Stress changes in the femoral head due to porous ingrowth surface replacement arthroplasty

Finite element stress analyses were conducted of the canine femoral head before and after implantation of various surface replacement-type components. The femoral head was replaced by four implant geometries; (a) shell, (b) shell with peg, (c) shell with rod, and (d) a new epiphyseal replacement design. All implants were modelled to simulate bony ingrowth along the underside of the shell and along the surfaces of the peg and rod. The results indicated that in the normal femur the forces are transferred from the articular surface through the femoral head cancellous bone to the inferior cortical shell of the femoral neck. After shell-type surface replacement, forces were transferred more distally at the rim of the shell and at the end of the peg or rod, thereby reducing the stresses in the proximal head cancellous bone. Computer simulation of bone remodelling due to proximal bone stress reduction was shown to accentuate the abnormality of the stress fields. Surface replacement with a lower modulus material created a less abnormal redistribution of bone stresses. The new epiphyseal replacement design resulted in stress distributions similar to those in the normal femoral head and minimal shear stresses at the implant/bone interface. These findings suggest that the epiphyseal replacement concept may provide better initial mechanical integrity and create a more benign milieu for adaptive bone remodelling than conventional, shell-type surface replacement components.     

Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review

Background

Pelvic reconstruction after hemipelvectomy can greatly improve the weight-bearing stability of the supporting skeleton and improve patients’ quality of life. Although an autograft can be used to reconstruct pelvic defects, the most suitable choice of autograft, i.e., the use of either femur or tibia, has not been determined. We aimed to analyze the mechanical stresses of a pelvic ring reconstructed using femur or tibia after hemipelvectomy using finite element (FE) analysis.

Methods

FE models of normal and reconstructed pelvis were established based on computed tomography images, and the stress distributions were analyzed under physiological loading from 0 to 500 N in both intact and restored pelvic models using femur or tibia.

Results

The vertical displacement of the intact pelvis was less than that of reconstructed pelvis, but there was no significant difference between the two reconstructed models. In FE analysis, the stress distribution of the intact pelvic model was bilaterally symmetric and the maximum stresses were located at the sacroiliac joint, arcuate line, ischiatic ramus, and ischial tuberosity. The maximum stress in each part of the reconstructed pelvis greatly exceeded that of the intact model. The maximum von Mises stress of the femur was 13.9 MPa, and that of the tibia was 6.41 MPa. However, the stress distribution was different in the two types of reconstructed pelvises. The tibial reconstruction model induced concentrated stress on the tibia shaft making it more vulnerable to fracture. The maximum stress on the femur was concentrated on the connections between the femur and the screws.

Conclusions

From a biomechanical point of view, the reconstruction of hemipelvic defects with femur is a better choice.     

Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury.

The present study measured early-stage adaptation of bone mineral (BMD) in the periarticular cancellous bone of the canine knee (stifle) joint after anterior cruciate ligament (ACL) transection (ACLX). Regional changes in BMD in the tibia and femur were analyzed by using quantitative computed tomography (qCT) at 3 wk and 12 wk after unilateral ACLX to determine whether there were focal points for BMD changes and whether these changes occurred early after the induced knee injury. BMD decreased rapidly after ACLX, and the more pronounced response was in the femur. In the 3-wk group, there were decreases in BMD in the tibia and the femur, and these changes were significant in the posterior-medial region of the femur, which showed a decrease of BMD in the ACLX limb (-0.048 +/- 0.011 g/cm(3)). In the 12-wk group, all regions in the tibia and femur exhibited significant decreases in BMD, and the average decrease was greatest in the posterior-medial region of the femur (-0.142 +/- 0.021 g/cm(3)). The regions of pronounced periarticular cancellous BMD adaptation corresponded to observed focal cartilage defects. Early decreases in BMD in the injured knee may be related to altered loading and kinematics in the knee and may be an important link in the pathogenesis of posttraumatic osteoarthritis.     

