Three-dimensional cortical and trabecular bone microstructure of the proximal ulna.

INTRODUCTION: The three-dimensional (3D) microstructure of the cortical and trabecular bone of the proximal ulna has not yet been described by means of high-resolution 3D imaging. An improved characterization can provide a better understanding of their relative contribution to resist impact load. The aim of this study is to describe the proximal ulna bone microstructure using micro-computed tomography (micro-CT) and relate it to gross morphology and function. MATERIALS AND METHODS: Five dry cadaveric human ulnae were scanned by micro-CT (17 µm/voxel, isotropic). Both qualitative and quantitative assessments were performed on sagittal image stacks. The cortical thickness of the trochlear notch and the trabecular bone microstructure were measured in the olecranon, bare area and coronoid. RESULTS: Groups of trabecular struts starting in the bare area, spanning towards the anterior and posterior side of the proximal ulna, were observed; within the coronoid, the trabeculae were orthogonal to the joint surface. Consistently among the ulnae, the coronoid showed the highest cortical thickness (1.66 ± 0.59 mm, p = 0.04) and the olecranon the lowest (0.33 ± 0.06 mm, p = 0.04). The bare area exhibited the highest bone volume fraction (BV/TV = 43.7 ± 22.4%), trabecular thickness (Tb.Th = 0.40 ± 0.09 mm) and lowest structure model index (SMI = - 0.28 ± 2.20, indicating plate-like structure), compared to the other regions (p = 0.04). CONCLUSIONS: Our microstructural results suggest that the bare area is the region where most of the loading of the proximal ulna is concentrated, whereas the coronoid, together with its anteromedial facet, is the most important bony stabilizer of the elbow joint. Studying the proximal ulna bone microstructure helps understanding its possible everyday mechanical loading conditions and potential fractures. LEVEL OF EVIDENCE: N.A.

Regional differences in the three-dimensional bone microstructure of the radial head: implications for observed fracture patterns.

INTRODUCTION: A characterization of the internal bone microstructure of the radial head could provide a better understanding of commonly occurring fracture patterns frequently involving the (antero)lateral quadrant, for which a clear explanation is still lacking. The aim of this study is to describe the radial head bone microstructure using micro-computed tomography (micro-CT) and to relate it to gross morphology, function and possible fracture patterns. MATERIALS AND METHODS: Dry cadaveric human radii were scanned by micro-CT (17 µm/pixel, isotropic). The trabecular bone microstructure was quantified on axial image stacks in four quadrants: the anterolateral (AL), posterolateral (PL), posteromedial (PM) and anteromedial (AM) quadrant. RESULTS: The AL and PL quadrants displayed the significantly lowest bone volume fraction and trabecular number (BV/TV range 12.3-25.1%, Tb.N range 0.73-1.16 mm-1) and highest trabecular separation (Tb.Sp range 0.59-0.82 mm), compared to the PM and AM quadrants (BV/TV range 19.9-36.9%, Tb.N range 0.96-1.61 mm-1, Tb.Sp range 0.45-0.74 mm) (p = 0.03). CONCLUSIONS: Our microstructural results suggest that the lateral side is the "weaker side", exhibiting lower bone volume faction, less trabeculae and higher trabecular separation, compared to the medial side. As the forearm is pronated during most falls, the underlying bone microstructure could explain commonly observed fracture patterns of the radial head, particularly more often involving the AL quadrant. If screw fixation in radial head fractures is considered, surgeons should take advantage of the "stronger" bone microstructure of the medial side of the radial head, should the fracture line allow this.

Discrete tomography in an in vivo small animal bone study.

