Intact Femur Research Articles

Assessment of mitochondrial activity in 3D human liver microtissues as a tool for mechanistic investigations of adverse drug effects

Specific cellular and inflammatory factors that contribute to the severity of pulmonary dysfunction after blunt chest trauma and osteosynthesis of femoral fractures are yet not fully understood. Therefore, we investigated alterations of the cytokine productive capacity of alveolar macrophages (AM) and Kupffer cells (KC) after femoral fracture stabilized with intramedullary pin with or without blunt chest trauma.In male C57BL/6N mice an intramedullary pin was implanted in an intact femur as the sham procedure. In trauma groups mice either received an isolated femoral fracture with subsequent fracture stabilization with an intramedullary pin (group Fx) or a combined trauma of blunt chest trauma and femur fracture also stabilized by an intramedullary pin (group TTFx). Animals were sacrificed 0 h, 6 h, 12 h, 24 h and 3 d after trauma induction. Cytokine concentrations were measured in plasma and supernatant of cultivated AM and KC by FACS analysis. Pulmonary and hepatic infiltration of polymorphonuclear leukocytes (PMN) was determined by Ly6G-staining.At 6 h, isolated femoral fracture with intramedullary stabilization resulted in a significantly increased productive capacity of KC (IL-6, TNF-α, CCL2, CCL3, CCL5 and CCL7) compared to sham animals. Combined trauma additionally resulted in an increased productive capacity of AM (IL-6, TNF-α, CCL2, CCL3, CCL4, CCL5 and CCL7) at 6 h and the effect was prolonged up to 3 d compared to controls. Combined trauma also led to a significant higher amount of plasma CCL2 at 3 d and plasma CCL7 at 6 h after the insult compared to group Fx. Compared to shams, pulmonary and hepatic infiltrations of PMNs were increased in group Fx and TTFx after 6 h, but in the combined trauma model the effect was prolonged up to 3 d.An intramedullary stabilized femur fracture alone results in a significant activation of the immune response. The combination of femoral fracture and blunt chest trauma however, results in an increased and prolonged activation of the inflammatory response. Transferred to the clinical setting, these results emphasize the critical role of severe chest trauma for treatment strategies of femoral fractures in multiple trauma patients.

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats.

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.

The Analysis of Biomechanical Properties of Proximal Femur after Implant Removal.

Introduction. To compare the biomechanical stability of the femur following the removal of proximal femoral nail antirotation (PFNA-II) and dynamic hip screw (DHS). Material and Methods. 56 paired cadaveric femurs were used as experimental and control groups. In the experimental group, PFNA-II and DHS were randomly inserted into femurs on both sides and then removed. Thereafter, compression load was applied until fracture occurred; biomechanical stability of the femurs and associated fracture patterns were studied. Results. The ultimate load and stiffness of the control group were 6227.8 ± 1694.1 N and 990.5 ± 99.8 N/mm, respectively. These were significantly higher than experimental group (p = 0.014, <0.001) following the removal of PFNA-II (4085.6 ± 1628.03 N and 656.3 ± 155.3 N/mm) and DHS (4001.9 ± 1588.3 N and 656.3 ± 155.3 N/mm). No statistical differences in these values were found between the 2 device groups (p = 0.84, 0.71), regardless of age groups. However, fracture patterns were different between two devices, intertrochanteric and subtrochanteric fractures. Conclusions. Mechanical stability of the proximal femurs does not differ after the removal of 2 different of fixation devices regardless of the age. However, it was significantly lower compared to an intact femur. Different fracture patterns have been shown following the removal of different fixation devices as there are variations in the site of stress risers for individual implants.

