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As personalized medicine advances, there is an escalating need for sophisticated tools to understand complex biomechanical phenomena in clinical research. Recognizing a significant gap, this study pioneers the development of patient-specific in silico models for tooth autotransplantation (TAT), setting a new standard for predictive accuracy and reliability in evaluating TAT outcomes. Development of the models relied on 6 consecutive cases of young patients (mean age 11.66 years ± 0.79), all undergoing TAT procedures. The development process involved creating detailed in silico replicas of patient oral structures, focusing on transplanting upper premolars to central incisors. These models underpinned finite element analysis simulations, testing various masticatory and traumatic scenarios. The models highlighted critical biomechanical insights. The finite element models indicated homogeneous stress distribution in control teeth, contrasted by shape-dependent stress patterns in transplanted teeth. The surface deviation in the postoperative year for the transplanted elements showed a mean deviation of 0.33 mm (±0.28), significantly higher than their contralateral counterparts at 0.05 mm (±0.04). By developing advanced patient-specific in silico models, we are ushering in a transformative era in TAT research and practice. These models are not just analytical tools; they are predictive instruments capturing patient uniqueness, including anatomical, masticatory, and tissue variables, essential for understanding biomechanical responses in TAT. This foundational work paves the way for future studies, where applying these models to larger cohorts will further validate their predictive capabilities and influence on TAT success parameters. [ABSTRACT FROM AUTHOR]

A demanding task of the musculoskeletal system is the attachment of tendon to bone at entheses. This region often presents a thin layer of fibrocartilage (FC), mineralized close to the bone and unmineralized close to the tendon. Mineralized FC deserves increased attention, owing to its crucial anchoring task and involvement in enthesis pathologies. Here, we analyzed mineralized FC and subchondral bone at the Achilles tendon-bone insertion of rats. This location features enthesis FC anchoring tendon to bone and sustaining tensile loads, and periosteal FC facilitating bone-tendon sliding with accompanying compressive and shear forces. Using a correlative multimodal investigation, we evaluated potential specificities in mineral content, fiber organization and mechanical properties of enthesis and periosteal FC. Both tissues had a lower degree of mineralization than subchondral bone, yet used the available mineral very efficiently: for the same local mineral content, they had higher stiffness and hardness than bone. We found that enthesis FC was characterized by highly aligned mineralized collagen fibers even far away from the attachment region, whereas periosteal FC had a rich variety of fiber arrangements. Except for an initial steep spatial gradient between unmineralized and mineralized FC, local mechanical properties were surprisingly uniform inside enthesis FC while a modulation in stiffness, independent from mineral content, was observed in periosteal FC. We interpreted these different structure-property relationships as a demonstration of the high versatility of FC, providing high strength at the insertion (to resist tensile loading) and a gradual compliance at the periosteal surface (to resist contact stresses). Mineralized fibrocartilage (FC) at entheses facilitates the integration of tendon in bone, two strongly dissimilar tissues. We focus on the structure-function relationships of two types of mineralized FC, enthesis and periosteal, which have clearly distinct mechanical demands. By investigating them with multiple high-resolution methods in a correlative manner, we demonstrate differences in fiber architecture and mechanical properties between the two tissues, indicative of their mechanical roles. Our results are relevant both from a medical viewpoint, targeting a clinically relevant location, as well as from a material science perspective, identifying FC as high-performance versatile composite. [Display omitted] [ABSTRACT FROM AUTHOR]

Metastases increase the risk of fracture when affecting the femur. Consequently, clinicians need to know if the patient's femur can withstand the stress of daily activities. The current tools used in clinics are not sufficiently precise. A new method, the CT-scan-based finite element analysis, gives good predictive results. However, none of the existing models were tested for reproducibility. This is a critical issue to address in order to apply the technique on a large cohort around the world to help evaluate bone metastatic fracture risk in patients. The aim of this study is then to evaluate 1) the reproducibility 2) the transposition of the reproduced model to another dataset and 3) the global sensitivity of one of the most promising models of the literature (original model). The model was reproduced based on the paper describing it and discussion with authors to avoid reproduction errors. The reproducibility was evaluated by comparing the results given in the original model by the original first team (Leuven, Belgium) and the reproduced model made by another team (Lyon, France) on the same dataset of CT-scans of ex vivo femurs. The transposition of the model was evaluated by comparing the results of the reproduced model on two different datasets. The global sensitivity analysis was done by using the Morris method and evaluates the influence of the density calibration coefficient, the segmentation, the orientations and the length of the femur. The original and reproduced models are highly correlated (r2 = 0.95), even though the reproduced model gives systematically higher failure loads. When using the reproduced model on another dataset, predictions are less accurate (r2 with the experimental failure load decreases, errors increase). The global sensitivity analysis showed high influence of the density calibration coefficient (mean variation of failure load of 84 %) and non-negligible influence of the segmentation, orientation and length of the femur (mean variation of failure load between 7 and 10 %). This study showed that, although being validated, the reproduced model underperformed when using another dataset. The difference in performance depending on the dataset is commonly the cause of overfitting when creating the model. However, the dataset used in the original paper (Sas et al., 2020a) and the Leuven's dataset gave similar performance, which indicates a lesser probability for the overfitting cause. Also, the model is highly sensitive to density parameters and automation of measurement may minimize the uncertainty on failure load. An uncertainty propagation analysis would give the actual precision of such model and improve our understanding of its behavior and is part of future work. [Display omitted] • Reproducibility of the femur failure load model is validated. • Transposition of the femur model shows different performances on two datasets. • Sensitivity of the model with respect to density-based parameters is high. • Sensitivity with respect to segmentation, orientation and femur length is not negligible. [ABSTRACT FROM AUTHOR]

