Effects of PTH treatment on tibial bone of ovariectomized rats assessed by in vivo micro-CT.

UNLABELLED: Using in vivo microcomputed tomography (micro-CT), we found in parathyroid hormone (PTH)-treated osteopenic rats linear increases in cortical and trabecular, due to increased trabecular thickness and number, bone mass. Bone was formed in cavities, leading to restoral of nearly cleaved trabeculae. For the first time, effects in PTH-treated rats were analyzed longitudinally. INTRODUCTION: Our aims were to over time (1) determine changes in trabecular thickness and number after PTH, (2) compare responses to PTH between the meta- and epiphysis, (3) determine effects of PTH on mineralization and mechanical properties, (4) determine locations of new bone formation due to PTH on a microlevel, and (5) determine the predictive value of bone structural properties for gain in bone mass after PTH. METHODS: Adult rats were divided into ovariectomy (OVX; n = 8), SHAM-OVX (n = 8), and OVX and PTH treatment (n = 9). Between weeks 8 and 14, PTH rats received daily subcutaneous PTH injections (60 microg/kg/day). At weeks 0, 8, 10, 12, and 14, in vivo micro-CT scans were made of the proximal and diaphyseal tibia. After sacrifice, all tibiae were tested in three-point bending. RESULTS: PTH increased bone volume fraction linearly over time in meta- and epiphysis, accompanied by increased trabecular thickness in both and increased trabecular number only in the latter one. CT-estimated mineralization increased in trabecular and remained constant in cortical bone. Ultimate load and energy were increased and ultimate displacement and stiffness unaltered compared to SHAM rats. For those trabeculae analyzed, bone was formed initially on places where it was most beneficial for increasing their strength and later on to all surfaces.

Micro-finite element simulation of trabecular-bone post-yield behaviour--effects of material model, element size and type.

Micro-finite element (micro-FE) analysis became a standard tool for the evaluation of trabecular bone mechanical properties. The accuracy of micro-FE models for linear analyses is well established. However, the accuracy of recently developed nonlinear micro-FE models for simulations of trabecular bone failure is not known. In this study, a trabecular bone specimen was compressed beyond the apparent yield point. The experiment was simulated using different micro-FE meshes with different element sizes and types, and material models based on cortical bone. The results from the simulations were compared with experimental results to study the effects of the different element and material models. It was found that a decrease in element size from 80 to 40 mum had little effect on predicted post-yield behaviour. Element type and material model had significant effects. Nevertheless, none of the established material models for cortical bone were able to predict the typical descent in the load-displacement curve seen during compression of trabecular bone.

Indirect determination of trabecular bone effective tissue failure properties using micro-finite element simulations.

Trabecular bone strength is marked not only by the onset of local yielding, but also by post-yield behavior. To study and predict trabecular bone elastic and yield properties, micro-finite element (micro-FE) models were successfully applied. However, trabecular bone strength predictions require micro-FE models incorporating post-yield behavior of trabecular bone tissue. Due to experimental difficulties, such data is currently not available. Here we used micro-FE modeling to determine failure behavior of trabecular bone tissue indirectly, by iteratively fitting FE simulation to experimental results. Failure parameters were fitted to an isotropic plasticity model based on Hill's yield function, using materially and geometrically nonlinear micro-FE models of seven bovine trabecular bone specimens. The predictive value of the averaged effective tissue properties was subsequently tested. The results showed that compression softening had to be included on the tissue level in order to accurately describe the apparent-level behavior of the bone specimens. A sensitivity study revealed that the simulated response was less sensitive to variations in the post-yield properties of the bone tissue than variations in the elastic and yield properties. Due to fitting of the tissue properties, apparent-level behavior could be accurately reproduced for each specimen separately. Predictions based on the averaged and fixed tissue properties were less accurate, due to inter-specimen variations in the tissue properties.

Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized wistar rats assessed by in vivo micro-computed tomography.

Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats. The aim of this study was to determine the influence of early and late zoledronic acid treatment on bone in ovariectomized rats, using in vivo micro-CT. Twenty-nine female Wistar rats were divided into the following groups: ovariectomy (OVX, n = 5), OVX and zoledronic acid (ZOL) at week 0 (n = 8), OVX and ZOL at week 8 (n = 7), and sham (n = 9). CT scans were made of the proximal tibia at weeks 0, 2, 4, 8, 12, and 16; and bone structural parameters were determined in the metaphysis. Two fluorescent labels were administered to calculate dynamic histomorphometric parameters. At week 16, all groups were significantly different from each other in bone volume fraction (BV/TV), connectivity density, and trabecular number (Tb.N), except for the early ZOL and control groups which were not significantly different for any structural parameter. After ZOL treatment at week 8, BV/TV, structure model index, Tb.N, and trabecular thickness significantly improved in the late ZOL group. The OVX and ZOL groups showed, respectively, higher and lower bone formation rates than the control group. Early ZOL treatment inhibited all bone microstructural changes seen after OVX. Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels. Early ZOL treatment resulted in a significantly better microstructure than late treatment. However, late treatment was still significantly better than no treatment.

Load distribution in the healthy and osteoporotic human proximal femur during a fall to the side.

Due to remodeling of bone architecture, an optimal structure is created that minimizes bone mass and maximizes strength. In the case of osteoporotic vertebral bodies, however, this process can create over-adaptation, making them vulnerable for non-habitual loads. In a recent study, micro-finite element models of a healthy and an osteoporotic human proximal femur were analyzed for the stance phase of gait. In the present study, tissue stresses and strains were calculated with the same proximal femur micro-finite element models for a simulated fall to the side onto the greater trochanter. Our specific objectives were to determine the contribution of trabecular bone to the strength of the proximal femurs for this non-habitual load. Further, we tested the hypothesis that the trabecular structure of osteoporotic bone is over-adapted to habitual loads. For that purpose, we calculated the load distributions and estimated the apparent yield and ultimate loads from linear analyses. Two different methods were used for this purpose, which resulted in very similar values, all in a realistic range. Distributions of maximal principal strain and effective strain in the entire model suggest that the contributions to bone strength of the trabecular and cortical structures are similar. However, a thick cortical shell is preferred over a dense trabecular core in the femoral neck. When the load applied to the osteoporotic femur was reduced to approximately 61% of the original value, strain distributions were created similar in value to those obtained for the healthy femur. Since a comparable reduction factor was found for habitual load cases, it was concluded that the osteoporotic femur was not 'over-adapted'.

The PTHrP-Ihh feedback loop in the embryonic growth plate allows PTHrP to control hypertrophy and Ihh to regulate proliferation.

Growth plate and long bone development is governed by biochemical signaling pathways of which the PTHrP-Ihh system is the best known. Other factors, such as BMPs, FGFs and mechanical loading, may interact with this system. This study aims at elucidating the relative importance of PTHrP and Ihh for controlling proliferation, and hypertrophy in fetal growth plate cartilage. We assessed the question why reduced Ihh expression leads to more pronounced effects on the number of non-hypertrophic cells and total bone formation, compared to PTHrP down-regulation. Using few basic equations, constituted from literature data, this paper shows how the PTHrP-Ihh feedback system can control different aspects of tissue differentiation at distinct locations. In particular, it is shown that (mechanical or biochemical) perturbations will affect proliferation via Ihh-related parameters, whereas changes in PTHrP-related parameters selectively interact with hypertrophy. This is contra-intuitive, since PTHrP acts to keep cells proliferating. In this context, the critical PTHrP level for keeping cells proliferating has been reconsidered. In addition, an explanation is provided for the aforementioned difference in effect between reduced Ihh and PTHrP expression.

Additional weight bearing during exercise and estrogen in the rat: the effect on bone mass, turnover, and structure.

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

Cortical bone development under the growth plate is regulated by mechanical load transfer.

Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections. We hypothesize that the development of cortical bone is governed by mechanical stimuli. We also hypothesize that trabecular and cortical bone share the same regulatory mechanisms for adaptation to mechanical loads. To test these hypotheses, we monitored the development of the tibial cortex in growing pigs, using micro-computer tomography and histology. We then tested the concept that regulatory mechanisms for trabecular bone adaptation can also explain cortical bone development using our mechanical stimulation theory, which could explain trabecular bone (re)modelling. The main results showed that, from the growth plate towards the diaphysis, the pores of the trabecular structure were gradually filled in with bone, which resulted in increased density and cortical bone. The computer model largely predicted this morphological development. We conclude that merging of metaphyseal trabeculae into cortex is likely to be governed by mechanical stimuli. Furthermore, cortex development of growing long bones can be explained as a form of trabecular bone adaptation, without the need for different regulatory mechanisms for cortical and trabecular bone.

Trabecular architecture can remain intact for both disuse and overload enhanced resorption characteristics.

The paradigm that bone metabolic processes are controlled by osteocyte signals have been the subject of investigation in many recent studies. One hypothesis is that osteoblast formation is enhanced by these signals, and that osteoclast resorption is enhanced by the lack of them. Reduced, or absent, osteocyte signaling can be an effect of reduced mechanical loading (disuse) or of defects in the canalicular network, due to microcracks. This would mean that bone is resorbed precisely there where it is mostly needed. In our study, we addressed this apparent contradiction. The purpose was to investigate how alternative strain-based local stimuli for osteoclasts to resorb bone would affect remodeling and adaptation of the trabecular architecture. For this purpose, a computer-simulation model was used, which couples morphological and mechanical effects of local bone metabolism to changes in trabecular architecture and density at large. Six resorption characteristics were studied in the model: (I) resorption occurs spatially random, (II) resorption is enhanced or (III) strongly enhanced where there is disuse, (IV) resorption is enhanced or (V) strongly enhanced where there are high strains, i.e. overload, and (VI) resorption is enhanced where there is disuse and where there are high strains. Results showed that the rates of structural adaptation to alternative loading were higher for disuse-controlled resorption than for overload-controlled resorption. Architecture and mass remained stable for all cases except (V) in which the structure deteriorated as in osteoporotic bone. We conclude that, given the potential of osteoblasts to form bone in highly strained areas, based on signals from osteocytes, osteoclast resorption can normally be compensated for.

Comparison of micro-level and continuum-level voxel models of the proximal femur.

Continuum-level finite element (FE) models became standard computational tools for the evaluation of bone mechanical behavior from in vivo computed tomography scans. Such scans do not account for the anisotropy of the bone. Instead, local mechanical properties in the continuum-level FE models are assumed isotropic and are derived from bone density, using statistical relationships. Micro-FE models, on the other hand, incorporate the anisotropic structure in detail. This study aimed to quantify the effects of assumed isotropy, by comparing continuum-level voxel models of a healthy and a severely osteoporotic proximal femur with recently analyzed micro-FE models of the same bones. The micro-model element size was coarsened to generate continuum FE models with two different element sizes (0.64 and 3.04 mm) and two different density-modulus relationships found in the literature for wet and ash density. All FE models were subjected to the same boundary conditions that simulated a fall to the side, and the stress and strain distributions, model stiffness and yield load were compared. The results indicated that the stress and strain distributions could be reproduced well with the continuum models. The smallest differences between the continuum-level model and micro-level model predictions of the stiffness and yield load were obtained with the coarsest element size. Better results were obtained for both continuum-element sizes when isotropic moduli were based on ash density rather than wet density.

Can the growth factors PTHrP, Ihh and VEGF, together regulate the development of a long bone?