Characterization of Femoral Component Initial Stability and Cortical Strain in a Reduced Stem-Length Design

BackgroundShort-stemmed femoral components facilitate reduced exposure surgical techniques while preserving native bone. A clinically successful stem should ideally reduce risk for stress shielding while maintaining adequate primary stability for biological fixation. We asked (1) how stem-length changes cortical strain distribution in the proximal femur in a fit-and-fill geometry and (2) if short-stemmed components exhibit primary stability on par with clinically successful designs. MethodsCortical strain was assessed via digital image correlation in composite femurs implanted with long, medium, and short metaphyseal fit-and-fill stem designs in a single-leg stance loading model. Strain was compared to a loaded, unimplanted femur. Bone-implant micromotion was then compared with reduced lateral shoulder short stem and short tapered-wedge designs in cyclic axial and torsional testing. ResultsFemurs implanted with short-stemmed components exhibited cortical strain response most closely matching that of the intact femur model, theoretically reducing the potential for proximal stress shielding. In micromotion testing, no difference in primary stability was observed as a function of reduced stem length within the same component design. ConclusionOur findings demonstrate that within this fit-and-fill stem design, reduction in stem length improved proximal cortical strain distribution and maintained axial and torsional stability on par with other stem designs in a composite femur model. Short-stemmed implants may accommodate less invasive surgical techniques while facilitating more physiological femoral loading without sacrificing primary implant stability.

Biomechanics of Fractures.

This video presents the digitized, original, reel-to-reel footage of Victor Frankel's groundbreaking 1960s experiments demonstrating the viscoelastic properties and fracture mechanics of loaded bone. As can be seen, novel instrumentation was used that resulted in an easily reproducible method of controlling bone loading rates. The innovation, and associated experiments, radically advanced our understanding of the mechanisms of acute fractures and bone's response to energy. Using the "Standard Torsion Testing Machine" that he helped design, the author explains how the mechanical and functional properties of bone are affected by various defects. Examples used include an intact dog femur, a femur with a hole in the cortex, and a femur with an open section defect. Slow motion depiction allows the viewer to appreciate the potential soft tissue damage associated with bone fragmentation and how this varies with energy input. The video concludes with a demonstration of the effect of torsional motion on the vasculature. Graphs produced by the torsion tester display torque versus angular deformation plots for each experiment. These illustrate the relationship between bone structure, fracture, and energy. The x-ray contrast segment provides an example of associated arterial damage secondary to a fracture. This previously unreleased piece of orthopaedic history provides viewers with perspective on the early days of biomechanical study and an easy-to-understand tutorial on acute fracture mechanics and the role of energy in injury.

Reproducibility of low-dose stereography measurements of femoral torsion after IM nailing of femoral shaft fractures and in intact femurs

IntroductionRotational malunion is a complication of intramedullary (IM) nailing for femur fractures. Symptoms can appear with 15° or more of axial deformity. None of the currently available measurement methods have a satisfactory reliability/irradiation ratio. The purpose of this study was to study the reproducibility of measuring femoral torsion with an EOS® low-dose stereography (LDX) system. HypothesisLDX is a reproducible method for measuring post-traumatic femoral torsion. Material and methodsThe intra- and inter-observer reproducibility was studied in 45 patients who had a femoral fracture treated by IM nailing. Both the injured and contralateral healthy femurs were modelled. Bland–Altman plots were used to analyze the measurements made by three different observers (two orthopedic surgeons and one radiologist). For a given comparison, the interval between the upper limit of agreement (ULA) and lower limit of agreement (LLA) had to be within [−5°; 5°] for the examination to qualify as reproducible. Measurements were made by three observers (A, B, C) on the injured and healthy femur. ResultsWith the fractured femurs (n=39), the intra-observer [LLA; ULA] interval was [−16.295; 12.977]; it was [−18.475; 16.744] for the A–B pairing, [−13.316; 13.532] for the B–C pairing and [−17.839; 19.355] for the A–C pairing. With the healthy femurs (n=37), the intra-observer [LLA; ULA] interval was [−7.909; 7.88]; it was [−11.924; 11.639] for the A–B pairing, [−12.654; 11.93] for the B–C pairing and [−11; 12.009] for the A–C pairing. DiscussionThe [LLA; ULA] intervals were greater than the [−5; +5] interval in all cases. LDX reproducibility is not sufficient for measuring femoral torsion after fracture or in healthy femurs. Observer experience, cohort size and the perfectible image quality are likely sources of bias. Conversely, the use of Bland–Altman plots and the multidisciplinary training of observers are major strengths of this study. Reproducibility will likely improve as the software is developed further and the image acquisition improves.

