Objectives. Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Methods. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results. The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T. >MIC. ), for an MIC of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and SCT. For MICs above 0.5 μg/ml, T. >MIC. in cancellous bone was only shorter than SCT. Considering an MIC of 4 μg/ml, no animals achieved the target of 40% T. >MIC. in plasma and cancellous bone, while less than 20% achieved it in SCT. Conclusion. The main finding of this study was short T. >MIC. in cancellous bone after intravenous administration of 1000 mg meropenem. Consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary. Cite this article: P. Hanberg, A. Lund, K. Søballe, M. Bue. Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis: An animal study. Bone Joint Res 2019;8:342–348. DOI: 10.1302/2046-3758.87.BJR-2018-0308.R1

Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft. 13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4). It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study

Objectives. Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Methods. Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Results. Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. Conclusion. These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures. Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620–628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2

Introduction. Bone fracture toughness is an important parameter in resistance of bone to monotonic and fatigue failure. Earlier studies on bone fracture toughness were focused on either cortical or cancellous bone, separately [1, 2]. Reported fracture toughness values indicated that cortical bone is tougher to break as compared to cancellous bone. In order to understand complete fracture of a whole bone, the interface between cortical and cancellous bone (named as corticellous bone) might play a crucial role and is interesting topic of research. The goal of this study was to identify fracture toughness in terms of J integral and fracture mechanism of the corticellous bone. Material and Methods. Corticellous bone samples (single edge notch bend specimen or SENB) were prepared from bovine proximal femur according to ASTM E399-90 standard (Fig.1). For corticellous bone, samples were prepared in such way that approximately half of the sample width consist of cortical bone and another half is cancellous bone. Precaution was taken while giving notch and pre-crack to corticellous bone that pre-crack should not enter from cortical to cancellous portion. All specimens were tested using a universal testing machine (Tinius Olsen, ± 100 N) under displacement rate of 100 µm/min until well beyond yield point. The fracture toughness parameter in terms of critical stress intensity (K. IC. ) was calculated according to ASTM E399-90 as given by, . (1). K. IC. =. PS. /. BW. 1.5. *. f. (. a. /. W. ). …. Where, P = applied load in kN, S = loading span in cm, B = specimen thickness in cm, W = specimen width in cm, a = total crack length, f(a/W) = geometric function. After the fracture test the J integral of each specimen was calculated using following equation. [ASTM E1820]. . (2). J. total. =. J. el. +. J. pl. =. K. IC. 2. /. E. ′. +. 2. A. pl. /. Bb. 0. …. Where, J. el. is J integral of the elastic deformation, J. pl. is J integral of the plastic deformation, E′=E for plane stress condition and E′= E/(1−ν. 2. ) for plane strain condition (E is elastic modulus; ν is Poisson's ratio), b. o. = W−a. o. , height of the un-cracked ligament, and A. pl. is the area of the plastic deformation part in the load–displacement curve. Result and Discussion. The fracture toughness in terms of critical stress intensity (K. IC. ) of corticellous bone was found to be 2.45 MPa.m. 1/2. The plastic part of J integral, J. pl. value of corticellous specimen was 9310 Jm. −2. , and shown to be 27 times of the J. el. value, 341 Jm. −. 2. Total J integral of corticellous bone was found to be 9651 Jm. −2. When crack travels through cortical portion and reaches at the interface, crack branching occurred and further it slows down (Fig.2). Indeed, more energy is required in plastic than elastic deformation. Conclusion. J integral of corticellous bone is found to higher which is due to plastic deformation and crack branches at the interface between cortical and cancellous bone. For any figures or tables, please contact the authors directly

