Intra-operator Repeatability of Manual Segmentations of the Hip Muscles on Clinical Magnetic Resonance Images.

The manual segmentation of muscles on magnetic resonance images is the gold standard procedure to reconstruct muscle volumes from medical imaging data and extract critical information for clinical and research purposes. (Semi)automatic methods have been proposed to expedite the otherwise lengthy process. These, however, rely on manual segmentations. Nonetheless, the repeatability of manual muscle volume segmentations performed on clinical MRI data has not been thoroughly assessed. When conducted, volumetric assessments often disregard the hip muscles. Therefore, one trained operator performed repeated manual segmentations (n = 3) of the iliopsoas (n = 34) and gluteus medius (n = 40) muscles on coronal T1-weighted MRI scans, acquired on 1.5 T scanners on a clinical population of patients elected for hip replacement surgery. Reconstructed muscle volumes were divided in sub-volumes and compared in terms of volume variance (normalized variance of volumes - nVV), shape (Jaccard Index-JI) and surface similarity (maximal Hausdorff distance-HD), to quantify intra-operator repeatability. One-way repeated measures ANOVA (or equivalent) tests with Bonferroni corrections for multiple comparisons were conducted to assess statistical significance. For both muscles, repeated manual segmentations were highly similar to one another (nVV: 2-6%, JI > 0.78, HD < 15 mm). However, shape and surface similarity were significantly lower when muscle extremities were included in the segmentations (e.g., iliopsoas: HD -12.06 to 14.42 mm, P < 0.05). Our findings show that the manual segmentation of hip muscle volumes on clinical MRI scans provides repeatable results over time. Nonetheless, extreme care should be taken in the segmentation of muscle extremities.

Morphologies in-between: The impact of the first steps on the human talus.

OBJECTIVE: The development of bipedalism is a very complex activity that contributes to shaping the anatomy of the foot. The talus, which starts ossifying in utero, may account for the developing stages from the late gestational phase onwards. Here, we explore the early development of the talus in both its internal and external morphology to broaden the knowledge of the anatomical changes that occur during early development. MATERIALS AND METHODS: The sample consists of high-resolution microCT scans of 28 modern juvenile tali (from 36 prenatal weeks to 2 years), from a broad chronological range from the Late Roman period to the 20th century. We applied geometric morphometric and whole-bone trabecular analysis to investigate the early talar morphological changes. RESULTS: In the youngest group (<6 postnatal months), the immature external shell is accompanied by an isotropic internal structure, with thin and densely packed trabeculae. After the initial attempts of locomotion, bone volume fraction decreases, while anisotropy and trabecular thickness increase. These internal changes correspond to the maturation of the external shell, which is now more defined and shows the development of the articular surfaces. DISCUSSION: The internal and external morphology of the human talus reflects the diverse load on the foot during the initial phases of the bipedal locomotion, with the youngest group potentially reflecting the lack of readiness of the human talus to bear forces and perform bipedal walking. These results highlight the link between mechanical loading and bone development in the human talus during the acquisition of bipedalism, providing new insight into the early phases of talar development.

Statistical Properties of a Virtual Cohort for In Silico Trials Generated with a Statistical Anatomy Atlas.

Osteoporosis-related hip fragility fractures are a catastrophic event for patient lives but are not frequently observed in prospective studies, and therefore phase III clinical trials using fractures as primary clinical endpoint require thousands of patients enrolled for several years to reach statistical significance. A novel answer to the large number of subjects needed to reach the desired evidence level is offered by In Silico Trials, that is, the simulation of a clinical trial on a large cohort of virtual patients, monitoring the biomarkers of interest. In this work we investigated if statistical aliasing from a custom anatomy atlas could be used to expand the patient cohort while retaining the original biomechanical characteristics. We used a pair-matched cohort of 94 post-menopausal women (at the time of the CT scan, 47 fractured and 47 not fractured) to create a statistical anatomy atlas through principal component analysis, and up-sampled the atlas in order to obtain over 1000 synthetic patient models. We applied the biomechanical computed tomography pipeline to the resulting virtual cohort and compared its fracture risk distribution with that of the original physical cohort. While the distribution of femoral strength values in the non-fractured sub-group was nearly identical to that of the original physical cohort, that of the fractured sub-group was lower than in the physical cohort. Nonetheless, by using the classification threshold used for the original population, the synthetic population was still divided into two parts of approximatively equal number.