Adequate deltoid and rotator cuff elongation in reverse shoulder arthroplasty is crucial to maximize postoperative functional outcomes and to avoid complications. Measurements of deltoid and rotator cuff elongation during preoperative planning can support surgeons in selecting a suitable implant design and position. Therefore, this study presented and evaluated a fully automated method for measuring deltoid and rotator cuff elongation. Complete scapular and humeral models were extracted from computed tomography scans of 40 subjects. First, a statistical shape model of the complete humerus was created and evaluated to identify the muscle attachment points. Next, a muscle wrapping algorithm was developed to identify the muscle paths and to compute muscle lengths and elongations after reverse shoulder arthroplasty implantation. The accuracy of the muscle attachment points and the muscle elongation measurements was evaluated for the 40 subjects by use of both complete and artificially created partial humeral models. Additionally, the muscle elongation measurements were evaluated for a set of 50 arthritic shoulder joints. Finally, a sensitivity analysis was performed to evaluate the impact of implant positioning on deltoid and rotator cuff elongation. For the complete humeral models, all muscle attachment points were identified with a median error < 3.5 mm. For the partial humeral models, the errors on the deltoid attachment point largely increased. Furthermore, all muscle elongation measurements showed an error < 1 mm for 75% of the subjects for both the complete and partial humeral models. For the arthritic shoulder joints, the errors on the muscle elongation measurements were <2 mm for 75% of the subjects. Finally, the sensitivity analysis showed that muscle elongations were affected by implant positioning. This study presents an automated method for accurately measuring muscle elongations during preoperative planning of shoulder arthroplasty. The results show that the accuracy in measuring muscle elongations is higher than the accuracy in indicating the muscle attachment points. Hence, muscle elongation measurements are insensitive to the observed errors on the muscle attachment points. Related to this finding, muscle elongations can be accurately measured for both a complete humeral model and a partial humeral model. Because the presented method also showed accurate results for arthritic shoulder joints, it can be used during preoperative shoulder arthroplasty planning, in which typically only the proximal humerus is present in the scan and in which bone arthropathy can be present. As the muscle elongations are sensitive to implant positioning, surgeons can use the muscle elongation measurements to refine their surgical plan. [ABSTRACT FROM AUTHOR]

Abstract Nutrition of articular cartilage relies mainly on diffusion and convection of solutes through the interstitial fluid due to the lack of blood vessels. The diffusion is controlled by two factors: steric hindrance and electrostatic interactions between the solutes and the matrix components. Aging comes with changes in the cartilage structure and composition, which can influence the diffusion. In this study, we treated fibrocartilage of mandibular condyle with ribose to induce an aging-like effect by accumulating collagen crosslinks. The effect of steric hindrance or electrostatic forces on the diffusion was analyzed using either charged (Hexabrix) or uncharged (Visipaque) contrast agents. Osteochondral plugs from young equine mandibular condyles were treated with 500 mM ribose for 7 days. The effect of crosslinking on mechanical properties was then evaluated via dynamic indentation. Thereafter, the samples were exposed to contrast agents and imaged using contrast-enhanced computed tomography (CECT) at 18 different time points up to 48 h to measure their diffusion. Normalized concentration of contrast agents in the cartilage and contrast agent diffusion flux, as well as the content of crosslink level (pentosidine), water, collagen, and glycosaminoglycan (GAG) were determined. Ribose treatment significantly increased the pentosidine level (from 0.01 to 7.6 mmol/mol collagen), which resulted in an increase in tissue stiffness (~1.5 fold). Interestingly, the normalized concentration and diffusion flux did not change after the induction of an increased level of pentosidine either for Hexabrix or Visipaque. The results of this study strongly suggest that sugar-induced collagen crosslinking in TMJ condylar cartilage does not affect the diffusion properties. Graphical abstract fx1 Highlights • Ribose incubation induced remarkable increase in pentosidine level of fibrocartilage. • Ribose-induced crosslinks increased the stiffness of fibrocartilage. • Diffusion of charged and uncharged solutions did not change after ribose incubation. [ABSTRACT FROM AUTHOR]

Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted β-tricalcium phosphate (β-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted β-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of β-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic remnants, bone, soft tissue), and additionally for (ii) the localization of the defect site in the post-implantation microCT dataset. Using the similarity matrix, a 94 ± 1% agreement was found between algorithmic results and the visual assessment of 556,800 pixels. Moreover, the comparison of the segmentation results of the same microCT and histology section further confirmed the validity of the present segmentation algorithm. This new technique could lead to a more common use of microCT in analyzing the complex 3D processes and to a better understanding of the biological processes occurring after the implantation of ceramic bone graft substitutes. Statement of Significance Calcium-phosphate scaffolds are being increasingly used to repair critical bone defects. Methods for the accurate characterization of the repair process are still lacking. The present study introduced and validated a novel image-processing technique, using micro-computed tomography (mCT) datasets, to investigate material phases present in biopsies. Specifically, the new method combined mCT datasets from the scaffold before and after implantation to access the characteristic data of the ceramic for more accurate analysis of bone biopsies, and as such to better understand the interactions of the scaffold design and the bone repair process. [ABSTRACT FROM AUTHOR]

Ultrasound propagation is widely used in the diagnosis of osteoporosis by providing information on bone mechanical quality. When it loses calcium, the tissue properties will first decrease. However, limited research about the influence of tissue properties on ultrasound propagation have been done due to the cumbersome experiment. The goal of this study was to explore the relationships between tissue modulus (Es) and speed of sound (SOS) through numerical simulations, and to study the influence of Es on the acoustical behavior in characterizing the local structural anisotropy and inhomogeneity. In this work, three-dimensional finite element (FE) simulations were performed on a cubic high-resolution (15 μm) bovine trabecular bone sample (4×4×4 mm 3 , BV/TV=0.18) mapped from micro-computed tomography. Ultrasound excitations of 50 kHz, 500 kHz and 2 MHz were applied in three orthogonal axes and the first arriving signal (FAS) was collected to quantify wave velocity. In this study, a strong power law relationship between Es and SOS was measured with estimated exponential index β =2.08–3.44 for proximal–distal (PD), anterior–posterior (AP) and medial–lateral (ML), respectively (all R 2 > 0.95 ). For various Es, a positive dispersion of sound speed with respect to sound frequency was observed and the velocity dispersion magnitude (VDM) was measured. Also, with Es=15 GPa in three orientations, the SOS in PD axis is 2009±120 m/s, faster than that of AP (1762±106 m/s) and ML (1798±132 m/s) ( f =2 MHz) directions. Besides, the standard deviation of SOS increases with the sound frequency and the Es in all directions except for that at 50 kHz. For the mechanical properties, the apparent modulus with certain Es was highest in the longitudinal direction compared with the transverse directions. It indicates that the tissue modulus combining with anisotropy and inhomogeneity has great influence on ultrasound propagation. Simulation results agree well with theoretical and experimental results. [ABSTRACT FROM AUTHOR]