Remodeling of the cancellous bone is more active than that of the cortical bone. It is known that the remodeling is governed by the intracancellous fluid pressure. Particularly, the lacunocanalicular pore (PLC) fluid pressure (FP) is essential for survival of the osteocyte and communication of remodeling signals between the PLC and intertrabecular pore (PIT). As a result, knowledge about the PLCFP generation of trabeculae is required to understand human cancellous bone biology. At this moment, the PLCFP measurement of human trabeculae is not reported. The purpose of this study was a direct measurement of PLCFP generation of human proximal femoral trabeculae in the direction of superior-to-fovea. Twenty one microscopic cylindrical trabecular specimens from trabeculae of five fresh human proximal femur (75 to 77 years) were fabricated using a micro-milling machine composed of the laser (Teemphotonics: 532nm), 3-dimensional PZT stage (PI Gmbh, resolution: 0.5nm), and microscope (lens: Navitar, and CCD: Hitachi) with the image processor. The fabrication resolution of the micro-milling machine was 0.4 um. Based on the trabecular trajectory of femoral head, the specimens were obtained in the direction of superior-to-fovea. The cylindrical specimen size had 120 um in diameter and 240 um in length. The test methods described in the previous study were utilized. The used undrained uniaxial strain condition could induce the maximum PLCFP within the trabecular elastic limit. The measured trabecular PLCFP (±SD) at the strain of 0.4% was 693.7±79.1 kPa. Since this experiment is equivalent to the instantaneous response of PLCFP with free flow boundaries after application of an extremely fast loading speed such an ideal step loading, a PLCFP generation in the physiological condition will be much less than the results obtained in this study. Base on the linear isotropic poroelasticity, the obtained Skempton's coefficient is almost 0. Thus, the load bearing capability by trabecular PLC fluid is negligible. The Biot coefficient is 0.35 which is higher than that of the cortical tissue (0.14). As a result, the intraosseous fluid communication through trabecular surfaces is active compared to that through Haversian canal surfaces. This imply that mass transports from the trabecular PLC into the PIT and from the PIT into the trabecular PLC could be significantly affected by the PITFP (the physiological blood systolic and diastolic pressure: 16 and 11 kPa, respectively) that acts as the FP boundary condition for the PLC flow. It is known that the PLC flow generates the electrical charges on the trabecular surface (‘+’ for being spouted into the PIT and ‘−’ for being flown into the PLC), which control differentiation and proliferation of the osteoblast and mesenchymal stem cell. Thus, significant changes in the PITFT could cause changes in the intra-trabecular PLC flow characteristics, mass transports between the PLC and PIT, and electrical charges on the trabeculae. Eventually, these could result in pathologies related to the trabecular remodeling

Aim. Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. The objective of this study was therefore to assess the concentration of cefuroxime in intervertebral disc (IVD), vertebral body cancellous bone, subcutaneous adipose tissue (SCT) and plasma pharmacokinetics after single dose administration by use of microdialysis (MD) in a large animal model. Method. Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 min. Measurements of cefuroxime were obtained from plasma, SCT, the vertebral cancellous bone and the IVD for 8 hours thereafter. MD was applied for sampling in solid tissues. The cefuroxime concentration in both the MD and plasma samples was determined using ultra-high performance liquid chromatography. Results. For both the IVD and the vertebral cancellous bone, the area under the concentration-curve from zero to the last measured value was significantly lower than that of free plasma. Tissue penetration of cefuroxime was incomplete for the IVD, whereas for vertebral cancellous bone and SCT it was not. Furthermore, the penetration of cefuroxime from plasma to IVD was delayed. Additionally, a noticeable prolonged elimination rate of cefuroxime in the IVD was found. The maximal concentration and the elimination of cefuroxime were reduced in IVD compared to both SCT and vertebral cancellous bone. Due to this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T>MIC) was significantly higher in IVD than in SCT, vertebral cancellous bone and free plasma for MICs up to 6 μg/ml. Conclusions. MD was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but due to a prolonged elimination, the best results regarding T>MIC was found in IVD