Computational dosimetry in MRI in presence of hip, knee or shoulder implants: do we need accurate surgery models?

Objective.To quantify the effects of different levels of realism in the description of the anatomy around hip, knee or shoulder implants when simulating, numerically, radiofrequency and gradient-induced heating in magnetic resonance imaging. This quantification is needed to define how precise the digital human model modified with the implant should be to get realistic dosimetric assessments.Approach. The analysis is based on a large number of numerical simulations where four 'levels of realism' have been adopted in modelling human bodies carrying orthopaedic implants.Main results. Results show that the quantification of the heating due to switched gradient fields does not strictly require a detailed local anatomical description when preparing the digital human model carrying an implant. In this case, a simple overlapping of the implant CAD with the body anatomy is sufficient to provide a quite good and conservative estimation of the heating. On the contrary, the evaluation of the electromagnetic field distribution and heating caused by the radiofrequency field requires an accurate description of the tissues around the prosthesis.Significance. The results of this paper provide hints for selecting the 'level of realism' in the definition of the anatomical models with embedded passive implants when performing simulations that should reproduce, as closely as possible, thein vivoscenarios of patients carrying orthopaedic implants.

A Cationic Contrast Agent in X-ray Imaging of Articular Cartilage: Pre-Clinical Evaluation of Diffusion and Attenuation Properties.

The aim of this study was the preliminary assessment of a new cationic contrast agent, the CA4+, via the analysis of spatial distribution in cartilage of ex vivo bovine samples, at micrometer and millimeter scale. Osteochondral plugs (n = 18) extracted from bovine stifle joints (n = 2) were immersed in CA4+ solution up to 26 h. Planar images were acquired at different time points, using a microCT apparatus. The CA4+ distribution in cartilage and saturation time were evaluated. Tibial plates from bovine stifle joints (n = 3) were imaged with CT, before and after 24 h-CA4+ bath immersion, at different concentrations. Afterward, potential CA4+ washout from cartilage was investigated. From microCT acquisitions, the CA4+ distribution differentiated into three distinct layers inside the cartilage, reflecting the spatial distribution of proteoglycans. After 24 h of diffusion, the iodine concentration reached in cartilage was approximately seven times that of the CA4+ bath. The resulting saturation time was 1.9 ± 0.9 h and 2.6 ± 2.9 h for femoral and tibial samples, respectively. Analysis of clinical CT acquisitions confirmed overall contrast enhancement of cartilage after 24 h immersion, observed for each CA4+ concentration. Distinct contrast enhancement was reached in different cartilage regions, depending on tissue's local features. Incomplete but remarkable washout of cartilage was observed. CA4+ significantly improved cartilage visualization and its qualitative analysis.

Classification Scheme of Heating Risk during MRI Scans on Patients with Orthopaedic Prostheses.

Due to the large variety of possible clinical scenarios, a reliable heating-risk assessment is not straightforward when patients with arthroplasty undergo MRI scans. This paper proposes a simple procedure to estimate the thermal effects induced in patients with hip, knee, or shoulder arthroplasty during MRI exams. The most representative clinical scenarios were identified by a preliminary frequency analysis, based on clinical service databases, collecting MRI exams of 11,658 implant carrier patients. The thermal effects produced by radiofrequency and switching gradient fields were investigated through 588 numerical simulations performed on an ASTM-like phantom, considering four prostheses, two static field values, seven MR sequences, and seven regions of imaging. The risk assessment was inspired by standards for radiofrequency fields and by scientific studies for gradient fields. Three risk tiers were defined for the radiofrequency, in terms of whole-body and local SAR averages, and for GC fields, in terms of temperature elevation. Only 50 out of 588 scenarios require some caution to be managed. Results showed that the whole-body SAR is not a self-reliant safety parameter for patients with metallic implants. The proposed numerical procedure can be easily extended to any other scenario, including the use of detailed anatomical models.