Automated three-dimensional finite element modelling of bone: a new method

Three-dimensional finite element stress analysis of bone is a key to understanding bone remodelling, assessing fracture risk, and designing prostheses; however, the cost and complexity of predicting the stress field in bone with accuracy has precluded the routine use of this method. A new, automated method of generating patient-specific three-dimensional finite element models of bone is presented — it uses digital computed tomographic (CT) scan data to derive the geometry of the bone and to estimate its inhomogeneous material properties. Cubic elements of a user-specified size are automatically defined and then individually assigned the CT scan-derived material properties. The method is demonstrated by predicting the stress, strain, and strain energy in a human proximal femur in vivo. Three-dimensional loading conditions corresponding to the stance phase of gait were taken from the literature and applied to the model. Maximum principal compressive stresses of 8–23 MPa were computed for the medial femoral neck. Automated generation of additional finite element models with larger numbers of elements was used to verify convergence in strain energy.     

A three-dimensional finite element analysis of the upper tibia

A three-dimensional finite element model of the proximal tibia has been developed to provide a base line for further modeling of prosthetic resurfaced tibiae. The geometry for the model was developed by digitizing coronal and transverse sections made with the milling machine, from one fresh tibia of average size. The load is equally distributed between the medial and lateral compartments over contact areas that were reported in the literature. An indentation test has been used to measure the stiffness and the ultimate strength of cancellous bone in four cadaver tibiae. These values provided the statistical basis for characterising the inhomogeneous distribution of the cancellous bone properties in the proximal tibia. All materials in the model were assumed to be linearly elastic and isotropic. Mechanical properties for the cortical bone and cartilage have been taken from the literature. Results have been compared with strain gage tests and with a two-dimensional axisymmetric finite element model both from the literature. Qualitative comparison between trabecular alignment, and the direction of the principal compressive stresses in the cancellous bone, showed a good relationship. Maximum stresses in the cancellous bone and cortical bone, under a load which occurs near stance phase during normal gait, show safety factors of approximately eight and twelve, respectively. The load sharing between the cancellous bone and the cortical bone has been plotted for the first 40 mm distally from the tibial eminence.     

Residual stress distribution in rabbit limb bones

The presence of the residual stresses in bone tissue has been noted and the authors have reported that there are residual stresses in bone tissue. The aim of our study is to measure the residual stress distribution in the cortical bone of the extremities of vertebrates and to describe the relationships with the osteon population density. The study used the rabbit limb bones (femur, tibia/fibula, humerus, and radius/ulna) and measured the residual stresses in the bone axial direction at anterior and posterior positions on the cortical surface. The osteons at the sections at the measurement positions were observed by microscopy. As a result, the average stresses at the hindlimb bones and the forelimb bones were 210 and 149 MPa, respectively. In the femur, humerus, and radius/ulna, the residual stresses at the anterior position were larger than those at the posterior position, while in the tibia, the stress at the posterior position was larger than that at the anterior position. Further, in the femur and humerus, the osteon population densities in the anterior positions were larger than those in the posterior positions. In the tibia, the osteon population density in the posterior position was larger than that in the anterior position. Therefore, tensile residual stresses were observed at every measurement position in the rabbit limb bones and the value of residual stress correlated with the osteon population density (r=0.55, P<0.01).     

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats.

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.     

Cross-sectional geometry of Pecos Pueblo femora and tibiae—A biomechanical investigation: I. Method and general patterns of variation

Variation in long bone cross-sectional geometry can be given a more precise functional interpretation using engineering beam theory. However, difficulties in measurement technique have generally prevented studies of large samples of cross sections in this way. In the present study, an automated system utilizing an electronic digitizer and computer software was used to analyze cross-sectional geometric properties of 11 femoral and tibial locations in 119 individuals from the Pecos Pueblo, New Mexico site. The data generated allow identification of clear differences in geometric properties between different regions of the femur and tibia. These differences appear to be related to specific in-vivo mechanical loadings of the lower limb bones, serving to reduce stress and strain under these loadings. The data are also used to investigate possible differences in loading of the femur and tibia in the Pecos and modern samples, and between humans and a nonhuman primate sample.     