Total shoulder arthroplasty is a well-established and widely accepted method of treatment for a variety of shoulder disorders, loosening of the glenoid prosthesis is the main complication in total shoulder arthroplasty, it is highly dependent on the quality of the glenoid cancellous bone. Very little is known about mechanical properties of this cancellous bone. The objectives of this study were to determine the mechanical properties (elastic modulus and strength) of glenoid cancellous bone in the axial, coronal and sagittal planes including regional variation using a uniaxial compression test. To our knowledge, this kind of study was not done before. Eleven scapulas were obtained from six fresh-frozen, unembalmed human cadavers (mean age eighty-eight years). Eighty-two cubic cancellous bone specimens of 6×6×6mm3 were used for mechanical testing in the three planes. The test was a uniaxial compression along each direction, Elastic modulus and strength were determined from the stress-strain curve. Apparent density was also calculated. The study showed significant differences in the mechanical properties with anatomic location and directions of loading. Young modulus and strength were found to be significantly higher at the posterior part of the glenoid with the weakest properties at the antero-inferior part. Cancellous bone was found to be anisotropic with higher mechanical properties in the latero-medial direction (perpendicular to the articular surface of the glenoid). The apparent density was on average equal to 0.29 g/cm3 with the higher values at the posterior and superior part of the glenoid. Good correlation between apparent density and elastic modulus was found only in the sagittal plane but not in the coronal and axial plane, the overall correlation was low (r2 = 0.22, p< 0.0001) which emphasizes the role of trabecular bone architecture in predicting mechanical properties. The mechanical properties determined in this study provide input data for finite element method analyses and may help to assist in uncemented shoulder prosthesis design

Aim. Cefuroxime is a time-dependent antibiotic widely used as intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2–3 hours. Due to the fact that postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates, we aimed to evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4-hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval. Method. This is preliminary data for 8 out of 16 female pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2×1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography. Results. The time with concentrations above the minimal inhibitory concentration (T>MIC) for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml, was superior in all compartments when administering cefuroxime as two single doses with 4-hours intervals. For the target MIC of 4 μg/ml, the mean T>MIC in all compartments ranged between 53–73% and 85–95% for Group A and B, respectively. For both groups the area under the concentration-curve (AUC) was higher for plasma compared to the remaining compartments, and the lowest AUCs were found in the vertebral cancellous bone and the IVD. There were no differences in AUC between the two groups. Furthermore, the maximal concentrations were lower for both vertebral cancellous bone and IVD compared to both SCT and plasma. When comparing the two groups, higher maximal concentrations were found in all compartments for Group A. Tissue penetration was incomplete and delayed for all compartments and comparable between the two groups. Conclusions. Despite comparable pharmacokinetic results between the two groups, Group B exhibited superior T>MIC in all compartments for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml. As such administration of cefuroxime as two single doses with 4-hours intervals provided sufficient cefuroxime spine tissue concentrations for a minimum of 85% of an 8-hour dosing interval, which may be acceptable for most spine procedures

Osteoarthrosis (OA) stands alongside cancer and heart disease as one of the major causes of suffering and disability amongst the elderly. Changes related to OA occur in all elements of the joint, and there are indications that sub-chondral cancellous bone plays a primary role in the cartilage degeneration in OA. Most previous investigations have been focused on moderate and late OA, whereas little is known about the changes in cancellous bone microstructure in human early OA. This study quantified cancellous bone microstructure in early-stage OA using three-dimensional (3D) methods. Subchondral cancellous bone specimens, produced from 10 human post-mortem early-stage osteoarthrotic (OA) proximal tibiae and 10 normal age- and gender-matched proximal tibiae, were allocated to 4 groups: medial OA, lateral control, normal medial control, and normal lateral control. OA initiates mostly at the medial condyle, and histological analysis was done to confirm this change. The cylindrical specimens were micro-computed tomography (micro-CT) scanned. From accurate 3D data sets, structural parameters were determined by means of true, unbiased and assumption-free 3D methods. The data were assessed statistically, and a p< 0.05 was considered significant. Our data supported the hypothesis that significant microstructural changes – other than density changes – occur in early-stage OA cancellous bone. OA cancellous bone is markedly plate-like, less anisotropic, less interconnected, but lower in mechanical properties which suggests a disorganisation in the microstructure as OA initiation. Structure model type best explains the mechanical properties for the OA and the normal controls. However, the determination coefficients (R2) for the OA group are largely reduced. These results indicate significant property and quality deterioration in early-stage OA subchondral cancellous bone