The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation of bone marrow adipocytes (BMAds) associated with a higher fracture risk and bone loss. A novel TZD analog MSDC-0602K with low affinity to PPARγ has been developed to reduce adverse effects of TZD therapy. However, the effect of MSDC-0602K on bone phenotype and bone marrow mesenchymal stem cells (BM-MSCs) in relation to obesity has not been intensively studied yet. Here, we investigated whether 8-week treatment with MSDC-0602K has a less detrimental effect on bone loss and BM-MSC properties in obese mice in comparison to first generation of TZDs, pioglitazone. Bone parameters (bone microstructure, bone marrow adiposity, bone strength) were examined by μCT and 3-point bending test. Primary BM-MSCs were isolated and measured for osteoblast and adipocyte differentiation. Cellular senescence, bioenergetic profiling, nutrient consumption and insulin signaling were also determined. The findings demonstrate that MSDC-0602K improved bone parameters along with increased proportion of smaller BMAds in tibia of obese mice when compared to pioglitazone. Further, primary BM-MSCs isolated from treated mice and human BM-MSCs revealed decreased adipocyte and higher osteoblast differentiation accompanied with less inflammatory and senescent phenotype induced by MSDC-0602K vs. pioglitazone. These changes were further reflected by increased glycolytic activity differently affecting glutamine and glucose cellular metabolism in MSDC-0602K-treated cells compared to pioglitazone, associated with higher osteogenesis. Our study provides novel insights into the action of MSDC-0602K in obese mice, characterized by the absence of detrimental effects on bone quality and BM-MSC metabolism when compared to classical TZDs and thus suggesting a potential therapeutical use of MSDC-0602K in both metabolic and bone diseases. [Display omitted] • MSDC-0602K improves bone quality and increases proportion of smaller BMAds in obese mice. • MSDC-0602K-treated mice show lower adipogenic differentiation with less senescent phenotype in primary BM-MSCs. • MSDC-0602K induces higher glycolytic activity in BM-MSCs compared to pioglitazone. • MSDC-0602-treated BM-MSCs prefer glutamine over glucose uptake in comparison to AT-MSCs. • Beneficial effect of MSDC-06002K in BM-MSCs manifests by absence of MPC inhibition. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to quantify the effects of understuffing and overstuffing UKA on bone stresses, load distribution and ligament strains. For that purpose, a numerical knee model of a cadaveric knee was developed and was validated against experimental measurements on that same knee. Good agreement was found among the numerical and experimental results. This study showed that, even if a medial UKA is well-aligned with normal soft tissue tension and with correct thickness of the tibia component, it induces a stiffness modification in the joint that alters the load distribution between the medial and lateral compartments, the bone stress and the ligament strain potentially leading to an osteoarthritic progression. [Copyright &y& Elsevier]

Abstract: Stem cell-mediated gene therapy for fracture repair, utilizes genetically engineered mesenchymal stem cells (MSCs) for the induction of bone growth and is considered a promising approach in skeletal tissue regeneration. Previous studies have shown that murine nonunion fractures can be repaired by implanting MSCs over-expressing recombinant human bone morphogenetic protein-2 (rhBMP-2). Nanoindentation studies of bone tissue induced by MSCs in a radius fracture site indicated similar elastic modulus compared to intact murine bone, eight weeks post-treatment. In the present study we sought to investigate temporal changes in microarchitecture and biomechanical properties of repaired murine radius bones, following the implantation of MSCs. High-resolution micro-computed tomography (micro-CT) was performed 10 and 35 weeks post MSC implantation, followed by micro-finite element (micro-FE) analysis. The results have shown that the regenerated bone tissue remodels over time, as indicated by a significant decrease in bone volume, total volume, and connectivity density combined with an increase in mineral density. In addition, the axial stiffness of limbs repaired with MSCs was 2–1.5 times higher compared to the contralateral intact limbs, at 10 and 35 weeks post-treatment. These results could be attributed to the fusion that occurred in between the ulna and radius bones. In conclusion, although MSCs induce bone formation, which exceeds the fracture site, significant remodeling of the repair callus occurs over time. In addition, limbs treated with an MSC graft demonstrated superior biomechanical properties, which could indicate the clinical benefit of future MSC application in nonunion fracture repair. [ABSTRACT FROM AUTHOR]

Abstract: An accurate prediction of bone strength in the human radius is of major interest because distal radius fractures are amongst the most common in humans. The objective of this study was to determine gender and age-related changes in bone morphometry at the radius and how these relate to bone strength. Specifically, our aims were to (i) analyze gender differences to get an insight into different bone quantities and qualities between women and men, (ii) to determine which microarchitectural bone parameters would best correlate with strength, (iii) to find the region of interest for the best assessment of bone strength, and (iv) to determine how loss of bone quality depends on age. Intact right forearms of 164 formalin-fixed cadavers from a high-risk elderly population were imaged with a new generation high-resolution pQCT scanner (HR-pQCT). Morphometric indices were derived for six different regions and were related to failure load as assessed by experimental uniaxial compression testing. Significant gender differences in bone quantity and quality were found that correlated well with measured failure load. The most relevant region to determine failure load based on morphometric indices assessed in this study was located just below the proximal end of the subchondral plate; this region differed from the one measured clinically today. Trends in bone changes with increasing age were found, even though for all morphometric indices the variation between subjects was large in comparison to the observed age-related changes. We conclude that HR-pQCT systems can determine how gender and age-related changes in morphometric parameters relate to bone strength, and that HR-pQCT is a promising tool for the assessment of bone quality in patient populations. [Copyright &y& Elsevier]

Abstract: Current practice to determine bone tissue modulus of murine cortical bone is to estimate it from three-point bending tests, using Euler–Bernoulli beam theory. However, murine femora are not perfect beams; hence, results can be inaccurate. Our aim was to assess the accuracy of beam theory, which we tested for two commonly used inbred strains of mice, C57BL/6 (B6) and C3H/He (C3H). We measured the three-dimensional structure of male and female B6 and C3H femora (N =20/group) by means of micro-computed tomography. For each femur five micro-finite element (micro-FE) models were created that simulated three-point bending tests with varying distances between the supports. Tissue modulus was calculated from beam theory using micro-FE results. The accuracy of beam theory was assessed by comparing the beam theory-derived moduli with the modulus as used in the micro-FE analyses. An additional set of fresh-frozen femora (10 B6 and 12 C3H) was biomechanically tested and subjected to the same micro-FE analyses. These combined experimental–computational analyses enabled an unbiased assessment of specimen-specific tissue modulus. We found that by using beam theory, tissue modulus was underestimated for all femora. Femoral geometry and size had strong effects on beam theory-derived tissue moduli. Owing to their relatively thin cortex, underestimation was markedly higher for B6 than for C3H. Underestimation was dependent on support width in a strain-specific manner. From our combined experimental–computational approach we calculated tissue moduli of 12.0±1.3 GPa and 13.4±2.1 GPa for B6 and C3H, respectively. We conclude that tissue moduli in murine femora are strongly underestimated when calculated from beam theory. Using image-based micro-FE analyses we could precisely quantify this underestimation. We showed that previously reported murine inbred strain-specific differences in tissue modulus are largely an effect of geometric differences, not accounted for by beam theory. We suggest a re-evaluation of the tissue properties obtained from three-point bending tests, especially in mouse genetics. [Copyright &y& Elsevier]