Effect of varus/valgus malalignment on bone strains in the proximal tibia after TKR: an explicit finite element study

Malalignment is the main cause of tibial component loosening. Implants that migrate rapidly in the first two post-operative years are likely to present aseptic loosening. It has been suggested that cancellous bone stresses can be correlated with tibial component migration. A recent study has shown that patient-specific finite element (FE) models have the power to predict the short-term behavior of tibial trays. The stresses generated within the implanted tibia are dependent on the kinematics of the joint; however, previous studies have ignored the kinematics and only applied static loads. Using explicit FE, it is possible to simultaneously predict the kinematics and stresses during a gait cycle. The aim of this study was to examine the cancellous bone strains during the stance phase of the gait cycle, for varying degrees of varus/valgus eccentric loading using explicit FE. A patient-specific model of a proximal tibia was created from CT scan images, including heterogeneous bone properties. The proximal tibia was implanted with a commercial total knee replacement (TKR) model. The stance phase of gait was simulated and the applied loads and boundary conditions were based on those used for the Stanmore knee simulator. Eccentric loading was simulated. As well as examining the tibial bone strains (minimum and maximum principal strain), the kinematics of the bone-implant construct are also reported. The maximum anterior-posterior displacements and internal-external rotations were produced by the model with 20 mm offset. The peak minimum and maximum principal strain values increased as the load was shifted laterally, reaching a maximum magnitude for -20 mm offset. This suggests that when in varus, the load transferred to the bone is shifted medially, and as the bone supporting this load is stiffer, the resulting peak bone strains are lower than when the load is shifted laterally (valgus). For this particular patient, the TKR design analyzed produced the highest cancellous bone strains when in valgus. This study has provided an insight in the variations produced in bone strain distribution when the axial load is applied eccentrically. To the authors' knowledge, this is the first time that the bone strain distribution of a proximal implanted tibia has been examined, also accounting for the kinematics of the tibio-femoral joint as part of the simulation. This approach gives greater insight into the overall performance of TKR.     

Design considerations for ceramic resurfaced femoral head: effect of interface characteristics on failure mechanisms

Ceramic hip resurfacing may offer improved wear resistance compared to metallic components. The study is aimed at investigating the effects of stiffer ceramic components on the stress/strain-related failure mechanisms in the resurfaced femur, using three-dimensional finite element models of intact and resurfaced femurs with varying stem–bone interface conditions. Tensile stresses in the cement varied between 1 and 5 MPa. Postoperatively, 20–85% strain shielding was observed inside the resurfaced head. The variability in stem–bone interface condition strongly influenced the stresses and strains generated within the resurfaced femoral head. For full stem–bone contact, high tensile (151–158 MPa) stresses were generated at the cup–stem junction, indicating risk of fracture. Moreover, there was risk of femoral neck fracture due to elevated bone strains (0.60–0.80% strain) in the proximal femoral neck region. Stresses in the ceramic component are reduced if a frictionless gap condition exists at the stem–bone interface. High stresses, coupled with increased strain shielding in the ceramic resurfaced femur, appear to be major concerns regarding its use as an alternative material.     

Concept and development of an orthotropic FE model of the proximal femur

PURPOSE: In contrast to many isotropic finite-element (FE) models of the femur in literature, it was the object of our study to develop an orthotropic FE "model femur" to realistically simulate three-dimensional bone remodelling. METHODS: The three-dimensional geometry of the proximal femur was reconstructed by CT scans of a pair of cadaveric femurs at equal distances of 2mm. These three-dimensional CT models were implemented into an FE simulation tool. Well-known "density-determined" bony material properties (Young's modulus; Poisson's ratio; ultimate strength in pressure, tension and torsion; shear modulus) were assigned to each FE of the same "CT-density-characterized" volumetric group.In order to fix the principal directions of stiffness in FE areas with the same "density characterization", the cadaveric femurs were cut in 2mm slices in frontal (left femur) and sagittal plane (right femur). Each femoral slice was scanned into a computer-based image processing system. On these images, the principal directions of stiffness of cancellous and cortical bone were determined manually using the orientation of the trabecular structures and the Haversian system. Finally, these geometric data were matched with the "CT-density characterized" three-dimensional femur model. In addition, the time and density-dependent adaptive behaviour of bone remodelling was taken into account by implementation of Carter's criterion. RESULTS: In the constructed "model femur", each FE is characterized by the principal directions of the stiffness and the "CT-density-determined" material properties of cortical and cancellous bone. Thus, on the basis of anatomic data a three-dimensional FE simulation reference model of the proximal femur was realized considering orthotropic conditions of bone behaviour. CONCLUSIONS: With the orthotropic "model femur", the fundamental basis has been formed to realize realistic simulations of the dynamical processes of bone remodelling under different loading conditions or operative procedures (osteotomies, total hip replacements, etc).     