This study aimed at assessing the feasibility of a discrete algebraic reconstruction technique (DART) to be used in in vivo small animal bone studies. The advantage of discrete tomography is the possibility to reduce the amount of X-ray projection images, which makes scans faster and implies also a significant reduction of radiation dose, without compromising the reconstruction results. Bone studies are ideal for being performed with discrete tomography, due to the relatively small number of attenuation coefficients contained in the image [namely three: background (air), soft tissue and bone]. In this paper, a validation is made by comparing trabecular bone morphometric parameters calculated from images obtained by using DART and the commonly used standard filtered back-projection (FBP). Female rats were divided into an ovariectomized (OVX) and a sham-operated group. In vivo micro-CT scanning of the tibia was done at baseline and at 2, 4, 8 and 12 weeks after surgery. The cross-section images were reconstructed using first the full set of projection images and afterwards reducing them in number to a quarter and one-sixth (248, 62, 42 projection images, respectively). For both reconstruction methods, similar changes in morphometric parameters were observed over time: bone loss for OVX and bone growth for sham-operated rats, although for DART the actual values were systematically higher (bone volume fraction) or lower (structure model index) compared to FBP, depending on the morphometric parameter. The DART algorithm was, however, more robust when using fewer projection images, where the standard FBP reconstruction was more prone to noise, showing a significantly bigger deviation from the morphometric parameters obtained using all projection images. This study supports the use of DART as a potential alternative method to FBP in X-ray micro-CT animal studies, in particular, when the number of projections has to be drastically minimized, which directly reduces scanning time and dose.

Mixed effects of caffeic acid phenethyl ester (CAPE) on joint inflammation, bone loss and gastrointestinal inflammation in a murine model of collagen antibody-induced arthritis.

OBJECTIVE: To investigate the effect of caffeic acid phenethyl ester (CAPE) on local and systemic inflammation and bone loss in collagen antibody-induced arthritis (CAIA) mice. METHODS: Four groups of mice (n = 8 per group) were allocated; control, CAPE (1 mg/kg), CAIA and CAIA + CAPE (1 mg/kg). Local inflammation and bone loss were evaluated using clinical paw scores, in vivo micro-computed tomography (micro-CT), histological assessment and tartrate-resistant acid phosphatase (TRAP) staining. Serum levels of C-reactive protein (CRP) and C-terminal telopeptide (CTX-1) were measured by ELISA. Jejunum and colon sections were evaluated histopathologically for damage and toxicity. RESULTS: Greater paw scores and percentage change in paw volume were observed in CAIA + CAPE compared to the control groups (p < 0.05). Bone volume over time remained unchanged (p = 0.94) and the number of multinucleated TRAP-positive cells was greatest in CAIA + CAPE mice (p < 0.05). CRP and CTX-1 levels did not differ between groups. CAIA + CAPE mice exhibited lower colon toxicity scores and a reduced percentage of cavitated goblet cells in the colon crypts compared with CAIA mice (p = 0.026 and p = 0.003, respectively). Histopathology in the jejunum was not altered. CONCLUSION: CAPE did not reduce paw inflammation or bone loss in CAIA mice. CAPE reduced histopathological changes in the colon of CAIA mice.

Regional Heterogeneity in the Configuration of the Intracortical Canals of the Femoral Shaft.

Three-dimensional (3D) characterization of cortical porosity, most of which is under 100 µm in diameter, is usually confined to measurements made in 3-4 mm diameter cylinders of bone. We used micro-computed tomography (micro-CT) scanning of entire transaxial cross sections of human proximal femoral shafts (30-35 mm diameter) to quantify regional variation in porosity within the same scan. Complete, up to 10-mm-thick, transaxial slices of femoral upper shafts from 8 female cadavers were studied (n = 3 aged 29-37 years, n = 5 aged 72-90 years). Scanning was performed using high-resolution micro-CT (8.65 µm/voxel). Micro-CT volumes (10 × 10 × 5 mm) were selected via software in the anterior, medial and lateral regions. Images were segmented with voids appearing as 3D-interconnected canals. The percent void-to-tissue volume (Vo.V/TV) and the corresponding void surface area/TV were 86-309% higher in older than younger subjects in anterior (p = 0.034), medial (p = 0.077), and lateral aspects (p = 0.034). Although not significant, void separation was reciprocally lower by 19-39%, and void diameter was 65% larger in older than younger subjects; void number tended to be 24-25% higher medially and laterally but not anteriorly. For all specimens combined, medially there was higher Vo.V/TV and void surface area/TV than anteriorly (+48%, p = 0.018; +33%, p = 0.018) and laterally (+56%, p = 0.062; +36%, p = 0.043). There is regional heterogeneity in the 3D microarchitecture of the intracortical canals of the femoral shaft. The higher void volume in advanced age appears to be due to larger, rather than more, pores. However, creation of new canals from existing canals may contribute, depending on the location. High-resolution micro-computed tomography scanning of entire bone segments enables quantification of the 3D microanatomy of the intracortical void network at multiple locations.