Endochondral ossification is the process of differentiation of cartilaginous into osseous tissue. Parathyroid hormone related protein (PTHrP), Indian hedgehog (Ihh) and vascular endothelial growth factor (VEGF), which are synthesized in different zones of the growth plate, were found to have crucial roles in regulating endochondral ossification. The aim of this study was to evaluate whether the three growth factors PTHrP, Ihh and VEGF, together, could regulate longitudinal growth in a normal human, fetal femur. For this purpose, a one-dimensional finite element (FE) model, incorporating growth factor signaling, was developed of the human, distal, femoral growth plate. It included growth factor synthesis in the relevant zones, their transport and degradation and their effects. Simulations ran from initial hypertrophy in the center of the bone until secondary ossification starts at approximately 3.5 months postnatal. For clarity, we emphasize that no mechanical stresses were considered. The FE model showed a stable growth plate in which the bone growth rate was constant and the number of cells per zone oscillated around an equilibrium. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates resulted, respectively, in more and less cells per zone and in increased and decreased bone growth rates. The FE model correctly reflected the development of a growth plate and the rate of bone growth in the femur. Simulations incorporating increased and decreased PTHrP and Ihh synthesis rates reflected growth plate pathologies and growth plates in PTHrP-/- and Ihh-/- mice. The three growth factors, PTHrP, Ihh and VEGF, could potentially together regulate tissue differentiation.

The role of computational models in the search for the mechanical behavior and damage mechanisms of articular cartilage.

Articular cartilage plays a vital role in the function of diarthrodial joints. Due to osteoarthritis degeneration of articular cartilage occurs. The initial event that triggers the pathological process of cartilage degeneration is still unknown. Cartilage damage due to osteoarthritis is believed to be mechanically induced. Hence, to investigate the initiation of osteoarthritis the stresses and strains in the cartilage must be determined. So far the most common method to accomplish that is finite element analysis. This paper provides an overview of computational descriptions developed for this purpose, and what they can be used for. Articular cartilage composition and structure are discussed in relation with degenerative changes, and how these affect mechanical properties.

A fibril-reinforced poroviscoelastic swelling model for articular cartilage.

From a mechanical point of view, the most relevant components of articular cartilage are the tight and highly organized collagen network together with the charged proteoglycans. Due to the fixed charges of the proteoglycans, the cation concentration inside the tissue is higher than in the surrounding synovial fluid. This excess of ion particles leads to an osmotic pressure difference, which causes swelling of the tissue. The fibrillar collagen network resists straining and swelling pressures. This combination makes cartilage a unique, highly hydrated and pressurized tissue, enforced with a strained collagen network. Many theories to explain articular cartilage behavior under loading, expressed in computational models that either include the swelling behavior or the properties of the anisotropic collagen structure, can be found in the literature. The most common tests used to determine the mechanical quality of articular cartilage are those of confined compression, unconfined compression, indentation and swelling. All theories currently available in the literature can explain the cartilage response occurring in some of the above tests, but none of them can explain these for all of the tests. We hypothesized that a model including simultaneous mathematical descriptions of (1) the swelling properties due to the fixed-change densities of the proteoglycans and (2) the anisotropic viscoelastic collagen structure, can explain all these test simultaneously. To study this hypothesis we extended our fibril-reinforced poroviscoelastic finite element model with our biphasic swelling model. We have shown that the newly developed fibril-reinforced poroviscoelastic swelling (FPVES) model for articular cartilage can simultaneously account for the reaction force during swelling, confined compression, indentation and unconfined compression as well as the lateral deformation during unconfined compression. Using this theory it is possible to analyze the link between the collagen network and the swelling properties of articular cartilage.

The effects of trabecular-bone loading variables on the surface signaling potential for bone remodeling and adaptation.