Feasibility Study And Establishing the Machining Process Parameter for Bio Medical Hip Implant of Titanium Material Using CNC Machine Through Conventional Route

Hip replacement refers to the process in which a damaged hip joint is surgically replaced with an artificial implant. It has been observed that all implants are not safe for use and some can cause serious complications to patient after surgery. A total hip replacement comprised of replacement of entire hip structure using an artificial prosthesis, during this surgical procedure, a stem is inserted into the patient’s femur for stability, and a ball replaces the head of the femur & the socket is also replaced with an artificial cup. The hip implantation was usually cemented in place, but it is also find that some surgeons use a cementless approach instead. The hybrid total hip replacement uses a combination of both, implanting the cup without cement and setting the stem in place with cement. So far as the availability of specific prosthesis for specific patients it is very difficult more over the prosthesis which will be available are not properly matching with the patients requirements due to change in morphology of human structure. Hence it is understand that there is a requirement of feasibility study for machining of the prosthesis based on the specific patient’s requirements. Considering the above need a network project has been undertaken by CSIR for the development of prosthesis through conventional route. The machining is being carried out by first taking the CT scan data of the patient using MIMICS software, and then this data is being analyzed with suitable load in ANSYS to find out the Stress and strain of this intact femur bone after that the CAD model of femoral stem had been prepared Solid with & without collar, then FEA of femur bone carried out by placement of prosthesis in actual bone by meshing in ANSYS. The result shows that the hollow prosthesis has a better effect than the solid prosthesis as the weight is further reduced and the effect can be further improved by using Ti Alloy as prosthesis material. The machining is being carried out using CNC Machining centre Mikron m/c by preparing the required programme as per the profile of the prosthesis and then the parting operation of the prosthesis is performed using CNC wire cut EDM machine, to get the final prosthesis.

Adolescent Hip Dislocation Combined With Proximal Femoral Physeal Fractures and Epiphysiolysis.

The risks and long-term effects of acute hip dislocation combined with proximal femoral physeal fractures and epiphysiolysis have been minimally addressed in the literature. This infrequent combination must be understood to avoid the major complications of complete separation of proximal femoral components during attempted reduction and to predict the probable outcome of surgical treatment. Medical records and imaging were retrospectively reviewed to identify patients with a diagnosis of severe to complete slipped capital femoral epiphysis (CFE) or proximal femoral epiphysiolysis in association with hip dislocation. The focus included possible anatomic/vascular disruption and their consequences. Twelve patients were identified. Nine dislocations were posterior; 3 were anterior. In 4 patients, the intact proximal femur was dislocated posteriorly. In 3 patients only the femoral neck was reduced, whereas the CFE remained dislocated. In 1 patient percutaneous pinning was done in the dislocated position before closed reduction. The reduction was successful. In 7 patients only the CFE (4 patients) or femoral neck (3 patients) was displaced at the initial presentation in the emergency room. One patient presented with posterior dislocation associated with complete separation of both components. Ten patients underwent open reduction and internal fixation. Two patients had closed reduction. Nine patients developed complete avascular necrosis, progressive collapse of the femoral head, and degenerative arthritis. Three subsequently had a total hip arthroplasty. One patient developed ischemic change limited to the femoral neck and a nonunion through the epiphysis. One patient had incomplete ischemic necrosis. Only 1 patient had no evidence of ischemic necrosis. This combination of injuries has several anatomic variations. Leaving the CFE dislocated while reducing only the femoral neck must be avoided. Reduction should be done in the operating room with muscle relaxation. The emergency room is not the venue for reduction. The risk of avascular necrosis is extremely high, whether the separation occurs during the acute dislocation or attempted reduction. Level IV-case series (retrospective review).

Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice

Intramedullary stabilization is frequently used to treat long bone fractures. Implants usually remain unless complications arise. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Here we report for the first time the implantation of intramedullary nails made of an Mg alloy containing 2% silver (Mg2Ag) into intact and fractured femora of mice. Prior in vitro analyses revealed an inhibitory effect of Mg2Ag degradation products on osteoclast differentiation and function with no impair of osteoblast function. In vivo, Mg2Ag implants degraded under non-fracture and fracture conditions within 210days and 133days, respectively. During fracture repair, osteoblast function and subsequent bone formation were enhanced, while osteoclast activity and bone resorption were decreased, leading to an augmented callus formation. We observed a widening of the femoral shaft under steady state and regenerating conditions, which was at least in part due to an uncoupled bone remodeling. However, Mg2Ag implants did not cause any systemic adverse effects. These data suggest that Mg2Ag implants might be promising for intramedullary fixation of long bone fractures, a novel concept that has to be further investigated in future studies. Statement of SignificanceBiodegradable implants are promising alternatives to standard steel or titanium implants to avoid implant removal after fracture healing. We therefore developed an intramedullary nail using a novel biodegradable magnesium-silver-alloy (Mg2Ag) and investigated the in vitro and in vivo effects of the implants on bone remodeling under steady state and fracture healing conditions in mice. Our results demonstrate that intramedullary Mg2Ag nails degrade in vivo over time without causing adverse effects. Importantly, radiographs, μCT and bone histomorphometry revealed a significant increase in callus size due to an augmented bone formation rate and a reduced bone resorption in fractures supported by Mg2Ag nails, thereby improving bone healing. Thus, intramedullary Mg2Ag nails are promising biomaterials for fracture healing to circumvent implant removal.

Biomechanical performance of retrograde nail for supracondylar fractures stabilization.

The study compared the biomechanical performance of retrograde nail used to stabilize supracondylar fracture (three different levels) by means of finite element analysis. Three different nail lengths (200, 260, and 300mm) of stainless steel and titanium nails were under consideration. Intact femur model was reconstructed from Digital Imaging and Communications in Medicine images of Thai cadaveric femur scanned by computed tomography spiral scanner, whereas geometry of retrograde nail was reconstructed with the data obtained from three-dimensional laser scanner. The retrograde nail was virtually attached to the femur before nodes and elements were generated for finite element model. The finite element models were analyzed in two stages, the early stage of fracture healing and the stage after fracture healing. The finding indicated that purchasing proximal locking screw in the bowing region of the femur may be at risk due to the high stresses at the implant and bone. There were no differences in stress level, elastic strain at a fracture gap, and bone stress between stainless steel and titanium implant. Since the intramedullary canal requires reaming to accommodate the retrograde nail, the length of retrograde nail should be as long as necessary. However, in case that the retrograde nail can be accommodated into the intramedullary canal without reaming, the longer retrograde nail can be used.

BMP-2 delivered via sucrose acetate isobutyrate (SAIB) improves bone repair in a rat open fracture model.