Abstract: Scaffolds, also called bioscaffolds, are needed in all tissue engineering applications as carriers for cells and biochemical factors, as constructs providing appropriate mechanical conditions, or as a combination of the two. The aim of this paper is to present recent developments in micro-computed tomography (μCT) analyses of scaffolds. The focus will be on imaging and quantification aspects in bone research, and will deal with the assessment of scaffold architecture and how it interacts with bone tissue. We show that micro-architectural imaging is a nondestructive and noninvasive procedure that allows a precise three-dimensional (3D) measurement of scaffold architecture. Direct μCT-based image analysis allows to accurately quantify scaffold porosity, surface area, and 3D measures such as pore size, pore distribution, and strut thickness; furthermore, it allows for a precise measurement of bone growth into the scaffold and onto its surface. This methodology is useful for quality control of scaffold fabrication processes, to assess scaffold degradation kinetics, and to assess bone tissue response. Even more so, in combination with bioreactors or in vivo animal models, μCT allows to qualitatively and quantitatively assess the spatial and temporal mineralization of bone tissue formation in scaffolds; such longitudinal studies improve the assessment of bone response due to scaffold architecture. Computational models will be helpful in further analyses of these data in order to improve our understanding of mechanical and biochemical stimuli on bone formation, and are likely to provide valuable knowledge to optimize scaffold design. [Copyright &y& Elsevier]

Finite element analysis (FEA) is the method of choice to nondestructively quantify stresses and strains in bones. Moderate to good estimates of bone strength can be obtained from continuum-level FEA. Improved predictive capacity is expected from microstructural FE models that represent the trabecular architecture in detail. With the advent of recently developed high-resolution in vivo bone imaging systems and the steady increase in computational power, such microstructural FE analyses are now becoming available to estimate bone strength in humans in a clinical setting. The procedure can help improve predictions of fracture risk, clarify the pathophysiology of skeletal diseases, and monitor the response to therapy. [Copyright &y& Elsevier]

Osteocytes are capable of remodeling their perilacunar bone matrix, which causes considerable variations in the shape and size of their lacunae. If these variations in lacunar morphology cause changes in the mechanical environment of the osteocytes, in particular local strains, they would subsequently affect bone mechanotransduction, since osteocytes are likely able to directly sense these strains. The purpose of this study is to quantify the effect of alterations in osteocyte lacunar morphology on peri-lacunar bone tissue strains. To this end, we related the actual lacunar shape in fibulae of six young-adult (5-month) and six old (23-month) mice, quantified by high-resolution micro-computed tomography, to microscopic strains, analyzed by micro-finite element modeling. We showed that peak effective strain increased by 12.6% in osteocyte cell bodies (OCYs), 9.6% in pericellular matrix (PCM), and 5.3% in extra cellular matrix (ECM) as the lacunae volume increased from 100-200 μm3 to 500–600 μm3. Lacunae with a larger deviation (>8°) in orientation from the longitudinal axis of the bone are exposed to 8% higher strains in OCYs, 6.5% in PCM, 4.2% in ECM than lacunae with a deviation in orientation below 8°. Moreover, increased lacuna sphericity from 0 to 0.5 to 0.7–1 led to 25%, 23%, and 13% decrease in maximum effective strains in OCYs, PCM, and ECM, respectively. We further showed that due to the presence of smaller and more round lacunae in old mice, local bone tissue strains are on average 5% lower in the vicinity of lacunae and their osteocytes of old mice compared to young. Understanding how changes in lacunar morphology affect the micromechanical environment of osteocytes presents a first step in unraveling their potential role in impaired bone mechanoresponsiveness with e.g. aging. • Variations in the morphology of lacunae resulted in alterations in local strain amplification. • Lacunae with a larger volume, more aligned with the bone longitudinal axis, and more elongated are exposed to higher strains. • Age-related changes in lacunar shape result in slightly lower local bone tissue strains. [ABSTRACT FROM AUTHOR]

PMMA bone cement has gained an important place in a variety of orthopaedic applications in the femur. However, appropriate data on the mechanical properties of bone-cement composites from the human femur are lacking. Therefore, the goal of this study was to determine the morphological and quasi-static compressive properties of proximal femoral bone-cement composites. Thirty trabecular bone specimens were extracted from fifteen pairs of human femoral heads using specimen-specific cutting guides to ensure an accurate alignment with the main trabecular direction (MTD). One specimen from each pair was augmented with PMMA bone cement, while the other one was left untreated. Specimens were scanned with μCT to determine morphological parameters and tested in quasi-static compression until failure. We found that the long axis of the specimens was highly aligned with the MTD (mean error < 5°). A higher compressive modulus and ultimate strength were observed for the bone-cement composite specimens (E = 5.7 ± 0.4 GPa; σ u = 77.9 ± 5.1 MPa) compared to the bone only specimens (E = 2.9 ± 0.7 GPa; σ u = 19.0 ± 5.8 MPa). Furthermore, the composites had a higher modulus, but lower strength than cement itself (E = 5.0 ± 0.3 GPa; σ u = 85.9 ± 2.7 MPa) and the composite modulus was significantly correlated with the bone volume fraction (BV/TV). These results are in contrast to previous findings on human vertebral bone, where the composite was more compliant than cement and no correlation was found between BV/TV and the composite modulus. Thus, properties of bone-cement composites cannot simply be applied across different anatomical sites; the site-specific differences in bone density and trabecular alignment should be taken into account. Collectively, the present results suggest that at low BV/TV, cement dominates the composite properties, while at high BV/TV, the contribution of bone becomes apparent, revealing a positive relationship between BV/TV and the on-axis modulus. [ABSTRACT FROM AUTHOR]

Prophylactic treatment is advised for metastatic bone disease patients with a high risk for fracture. Femoroplasty provides a minimally invasive procedure to stabilize the femur by injecting bone cement into the lesion. However, uncertainty remains whether it provides sufficient mechanical strength to the weight-bearing femur. The goal of this study was to quantify the improvement in bone stiffness, failure load and energy to failure due to cement augmentation of metastatic lesions at varying locations in the proximal femur. Eight pairs of human cadaveric femurs were mechanically tested until failure in a single-leg stance configuration. In each pair, an identical defect was milled in the left and right femur using a programmable milling machine to simulate an osteolytic lesion. The location of the defects varied amongst the eight pairs. One femur of each pair was augmented with polymethylmethacrylate, while the contralateral femur was left untreated. Digital image correlation was applied to measure strains on the bone surface during mechanical testing. Only femurs with a critical lesion showed an improvement in failure load and energy to failure due to augmentation. In these femurs, bone strength improved with 28% (±17%) on average and energy to failure with 58% (±41%), while stiffness did not show a significant improvement. The strain measurements from digital image correlation showed that cement augmentation reinforced the lesion, resulting in reduced strain magnitudes in the bone tissue adjacent to the lesion. The results indicate that femoroplasty may be an effective treatment to prevent fractures in several metastatic bone disease patients. However, the large scatter in the data clarifies the need for developing strategies to identify those patients who will benefit the most from the procedure. [ABSTRACT FROM AUTHOR]