Dual-Energy Computed Tomography Applications to Reduce Metal Artifacts in Hip Prostheses: A Phantom Study.

Metal components of hip prostheses cause severe artifacts in CT images, influencing diagnostic accuracy. Metal artifact reduction (MAR) software and virtual monoenergetic reconstructions on dual-energy CT (DECT) systems are possible solutions that should be considered. In this study, we created a customized adjustable phantom to quantify the severity of artifacts on periprosthetic tissues (cortical and spongious bone, soft tissues) for hip prostheses. The severity of artifacts was classified by different thresholds of deviation from the CT numbers for reference objects not affected by artifacts. The in vitro setup was applied on four unilateral and three bilateral configurations of hip prostheses (made of titanium, cobalt, and stainless steel alloys) with a DECT system, changing the energy of virtual monoenergetic reconstructions, with and without MAR. The impact of these tools on the severity of artifacts was scored, looking for the best scan conditions for the different configurations. For titanium prostheses, the reconstruction at 110 keV, without MAR, always minimized the artifacts. For cobalt and stainless-steel prostheses, MAR should always be applied, while monoenergetic reconstruction alone did not show clear advantages. The available tools for reducing metal artifacts must therefore be applied depending on the examined prosthetic configuration.

An infant burial from Arma Veirana in northwestern Italy provides insights into funerary practices and female personhood in early Mesolithic Europe.

The evolution and development of human mortuary behaviors is of enormous cultural significance. Here we report a richly-decorated young infant burial (AVH-1) from Arma Veirana (Liguria, northwestern Italy) that is directly dated to 10,211-9910 cal BP (95.4% probability), placing it within the early Holocene and therefore attributable to the early Mesolithic, a cultural period from which well-documented burials are exceedingly rare. Virtual dental histology, proteomics, and aDNA indicate that the infant was a 40-50 days old female. Associated artifacts indicate significant material and emotional investment in the child's interment. The detailed biological profile of AVH-1 establishes the child as the earliest European near-neonate documented to be female. The Arma Veirana burial thus provides insight into sex/gender-based social status, funerary treatment, and the attribution of personhood to the youngest individuals among prehistoric hunter-gatherer groups and adds substantially to the scant data on mortuary practices from an important period in prehistory shortly following the end of the last Ice Age.

Characterization of Structural Bone Properties through Portable Single-Sided NMR Devices: State of the Art and Future Perspectives.

Nuclear Magnetic Resonance (NMR) is a well-suited methodology to study bone composition and structural properties. This is because the NMR parameters, such as the T2 relaxation time, are sensitive to the chemical and physical environment of the 1H nuclei. Although magnetic resonance imaging (MRI) allows bone structure assessment in vivo, its cost limits the suitability of conventional MRI for routine bone screening. With difficulty accessing clinically suitable exams, the diagnosis of bone diseases, such as osteoporosis, and the associated fracture risk estimation is based on the assessment of bone mineral density (BMD), obtained by the dual-energy X-ray absorptiometry (DXA). However, integrating the information about the structure of the bone with the bone mineral density has been shown to improve fracture risk estimation related to osteoporosis. Portable NMR, based on low-field single-sided NMR devices, is a promising and appealing approach to assess NMR properties of biological tissues with the aim of medical applications. Since these scanners detect the signal from a sensitive volume external to the magnet, they can be used to perform NMR measurement without the need to fit a sample inside a bore of a magnet, allowing, in principle, in vivo application. Techniques based on NMR single-sided devices have the potential to provide a high impact on the clinical routine because of low purchasing and running costs and low maintenance of such scanners. In this review, the development of new methodologies to investigate structural properties of trabecular bone exploiting single-sided NMR devices is reviewed, and current limitations and future perspectives are discussed.

Interleukin-6 neutralization ameliorates symptoms in prematurely aged mice.