Introduction: In postmenopausal female patients with hip osteoarthritis, osteoporosis as well as altered local trabecular bone architecture may lead to a increased migration of uncemented hip prostheses. 1. ,. 2. The aim of this study was to determine whether 3D bone architecture and mechanical properties of intertrochanteric cancellous bone in the proximal femur predict RSA migration of uncemented femoral stems. Materials and Methods: The study population consisted of 61 female patients with primary hip osteoarthritis. Informed consent was obtained prior to any study-related procedures. The Ethical Committee approved the study protocol. All patients underwent a total hip replacement (ABG II, Stryker) with uncemented proximally hydroxyapatite-coated femoral stem with tantalum RSA markers. Ceramicceramic bearing surfaces were used. A uniplanar type of RSA setup was applied. The RSA examinations were performed postoperatively and at 3, 6, and 12 months. During surgery, cancellous bone biopsy was taken from the proximal femur from the site of stem implantation. The specimens were scanned with micro-CT. 3D analysis of trabecular bone geometry and BMD was performed using CTAn software. After micro-CT imaging, the trochanteric cancellous bone specimens were subjected to a destructive compression test. Maximum force and stiffness were calculated. Linear regression analysis was applied to study correlations between different parameters investigated. Results: The patients exhibited major differences in the density and structural quality of intertrochanteric cancellous bone. Significant correlations were found between the measured biomechanical parameters and the structural parameters calculated from micro-CT data. Unexpectedly, the quality of intertrochanteric cancellous bone did not predict RSA migration of the femoral stems. The femoral stems reached high stability within 3 months and there were no significant differences in the axial and rotational migration of the femoral stems between the patients with normal or poor quality of the intertrochanteric cancellous bone. Discussion: The 3D bone architecture, mineral density and mechanical properties of the local intertrochanteric cancellous bone do not seem to serve as predictors of femoral stem migration. The observation suggests that the significance of cancellous bone quality for the initial stability of uncemented femoral stems has been over-emphasized

Three 3mm transverse slices were sectioned from the distal cancellous region of seven fresh-frozen cadaveric humerii. Each slice was marked with a 3x3mm grid, and subjected to compressive testing using a flat cylindrical indenter (1.6mm diameter). Indentation modulus and strength were calculated for each site, and pooled into nine anatomically-defined regions. The most distal slice had higher moduli values (p< 0.05), and the posterior capitellar region had lower moduli values (p< 0.05). There were no slice or regional differences in strength. This suggests that surgical procedures requiring cancellous fixation utilize the most distal aspect of the humerus while avoiding the posterior capitellum. To quantify the indentation strength and modulus of distal humeral cancellous bone, and identify any regional variations. Cancellous bone modulus in the distal humerus decreases from distal to proximal. The posterior capitellum has a lower modulus than the other regions of the distal humerus. The influence of slice depth emphasizes the importance of minimizing the amount of bone removed during prosthetic replacement. Regional variations in modulus suggest that the posterior capitellum should be avoided during fixation of implants or placement of screws. Three 3mm transverse cancellous bone slices obtained from the distal end of each of seven fresh-frozen cadaveric specimens were subjected to compressive testing using a materials testing machine with a 1.6mm flat cylindrical indenter. Testing was performed in a 3x3mm grid. The indentation modulus and local strength were calculated for each test site, and then averaged into nine regions defined by the capitellum, medial and lateral trochlea, and anterior, central and posterior sections for each slice. Mean modulus was found to be 309.8±242.0 MPa (range: 2.9–1041.7 MPa). Yield strength averaged 4.4±2.5 MPa (range: 0.6–16.3 MPa). The highest modulus was found in the distal-most slice (p< 0.05). The lowest modulus region was the posterior capitellum (p< 0.05). There were no differences in strength between slices or across the nine regions. A comparison with proximal tibial cancellous bone properties suggests the distal humerus may carry loads approaching 30% of those at the knee, assuming that bone adapts to stress magnitudes. Funding: Natural Sciences and Engineering Research Council; University of Western Ontario