Human bone morphogenetic proteins (BMPs) are an alternative to bone graft for the treatment of high-energy open fractures. The standard delivery system for BMP-2 is a porous collagen sponge, but we have previously found that the biocompatible, high viscosity carrier, Sucrose acetate isobutyrate (SAIB) is an effective and potentially less invasive alternative. The efficacy of SAIB as a BMP-2 delivery system was examined in an open fracture model featuring a femoral osteotomy with periosteal stripping in 9-week-old male Sprague Dawley rats. SAIB containing BMP-2 (SAIB/BMP-2) was delivered into the fracture site during surgery and an additional group was further co-treated with zoledronic acid and hydroxyapatite nanoparticles (SAIB/BMP-2/HA/ZA). These were compared to untreated fractures and SAIB carrier alone (negative controls), and BMP-2 loaded collagen sponge (positive control). The rate of radiographic union and the biomechanical properties of the healed fractures were compared after 6-week. Untreated and SAIB-treated fractures showed poor repair, with 53% and 64%, respectively, not bridged at 6 week. In contrast, collagen/BMP-2, SAIB/BMP-2, and SAIB/BMP-2/HA/ZA showed significantly increased union (100%, 100%, and 94%, respectively, p < 0.05). Four-point bend testing revealed that collagen/BMP-2 and SAIB/BMP-2/HA/ZA restored the strength of fractured femora to that of intact femora by 6 week, whereas untreated and SAIB remained less than intact controls by 60% and 67%, respectively (p < 0.05). Overall, the SAIB/BMP-2/HA/ZA formulation was comparable to BMP-2 infused collagen sponge in terms of promoting open fractures repair, but with the additional potential for less invasive delivery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1168-1176, 2016.

The biomechanical effect of anteversion and modular neck offset on stress shielding for short-stem versus conventional long-stem hip implants

Short-stem hip implants are increasingly common since they preserve host bone stock and presumably reduce stress shielding by improving load distribution in the proximal femur. Stress shielding may lead to decreased bone density, implant loosening, and fracture. However, few biomechanical studies have examined short-stem hip implants. The purpose of this study was to compare short-stem vs. standard length stemmed implants for stress shielding effects due to anteversion–retroversion, anterior–posterior position, and modular neck offset.Twelve artificial femurs were implanted with either a short-stem modular-neck implant or a conventional length monolithic implant in 0° or 15° of anteversion. Three modular neck options were tested in the short-stem implants. Three control femurs remained intact. Femurs were mounted in adduction and subjected to axial loading. Strain gauge values were collected to validate a Finite Element (FE) model, which was used to simulate the full range of physiologically possible anteversion and anterior–posterior combinations (n = 25 combinations per implant). Calcar stress was compared between implants and across each implant's range of anteversion using one and two-way ANOVA. Stress shielding was defined as the overall change in stress compared to an intact femur.The FE model compared well with experimental strains (intact: slope = 0.898, R = 0.943; short-stem: slope = 0.731, R = 0.948; standard-stem: slope = 0.743, R = 0.859); correction factors were used to adjust slopes to unity. No implant anteversion showed significant reduction in stress shielding (α = 0.05, p > 0.05). Stress shielding was significantly higher in the standard-stem implant (63% change from intact femur, p < 0.001) than in short-stem implants (29–39% change, p < 0.001).Short-stem implants reduce stress shielding compared to standard length stemmed implants, while implant anteversion and anterior–posterior position had no effect. Therefore, short-stem implants have a greater likelihood of maintaining calcar bone strength in the long term.

A digital image analysis method for measuring femoral neck shaft angle and anteversion angle: A pilot study

Femur is widely studied in the fields of orthopedics, anthropology, forensic and human kinematics. This study aims to measure neck-shaft angle (NSA) and anteversion angle (FNA) in adult dry femora using digital image analysis software ‘Image J’. A total of 100 (50 right and 50 left) intact human adult femora were studied. The data was analyzed using SPSS software. The mean NSA and FNA in femora (n=100) was 124.95±6.09⁰ & 13.45±8.58⁰ respectively. The mean NSA in left and right femora was 125.12±5.22⁰ & 124.78±6.9⁰ respectively. The mean FNA in left and right femora was 12.9±8.22⁰ & 14±8.98⁰ respectively. There was no significant side difference in both NSA and FNA. The mean NSA was lower than most of the western studies but it was comparable with most other Indian studies and also Japanese studies. Though the mean FNA was within the range of previous Indian studies but is higher than most other observations. We attribute these numerical differences to different morphometric techniques and measuring points.