Hutchinson-Gilford progeria syndrome (HGPS) causes premature aging in children, with adipose tissue, skin and bone deterioration, and cardiovascular impairment. In HGPS cells and mouse models, high levels of interleukin-6, an inflammatory cytokine linked to aging processes, have been detected. Here, we show that inhibition of interleukin-6 activity by tocilizumab, a neutralizing antibody raised against interleukin-6 receptors, counteracts progeroid features in both HGPS fibroblasts and LmnaG609G/G609G progeroid mice. Tocilizumab treatment limits the accumulation of progerin, the toxic protein produced in HGPS cells, rescues nuclear envelope and chromatin abnormalities, and attenuates the hyperactivated DNA damage response. In vivo administration of tocilizumab reduces aortic lesions and adipose tissue dystrophy, delays the onset of lipodystrophy and kyphosis, avoids motor impairment, and preserves a good quality of life in progeroid mice. This work identifies tocilizumab as a valuable tool in HGPS therapy and, speculatively, in the treatment of a variety of aging-related disorders.

Single-sided NMR to estimate morphological parameters of the trabecular bone structure.

PURPOSE: Single-sided 1 H-NMR is proposed for the estimation of morphological parameters of trabecular bone, and potentially the detection of pathophysiological alterations of bone structure. In this study, a new methodology was used to estimate such parameters without using an external reference signal, and to study intratrabecular and intertrabecular porosities, with a view to eventually scanning patients. METHODS: Animal trabecular bone samples were analyzed by a single-sided device. The Carr-Purcell-Meiboom-Gill sequence of 1 H nuclei of fluids, including marrow, confined inside the bone, was analyzed by quasi-continuous T2 distributions and separated into two 1 H pools: short and long T2 components. The NMR parameters were estimated using models of trabecular bone structure, and compared with the corresponding micro-CT. RESULTS: Without any further assumptions, the internal reference parameter (short T2 signal intensity fraction) enabled prediction of the micro-CT parameters BV/TV (volume of the trabeculae/total sample volume) and BS/TV (external surface of the trabeculae/total sample volume) with linear correlation coefficient >0.80. The assignment of the two pools to intratrabecular and intertrabecular components yielded an estimate of average intratrabecular porosity (33 ± 5)%. Using the proposed models, the NMR-estimated BV/TV and BS/TV were found to be linearly related to the corresponding micro-CT values with high correlation (>0.90 for BV/TV; >0.80 for BS/TV) and agreement coefficients. CONCLUSION: Low-field, low-cost portable devices that rely on intrinsic magnetic field gradients and do not use ionizing radiation are viable tools for in vitro preclinical studies of pathophysiological structural alterations of trabecular bone.

Squeaking and other noises in patients with ceramic-on-ceramic total hip arthroplasty.

INTRODUCTION: Noise in ceramic-on-ceramic (CoC) total hip arthroplasty (THA) is a potential symptom of abnormal bearing wear. Squeaking and other prosthetic hip noises are multi-factorial phenomena that can be analysed and may provide prognostic information. METHODS: 46 patients with noisy CoC bearings were investigated using X-ray, computed tomography and joint fluid analysis, and classified into either high or low risk of ceramic liner fracture groups according to previously published guidelines. Noise events from the bearings of 16 high risk cases which were subsequently revised were compared with 30 patients in the low risk control group who did not undergo revision. Noise events were analysed for their physical characteristics using a standardised protocol and classified as either low frequency and short duration 'clicking' or long duration and high frequency 'squeaking'. RESULTS: The peak frequency of squeaking during forward walking was significantly higher for patients in the case group who were revised, compared with the control group. The patient-reported onset of squeaking (46 months postoperatively) was earlier than short-noise emissions (82 months). In the standardised sequence of movements, short-noise always occurred more frequently than squeaking. Small heads (28 mm) were more likely to develop short-noise, while large heads (⩾32 mm) were more likely to develop squeaking. DISCUSSION: Noise evaluation may provide additional value for predicting failure of CoC bearings, though some questions should be better investigated in a dedicated prospective trial.

Long term breeding of the Lmna G609G progeric mouse: Characterization of homozygous and heterozygous models.