Secure fracture fixation is still a major challenge in orthopedic surgery, especially in osteoporotic bone. While numerous studies have investigated the effect of implant loading on the peri-implant bone after screw insertion, less focus has been put on bone damage that may occur due to the screw insertion process itself. Therefore, the aim of this study was to localize and quantify peri-implant bone damage caused by screw insertion. We used non-invasive three-dimensional micro-computed tomography to scan twenty human femoral bone cores before and after screw insertion. After image registration of the pre- and post-insertion scans, changes in the bone micro-architecture were identified and quantified. This procedure was performed for screws with a small thread size of 0.3 mm (STS, N = 10) and large thread size of 0.6 mm (LTS, N = 10). Most bone damage occurred within a 0.3 mm radial distance of the screws. Further bone damage was observed up to 0.6 mm and 0.9 mm radial distance from the screw, for the STS and LTS groups, respectively. While a similar amount of bone damage was found within a 0.3 mm radial distance for the two screw groups, there was significantly more bone damage for the LTS group than the STS group in volumes of interest between 0.3–0.6 mm and 0.6–0.9 mm. In conclusion, this is the first study to localize and quantify peri-implant bone damage caused by screw insertion based on a non-invasive, three-dimensional, micro-CT imaging technique. We demonstrated that peri-implant bone damage already occurs during screw insertion. This should be taken into consideration to further improve primary implant stability, especially in low quality osteoporotic bone. We believe that this technique could be a promising method to assess more systematically the effect of peri-implant bone damage on primary implant stability. Furthermore, including peri-implant bone damage due to screw insertion into patient-specific in silico models of implant-bone systems could improve the accuracy of these models. [ABSTRACT FROM AUTHOR]

The thumb has played a key role in primate evolution due to its involvement in grasping and manipulation. A large component of this wide functionality is by virtue of the uniquely shaped trapeziometacarpal (TMC) joint. This TMC joint allows for a broad range of functional positions, but how its bone structure is adapted to withstand such a large variety of loading regimes is poorly understood. Here, we outline a novel, integrated finite element - micro finite element (FE-µFE) workflow to analyse strain distributions across the internal bony architecture. We have applied this modelling approach to study functional adaptation in the bonobo thumb. More specifically, the approach allows us to evaluate how strain is distributed through the trapezium upon loading of its distal articular facet. As loading conditions, we use pressure distributions for different types of grasping that were estimated in a previous study. Model evaluation shows that the simulated strain values fall within realistic boundaries of the mechanical response of bone. The results show that the strain distributions between the simulated grasps are highly similar, with dissipation towards the proximo-ulnar cluster of trabeculae regardless of trapezial bone architecture. This study presents an innovative FE-µFE approach to simulating strain distributions, and yields insight in the functional adaptation of the TMC joint in bonobos. [ABSTRACT FROM AUTHOR]

Secure fixation of fractured osteoporotic bone is a serious clinical challenge mainly because the reduced mechanical competence of low-density bone hampers proper implant fixation. Recent experimental findings have shown strong evidence for a rather complex bone-implant interface contact behavior, with frictional and non-linear mechanical properties. Furthermore, the bone microarchitecture is highly diverse even within the same anatomical site of a specific individual. Due to this intrinsic variability experimental studies that could analyze in detail the contributions of screw designs and thread geometry would require a very large amount of bone specimens; this hampers finding potential improvements for implant fixation. As a complementary approach, computational methods may overcome this limitation, since the same specimen can be tested repeatedly in numerous configurations and under various loading conditions. Recent advances in imaging techniques combined with parallel computing methods have enabled the creation of high-resolution finite-element models that are able to represent bone-implant systems in great detail. Yet, the predictive power of the mechanical competence of bone-implant systems is still limited, both on the apparent level and on the local microstructural level. The current strategy in high-resolution FE models to model the bone-implant interface, employing fully bonded cube-like elements, needs to be reconsidered, refined and validated, such that it mimics more closely the actual non-linear mechanical behavior as observed in vitro in order to exploit the full potential of numeric models as an effective, complementary research method to physical in vitro models. [ABSTRACT FROM AUTHOR]

Visualization and quantification of bone microarchitecture in the human knee allows gaining insight into normal bone structure, and into the structural changes occurring in the onset and progression of bone diseases such as osteoporosis and osteoarthritis. However, current imaging modalities have limitations in capturing the intricacies of bone microarchitecture. Photon counting computed tomography (PCCT) is a promising imaging modality that presents high-resolution three-dimensional visualization of bone with a large field of view. However, the potential of PCCT in assessing trabecular microstructure has not been investigated yet. Therefore, this study aimed to evaluate the accuracy of PCCT in quantifying bone microstructure and bone mechanics in the knee. Five human cadaveric knees were scanned ex vivo using a PCCT scanner (Naetom alpha, Siemens, Germany) with an in-plane resolution of 146.5 μm and slice thickness of 100 μm. To assess accuracy, the specimens were also scanned with a high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT II, Scanco Medical, Switzerland) with a nominal isotropic voxel size of 60.7 μm as well as with micro-computed tomography (micro-CT; TESCAN UniTOM XL, Czech Republic) with a nominal isotropic voxel size of 25 μm which can be considered gold standards for in vivo and ex vivo scanning, respectively. The thickness and porosity of the subchondral bone and the microstructure of the underlying trabecular bone were assessed in the load bearing regions of the proximal tibia and distal femur. The apparent Young's modulus was determined by micro-finite element (μFE) analysis of subchondral trabecular bone (STB) in the load bearing regions of the proximal tibia using PCCT, HR-pQCT and micro-CT images. The correlation between PCCT measurements and micro-CT and HR-pQCT, respectively, was calculated. The coefficients of determination (R2) between PCCT and micro-CT based parameters, ranged from 0.69 to 0.87. The coefficients of determination between PCCT and HR-pQCT were slightly higher and ranged from 0.71 to 0.91. Apparent Young's modulus, assessed by μFE analysis of PCCT images, correlated well with that of micro-CT (R2 = 0.80, mean relative difference = 19 %). However, PCCT overestimated the apparent Young's modulus by 47 %, but the correlation (R2 = 0.84) remained strong when compared to HR-pQCT. The results of this study suggest that PCCT can be used to quantify bone microstructure in the knee. • Bone microstructure can be quantified using photon counting CT (PCCT). • PCCT-based bone microarchitecture was validated by micro-CT and HR-pQCT. • PCCT-based quantification of bone stiffness was validated by micro-CT and HR-pQCT. • PCCT is a novel technique for future in vivo microstructural imaging. [ABSTRACT FROM AUTHOR]