The X-Linked Inhibitor of Apoptosis Protein Inhibitor Embelin Suppresses Inflammation and Bone Erosion in Collagen Antibody Induced Arthritis Mice.

OBJECTIVE: To investigate the effect of Embelin, an inhibitor of X-Linked Inhibitor of Apoptosis Protein (XIAP), on inflammation and bone erosion in a collagen antibody induced arthritis (CAIA) in mice. METHODS: Four groups of mice (n = 6 per group) were allocated: CAIA untreated mice, CAIA treated with Prednisolone (10 mg/kg/day), CAIA treated with low dose Embelin (30 mg/kg/day), and CAIA treated with high dose Embelin (50 mg/kg/day). Joint inflammation was evaluated using clinical paw score and histological assessments. Bone erosion was assessed using micro-CT, tartrate resistant acid phosphatase (TRAP) staining, and serum carboxy-terminal collagen crosslinks (CTX-1) ELISA. Immunohistochemistry was used to detect XIAP protein. TUNEL was performed to identify apoptotic cells. RESULTS: Low dose, but not high dose Embelin, suppressed inflammation as reflected by lower paw scores (P < 0.05) and lower histological scores for inflammation. Low dose Embelin reduced serum CTX-1 (P < 0.05) and demonstrated lower histological score and TRAP counting, and slightly higher bone volume as compared to CAIA untreated mice. XIAP expression was not reduced but TUNEL positive cells were more abundant in Embelin treated CAIA mice. CONCLUSION: Low dose Embelin suppressed inflammation and serum CTX-1 in CAIA mice, indicating a potential use for Embelin to treat pathological bone loss.

Modic (endplate) changes in the lumbar spine: bone micro-architecture and remodelling.

PURPOSE: In the literature, inter-vertebral MRI signal intensity changes (Modic changes) were associated with corresponding histological observations on endplate biopsies. However, tissue-level studies were limited. No quantitative histomorphometric study on bone biopsies has yet been conducted for Modic changes. The aim of this study was to characterise the bone micro-architectural parameters and bone remodelling indices associated with Modic changes. METHODS: Forty patients suffering from disabling low back pain, undergoing elective spinal surgery, and exhibiting Modic changes on MRI (Modic 1, n = 9; Modic 2, n = 25; Modic 3, n = 6), had a transpedicular vertebral body biopsy taken of subchondral bone. Biopsies were first examined by micro-CT, for 3D morphometric analysis of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation, trabecular number, and structure model index. Then, samples underwent histological analysis, for determination of bone remodelling indices: osteoid surface to bone surface ratio (OS/BS), eroded surface to bone surface (ES/BS) and osteoid surface to eroded surface ratio (OS/ES). RESULTS: Micro-CT analysis revealed significantly higher BV/TV (up to 70% increase, p < 0.01) and Tb.Th (up to +57%, p < 0.01) in Modic 3 biopsies, compared to Modic 1 and 2. Histological analysis showed significantly lower OS/BS in Modic 2 biopsies (more than 28% decrease, p < 0.05) compared to 1 and 3. ES/BS progressively decreased from Modic 1 to 2 to 3, whereas OS/ES progressively increased with significantly higher values in Modic 3 (up to 159% increase, p < 0.05) than in Modic 1 and 2. CONCLUSIONS: Significant differences were found in bone micro-architectural parameters and remodelling indices among Modic types. Modic 1 biopsies had evidence of highest bone turnover, possibly due to an inflammatory process; Modic 2 biopsies were consistent with a reduced bone formation/remodelling stage; Modic 3 biopsies suggested a more stable sclerotic phase, with significantly increased BV/TV and Tb.Th compared to Modic 1 and 2, linked to increased bone formation and reduced resorption.

Subregional DXA-derived vertebral bone mineral measures are stronger predictors of failure load in specimens with lower areal bone mineral density, compared to those with higher areal bone mineral density.