The transgenic LmnaG609G progeric mouse represents an outstanding animal model for studying the human Hutchinson-Gilford Progeria Syndrome (HGPS) caused by a mutation in the LMNA gene, coding for the nuclear envelope protein Lamin A/C, and, as an important, more general scope, for studying the complex process governing physiological aging in humans. Here we give a comprehensive description of the peculiarities related to the breeding of LmnaG609G mice over a prolonged period of time, and of many features observed in a large colony for a 2-years period. We describe the breeding and housing conditions underlining the possible interference of the genetic background on the phenotype expression. This information represents a useful tool when planning and interpreting studies on the LmnaG609G mouse model, complementing any specific data already reported in the literature about this model since its production. It is also particularly relevant for the heterozygous mouse, which mirrors the genotype of the human pathology however requires an extended time to manifest symptoms and to be carefully studied.

CoCr porous scaffolds manufactured via selective laser melting in orthopedics: Topographical, mechanical, and biological characterization.

Over the last decade, advances in additive manufacturing have allowed to obtain complex 3D porous lattice in materials suitable for orthopedic applications. Whereas 3D-melted titanium alloys have been extensively investigated, little is the current knowledge on the feasibility of bone-replicating CoCr porous scaffolds manufactured via selective laser melting (SLM). Moreover, the effect of topography on bone cells viability and proliferation has not been fully explored yet. Small cylindrical porous lattices were modeled from micro-CT images of human trabecular bone, and from the repetition of spherical-hollow and body-centered cubic unit cells, and manufactured via SLM from CoCr powder. Macro- and microcharacterization of the porous samples were assessed using optical microscope, micro-CT, and SEM. The scaffolds mechanical properties, measured via ISO testing, compared well with those of the human bone. Osteoblast-like cells proliferation and viability were assessed in vitro, and compared to those cultured on a standard nonporous implant-to-bone interface, showing steady increase on all geometries over time. SEM analysis confirmed the quality of cells morphology, spread, and organization on all lattices. The SLM process appeared not to alter the biocompatibility of CoCr; however, 15-100 µm irregularities and macroalterations were observed in the porous scaffolds with respect to the 3D nominal models. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2343-2353, 2019.

Bone volume-to-total volume ratio measured in trabecular bone by single-sided NMR devices.

PURPOSE: Reduced bone strength is associated with a loss of bone mass, usually evaluated by dual-energy X-ray absorptiometry, although it is known that the bone microstructure also affects the bone strength. Here, a method is proposed to measure (in laboratory) the bone volume-to-total volume ratio by single-sided NMR scanners, which is related to the microstructure of the trabecular bone. METHODS: Three single-sided scanners were used on animal bone samples. These low-field, mobile, low-cost devices are able to detect the NMR signal, regardless of the sample sizes, without the use of ionizing radiations, with the further advantage of signal localization offered by their intrinsic magnetic field gradients. RESULTS: The performance of the different single-sided scanners have been discussed. The results have been compared with bone volume-to-total volume ratio by micro CT and MRI, obtaining consistent values. CONCLUSIONS: Our results demonstrate the feasibility of the method for laboratory analyses, which are useful for measurements like porosity on bone specimens. This can be considered as the first step to develop an NMR method based on the use of a mobile single-sided device, for the diagnosis of osteoporosis, through the acquisition of the signal from the appendicular skeleton, allowing for low-cost, wide screening campaigns. Magn Reson Med 79:501-510, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures.

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25-72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25-68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p < 0.05) lower bone volume/trabecular volume ratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volume ratio (p = 0.003) and mean trabecular thickness (p < 0.001) and greater mean trabecular separation (p = 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstructure.

Multiple loading conditions analysis can improve the association between finite element bone strength estimates and proximal femur fractures: a preliminary study in elderly women.

