Subchondral Bone Osteocyte Lacunae Morphology in End-Stage Osteoarthritis of the Human Tibial Plateau.

Subchondral bone remodeling, mediated by osteocytes within the lacuno-canalicular network, plays a crucial role in osteoarthritis (OA) progression. Following cell death, lacunae preserve integrity, offering insights into bone remodeling mechanisms. Limited and controversial data on osteocyte lacuna morphology in OA result from small sample sizes and two-dimensional (2D) techniques that have been used thus far. This study aimed to quantify three-dimensional (3D) osteocyte lacunar characteristics at well-defined tibial plateau locations, known to be differently affected by OA. Specifically, 11 tibial plateaus were obtained from end-stage knee-OA patients with varus deformity. Each plateau provided one sample from the less affected lateral compartment and two samples from the medial compartment, at minimum and maximum bone volume fraction (BV/TV) locations. High-resolution desktop micro-computed tomography (micro-CT) at 0.7 µm voxel resolution imaged the 33 samples. Lacuna number density (Lc.N/BV) and lacuna volume density (Lc.TV/BV) were significantly lower (p < 0.02) in samples from the medial side with maximum BV/TV compared to lateral side samples. In the medial compartment at maximum local BV/TV, mean lacuna volume (Lc.V), total lacuna volume (Lc.TV), and Lc.TV/BV were significantly (p < 0.001) lower than in the region with minimum BV/TV. Lc.N/BV was also significantly lower (p < 0.02) at the maximum local BV/TV location compared to the region with minimum BV/TV. Our findings suggest that subchondral bone lacunae adapt to the changing loads in end-stage OA.

Photon-Counting Computed Tomography for Microstructural Imaging of Bone and Joints.

PURPOSE OF REVIEW: Recently, photon-counting computed tomography (PCCT) has been introduced in clinical research and diagnostics. This review describes the technological advances and provides an overview of recent applications with a focus on imaging of bone. RECENT FINDINGS: PCCT is a full-body scanner with short scanning times that provides better spatial and spectral resolution than conventional energy-integrating-detector CT (EID-CT), along with an up to 50% reduced radiation dose. It can be used to quantify bone mineral density, to perform bone microstructural analyses and to assess cartilage quality with adequate precision and accuracy. Using a virtual monoenergetic image reconstruction, metal artefacts can be greatly reduced when imaging bone-implant interfaces. Current PCCT systems do not allow spectral imaging in ultra-high-resolution (UHR) mode. Given its improved resolution, reduced noise and spectral imaging capabilities PCCT has diagnostic capacities in both qualitative and quantitative imaging that outperform those of conventional CT. Clinical use in monitoring bone health has already been demonstrated. The full potential of PCCT systems will be unlocked when UHR spectral imaging becomes available.

Evaluation of the superior pubic ramus and supra acetabular corridors using statistical shape modelling.

INTRODUCTION: The incidence of osteoporotic pelvic fractures is increasing. The broken anterior pelvic ring is preferentially fixed with long intramedullary screws, which require a good understanding of the patient-specific anatomy to prevent joint perforation. The aim of this study was to assess the variability of the superior pubic ramus and the supra acetabular corridors' length and width using statistical shape modelling. MATERIALS AND METHODS: A male and female statistical shape model was made based on 59 forensic CT scans. For the superior pubic ramus and the supra acetabular corridor the longest and widest completely fitting cylinder was created for the first 5 principal components (PC) of both models, male and female pelvises separately. RESULTS: A total of 59 pelvises were included in this study of which 36 male and 23 female. The first 5 principal components explained 75% and 79% of the pelvic variation in males and females, respectively. Within 3 PCs of the female statistical shape model (SSM) a superior pubic ramus corridor of < 7.3 mm was found, 5.5 mm being the narrowest linear corridor measured. Both corridors in all PCs of the male SSM measured > 7.3 mm. CONCLUSION: Within females a 7.3 mm and 6.5 mm screw won't always fit in the superior pubic ramus corridor, especially if a flat sacrum, a small pelvis or a wide subpubic angle are present. The supra acetabular corridor did not seem to have sex-specific differences. In the supra-acetabular corridor there was always enough space to accommodate a 7.3 mm screw, both in males and females.