It is widely believed that mechanical forces affect trabecular bone structure and orientation. The cellular mechanisms involved in this relationship, however, are poorly understood. In earlier work we developed a theoretical, computational framework, coupling bone-cell metabolic expressions to the local mechanical effects of external bone loading. This theory is based on the assumption that osteocytes within the bone tissue control the recruitment of bone-resorbing osteoclasts and bone-forming osteoblasts, by sending strain-energy-density (SED) related signals to trabecular surfaces through the osteocytic, canalicular network. The theory explains the known morphological effects of external bone-loading variations in magnitude and frequency. It also explains the development of osteoporosis, as an effect of increased osteoclast resorption due to estrogen deficiency in postmenopausal women, and to reduced physical activity levels in general. However, the theory uses lumped variables to represent the mechanisms of osteocyte mechano-sensing and signaling. The question is whether these mechanisms could not be specified in a more realistic way. On the one hand, anabolic osteocyte signals might be triggered by the local mechanical loading variables they experience directly, as we assumed in our original theory. On the other hand, osteocyte signals might be triggered by fluid flow in the osteocytic network at large, as was suggested by others. For that purpose we compared the effects of SED, maximal principal strain and volumetric strain as representing local loading variables, to their spatial gradients on the morphological predictions of our computational model. We found that, in concept, they all produced reasonable trabecular structures. However, the predicted trabecular morphologies based on SED as the triggering variable were more realistic in dimensions and relevant metabolic parameters.

A theoretical framework for strain-related trabecular bone maintenance and adaptation.

It is assumed that density and morphology of trabecular bone is partially controlled by mechanical forces. How these effects are expressed in the local metabolic functions of osteoclast resorption and osteoblast formation is not known. In order to investigate possible mechano-biological pathways for these mechanisms we have proposed a mathematical theory (Nature 405 (2000) 704). This theory is based on hypothetical osteocyte stimulation of osteoblast bone formation, as an effect of elevated strain in the bone matrix, and a role for microcracks and disuse in promoting osteoclast resorption. Applied in a 2-D Finite Element Analysis model, the theory explained the formation of trabecular patterns. In this article we present a 3-D FEA model based on the same theory and investigated its potential morphological predictability of metabolic reactions to mechanical loads. The computations simulated the development of trabecular morphological details during growth, relative to measurements in growing pigs, reasonably realistic. They confirmed that the proposed mechanisms also inherently lead to optimal stress transfer. Alternative loading directions produced new trabecular orientations. Reduction of load reduced trabecular thickness, connectivity and mass in the simulation, as is seen in disuse osteoporosis. Simulating the effects of estrogen deficiency through increased osteoclast resorption frequencies produced osteoporotic morphologies as well, as seen in post-menopausal osteoporosis. We conclude that the theory provides a suitable computational framework to investigate hypothetical relationships between bone loading and metabolic expressions.

A three-dimensional digital image correlation technique for strain measurements in microstructures.

A three-dimensional digital image correlation technique is presented for strain measurements in open-cell structures such as trabecular bone. The technique uses high-resolution computed tomography images for displacement measurements in the solid structure. In order to determine the local strain-state within single trabeculae, a tetrahedronization method is used to fill the solid structure with tetrahedrae. Displacements are calculated at the nodes of the tetrahedrae. The displacement data is subsequently converted to a deformation tensor in each of the tetrahedral element centers with a least-squares estimation method. Because the trabeculae are represented by a mesh, it is possible to deform this mesh according to the deformation tensor and, at the same time, visualize the calculated local strain in the deformed mesh with a finite element post-processing tool. In this way, the deformation of a single trabecula from an aluminum foam sample was determined and validated with rendered images of the three-dimensional sample. A precision analysis showed that a rigid translation or rotation does not affect the accuracy. Typical values for the standard deviation in the displacement and strain components are 2.0 microm and 0.01, respectively. Presently, the precision limits the technique to strain measurements beyond the yield strain.

Augmentation in anterior cruciate ligament reconstruction-a histological and biomechanical study on goats.

We studied reconstruction of the anterior cruciate ligament (ACL) in skeletally mature goats. In one group, the autogenous tissue was augmented with polydioxanone (PDS), the other group had no augmentation. Histological complete incorporation and remodeling of the transplant was found in both groups. The newly formed connective tissues gradually assumed the microscopic properties of the normal ligament. The augmented group showed a delay in remodeling and maturation of the fiber bundles. Mechanically, the PDS-augmented transplants were stronger than the nonaugmented transplants immediately after surgery. During the first 6 weeks, a rapid decrease in strength of the augmented transplants was found, whereas the strength of the nonaugmented group gradually increased. The results of our experiment do not favor augmentation of autografts in reconstruction of the ACL.