Due to the rising life expectancy, bone diseases (e.g. osteoporosis, osteoarthritis) and trauma (e.g. fracture) have become an important socio-economic burden. Accurate visualization and quantification of the bone microstructure in vivo is seen as an important step to enhance diagnosis and treatment. Micro-computed tomography (microCT) has become the gold standard in three-dimensional (3D) imaging of trabecular bone structure. Yet, usage is limited to ex vivo analyses, hence, it cannot be used to evaluate bone and bone adaptive responses in a patient. High-resolution peripheral computed tomography (HR-pQCT) is considered the best technique to measure the bone microarchitecture in vivo. By design HR-pQCT is limited to scanning extremities, such as the distal radius and distal tibia with a limited field of view and long scanning time (~2 à 3 min. for a stack of 0.9 cm). Cone-beam computed tomography (CBCT) is a promising alternative with a much larger field of view. Yet, CBCT is challenged by artefacts that reduce image contrast, such that it is currently being used for qualitative evaluation only. Therefore, the aims of this work were first to enhance image contrast and second to determine the accuracy of high-resolution CBCT for bone microarchitectural assessment. Trapezia of nineteen female arthritic patients were scanned twice ex vivo; once using CBCT (NewTom 5G, Cefla, Verona, Italy) at a nominal voxel size of 75 μm and once using microCT (SkyScan 1172, Bruker, Kontich, Belgium) at a voxel size of 19.84 μm. The CBCT-scans were reconstructed following 2 protocols: (1) using the commercial software delivered with the scanner and (2) using in-house developed software. After reconstruction and image processing, the images were segmented using adaptive thresholding. Bone morphometric parameters including bone volume (BV), total tissue volume (TV), bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N) were calculated. Statistical evaluations were made at a significance level of 5%. Significant correlations were found between the CBCT-based bone parameters and the microCT-based parameters with R 2  > 0.68 The in-house reconstructed software outperformed the commercial software. Smaller bias (overestimation of Tb.Th decreased from 114.24% to 59.96%) as well as higher correlations were observed for the in-house processed images. Still, a significant overestimation was observed for BV/TV and Tb. Th and an underestimation for Tb.N. We conclude that our CBCT image reconstruction improved image contrast which allowed for an accurate quantification of trabecular bone microarchitecture. [ABSTRACT FROM AUTHOR]

Osteocyte lacunae are small cavities within the bone matrix. Their dimensions and spatial arrangement affect bone mechanical properties. Furthermore, their size and shape affect the strain in bone tissue close to the lacunae; hence, they are supposed to affect the mechanosensory function of the osteocytes residing in the lacunae. It was the purpose of this study to quantify the morphological features of osteocyte lacunae, whether these are affected by aging and whether these vary among different anatomical location. In addition, we aimed at quantifying the vascular canals as these affect bone's microporosity too. We quantified the microporosity in the fibular midshaft of young-adult and old female C57BL/6 mice. Using micro-computed tomography (μCT), we found that advanced age was associated with a significantly decreased vascular canal number and volume density. In aged mice, the mean volume of the lacuna was significantly smaller than in young animals and they were more round. Lacuna number density close to the neutral axis of the fibula was higher in older mice than in young ones. The characterization of bone microporosity presents a first step in further unraveling their potential role in age-related reductions in bone strength. [ABSTRACT FROM AUTHOR]

Elbow trauma is often accompanied by a loss of independence in daily self-care activities, negatively affecting patients' quality of life. Finite element models can help gaining profound knowledge about native human joint mechanics, which is crucial to adequately restore joint functionality after severe injuries. Therefore, a finite element model of the elbow is required that includes both the radio-capitellar and ulno-trochlear joint and is subjected to loads realistic for activities of daily living. Since no such model has been published, we aim to fill this gap. For comparison, 8 intact cadaveric elbows were subjected to loads of up to 1000 N, after they were placed in an extended position. At each load step, the displacement of the proximal humerus relative to the distal base plate was measured with optical tracking markers and the joint pressure was measured with a pressure mapping sensor. Analogously, eight finite element models were created based on subject-specific CT scans of the corresponding elbow specimens. The CT scans were registered to the positions of tantalum beads in the experiment. The optically measured displacements were applied as boundary conditions. We demonstrated that the workflow can predict the experimental contact pressure distribution with a moderate correlation, the experimental peak pressures in the correct joints and the experimental stiffness with moderate to excellent correlation. The predictions of peak pressure magnitude, contact area and load share on the radius require improvement by precise representation of the cartilage geometry and soft tissues in the model, and proper initial contact in the experiment. [ABSTRACT FROM AUTHOR]

Articular cartilage covers the temporomandibular joint (TMJ) and provides smooth and nearly frictionless articulation while distributing mechanical loads to the subchondral bone. The thickness of the cartilage is considered to be an indicator of the stage of development, maturation, aging, loading history, and disease. The aim of our study was to develop a method for ex vivo assessment of the thickness of the cartilage that covers the TMJ and to compare that with two other existing methods. Eight porcine TMJ condyles were used to measure cartilage thickness. Three different methods were employed: needle penetration, micro-computed tomography (micro-CT), and histology; the latter was considered the gold standard. Histology and micro-CT scanning results showed no significant differences between thicknesses throughout the condyle. Needle penetration produced significantly higher values than histology, in the lateral and anterior regions. All three methods showed the anterior region to be thinner than the other regions. We concluded that overestimated thickness by the needle penetration is caused by the penetration of the needle through the first layer of subchondral bone, in which mineralization is less than in deeper layers. Micro-CT scanning method was found to be a valid method to quantify the thickness of the cartilage, and has the advantage of being non-destructive. [ABSTRACT FROM AUTHOR]

Abstract: Dynamic implant cut-out is a frequent complication associated with surgical fracture fixation. In this in vitro study, we investigated the influence of the local trabecular bone microstructure on the rate and path of implant migration. Dynamic hip screws were implanted into six human femoral head specimens with a wide range of bone volume fractions. The specimens were subjected to image-guided failure assessment using physiological dynamic hip loading. Mechanical testing was used intermittently with high-resolution computed tomography scanning. A high correlation was found between the bone volume fraction and implant migration (R 2 =0.95). Profiles of the bone-implant interface were computed based on the positions of the screw and the femoral head. With a larger interface, the implant migration rate was smaller. The bone-implant interface was significantly smaller on the approximated screw migration path than if it had been on a straight line in loading direction. We thus hypothesize that implants migrate on a path of least resistance. This would indicate a relevant mechanism for targeted surgical intervention. [Copyright &y& Elsevier]