High-Resolution Cone-Beam Computed Tomography is a Fast and Promising Technique to Quantify Bone Microstructure and Mechanics of the Distal Radius.

Obtaining high-resolution scans of bones and joints for clinical applications is challenging. HR-pQCT is considered the best technology to acquire high-resolution images of the peripheral skeleton in vivo, but a breakthrough for widespread clinical applications is still lacking. Recently, we showed on trapezia that CBCT is a promising alternative providing a larger FOV at a shorter scanning time. The goals of this study were to evaluate the accuracy of CBCT in quantifying trabecular bone microstructural and predicted mechanical parameters of the distal radius, the most often investigated skeletal site with HR-pQCT, and to compare it with HR-pQCT. Nineteen radii were scanned with four scanners: (1) HR-pQCT (XtremeCT, Scanco Medical AG, @ (voxel size) 82 µm), (2) HR-pQCT (XtremeCT-II, Scanco, @60.7 µm), (3) CBCT (NewTom 5G, Cefla, @75 µm) reconstructed and segmented using in-house developed software and (4) microCT (VivaCT40, Scanco, @19 µm-gold standard). The following parameters were evaluated: predicted stiffness, strength, bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The overall accuracy of CBCT with in-house optimized algorithms in quantifying bone microstructural parameters was comparable (R2 = 0.79) to XtremeCT (R2 = 0.76) and slightly worse than XtremeCT-II (R2 = 0.86) which were both processed with the standard manufacturer's technique. CBCT had higher accuracy for BV/TV and Tb.Th but lower for Tb.Sp and Tb.N compared to XtremeCT. Regarding the mechanical parameters, all scanners had high accuracy (R2 [Formula: see text] 0.96). While HR-pQCT is optimized for research, the fast scanning time and good accuracy renders CBCT a promising technique for high-resolution clinical scanning.

Estrogen receptor alpha signaling in extrahypothalamic neurons during late puberty decreases bone size and strength in female but not in male mice.

Sexually dimorphic bone structure emerges largely during puberty. Sex steroids are critical for peak bone mass acquisition in both genders. In particular, the biphasic effects of estrogens mediate the skeletal sexual dimorphism. However, so far the stimulatory vs inhibitory actions of estrogens on bone mass are not fully explained by direct effects on bone cells. Recently, it has become evident that there is possible neuroendocrine action of estrogen receptor alpha (ERα) on the skeleton. Based on these considerations, we hypothesized that neuronal ERα-signaling may contribute to the skeletal growth during puberty. Here, we generated mice with tamoxifen-inducible Thy1-Cre mediated ERα inactivation during late puberty specifically in extrahypothalamic neurons (N-ERαKO). Inactivation of neuronal ERα did not alter the body weight in males, whereas N-ERαKO females exhibited a higher body weight and increased body and bone length compared to their control littermates at 16 weeks of age. Ex vivo microCT analysis showed increased radial bone expansion of the midshaft femur in female N-ERαKO along with higher serum levels of insulin-like growth factor (IGF)-1 as well as IGF-binding protein (IGFBP)-3. Furthermore, the 3-point bending test revealed increased bone strength in female N-ERαKO. In contrast, inactivation of neuronal ERα had no major effect on bone growth in males. In conclusion, we demonstrate that central ERα-signaling limits longitudinal bone growth and radial bone expansion specifically in females potentially by interacting with the GH/IGF-1 axis.

Automated muscle elongation measurement during reverse shoulder arthroplasty planning.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Does Unicondylar Knee Arthroplasty Affect Tibial Bone Strain? A Paired Cadaveric Comparison of Fixed- and Mobile-bearing Designs.