Experimental substantiation of combined fixation of tumor endoprothesis for the replacement of diaphyseal defects of rat long bones

Goal: to compare the durability of fixation of endoprothesis for replacement of postresection femur defects in experimental animals under bending and strain loading. Methods: investigation was performed on 20 non-linear white rats at the age of 6 months. Partial resection of femur middle 1/3 and defect replacement with modular endoprothesis was performed. Average diameter and lenght of intramedullary canal of rat femur were defined using radiographic and osteometrtic investigation of the rats of analogous age, gender and body-weight. The sizes of intramedullary stems for fixation of endoprothesis in bone canals were claculated using obtained data. Plate was fixed with screws to the body of endoprothesis and after implantation it adjoined tightly to distal femur fragment. Intramedullary stems and plate were covered with a layer of corundum ceramics. The animals were devided on 2 groups: experimental group — using of modular endoprtohesis with plate; control group — using of modular endoprtohesis without plate. 3 months after operation the durability of endoprothesis fixation to bone diaphysis were studied under bending and strain loading. Results: control group — just in 3 rats of 10 the stable fixation of endoprothesis was observed. According to index of bending moment the best results were revealed for intact femurs — (1,89 ± 0,81) N•m. Conclusion: use of endoprothesis with additional plate fixation allowed to obtain more durable fixation «implant-bone» and significantly decreased the quantity of postoperative complictions.

Full circle: 3D femoral mapping demonstrates age-related changes that influence femoral implant positioning

The geometry of the femur is important in the final position of an intramedullary implant; we hypothesised that the femoral geometry changes with age and this may predispose the elderly to anterior mal-positioning of these implants. We used CT DICOM data of 919 intact left femora and specialist software that allowed us to defined landmarks for measurement reference – such as the linea aspera – on a template bone that could be mapped automatically to the entire database. We found that older (>80 years) cortical bone is up to 1.5mm thinner anteriorly and 2mm thinner posteriorly than younger (<40 years) bone but the rate of change of posterior to anterior cortex thickness is greater in the older bone. We also found the isthmus in the elderly to be more distal and less substantial than in the younger bone. This study has demonstrated femoral geometry changes with age that may explain our perception that the elderly are at increased risk for anterior mal-positioning of intramedullary implants.

Ultrasound-assisted external fixation: a technique for austere environments

IntroductionUltrasound-assisted external fixation of long bones has the potential to enhance extremity damage control surgery in locations without fluoroscopy, such as forward surgical elements, the intensive care unit, and spacecraft....

Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during the bone repair process.

Osteoblasts, osteoclasts, chondrocytes, and macrophages that participate in the bone repair process are derived from hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). However, the roles of these stem cells during the repair of injured bone tissue are still unclear. In the present study, we examined the effects of bone defect on HSCs and MSCs in bone marrow and spleen in 75 mice and its mechanism. We analyzed the HSC and MSC populations in these tissues of a mouse with femoral bone damage by using flow cytometry. The number of HSCs in the bone marrow of mice with damaged femurs was significantly lower than the number of these cells in the bone marrow of the contralateral intact femurs on day 2 after injury. Meanwhile, the number of MSCs in the bone marrow of mice with damaged femurs was significantly higher than that of the contralateral femurs. Both intraperitoneal administration of AMD3100, a C-X-C chemokine receptor 4 (CXCR4) antagonist, and local treatment with an anti-stromal cell-derived factor-1 (SDF-1) antibody blunted the observed decrease in HSC and increase in MSC populations within the bone marrow of injured femurs. In conclusion, the present study revealed that there is a concurrent decrease and increase in the numbers of HSCs and MSCs, respectively, in the bone marrow during repair of mouse femoral bone damage. Furthermore, the SDF-1/CXCR4 system was implicated as contributing to the changes in these stem cell populations upon bone injury.