Measurement of areal bone mineral density (aBMD) in intravertebral subregions may increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)-derived parameters for vertebral fragility. This study investigated whether DXA-derived bone parameters in vertebral subregions were better predictors of vertebral bone strength in specimens with low aBMD, compared to those with higher aBMD. Twenty-five lumbar vertebrae (15 embalmed and 10 fresh-frozen) were scanned with posteroanterior- (PA) and lateral-projection DXA, and then mechanically tested in compression to ultimate failure. Whole-vertebral aBMD and bone mineral content (BMC) were measured from the PA- and lateral-projection scans and within 6 intravertebral subregions. Multivariate regression was used to predict ultimate failure load by BMC, adjusted for vertebral size and specimen fixation status across the whole specimen set, and when subgrouped into specimens with low aBMD and high aBMD. Adjusted BMC explained a substantial proportion of variance in ultimate vertebral load, when measured over the whole vertebral area in lateral projection (adjusted R (2) 0.84) and across the six subregions (ROIs 2-7) (adjusted R (2) range 0.58-0.78). The association between adjusted BMC, either measured subregionally or across the whole vertebral area, and vertebral failure load, was increased for the subgroup of specimens with identified 'low aBMD', compared to those with 'high aBMD', particularly in the anterior subregion where the adjusted R (2) differed by 0.44. The relative contribution of BMC measured in vertebral subregions to ultimate failure load is greater among specimens with lower aBMD, compared to those with higher aBMD, particularly in the anterior subregion of the vertebral body.

Time-elapsed microstructural imaging of failure of the reverse shoulder implant.

BACKGROUND: Reverse Shoulder Arthroplasties (RSA) have become a primary choice for improving shoulder function and pain. However, the biomechanical failure mechanism of the humeral component is still unclear. The present study reports a novel protocol for microstructural imaging of the entire humerus implant under load before and after fracture. METHODS: A humerus specimen was obtained from a 75-year-old male donor. An expert surgeon implanted the specimen with a commonly used RSA implant (Aequalis reversed II, Stryker Orthopaedics, USA) and surgical procedure. The physiological glenohumeral contact force that maximized the distal implant migration was selected from a public repository ( orthoload.com ). Imaging and concomitant mechanical testing were performed using a large-volume micro-CT scanner (Nikon XT H 225 ST) and a custom-made compressive stage. Both when intact and once implanted, the specimen was tested under a pre-load and by imposing a constant deformation causing a physiological reaction load (650 N, 10 degrees adducted). The deformation of the implanted specimen was then increased up to fracture, which was identified by a sudden drop of the reaction force, and the specimen was then re-scanned. RESULTS: The specimen's stiffness decreased from 874 N/mm to 464 N/mm after implantation, producing movements of the bone-implant interface consistent with the implant's long-term stability reported in the literature. The micro-CT images displayed fracture of the tuberosity, caused by a combined compression and circumferential tension, induced by the distal migration of the implant. CONCLUSION: The developed protocol offers detailed information on implant mechanics under load relative to intact conditions and fracture, providing insights into the failure mechanics of RSA implants. This protocol can be used to inform future implant design and surgical technique improvements.

Quantifying the immediate post-implantation strain field of cadaveric tibiae implanted with cementless tibial trays: A time-elapsed micro-CT and digital volume correlation analysis during stair descent.

Primary stability, the mechanical fixation between implant and bone prior to osseointegration, is crucial for the long-term success of cementless tibial trays. However, little is known about the mechanical interplay between the implant and bone internally, as experimental studies quantifying internal strain are limited. This study employed digital volume correlation (DVC) to quantify the immediate post-implantation strain field of five cadaveric tibiae implanted with a commercially available cementless titanium tibial tray (Attune, DePuy Synthes). The tibiae were subjected to a five-step loading sequence (0-2.5 bodyweight, BW) replicating stair descent, with concomitant time-elapsed micro-CT imaging. With progressive loads, increased compression of trabecular bone was quantified, with the highest strains directly under the posterior region of the tibial tray implant, dissipating with increasing distance from the bone-implant interface. After load removal of the last load step (2.5BW), residual strains were observed in all of the five tibiae, with residual strains confined within 3.14 mm from the bone-implant interface. The residual strain is reflective of the observed initial migration of cementless tibial trays reported in clinical studies. The presence of strains above the yield strain of bone accepted in literature suggests that inelastic properties should be included within finite element models of the initial mechanical environment. This study provides a means to experimentally quantify the internal strain distribution of human tibia with cementless trays, increasing the understanding of the mechanical interaction between bone and implant.