BACKGROUND: Unexplained pain in the medial proximal tibia frequently leads to revision after unicondylar knee arthroplasty (UKA). As one of the most important factors for osteogenic adaptive response, increased bone strain following UKA has been suggested as a possible cause. QUESTIONS/PURPOSES: In this study we: (1) performed a cadaver-based kinematic analysis on paired cadaveric specimens before and after mobile-bearing and fixed-bearing UKA; and (2) simultaneously characterized the strain distribution in the anterior and posterior proximal tibia during squatting. METHODS: Five pairs of fresh, frozen full-leg cadaver specimens (four male, one female, 64 years to 87 years) were subjected to a dynamic squatting motion on a kinematic rig to simulate joint loading for a large ROM. Forces were applied to the quadriceps and hamstrings during the simulation while an infrared camera system tracked the location of reflective markers attached to the tibia and femur. Tibial cortical bone strain was measured with stacked strain gauge rosettes attached at predefined anterior and posterior positions on the medial cortex. Pairwise implantation of mobile-bearing (UKAMB) and fixed-bearing implants (UKAFB) allowed a direct comparison of right and left knees from the same donor through a linear mixed model. RESULTS: UKAMB more closely replicated native kinematics in terms of tibial rotation and in AP and mediolateral translation. Maximum principal bone strain values were consistently increased compared with native (anteromedial, mean [± SD] peak strain: 311 µÎµ ± 190 and posterior, mean peak strain: 321 µÎµ ± 147) with both designs in the anteromedial (UKAFB, mean peak strain: 551 µÎµ ± 381, Cohen's d effect size 1.3 and UKAMB, mean peak strain: 596 µÎµ ± 564, Cohen's d effect size 1.5) and posterior (UKAFB, mean peak strain: 505 µÎµ ± 511, Cohen's d effect size 1.3 and UKAMB, mean peak strain: 633 µÎµ ± 424, Cohen's d effect size 2.1) region. However, in the anterolateral region of the medial tibial bone, UKAFB demonstrated the overall largest increase in strain (mean peak strain: 1010 µÎµ ± 787, Cohen's d effect size 1.9), while UKAMB (613 µÎµ ± 395, Cohen's d effect size 0.2) closely replicated values of the native knee (563 µÎµ ± 234). CONCLUSION: In this in vitro cadaver study both UKAMB and UKAFB led to an increase in bone strain in comparison with the native knee. However, in the anterolateral region of the medial tibial plateau, proximal tibial bone strain was lower after UKAMB and UKAFB. Both UKAMB and UKAFB lead to comparable increases in anteromedial and posterior tibial strain in comparison with the native knee. In the anterolateral region of the medial tibial plateau UKA, proximal tibial bone strain was closer to the native knee after UKAMB than after UKAFB. In an attempt to link kinematics and strain behavior of these designs there seemed to be no obvious relation. CLINICAL RELEVANCE: Further clinical research may be able to discern whether the observed differences in cortical strain after UKA is associated with unexplained pain in patients and whether the observed differences in cortical bone strain between mobile-bearing and fixed unicondylar designs results in a further difference in unexplained pain.

Mechanical Loading Differentially Affects Osteocytes in Fibulae from Lactating Mice Compared to Osteocytes in Virgin Mice: Possible Role for Lacuna Size.

Hormonal changes during lactation are associated with profound changes in bone cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger lacuna shape theoretically enhances the transmission of mechanical signals to osteocytes. We aimed to provide experimental evidence supporting this theory by comparing the mechanoresponse of osteocytes in the bone of lactating mice, which have enlarged lacunae due to osteocytic osteolysis, with the response of osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse was measured in excised fibulae that were cultured in hormone-free medium for 24 h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 µÎµ, 5 Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and sclerostin and ß-catenin protein expression (immunohistochemistry). Loading decreased Sost expression by ~ threefold in fibulae of lactating mice. The loading-induced decrease in sclerostin protein expression by osteocytes was larger in lactating mice (55% decrease ± 14 (± SD), n = 8) than virgin mice (33% decrease ± 15, n = 7). Mechanical loading upregulated ß-catenin expression in osteocytes in lactating mice by 3.5-fold (± 0.2, n = 6) which is significantly (p < 0.01) higher than the 1.6-fold increase in ß-catenin expression by osteocytes in fibulae from virgin mice (± 0.12, n = 4). These results suggest that osteocytes in fibulae from lactating mice with large lacunae may respond stronger to mechanical loading than those from virgin mice. This could indicate that osteocytes residing in larger lacuna show a stronger response to mechanical loading.

Aging, Osteocytes, and Mechanotransduction.