Internal strain gradients quantified in bone under load using high-energy X-ray scattering

High-energy synchrotron X-ray scattering (>60 keV) allows noninvasive quantification of internal strains within bone. In this proof-of-principle study, wide angle X-ray scattering maps internal strain vs position in cortical bone (murine tibia, bovine femur) under compression, specifically using the response of the mineral phase of carbonated hydroxyapatite. The technique relies on the response of the carbonated hydroxyapatite unit cells and their Debye cones (from nanocrystals correctly oriented for diffraction) to applied stress. Unstressed, the Debye cones produce circular rings on the two-dimensional X-ray detector while applied stress deforms the rings to ellipses centered on the transmitted beam. Ring ellipticity is then converted to strain via standard methods. Strain is measured repeatedly, at each specimen location for each applied stress. Experimental strains from wide angle X-ray scattering and an attached strain gage show bending of the rat tibia and agree qualitatively with results of a simplified finite element model. At their greatest, the apatite-derived strains approach 2500 με on one side of the tibia and are near zero on the other. Strains maps around a hole in the femoral bone block demonstrate the effect of the stress concentrator as loading increased and agree qualitatively with the finite element model. Experimentally, residual strains of approximately 2000 με are present initially, and strain rises to approximately 4500 με at 95 MPa applied stress (about 1000 με above the strain in the surrounding material). The experimental data suggest uneven loading which is reproduced qualitatively with finite element modeling.     

Finite element analysis of retroacetabular osteolytic defects following total hip replacement

Periprosthetic osteolysis in the retroacetabular region with cancellous bone loss is a recognized phenomenon in the long-term follow-up of total hip replacement. The effects on load transfer in the presence of defects are less well known. A finite element model incorporating a retroacetabular defect behind a cementless component was validated against a 4th generation sawbone pelvis. Computational predictions of surface strain and von Mises stresses were closely correlated to experimental findings. The presence of a cancellous defect increased von Mises stress in the cortical bone of the medial wall of the pelvis. At a load of 600 N this was under the predicted failure stress for cortical bone. Increases in the cup size relative to the acetabulum caused increased stress in the cortical bone of the lateral wall of the pelvis, adjacent to the acetabulum. We are confident that our modeling approach can be applied to patient specific defects to predict pelvis stress with large loads and a range of activities.     

Structural and Mechanical Improvements to Bone Are Strain Dependent with Axial Compression of the Tibia in Female C57BL/6 Mice

Strain-induced adaption of bone has been well-studied in an axial loading model of the mouse tibia. However, most outcomes of these studies are restricted to changes in bone architecture and do not explore the mechanical implications of those changes. Herein, we studied both the mechanical and morphological adaptions of bone to three strain levels using a targeted tibial loading mouse model. We hypothesized that loading would increase bone architecture and improve cortical mechanical properties in a dose-dependent fashion. The right tibiae of female C57BL/6 mice (8 week old) were compressively loaded for 2 weeks to a maximum compressive force of 8.8N, 10.6N, or 12.4N (generating periosteal strains on the anteromedial region of the mid-diaphysis of 1700 με, 2050 με, or 2400 με as determined by a strain calibration), while the left limb served as an non-loaded control. Following loading, ex vivo analyses of bone architecture and cortical mechanical integrity were assessed by micro-computed tomography and 4-point bending. Results indicated that loading improved bone architecture in a dose-dependent manner and improved mechanical outcomes at 2050 με. Loading to 2050 με resulted in a strong and compelling formation response in both cortical and cancellous regions. In addition, both structural and tissue level strength and energy dissipation were positively impacted in the diaphysis. Loading to the highest strain level also resulted in rapid and robust formation of bone in both cortical and cancellous regions. However, these improvements came at the cost of a woven bone response in half of the animals. Loading to the lowest strain level had little effect on bone architecture and failed to impact structural- or tissue-level mechanical properties. Potential systemic effects were identified for trabecular bone volume fraction, and in the pre-yield region of the force-displacement and stress-strain curves. Future studies will focus on a moderate load level which was largely beneficial in terms of cortical/cancellous structure and cortical mechanical function.     