Imaging of the Microstructural Failure Mechanism in the Human Hip.

Imaging the bone microstructure under progressively increasing loads allows for observing the microstructural failure behavior of bone. Here, we describe a protocol for obtaining a sequence of three-dimensional microstructural images of the entire proximal femur under progressively increasing deformation, causing clinically relevant fractures of the femoral neck. The protocol is demonstrated using four femora from female donors aged 66-80 years at the lower end of bone mineral density in the population (T-score range = -2.09 to -4.75). A radio-transparent compressive stage was designed for loading the specimens replicating a one-leg stance, while recording the applied load during micro-computed tomography (micro-CT) imaging. The field of view was 146 mm wide and 132 mm high, and the isotropic pixel size was 0.03 mm. The force increment was based on finite-element predictions of the fracture load. The compressive stage was used to apply the displacement to the specimen and enact the prescribed force increments. Sub-capital fractures due to opening and shear of the femoral neck occurred after four to five load increments. The micro-CT images and the reaction force measurements were processed to study the bone strain and energy absorption capacity. Instability of the cortex appeared at the early loading steps. The subchondral bone in the femoral head displayed large deformations reaching 16% before fracture, and a progressive increase in the support capacity up to fracture. The deformation energy linearly increased with the displacement up to fracture, while the stiffness decreased to near-zero values immediately before fracture. Three-fourths of the fracture energy was taken by the specimen during the final 25% force increment. In conclusion, the protocol developed revealed a remarkable energy absorption capacity, or damage tolerance, and a synergic interaction between the cortical and trabecular bone at an advanced donor age.

Measurement of subregional vertebral bone mineral density in vitro using lateral projection dual-energy X-ray absorptiometry: validation with peripheral quantitative computed tomography.

Although a strong relationship exists between areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) and bone strength, the predictive validity of aBMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA may be improved by assessing aBMD within vertebral subregions, rather than relying on an estimate derived from the total area of the vertebra. The objective of this study was to validate a method of measuring subregional vertebral aBMD in vitro using lateral-projection DXA against subregional volumetric BMD (vBMD) measured with peripheral quantitative computed tomography (pQCT). A mixed set of 49 lumbar and thoracic vertebrae from 25 donors were scanned using lateral-projection DXA and pQCT. aBMD and apparent vBMD were measured in 7 vertebral regions (1 total area and 6 subregions) from the lateral DXA scan. vBMD was calculated in anatomically equivalent regions from pQCT scan data, using a customised software program designed to increase efficiency of the analysis process. Significant differences in densitometric parameters between subregions were observed by DXA and pQCT (P < 0.01). Subregional vBMD derived from pQCT was explained by a significant proportion of the variance in DXA-derived aBMD (R (2) = 0.51-0.67, P < 0.05) and apparent vBMD (R (2) = 0.64-0.75, P < 0.05). These results confirm the validity of measuring aBMD in vertebral subregions using lateral-projection DXA. The clinical significance should now be explored.

Micro-CT scan optimisation for mechanical loading of tibia with titanium tibial tray: A digital volume correlation zero strain error analysis.

Primary stability of press-fit tibial trays is achieved by introducing an interference fit between bone and implant. The internal cancellous bone strains induced during this process and during loading have yet to be quantified experimentally. Advancements in large-gantry micro-CT imaging and digital volume correlation (DVC) allow quantification of such strains. However, before undertaking such a test, experimental requirements and DVC performance need to be examined, particularly considering the presence of a large orthopaedic implant (tibial tray). The aim of this study was to assess the DVC zero-strain accuracy (mean absolute error: MAER) and precision (standard deviation of error: SDER) on a cadaveric human tibia implanted with a titanium press-fit tray across four plausible scanning configurations, using a cabinet micro-CT system (Nikon XT H 225 ST). These varied in rotation step and resulting scanning time (106 min vs. 66 min), presence or absence of a 2 mm-thick aluminium cylinder for mechanical testing, and X-ray tube voltage (150 kVp vs. 215 kVp). One proximal tibia was implanted and micro-CT scanned (42 µm/pixel), with repeated scanning and specimen repositioning in between. DVC (DaVis, LaVision, direct correlation) was performed on nine cubic volumes of interest (VOIs: 13.4 mm-side) and across the entire proximal tibia. Strain errors were comparable across the four scanning configurations and sufficiently low for assessing bone within its elastic region in VOIs (MAER=223-540 µÎµ; SDER=88-261 µÎµ) and at organ level (MAER=536 µÎµ; SDER=473 µÎµ). Whilst the investigated experimental conditions, including a large titanium implant, present added complexity for DVC analysis, scans of sufficient quality can be achieved, reaching a compromise between the DVC requirements and the wanted application. The approach used for choosing the X-ray source settings considering the transmitted X-ray signal intensity and source power, is also discussed.