PURPOSE OF REVIEW: The bone is able to adapt its structure to mechanical signals via the bone remodeling process governed by mechanosensitive osteocytes. With aging, an imbalance in bone remodeling results in osteoporosis. In this review, we hypothesized that changes in lacunar morphology underlie the decreased bone mechanoresponsiveness to mechanical loading with aging. RECENT FINDINGS: Several studies have reported considerable variations in the shape of osteocytes and their lacunae with aging. Since osteocytes can sense matrix strain directly via their cell bodies, the variations in osteocyte morphology may cause changes in osteocyte mechanosensitivity. As a consequence, the load-adaptive response of osteocytes may change with aging, even when mechanical loading would remain unchanged. Though extensive quantitative data is lacking, evidence exists that the osteocyte lacunae are becoming smaller and more spherical with aging. Future dedicated studies might reveal whether these changes would affect osteocyte mechanosensation and the subsequent biological response, and whether this is (one of) the pathways involved in age-related bone loss.

Load sharing and ligament strains in balanced, overstuffed and understuffed UKA. A validated finite element analysis.

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.

Developing Advanced Patient-Specific In Silico Models: A New Era in Biomechanical Analysis of Tooth Autotransplantation.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Accuracy of photon-counting computed tomography for the measurement of bone quality in the knee.

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.

The Quantification of Bone Mineral Density Using Photon Counting Computed Tomography and its Implications for Detecting Bone Remodelling.

High-Resolution peripheral quantitative CT (HR-pQCT) has become standard practice when quantifying volumetric bone mineral density (vBMD) in vivo. Yet, it is only accessible to peripheral sites, with small fields of view and lengthy scanning times. This limits general applicability in clinical workflows. The goal of this study was to assess the potential of Photon Counting CT (PCCT) in quantitative bone imaging. Using the European Forearm Phantom, PCCT was calibrated to hydroxy-apatite (HA) density. Eight cadaveric forearms were scanned twice with PCCT, and once with HR-pQCT. The dominant forearm of two volunteers was scanned twice with PCCT. In each scan the carpals were delineated. At bone-level, accuracy was assessed with a paired measurement of total vBMD (Tt.vBMD) calculated with PCCT and HR-pQCT. At voxel-level, repeatability was assessed by image registration and voxel-wise subtraction of the ex vivo PCCT scans. In an ideal scenario, this difference would be zero; any deviation was interpreted as falsely detected remodelling. For clinical usage, the least detectable remodelling was determined by finding a threshold in the PCCT difference image that resulted in a classification of bone formation and resorption below acceptable noise levels (<0.5%). The paired measurement of Tt.vBMD had a Pearson correlation of 0.986. Compared to HR-pQCT, PCCT showed a bias of 7.46 mgHA/cm3. At voxel-level, the repeated PCCT scans showed a bias of 17.66 mgHA/cm3 and standard error of 96.23 mgHA/cm3. Least detectable remodelling was found to be 250 mgHA/cm3, for which 0.37% of the voxels was incorrectly classified as newly added or resorbed bone. In vivo, this volume increased to 0.97%. Based on the cadaver data we conclude that PCCT can be used to quantify vBMD and bone turnover. We provided proof of principle that this technique is also accurate in vivo, hence, that it has high potential for clinical applications.

In quantitative computed tomography (QCT) , bone images have grey values that reflect the local bone mineral content within each voxel. Aggregated over large bone regions, a total bone mineral density can be calculated, which helps in identifying weak bones and fracture risk. At small scales, QCT can detect where bone is being formed, and thus the bone mineral content increases, and where bone is being removed, and thus the bone mineral content decreases. These measurements are typically done with high-resolution peripheral QCT (HR-pQCT). However, HR-pQCT can only scan small regions of the arms and legs, for which a long scanning time is needed. This makes it challenging to use HR-pQCT in a clinical context. Photon Counting CT (PCCT) is a new CT device that can scan bone with an image quality similar to HR-pQCT, yet it can scan faster and cover a larger area. Used at the large scale, our results indicate that PCCT and HR-pQCT can be used interchangeably for the quantification of bone mineral density in large bone regions. Used at small scales, our results indicate that both technologies can detect changes in bone mineral content with similar sensitivity. These results demonstrate that PCCT enables the use of these QCT analyses in a clinical context.

Inter-laboratory reproduction and sensitivity study of a finite element model to quantify human femur failure load: Case of metastases.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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 %). CONCLUSION: 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.

Glucocorticoid-induced changes in the geometry of osteoclast resorption cavities affect trabecular bone stiffness.