Neovascularization of osteoporotic metaphyseal bone defects: A morphometric micro-CT study

PurposeNeovascularization is essential for bone regeneration in fractures. This study aimed to investigate the microvascular morphology and distribution in the non-injured femur and the neovascularization of the metaphyseal critical size defect in a small animal model of osteoporosis. Materials and methodsFemale rats (n=7) were ovariectomized (OVX) and received a multideficiency diet. Three months after OVX, a 5mm wedge shaped critical size defect was cut at the distal femoral metaphysis and stabilized with a T-shaped mini-plate. After six weeks, the animals were euthanized, and femora were removed and decalcified for micro-CT measurement of fracture neovascularization. ResultsNo fracture healing was observed along the critical size defects. In the non-injured bone, micro-vessel distribution showed a specific pattern, thereby enabling a differentiation between epi-, meta- and diaphysis. Micro-CT based morphometry revealed a significant reduction of the vascular volume fraction as well as the vascular thickness (p<0.001) in the critical size defect compared to the intact contralateral femur. Blood volume related vascular surface (vascular surface/volume) increased significantly (p<0.001). Connectivity density and tissue volume related vascular surface (vascular surface density) did not change significantly. ConclusionsMicro-CT based vascular morphometry demonstrated differences between epi-, meta- and diaphysis in the non-injured bone as well as differences between the critical size defect and the non-injured metaphysis. As angiogenesis is a crucial prerequisite that precedes osteogenesis, our results may influence further evaluation of osteoconductive or osteogenic biomaterials in this small animal model of osteoporosis.

Selecting boundary conditions in physiological strain analysis of the femur: Balanced loads, inertia relief method and follower load

Selection of boundary constraints may influence amount and distribution of loads. The purpose of this study is to analyze the potential of inertia relief and follower load to maintain the effects of musculoskeletal loads even under large deflections in patient specific finite element models of intact or fractured bone compared to empiric boundary constraints which have been shown to lead to physiological displacements and surface strains. The goal is to elucidate the use of boundary conditions in strain analyses of bones.Finite element models of the intact femur and a model of clinically relevant fracture stabilization by locking plate fixation were analyzed with normal walking loading conditions for different boundary conditions, specifically re-balanced loading, inertia relief and follower load.Peak principal cortex surface strains for different boundary conditions are consistent (maximum deviation 13.7%) except for inertia relief without force balancing (maximum deviation 108.4%). Influence of follower load on displacements increases with higher deflection in fracture model (from 3% to 7% for force balanced model).For load balanced models, follower load had only minor influence, though the effect increases strongly with higher deflection. Conventional constraints of fixed nodes in space should be carefully reconsidered because their type and position are challenging to justify and for their potential to introduce relevant non-physiological reaction forces. Inertia relief provides an alternative method which yields physiological strain results.

Activity intensity, assistive devices and joint replacement influence predicted remodelling in the proximal femur

Bone morphology and density changes are commonly observed following joint replacement, may contribute to the risks of implant loosening and periprosthetic fracture and reduce the available bone stock for revision surgery. This study was presented in the 'Bone and Cartilage Mechanobiology across the scales' WCCM symposium to review the development of remodelling prediction methods and to demonstrate simulation of adaptive bone remodelling around hip replacement femoral components, incorporating intrinsic (prosthesis) and extrinsic (activity and loading) factors. An iterative bone remodelling process was applied to finite element models of a femur implanted with a cementless total hip replacement (THR) and a hip resurfacing implant. Previously developed for a cemented THR implant, this modified process enabled the influence of pre- to post-operative changes in patient activity and joint loading to be evaluated. A control algorithm used identical pre- and post-operative conditions, and the predicted extents and temporal trends of remodelling were measured by generating virtual X-rays and DXA scans. The modified process improved qualitative and quantitative remodelling predictions for both the cementless THR and resurfacing implants, but demonstrated the sensitivity to DXA scan region definition and appropriate implant-bone position and sizing. Predicted remodelling in the intact femur in response to changed activity and loading demonstrated that in this simplified model, although the influence of the extrinsic effects were important, the mechanics of implantation were dominant. This study supports the application of predictive bone remodelling as one element in the range of physical and computational studies, which should be conducted in the preclinical evaluation of new prostheses.