This is a preliminary case-control study on osteopenic/osteoporotic elderly women, testing the association of proximal femur fracture with minimum femoral strength, as derived from finite element (FE) analysis in multiple loading conditions. Fracture cases (n=22) in acute conditions were enrolled among low-trauma fractures admitted in various hospitals in the Emilia Romagna Region, Italy. Women with no history of low-trauma fractures were enrolled as controls (n=33). Patients were imaged with DXA to obtain aBMD, and with a bilateral full femur CT scan. FE-strength was derived in stance and fall configurations: (i) as the minimum strength among those obtained for multiple loading conditions spanning a domain of plausible force directions, and (ii) as the strength associated to the most commonly used single loading conditions. The association of FE-strength and aBMD with fractures was tested with logistic regression models, deriving odds ratios (ORs) and area under the receiver operating characteristic curve (AUC). FE-strength from multiple loading conditions better classified fracture cases from controls (OR per SD change=9.6, 95% CI=3.0-31.3, AUC=0.87 in stance; OR=9.5, 95% CI=2.9-31.2, AUC=0.88 in fall) compared to aBMD (OR=3.6, 95% CI=1.6-8.2, AUC=0.79 for total femur aBMD), while FE-strength results from the most commonly used single loading conditions were similar to aBMD. Only FE-strength from multiple loading conditions remained significant in age- and aBMD-adjusted models (OR=10.5, 95% CI=1.8-61.3, AUC=0.95). In summary, we highlighted the importance of considering different loading conditions to identify bone weakness, and confirmed that femoral FE-strength estimates may add value to aBMD predictions in elderly osteopenic/osteoporotic women.

MHC class II transactivator is an in vivo regulator of osteoclast differentiation and bone homeostasis co-opted from adaptive immunity.

The molecular networks controlling bone homeostasis are not fully understood. The common evolution of bone and adaptive immunity encourages the investigation of shared regulatory circuits. MHC Class II Transactivator (CIITA) is a master transcriptional co-activator believed to be exclusively dedicated for antigen presentation. CIITA is expressed in osteoclast precursors, and its expression is accentuated in osteoporotic mice. We thus asked whether CIITA plays a role in bone biology. To this aim, we fully characterized the bone phenotype of two mouse models of CIITA overexpression, respectively systemic and restricted to the monocyte-osteoclast lineage. Both CIITA-overexpressing mouse models revealed severe spontaneous osteoporosis, as assessed by micro-computed tomography and histomorphometry, associated with increased osteoclast numbers and enhanced in vivo bone resorption, whereas osteoblast numbers and in vivo bone-forming activity were unaffected. To understand the underlying cellular and molecular bases, we investigated ex vivo the differentiation of mutant bone marrow monocytes into osteoclasts and immune effectors, as well as osteoclastogenic signaling pathways. CIITA-overexpressing monocytes differentiated normally into effector macrophages or dendritic cells but showed enhanced osteoclastogenesis, whereas CIITA ablation suppressed osteoclast differentiation. Increased c-fms and receptor activator of NF-κB (RANK) signaling underlay enhanced osteoclast differentiation from CIITA-overexpressing precursors. Moreover, by extending selected phenotypic and cellular analyses to additional genetic mouse models, namely MHC Class II deficient mice and a transgenic mouse line lacking a specific CIITA promoter and re-expressing CIITA in the thymus, we excluded MHC Class II expression and T cells from contributing to the observed skeletal phenotype. Altogether, our study provides compelling genetic evidence that CIITA, the molecular switch of antigen presentation, plays a novel, unexpected function in skeletal homeostasis, independent of MHC Class II expression and T cells, by exerting a selective and intrinsic control of osteoclast differentiation and bone resorption in vivo.

3D identification of trabecular bone fracture zone using an automatic image registration scheme: A validation study.

Accurate identification of the local fracture zone is an important step towards the failure assessment of trabecular bone. In previous in-vitro studies, local fracture zones were visually identified in micro-CT images by experienced observers. This is a time-consuming and observer-dependent approach and it prevents any large-scale analysis of local trabecular fracture regions. The scope of this study is the application and validation of a new registration scheme for the automatic identification of trabecular bone fracture zones. Six human trabecular specimens were extracted from different anatomical sites. Five specimens were mechanically tested and scanned using micro-CT. For each specimen pre- and post-failure micro-CT datasets were obtained. The sixth specimen was scanned twice without any mechanical compression and was used to test the accuracy of the proposed scheme. The registration scheme was applied to the acquired datasets for the automatic identification of the fracture zone. The proposed scheme comprises of a three-dimensional (3D) automatic registration method to define the differences between the two datasets, and the application of a criterion for defining slices of the pre-failure dataset as "broken" or "unbroken". Identifications of the fracture zones were qualitatively validated against visual identification of observers. Furthermore, "full 3D" fracture zone identification, based on the presented scheme, was proposed. The proposed scheme proved to be more accurate and significantly faster than the currently used visual process.