The cancellous bone adjacent to major load-bearing joints such as the hip and knee has complex architecture. The loading patterns across these joints influence the architecture of the cancellous bone, which varies according to the magnitude and direction of these forces. Articular lesions are associated with alterations in the loading patterns and hence change to the cancellous architecture. The fractal dimension, as a numerical descriptor of complex shapes, enables these changes to be quantitated. The fractal analysis was performed by a box counting method. The perimeter of binary profiles of cancellous bone samples was measured for different box sizes. The fractal dimension is 1-D (where D is the slope of the straight-line segments from the plot of log of perimeter versus of log box size). Samples of cancellous bone were taken at autopsy from three subchondral regions, superior to the fovea in the femoral head (n=56) and the tibial (n=25) and femoral (n=25) condyles of the knee. There were three straight-line segments identified on the log-log plot, for each subject, indicating a fractal dimension over three different ranges of scale. Fractal 1 describes the complexity of bone surface detail influenced by osteoclast and osteoblast activity, fractal 2 describes the shape or form of individual trabeculae and fractal 3 describes the overall spatial complexity of the cancellous structure. The results show that for fractal 1, all three regions are the same. For fractal 2, the femoral head is greater than the condyles (1.40±0.07 versus 1.36±0.05 and 1.36±0.05) and for fractal 3, the femoral head is significantly greater than the condyles (1.76±0.06 versus 1.73±0.04 and 1.70±0.05). These data show that cancellous bone architecture differs between skeletal sites. In particular, the fine surface detail influenced by bone cell activity and described by fractal 1 is the same in each region, while the shape of individual trabeculae as described by fractal 2 is more complex in the femoral head. The overall spatial complexity of the cancellous structure as described by fractal 3 is the same in each condyle of the knee while in the femoral head it is significantly greater. The fractal dimension, as a descriptor of complexity, enables the effect of differences in the mechanical micro-environment on cancellous bone architecture to be quantified so that pathology affecting these regions can be studied

Summary. At the clinical CT image resolution level, there is no influence of the image voxel size on the derived finite element human cancellous bone models. Introduction. Computed tomography (CT)-based finite element (FE) models have been proved to provide a better prediction of vertebral strength than dual-energy x-ray absorptiometry [1]. FE models based on µCTs are able to provide the golden standard results [2], but due to the sample size restriction of the µCT and the XtremeCT machines, the clinical CT-based FE models is still the most promising tool for the in vivo prediction of vertebrae's strength. It has been found [3] that FE predicted Young's modulus of human cancellous bone increases as the image voxel size increases at the µCT resolution level [3]. However, it is still not clear whether the image voxel size in the clinical range has an impact on the predicted mechanical behavior of cancellous bone. This study is designed to answer this question. Methods. For this study, 6 thoracolumbar vertebrae (Th12) obtained from the female donors were scanned in the non-dissected cadavers under 2 different resolutions – group A: 120 kVp, 100 mAs, with a resolution of 0.29×0.29×1.3 mm. 3. ; group B: 120 kVp, 360 mAs, with a resolution of 0.18×0.18×0.6 mm. 3. A solid calibration phantom (QRM-BDC) was placed beneath the cadavers during the scans. Cuboids with the size of 12.3×12.3×14.3 mm. 3. were cropped from the center of each vertebral body. The FE model was created by converting each image voxel into hexahedron (C3D8). Inhomogeneous material property was defined for the cuboid [4], i.e. the image greyscale value were firstly calibrated into the bone mineral density (BMD), then the Young's modulus and yield stress were calculated from the BMD [5] for each element. Statistical analysis was performed to compare the FE predicted mechanical properties between the groups and the significance level was set to 95% (α=0.05). Results. The trabecular structure is more clearly mimicked in the models from group B than those from group A. The modulus (mean ± SE) in group A is 5.9% higher than that in group B (193.33 ± 31.67 MPa vs. 182.50 ± 27.07 MPa). The yield strength (mean ± SE) in group A is 6.4% higher than that in group B (0.99 ± 0.21MPa vs. 0.93 ± 0.17MPa). However, the paired t-test shows there is no significant difference of the mechanical properties in the two groups (p=0.109 for the modulus and p=0.234 for the yield strength). Discussion. This study shows that there is no influence of the voxel size on the clinical CT derived FE cancellous bone models. This finding can help choose a better, less invasive CT protocol for the patient when creating a clinical CT image based FE model. Acknowledgements. This study is financially supported by the Federal Ministry of Education and Research and the state of Hamburg, Germany

