model for bone research and establish a method to screen for novel osteoprotective compounds.     

A multiscale model of cardiac concentric hypertrophy incorporating both mechanical and hormonal drivers of growth

Biomechanics and Modeling in Mechanobiology - Growth and remodeling in the heart is driven by a combination of mechanical and hormonal signals that produce different patterns of growth in response...