Abstract: The failure mechanisms of bone–implant constructs are still incompletely understood, because the role of the peri-implant bone in implant stability is unclear. We hypothesized that implant fixation failure is preceded by substantial peri-implant bone failure. A new device was developed that combines mechanical testing of large bone–implant constructs with high-resolution peripheral quantitative computed tomography, following the principles of image-guided failure assessment (IGFA). In this study, we investigated the push-in failure behavior of dynamic hip screws (DHS) implanted in human cadaveric femoral heads. For the first time the fixation failure of a clinically used implant in human trabecular bone could be experimentally visualized at the microstructural level. The ultimate force was highly correlated with the peri-implant bone volume fraction (R 2 =0.85). We demonstrated that primary fixation failure of DHS implants was accompanied by trabecular bone failure in the immediate peri-implant bone region only. Such experimental data are crucial to enhance the understanding on the quality of the bone–implant interface and of the trabecular bone in the process of implant fixation failure. We believe that this newly developed device will be beneficial for the development of new implant designs, especially for use in osteoporotic bone. [Copyright &y& Elsevier]

High-resolution in vivo bone micro-architecture assessment, as possible now for the distal forearm, in combination with bone remodelling simulation algorithms could, eventually, predict patient-specific bone morphology changes. To simulate load-adaptive bone remodelling, however, physiological loading conditions must be defined. In this paper we test a previously developed algorithm to estimate such physiological loading conditions from the bone micro-architecture. The aims of this study were to investigate if realistic boundary forces and moments are predicted for the scanned distal radius section and how these predicted forces and moments should be distributed to the scanned section in order to obtain a load transfer similar to that in situ. Images at in vivo resolution were generated for the clinically measured section of nine distal radius cadaver bones, converted to micro-finite element models and used for load estimation. Models of the full distal radius were created to analyse tissue loading distributions of the sections in situ. It was found that predicted forces and moments at the boundaries of the scanned region varied considerably but, when translated to equivalent radiocarpal joint forces, agreed well with values reported in the literature. Bone tissue loading distribution was in best agreement with in situ distributions when loading was applied to an extra layer of material at both ends of the clinical scan region. The agreement of the predicted loading to previous studies and the wide range of predicted loading values indicate that subject-specific bone loading estimation is possible and necessary. [ABSTRACT FROM AUTHOR]

Abstract: The quality of the peri-implant bone and the strength of the bone–implant interface are important factors for implant anchorage. With regard to peri-implant bone, cortical and trabecular compartments both contribute to the load transfer from the implant to the surrounding bone but their relative roles have yet to be investigated in detail. However, this knowledge is crucial for the better understanding of implant failure and for the development of new implants. This is especially true for osteoporotic bone, which is characterized by a deterioration of the trabecular architecture and a thinning of the cortical shell, leading to a higher probability of implant loosening. The aim of this study was to investigate the relative biomechanical roles of cortical and trabecular bone on implant pull-out stiffness in human vertebrae. The starting point of our investigation was a micro-computed tomography scan of an adult human vertebra. The cortical shell was identified and an implant was digitally inserted into the vertebral body. Pull-out tests were simulated with micro-finite element analysis and the apparent stiffness of the system with various degrees of shell thickness and bone volume fraction was computed. Our computational models demonstrated that cortical bone, although being very thin, plays a major role in the mechanical competence of the bone–implant construct. [Copyright &y& Elsevier]

Abstract: It is known that low bone quality, caused for instance by osteoporosis, not only increases the risk of fractures, but also decreases the performance of fracture implants; yet the specific mechanisms behind this phenomenon are still largely unknown. We hypothesized that especially peri-implant bone microstructure affects implant stability in trabecular bone, to a greater degree than more distant bone. To test this hypothesis we performed a computational study on implant stability in trabecular bone. Twelve humeral heads were measured using micro-computed tomography. Screws were inserted digitally into these heads at 25 positions. In addition, at each screw location, a virtual biopsy was taken. Bone structural quality was quantified by morphometric parameters. The stiffness of the 300 screw-bone constructs was quantified as a measure of implant stability. Global bone density correlated moderately with screw–bone stiffness (r2 =0.52), whereas local bone density was a very good predictor (r2 =0.91). The best correlation with screw–bone stiffness was found for local bone apparent Young''s modulus (r2 =0.97), revealing that not only bone mass but also its arrangement in the trabecular microarchitecture are important for implant stability. In conclusion, we confirmed our hypothesis that implant stability is affected by the microstructural bone quality of the trabecular bone in the direct vicinity of the implant. Local bone density was the best single morphometric predictor of implant stability. The best predictability was provided by the mechanical competence of the peri-implant bone. A clinical implication of this work is that apparently good bone stock, such as assessed by DXA, does not guarantee good local bone quality, and hence does not guarantee good implant stability. New tools that could quantify the structural or mechanical quality of the peri-implant bone may help improve the surgical intervention in reaching better clinical outcomes for screw fixation. [Copyright &y& Elsevier]

Abstract: High-resolution peripheral quantitative computed tomography (HR-pQCT) is clinically available today and provides a non-invasive measure of 3D bone geometry and micro-architecture with unprecedented detail. In combination with microarchitectural finite element (μFE) models it can be used to determine bone strength using a strain-based failure criterion. Yet, images from only a relatively small part of the radius are acquired and it is not known whether the region recommended for clinical measurements does predict forearm fracture load best. Furthermore, it is questionable whether the currently used failure criterion is optimal because of improvements in image resolution, changes in the clinically measured volume of interest, and because the failure criterion depends on the amount of bone present. Hence, we hypothesized that bone strength estimates would improve by measuring a region closer to the subchondral plate, and by defining a failure criterion that would be independent of the measured volume of interest. To answer our hypotheses, 20% of the distal forearm length from 100 cadaveric but intact human forearms was measured using HR-pQCT. μFE bone strength was analyzed for different subvolumes, as well as for the entire 20% of the distal radius length. Specifically, failure criteria were developed that provided accurate estimates of bone strength as assessed experimentally. It was shown that distal volumes were better in predicting bone strength than more proximal ones. Clinically speaking, this would argue to move the volume of interest for the HR-pQCT measurements even more distally than currently recommended by the manufacturer. Furthermore, new parameter settings using the strain-based failure criterion are presented providing better accuracy for bone strength estimates. [Copyright &y& Elsevier]