The influence of controlled mechanical loading on osseointegration was investigated using an in vivo device implanted in the distal lateral femur of five male rabbits. Compressive loads (1 MPa, 1 Hz, 50 cycles/day, 4 weeks) were applied to a porous coated titanium cylindrical implant (5mm diameter, 2mm width, 75% porosity, 350ìm average pore diameter) and the underlying cancellous bone.. The contralateral limb served as an unloaded control. MicroCT scans at 28 μm resolution were taken of a 4 × 4mm cylindrical region of interest that included cancellous bone below the implant. A scanning electron microscope with a backscattered electron (BSE) detector was used to quantify the percent bone ingrowth and periprosthetic bone in undecalcified sections through the same region of interest. A mixed effects model was used to account for the correlation of the outcome measures within rabbits.. The percent bone ingrowth was significantly greater in the loaded limb (19 +/− 4%) compared to the unloaded control limb (16 +/− 4%, p=0.016) as measured by BSE imaging. The underlying cancellous periprosthetic tissue bone volume fraction was not different between the loaded (0.26 +/− 0.06) and unloaded control limb (0.27 +/− 0.07, p=0.81) by microCT. BSE imaging also showed no difference in the percent area of periprosthetic bone (27 +/− 10% loaded vs. 23 +/− 10% unloaded, p=0.25). Cyclic mechanical loading significantly enhanced bone ingrowth into a titanium porous coated surface compared to the unloaded controls

Osteochondral allografts (frozen uncontrolled, or cryo-protected with dimethyl sulfoxide) were transplanted into medial femoral condyles of eighteen sheep. Cores from the ipsilateral graft site served as autografts for the contralateral limb. Analysis of graft and host cancellous bone microarchitecture by μCT at three months post transplant demonstrated no significant differences among the treatment groups. Dramatic bone resorption at the graft–host interface, however, occurred in up to 1/3 of condyles from all treatment groups, including fresh autografts suggesting that factors other than donor source or tissue storage played an important role in the bone incorporation of osteochondral grafts. The purpose of this study was to study the effect of different freezing protocols on periarticular cancellous bone architecture after osteochondral allograft transplantation. There were no significant differences in graft or host cancellous bone architecture among the groups (autografts, frozen allografts, cryopreserved allografts). Dramatic resorption of graft bone in condyles from all treatment groups suggested that factors other than donor source or tissue storage played important roles during incorporation of osteochondral grafts. Graft positioning, graft orientation, and recipient bed necrosis may play significant roles during incorporation of osteochondral graft bone. Osteochondral allografts (10 mm diameter) were transplanted into medial femoral condyles of eighteen skeletally mature Suffolk ewes. Allografts were frozen (–80°C) without cryoprotectant (FROZ) or treated with dimethyl sulfoxide (cryoprotectant) and frozen (–80°C at 1°C · min. −1. ) (CRYO). Osteochondral cores removed from ipsilateral graft sites served as fresh autografts (AUTO) for the contralateral medial femoral condyles. Condyles were harvested at three months and scanned (micro computed tomography –μCT). Three dimensional μCT data of graft and host cancellous bone regions were analyzed for bone volume fraction, trabecular thickness, bone surface–volume ratio, and trabecular anisotropy. No morphological differences were found among treatment groups. Excessive bone resorption of graft and interface precluded analysis of some samples from each group (ALLO — 2/9, CRYO — 3/9, AUTO — 6/18). Dramatic bone loss did not correlate with poor graft orientation, placement, infection, or recipient–bed necrosis, but a combination of these factors may contribute to excessive cancellous bone resorption in osteochondral grafts. Funding: Medical Research Council of Canada, Canadian Institutes of Health Research, No commercial funding. Please contact author for figures and/or diagrams