The mechanical consequences of mineralization in embryonic bone.

The purpose of this study was to examine the effect of mineralization on the mechanical properties of embryonic bone rudiments. For this purpose, four-point bending experiments were performed on unmineralized and mineralized embryonic mouse ribs at 16 and 17 days of gestational age. Young's modulus was calculated using force-displacement data from the experiment in combination with finite element analysis (FEA). For the unmineralized specimens, a calculated average for the Young's modulus of 1.11 (+/- 0.62) MPa was established after corrections for sticking to the four-point bending device and aspect ratio, which is the ratio between the length of the bone and its diameter. For the mineralized specimens, the value was 117 (+/- 62) MPa after corrections. Hence, Young's moduli of embryonic bone rudiments increase by two orders of magnitude within 1 day, during endochondral ossification. As an effect, the hypertrophic chondrocytes in the calcifying cartilage experience a significant change in their mechanical environment. The chondrocytes are effectively stress shielded, which means that they do not carry stresses since stresses are supported by the stiffest parts of the tissue, which are in this case the diaphyseal cortex and the calcified matrix. The deformability of the hypertrophic chondrocytes is, therefore, severely reduced. Since the transition is so sudden and enormous, it can be seen as a process of 'catastrophic' proportion for the hypertrophic chondrocytes. The subsequent resorption of calcified cartilage and the expansion of the marrow cavity could be consequential to stress shielding.

The osteoporotic vertebral structure is well adapted to the loads of daily life, but not to infrequent "error" loads.

Osteoporotic vertebral fractures typically have a gradual onset, frequently remain clinically undetected, and do not seem to be related to traumatic events. The osteoporotic vertebrae may therefore be expected to display a less "optimal" bone architecture, leading to an uneven load distribution over the bone material. We evaluated the trabecular load distribution in an osteoporotic and a healthy vertebra under normal daily loading by combining three recent innovations: high resolution computed tomography (microCT) of entire bones, microfinite element analyses (microFEA), and parallel supercomputers. Much to our surprise, the number of highly loaded trabeculae was not higher in the osteoporotic vertebra than in the healthy one under normal daily loads (8% and 9%, respectively). The osteoporotic trabeculae were more oriented in the longitudinal direction, compensating for effects of bone loss and ensuring adequate stiffness for normal daily loading. The increased orientation did, however, make the osteoporotic structure less resistant against collateral "error" loads. In this case, the number of overloaded trabeculae in the osteoporotic vertebra was higher than in the healthy one (13% and 4%, respectively). These results strengthen the paradigm of a strong relationship between bone morphology and external loads applied during normal daily life. They also indicate that vertebral fractures result from actions like forward flexion or lifting, loads that may not be "daily" but are normally not traumatic either. If future clinical imaging techniques would enable such high-resolution images to be obtained in vivo, the combination of microCT and microFEA would produce a powerful tool to diagnose osteoporosis.

Stresses in the local collagen network of articular cartilage: a poroviscoelastic fibril-reinforced finite element study.

Osteoarthritis (OA) is a multifactorial disease, resulting in diarthrodial joint wear and eventually destruction. Swelling of cartilage, which is proportional to the amount of collagen damage, is an initial event of cartilage degeneration, so damage to the collagen fibril network is likely to be one of the earliest signs of OA cartilage degeneration. We propose that the local stresses and strains in the collagen fibrils, which cause the damage, cannot be determined dependably without taking the local arcade-like collagen-fibril structure into account. We investigate this using a poroviscoelastic fibril-reinforced FEA model. The constitutive fibril properties were determined by fitting numerical data to experimental results of unconfined compression and indentation tests on samples of bovine patellar articular cartilage. It was demonstrated that with this model the stresses and strains in the collagen fibrils can be calculated. It was also exhibited that fibrils with different orientations at the same location can be loaded differently, depending on the local architecture of the collagen network. To the best of our knowledge, the present model is the first that can account for these features. We conclude that the local stresses and strains in the articular cartilage are highly influenced by the local morphology of the collagen-fibril network.