Abstract: In osteoporotic bones, resorption exceeds formation during the remodelling phase of bone turnover. As a consequence, decreased bone volume and bone contact result in the peri-implant region. This may subsequently lead to loss of fixation. In this study we investigated whether the presence of nonresorbable, osteoconductive hydroxyapatite (HA) particles could help maintain a denser and more functional peri-implant bone structure. Titanium screws were implanted into the proximal tibial metaphysis of four months old, ovariectomized Wistar rats (n =60). In the right tibia, the drill hole was first filled with HA particles, while the left tibia served as a control without HA particles. Histological analysis demonstrated that during the remodelling phase the amount of newly formed bone was significantly higher on the HA over the control side. Micro-CT analysis corroborated the significant changes over time as well as differences in peri-implant bone volume density between treatment and control group. Mechanical tests demonstrated that the pull-out force was greater with HA particles. These results indicate that HA particles are able to induce and maintain for a longer time a denser peri-implant bone mantle in osteoporotic bone, which may have important implications in the prevention of implant migration and cut-outs. [Copyright &y& Elsevier]

Abstract: Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength. Bone strength depends, among others, on bone density, bone geometry and its internal architecture. With the recent introduction of a new generation high-resolution 3D peripheral quantitative computed tomography (HR-pQCT) system, direct quantification of structural bone parameters has become feasible. Furthermore, it has recently been demonstrated that bone mechanical competence can be derived from HR-pQCT based micro-finite element modeling (μFE). However, reproducibility data for HR-pQCT-derived mechanical indices is not well-known. Therefore, the aim of this study was to quantify reproducibility of HR-pQCT-derived indices. We measured 14 distal formalin-fixed cadaveric forearms three times and analyzed three different regions for each measurement. For each region cortical and trabecular parameters were determined. Reproducibility was assessed with respect to precision error (PE) and intraclass correlation coefficient (ICC). Reproducibility values were found to be best in all three regions for the full bone compartment with an average PE of 0.79%, followed by the cortical compartment (PE=1.19%) and the trabecular compartment with an average PE of 2.31%. The mechanical parameters showed similar reproducibility (PE=0.48%–2.93% for bone strength and stiffness, respectively). ICC showed a very high reproducibility of subject-specific measurements, ranging from 0.982 to 1.000, allowing secure identification of individual donors ranging from healthy to severely osteoporotic subjects. From these in vitro results we conclude that HR-pQCT derived morphometric and mechanical parameters are highly reproducible such that differences in bone structure and strength can be detected with a reproducibility error smaller than 3%; hence, the technique has a high potential to become a tool for detecting bone quality and bone competence of individual subjects. [Copyright &y& Elsevier]

Abstract: The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, β-tricalcium phosphate (β-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220μm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510μm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260μm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks. [Copyright &y& Elsevier]

High-resolution peripheral quantitative computed tomography (HR-pQCT) devices can scan extremities at bone microstructural level in vivo and are used mainly in research of bone diseases. Two HR-pQCT scanners are commercially available to date: XtremeCT (first generation) and XtremeCT-II (second generation) from Scanco Medical AG (Switzerland). Recently, we have proposed an adaptive local thresholding (AT) technique and showed that it can improve quantification accuracy of bone microstructural parameters, with visually less sharp cone-beam CT (CBCT) images providing a similar accuracy than XtremeCT. The aim of this study was to evaluate whether the AT segmentation technique could enhance the accuracy of HR-pQCT in quantifying bone microstructural images and to assess whether the agreement between XtremeCT and XtremeCT-II could be improved. Nineteen radii were scanned with three scanners from Scanco Medical AG: (1) XtremeCT at 82 μm, (2) XtremeCT-II at 60.7 μm and (3) the small animal microCT scanner VivaCT40 at 19 μm voxel size. The scans were segmented applying two different methods, once following the manufacturer standard technique (ST), and once by means of AT. Three-dimensional (3D) morphological analysis was performed on the trabecular volume of the segmented images using the manufacturer's standard software to calculate bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The average accuracy of XtremeCT improved from R 2 = 0.76 (ST) to 0.85 (AT) and reached the same level of accuracy as XtremeCT-II with ST (R 2 = 0.86). The largest improvements were obtained for BV/TV and Tb.Th. For XtremeCT-II, mean accuracy improved slightly from R 2 = 0.86 (ST) to 0.89 (AT). For both segmentations and both scanners, the standard section was quantified slightly more accurate than the subchondral section. The agreement between the scanners was enhanced from R 2 = 0.89 (ST) to 0.98 (AT). In conclusion, AT can enhance the accuracy of XtremeCT to quantify distal radius bone microstructural parameters close to XtremeCT-II level and increases the agreement between the two HR-pQCT scanners. High-resolution peripheral quantitative computed tomography, segmentation, bone microstructural parameters. • Adaptive local thresholding technique (AT) can enhance the accuracy of HR-pQCT. • AT increases the agreement between the two HR-pQCT scanners. • In future, AT may help decreasing scanning time and dose. [ABSTRACT FROM AUTHOR]

Over the last decades, the use of high-resolution imaging systems to assess bone microstructural parameters has grown immensely. Yet, no standard defining the quantification of these parameters exists. It has been reported that different voxel size and/or segmentation techniques lead to different results. However, the effect of the evaluation software has not been investigated so far. Therefore, the aim of this study was to compare the bone microstructural parameters obtained with two commonly used commercial software packages, namely IPL (Scanco, Switzerland) and CTan (Bruker, Belgium). We hypothesized that even when starting from the same segmented scans, different software packages will report different results. Nineteen trapezia and nineteen distal radii were scanned at two resolutions (20 μm voxel size with microCT and HR-pQCT 60 μm). The scans were segmented using the scanners' default protocol. The segmented images were analyzed twice, once with IPL and once with CTan, to quantify bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N) and specific bone surface (BS/BV). Only small differences between IPL and CTan were found for BV/TV. For Tb.Th, Tb.Sp and BS/BV high correlations (R 2 ≥ 0.99) were observed between the two software packages, but important relative offsets were observed. For microCT scans, the offsets were relative constant, e.g. , around 15% for Tb.Th. However, for the HR-pQCT scans the mean relative offsets ranged over the different bone samples (e.g. , for Tb.Th from 14.5% to 19.8%). For Tb.N, poor correlations (0.43 ≤ R 2 ≤ 0.81) for all tested cases were observed. We conclude that trabecular bone microstructural parameters obtained with IPL and CTan cannot be directly compared except for BV/TV. For Tb.Th, Tb.Sp and BS/BV, correction factors can be determined, but these depend on both the image voxel size and specific anatomic location. The two software packages did not produce consistent data on Tb.N. The development of a universal standard seems desirable. • Bone parameters calculated with IPL and CTan cannot be directly compared. • General correction factors can only be calculated for some of the bone parameters. • Development of a universal standard for calculation of bone parameters is desirable. [ABSTRACT FROM AUTHOR]