Relationships between tibial articular cartilage, in vivo external joint moments and static alignment in end-stage knee osteoarthritis: A micro-CT study.

Biomechanical factors (e.g., joint loading) have a significant role in the progression of osteoarthritis (OA). However, some relationships between in vivo joint loading indices and tibial cartilage thickness are conflicting. This study investigated relationships between pre-operative in vivo external knee joint moments, joint alignment and regional tibial cartilage thickness using micro-CT in subjects with end-stage knee OA. Tibial plateaus from 25 patients that underwent knee replacement for OA were micro-CT scanned (17 µm/voxel). Prior to surgery, subjects underwent gait analysis to calculate external knee moments. The mechanical axis deviation (MAD) was obtained from pre-operative radiographs. Cartilage thickness (Cart.Th) was analyzed from micro-CT images, in anteromedial, anterolateral, posteromedial and posterolateral subregions of interest. Medial-to-lateral Cart.Th ratios were also explored. Relationships between Cart.Th and joint loading indices were examined using Pearson's correlations. Significant correlations were found between Cart.Th and joint loading indices, positive anteromedially with the first peak knee adduction moment (r = 0.55, p < 0.01) and external rotation moment (ERM; r = 0.52, p < 0.01), and negative with MAD (r = -0.76, p < 0.001). In the lateral regions, these correlations had opposite signs. The medial-to-lateral Cart.Th ratio correlated strongly with ERM (r = 0.63, p = 0.001) and MAD (r = -0.75, p < 0.001). Joint loading indices correlated with regional cartilage thickness values and their medial-to-lateral ratios in end-stage knee OA subjects, with higher regional loads corresponding to thinner cartilage. These relationships have the opposite sign compared to the subchondral bone microarchitecture found in our previous study on the same specimens, which may suggest a complementary bone-cartilage interplay in response to loading.

A semiautomated method to quantitatively assess osteolytic lesion volume and bone mineral density within acetabular regions of interest from CT.

The objectives of this study were to (1) develop a semiautomated method to obtain lesion volume and bone mineral density (BMD) in terms of Hounsfield units from pelvic computed tomography (CT) scans in three regions of interest, and (2) assess accuracy and reliability of the method based on cadaveric CT scans. Image artefacts due to metal implants reduce CT clarity and are more severe with more than one implant in situ. Therefore, accuracy and reliability tests were performed with varying numbers of total hip arthroplasties implanted. To test the accuracy of lesion size measurements, microcomputed tomography was used as a reference. Mean absolute error ranged from 36 to 284 mm3 after five measurements. Intra- and inter-operator reliability of the entire method was measured for a selection of parameters. All coefficient of variation values were good to excellent for CT scans of the native pelvic anatomy and a CT scans of the same pelvis with one and two implants in situ. Accuracy of quantifying lesion volume decreased with decreasing CT image clarity by 0.6%-3.6% mean absolute relative error. Reliability of lesion volume measurement decreased with decreasing CT clarity. This was also the case for reliability of BMD measurements in the region most disrupted by metal artefact. The presented method proposes an approach for quantifying bone loss which has been proven to be accurate, reliable, and clinically applicable.

Ex vivo assessment of surgically repaired tibial plateau fracture displacement under axial load using large-volume micro-CT.