Introduction: Vertebroplasty is increasingly used in the treatment of painful osteoporotic vertebral fractures, and involves transpedicular injection of bone cement into the fractured vertebral body. Effective infiltration of the vertebral body cancellous bone by the cement is determined by the cement viscosity, and by the permeability of the bone. However, it is unclear how permeability is influenced by regional variations in porosity and architecture of bone within the vertebral body. The aim of the present study was to investigate how permeability is influenced by porosity and architecture of cancellous bone mimics. Methods: Cylindrical polyamide mimics of two types of cancellous bone structures were fabricated using selective laser sintering (SLS) techniques. Structure A had the rod-like vertical and horizontal trabeculae typical of the anterior vertebral body, while structure B had oblique trabeculae typical of the posterior-lateral vertebral body. Structure B had fewer trabeculae than A. Porosities of 80 and 90% were represented for both structures. Golden syrup, which has a viscosity similar to bone cement. 1. , was injected into the mimics at a constant speed using a ram driven by a materials testing machine. Pressure drop measurements across the mimic, made using a differential pressure transducer, were obtained at five different injection speeds. Permeability of each mimic was calculated from these measurements. 2. Two more repeat permeability measurements were performed on each mimic. Results: Repeat measurements were always within 12% of the mean value. For structure A the mean permeabilities were 1.26×10-7 and 1.82×10-7m2 for the 80 and the 90% porosity mimics respectively. The corresponding mean permeabilities for structure B were 1.92×10-7 and 2.86×10-7m2. Discussion: These preliminary results indicate that higher permeabilities occur in structures with higher porosities, and with structures containing fewer trabeculae that are arranged obliquely. Since permeability is a determinant of cement infiltration, taking into account patient-specific bone architecture parameters may improve the safety and clinical outcome of vertebroplasty. Future experiments will clarify in more detail the architectural parameters that have greatest effect on permeability

Structure model type and trabecular thickness are important characteristics in describing cancellous bone architecture. It has been qualitatively observed that a radical change of trabeculae from plate-like to rod-like occurs in aging, bone remodeling, and osteoporosis. Thickness of trabeculae has traditionally been measured using model-based histomorphometric methods on two-dimensional (2-D) sections. However, no quantitative study has been published based on three-dimensional (3-D) methods on the age-related changes in structure model type and trabecular thickness for human peripheral (tibial) cancellous bone. In this study, 160 human proximal tibial cancellous bone specimens from 40 normal donors, aged 16 to 85 years, were collected. These specimens were micro-CT scanned, then the micro-CT images were segmented using optimal thresholds. From accurate 3-D data sets, structure model type and trabecular thickness were quantified by means of novel 3-D methods. Structure model type was assessed by calculating the structure model index (SMI). The SMI was quantified based on a differential analysis of the triangulated bone surface of a structure. This technique allowed quantification of structure model type, such as plate, rod objects or mixture of plates or rods. Trabecular thickness was calculated directly from 3-D images, which is especially important for an a priori unknown or changing structure. Furthermore, 2-D trabecular thickness was also calculated based on the plate model. Our results showed that structure model type changed towards more rod-like in the elderly, and that trabecular thickness declined significantly with age. These changes become significant after 80 years of age for human tibial cancellous bone, whereas both properties seem to remain relatively unchanged between 20 and 80 years. Although a fairly close relationship was seen between 3-D trabecular thickness and 2-D trabecular thickness, real 3-D trabecular thickness was significantly underestimated using 2-D method