Bone fracture risk can increase through bone microstructural changes observed in bone pathologies, such as glucocorticoid-induced osteoporosis. Resorption cavities present one of these microstructural aspects. We recently found that glucocorticoids (GCs) affect the shape of the resorption cavities. Specifically, we found that in the presence of GC osteoclasts (OCs) cultured on bone slices make more trenchlike cavities, compared to rather round cavities in the absence of GCs, while the total eroded surface remained constant. For this study, we hypothesized that trenchlike cavities affect bone strength differently compared to round cavities. To test this hypothesis, we cultured OCs on bone slices in the presence and absence of GC and quantified their dimensions. These data were used to model the effects of OC resorption cavities on bone mechanical properties using a validated beam-shell finite element model of trabecular bone. We demonstrated that a change in the geometry of resorption cavities is sufficient to affect bone competence. After correcting for the increased EV/BV with GCs, the difference to the control condition was no longer significant, indicating that the GC-induced increase in EV/BV, which is closely related to the shape of the cavities, highly determines the stiffness effect. The lumbar spine was the anatomic site most affected by the GC-induced changes on the shape of the cavities. These findings might explain the clinical observation that the prevalence of vertebral fractures during GC treatment increases more than hip, forearm and other nonvertebral fractures.

Transmission of whole-body vibration and its effect on muscle activation.

The aim of current study was to measure the transmission of whole-body vibration through the entire body and to relate this to body posture and induced muscular activation. Eight clinically healthy subjects performed 3 static body postures-high squat (135°), deep squat (110°), and erect stance, whereas vibration transmission was assessed over a wide range of accelerations (from 0.33 to 7.98 g) and frequencies (from 30 to 50 Hz). To assess the vibration transmission, 9 triaxial accelerometers were attached from the ankle up to the head and the root mean square of acceleration signal of each site-specific body point was calculated. Additionally, muscle activity from 7 lower limb muscles was recorded. The results showed a significant attenuation of the platform accelerations transmitted from the feet to the head. Compared with erect stance, knee bent posture significantly diminished vibration transmission at the hip, spine, and the head (p < 0.05). Vibration transmission to the spine was significantly lower in deep vs. high squat (p < 0.05), suggesting that further knee bending may reduce the risk of overloading the spine. Vibration increased the muscle activity in most leg and hip muscles during both squat postures, although, on average, no clear dose-response relationship between the acceleration and/or frequency and muscle response was found. The muscular activation of vastus medialis and rectus femoris showed clear negative correlation to the vibration transmission at the sternum. The specific vibration parameters used in the present study can be considered as safe and suitable for a training program. Moreover, the present results contribute to optimize the most advantageous whole-body vibration protocol and to determine the beneficial effects on muscle and bone.

Fracture risk assessment and evaluation of femoroplasty in metastatic proximal femurs. An in vivo CT-based finite element study.

The goal of this study was twofold. First, we aimed to evaluate the accuracy of a finite element (FE) model to predict bone fracture in cancer patients with proximal femoral bone metastases. Second, we evaluated whether femoroplasty could effectively reduce fracture risk. A total of 89 patients were included, with 101 proximal femurs affected with bone metastases. The accuracy of the model to predict fracture was evaluated by comparing the FE failure load, normalized for body weight, against the actual occurrence of fracture during a 6-month follow-up. Using a critical threshold, the model could identify whether femurs underwent fracture with a sensitivity of 92% and a specificity of 66%. A virtual treatment with femoroplasty was simulated in a subset of 34 out of the 101 femurs; only femurs with one or more well-defined lytic lesions were considered eligible for femoroplasty. We modeled their lesions, as well as the surrounding 4 mm of trabecular bone, to be augmented with bone cement. The simulation of femoroplasty increased the median failure load of the FE model by 57% for lesions located in the head/neck of the femur. At this lesion location, all high risk femurs that had fractured during follow-up effectively moved from a failure load below the critical threshold to a value above. For lesions located in the trochanteric region, no definite improvement in failure load was found. Although additional validation studies are required, our results suggest that femoroplasty can effectively reduce fracture risk for several osteolytic lesions in the femoral head/neck.

A combined experimental and finite element analysis of the human elbow under loads of daily living.

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.

Structural and functional heterogeneity of mineralized fibrocartilage at the Achilles tendon-bone insertion.

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). STATEMENT OF SIGNIFICANCE: 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.

Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity.

Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.