Finite-element modelling of femoral shaft fracture fixation techniques post total hip arthroplasty.

The presence of a femoral prosthesis superior to a shaft fracture severely complicates fixation and treatment. This study uses two-dimensional, multithickness, plane stress finite-element models of a femur with prosthesis to investigate the stresses developed with the application of three popular fixation techniques: revision to a long stem prosthesis, lateral plating with a cortical bone allograft strut and cerclage wires, and custom plate application with proximal Parham band fixation with distal cortical screws (Ogden plate). The plate and bone contact as well as the fracture site contact were modelled by using orthotropic elements with custom-fit moduli so that only the normal stress to the interface was significant. A thermal analogy was used to model the cerclage and Parham band preloads so that representative preloads in the proximal fixation of the two types of plate treatments could be modelled. A parametric study was performed with the long-prosthesis model to show variations in stem lengths of one, two and three femoral diameters distal to the fracture site. The Ogden plate model showed a transfer of tensile stress near the proximal-most band, with the highest tensile stress being at the fracture site with evidence of stress shielding of the proximal lateral cortex. The cortical bone strut model showed a transfer of tensile stress to the bone strut but showed less shielding of the proximal cortex. The cerclage wires at the base of the bone strut showed the highest changes in load with the distalmost wire increasing to almost four times its original preload.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fracture prediction for the proximal femur using finite element models: Part I--Linear analysis.

Over 90 percent of the more than 250,000 hip fractures that occur annually in the United States are the result of falls from standing height. Despite this, the stresses associated with femoral fracture from a fall have not been investigated previously. Our objectives were to use three-dimensional finite element models of the proximal femur (with geometries and material properties based directly on quantitative computed tomography) to compare predicted stress distributions for one-legged stance and for a fall to the lateral greater trochanter. We also wished to test the correspondence between model predictions and in vitro strain gage data and failure loads for cadaveric femora subjected to these loading conditions. An additional goal was to use the model predictions to compare the sensitivity of several imaging sites in the proximal femur which are used for the in vivo prediction of hip fracture risk. In this first of two parts, linear finite element models of two unpaired human cadaveric femora were generated. In Part II, the models were extended to include nonlinear material properties for the cortical and trabecular bone. While there was poor correspondence between strain gage data and model predictions, there was excellent agreement between the in vitro failure data and the linear model, especially using a von Mises effective strain failure criterion. Both the onset of structural yielding (within 22 and 4 percent) and the load at fracture (within 8 and 5 percent) were predicted accurately for the two femora tested. For the simulation of one-legged stance, the peak stresses occurred in the primary compressive trabeculae of the subcapital region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ontogenetic change of bone microstructures and its ethological implication in Champsosaurus (Diapsida,Choristodera)

Compact cortex in a Champsosaurus (Diapsida, Choristodera) femur is ontogenetically replaced with extensively developed cancellous bone. This histological shift, together with retention of calcified cartilage to late ontogenetic stage, was previously considered to show that adult champsosaurs were more adapted to aquatic environments than juveniles. However, the new histological examination reveals the nearly amedullar condition of a juvenile femur consisting of thick periosteal cortex and less cancellous bone tissue and the amedullar but more porous condition of adult femora. This likely demonstrates that the femoral inner structure of the juvenile is denser than those of the adults, and therefore, juveniles were more aquatic. It is suggested that morphological variations between two sympatric species of Champsosaurus reflect sexual dimorphism in a single species and limb bones with more robust morphology, showing better terrestrial adaptation for nesting on land, belong to females. The similarity of gross limb bone morphology between juveniles and inferred adult males indicates aquatic habitats for juveniles, coincident with the new interpretation of bone microstructures. No differences are, however, recognised in femoral microstructure between inferred sexes in adults. The possibly lowered density of femur in adults is considered as an adaptation to increase the mobility in water.     