The purpose of the study was to assess the incorporation of defatted, and deproteinated bovine cancellous bone in a sheep bone graft model. Cylindrical defects were created in the femoral condyles of 12 sheep using custom-made trephines. The defect was filled with a cylinder of prepared bovine bone. The removed cylinder of bone was implanted into a defect created in the opposite femoral condlyle. Fluorochrome bone labels were administered over an 8-week period and the sheep sacrificed at 10 weeks. Undecalcified thin bone sections were viewed with a fluorescent microscope. ln one sheep there was a technical problem leading to unsatisfactory histology. All other sheep showed similar histology. The autograft incorporated rapidly with the graft showing a rim of reactive bone and the graft itself showing rapid laying down of new bone on its surface. The xenograft showed a similar reactive rim of new bone with deposition of new bone throughout the graft and resorption of the graft material. This study demonstrates that specially prepared bovine cancellous bone can act as a scaffold for the depostion of new bone in a sheep model. The role of this material in humans is to be evaluated

Introduction: The SonicPin technology uses ultrasonic energy to weld polymer into bone (BoneWelding), thus forming a bond between implant and bone. The aim of this study was to determine the mechanical capabilities of the SonicPin in comparison to conventional techniques using generic mechanical load conditions. Methods: Blocks of cancellous bone served as test specimens for generic tests. Two blocks respectively were fixed using either the SonicPin, a titanium cancellous bone screw (ASNIS) or a PLLA pin-screw system (Inion OTPS). The samples were then clamped into a test device and mechanically tested. Tests included pull-out, shear and 4-point-bending. To examine the mechanical performance of the Son-icPin in a realistic fracture model 12 fresh frozen tibiae were osteotomized through the medial apex of the pla-fond, simulating a horizontal fracture of the medial malleolus. The tibiae were treated with either the Son-icPin or with 4.0-millimeter partially threaded titanium screws. Mechanical testing was performed by applying a compressive load 17 degrees from the long axis of the tibia to simulate supination-adduction loading. Results: The bond between implant and bone exceeded the strength of the SonicPin itself. Using 2 SonicPins load levels were similar to those obtained with the cancellous screw or the PLLA fixation (p> 0,05). Discussion: Ultrasonic welding of polymer into bone seems to be a promising technology to be used in orthopaedic surgery. Applying the SonicPin in fractures of the medial malleolus may be considered after slight modifications such as larger diameter or longer pins

There is a great need for suitable large animal models that closely resemble osteoporosis in humans, and that they have adequate bone size for bone prosthesis and biomaterial research. This study aimed to investigate effects of a 7 month glucocorticoid (GC) treatment alone without ovariectomy on the properties of sheep cancellous bone. Eighteen female sheep were randomly allocated into 3 groups: group 1 (GC-1) received GC (0.60mg/kg/day methylprednisolone) 5 days weekly for 7 months; group 2 (GC-2) received the same treatment regime for 7 months, and further observed for 3 months without GC; and group 3 served as the control group, and left untreated for 7 months. The sheep received restricted diet. After 7 months of GC treatment. Cancellous bone volume fraction of the 5th lumbar vertebra in the GC-1 group was reduced by −35%, trabecular thickness by −28%, and changed from typical plate structure to a combination of plate and rod structure with increased connectivity by 202%. Bone strength was reduced by 52%. Bone formation marker, serum osteocalcin of GC-1, was reduced by 71% at 7 months, but recovered with an increase of 45% at 10 month in the GC-2 group. Similar trends were also seen in the femur and tibia. At 10 months, the GC-2 group had microarchitectural and mechanical properties similar to the level of the control sheep. We have demonstrated in this study that 7 month high-dose GC on bone density and microarchitecture are comparable with those observed in human after long-term GC treatment. Moreover, we have shown that the bone quality with regard to strength and microarchitecture recovers after 3 months further observation without GC. This suggests that a prolonged administration of GC is needed for long-term observation to keep osteopenic bone. The model will be useful in pre-clinical studies