Analysis of forces of ACL reconstructions at the tunnel entrance: is tunnel enlargement a biomechanical problem?

Bone tunnel enlargement is a common phenomenon following reconstruction of the anterior cruciate ligament (ACL). Biomechanical and biological factors have been reported as potential causes of this problem. However, there is no analysis of forces between the graft and bone, as the graft changes direction at the bone tunnel entrance. The purpose of this study was to study these 'redirecting forces'. Magnetic resonance images of 10 patients with an ACL reconstruction (age: 26+/-6.8 years) were used to determine the angle between graft and drill holes. Vector analysis was used to calculate the direction and magnitude of the perpendicular component of the force between the bone tunnel and the graft at the entrance of the bone tunnel. Force components were projected into the radiographically important sagittal and coronal planes. Tension of ACL reconstructions was recorded during passive knee motion in 10 cadaveric knee experiments (age: 28.9+/-10.6 years) and the tension multiplied with the force component for each plane. Results are reported for the coronal and sagittal planes, respectively: For -10 degrees of extension, the percentages of graft tension were determined to be 17+/-7 (max: 26; min: 7%) and 26+/-9 (max: 39; min: 16%) for the tibia. They were 59+/-6 (max: 66; min: 48%) and 99+/-1 (max: 1.00; min: 99%) for the femur. Force components were 14.68+/-6.54 and 25.73+/-12.96 N for the tibial tunnel. For the femoral tunnel, they were 52.48+/-19.03 and 90.77+/-32.06 N. Percentages of graft tension and force components were significantly higher for the femoral tunnel compared with the tibial tunnel. Moreover, in the sagittal direction, force components for the femoral tunnel were significantly higher compared with the coronal plane (Wilcoxon test, p < 0.01). The differences in force components calculated in this study corresponds with the amount of tunnel enlargement in the radiographic planes in the literature providing evidence that biomechanical forces play a key role in postoperative tunnel expansion.     

Effects of disrupted beta1-integrin function on the skeletal response to short-term hindlimb unloading in mice.

The study was designed to determine whether beta1-integrin plays a role in mediating the acute skeletal response to mechanical unloading. Transgenic (TG) mice were generated to express a dominant negative form of beta1-integrin under the control of the osteocalcin promoter, which targets expression of the transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice were subjected to hindlimb unloading by tail suspension for 1 wk. Pair-fed, normally loaded WT and TG mice served as age-matched controls. Bone samples from each mouse were processed for quantitative bone histomorphometry and biomechanical testing. The skeletal phenotype of TG mice was characterized by lower cancellous bone mass in the distal femoral metaphysis (-52%) and lumbar vertebral body (-20%), reduced curvature of the proximal tibia (-20%), and decreased bone strength (-20%) and stiffness (-23%) of the femoral diaphysis with relatively normal indexes of cancellous bone turnover. Hindlimb unloading for only 1 wk induced a 10% decline in tibial curvature and a 30% loss of cancellous bone in the distal femur due to a combination of increased bone resorption and decreased bone formation in both WT and TG mice. However, the strength and stiffness of the femoral diaphysis were unaffected by short-term hindlimb unloading in both genotypes. The observed increase in osteoclast surface was greater in unloaded TG mice (92%) than in unloaded WT mice (52%). Cancellous bone formation rate was decreased in unloaded WT (-29%) and TG (-15%) mice, but, in contrast to osteoclast surface, the genotype by loading interaction was not statistically significant. The results indicate that altered integrin function in mature osteoblasts may enhance the osteoclastic response to mechanical unloading but that it does not have a major effect on the development of cancellous osteopenia in mice during the early stages of hindlimb unloading.