Postoperative weight bearing has the potential to generate fragmental motion of surgically repaired tibial plateau fractures (TPFs), which may contribute to loss of fracture reduction. The effect of loading on the internal distribution of fragmentary displacements is currently unknown. The aim of this study was to determine the internal displacements of surgically repaired split TPFs due to a three-bodyweight load, using large-volume micro-CT imaging and image correlation. Fractures were generated and surgically repaired for two cadaveric specimens. Load was applied to the specimens inside a large-volume micro-CT system and scanned at 0.046 mm isotropic voxel size. Pre- and post-loading images were paired, co-registered, and internal fragmentary displacements quantified. Internal fragmental displacements of the cadaveric bones were compared to in vivo displacements measured in the lateral split fragments of TPFs in a clinical cohort of patients who had similar surgical repair and were prescribed pain tolerated postoperative weight bearing. The split fragments of cadaveric specimens displaced, on average, less than 0.3 mm, consistent with in vivo measurements. Specimen one rotated around the mediolateral axis, while specimen two displaced consistently caudally. Specimen two also had varying displacements along the mediolateral axis where, at the fracture site, the fragment displaced caudally and laterally, while the most lateral edge of the tibial plateau displaced caudally and medially. The methods applied in this study can be used to measure internal fragmental motion within TPFs.

In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta.

Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (IUT) may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knockin mouse with a classical glycine substitution in type I collagen [alpha1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic tissues differentiated to trabecular and cortical bone cells and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (P < .05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting IUT as a promising approach for the treatment of genetic bone diseases.

Body Anthropometry and Bone Strength Conjointly Determine the Risk of Hip Fracture in a Sideways Fall.

We hypothesize that variations of body anthropometry, conjointly with the bone strength, determine the risk of hip fracture. To test the hypothesis, we compared, in a simulated sideways fall, the hip impact energy to the energy needed to fracture the femur. Ten femurs from elderly donors were tested using a novel drop-tower protocol for replicating the hip fracture dynamics during a fall on the side. The impact energy was varied for each femur according to the donor's body weight, height and soft-tissue thickness, by adjusting the drop height and mass. The fracture pattern, force, energy, strain in the superior femoral neck, bone morphology and microarchitecture were evaluated. Fracture patterns were consistent with clinically relevant hip fractures, and the superior neck strains and timings were comparable with the literature. The hip impact energy (11 - 95 J) and the fracture energy (11 - 39 J) ranges overlapped and showed comparable variance (CV = 69 and 61%, respectively). The aBMD-based definition of osteoporosis correctly classified 7 (70%) fracture/non-fracture cases. The incorrectly classified cases presented large impact energy variations, morphology variations and large subcortical voids as seen in microcomputed tomography. In conclusion, the risk of osteoporotic hip fracture in a sideways fall depends on both body anthropometry and bone strength.

Damage tolerance and toughness of elderly human femora.

Observations of elastic instability of trabecular bone cores supported the analysis of cortical thickness for predicting bone fragility of the hip in people over 60 years of age. Here, we falsified the hypothesis that elastic instability causes minimal energy fracture by analyzing, with a micrometric resolution, the deformation and fracture behavior of entire femora. Femur specimens were obtained from elderly women aged between 66 - 80 years. Microstructural images of the proximal femur were obtained under 3 - 5 progressively increased loading steps and after fracture. Bone displacements, strain, load bearing and energy absorption capacity were analyzed. Elastic instability of the cortex appeared at early loading stages in regions of peak compression. No elastic instability of trabecular bone was observed. The subchondral bone displayed local crushing in compression at early loading steps and progressed to 8 - 16% compression before fracture. The energy absorption capacity was proportional to the displacement. Stiffness decreased to near-zero values before fracture. Three-fourth of the fracture energy (10.2 - 20.2 J) was dissipated in the final 25% force increment. Fracture occurred in regions of peak tension and shear, adjacent to the location of peak compression, appearing immediately before fracture. Minimal permanent deformation was visible along the fracture surface. Elastic instability modulates the interaction between cortical and trabecular bone promoting an elastically stable fracture behavior of the femur organ, load bearing capacity, toughness, and damage tolerance. These findings will advance current methods for predicting hip fragility.

Investigating in vivo knee volumetric bone mineral density and walking gait mechanics in healthy people.

The aim of this study was to investigate if the distribution of subchondral volumetric bone mineral density (vBMD) from peripheral quantitative computed tomography (pQCT) is related to estimates of knee joint loads calculated during walking gait in healthy young people. We recruited 19 young (age 18-40 years) healthy people with no self-reported knee pain or pathology. For all participants we collected two forms of data: (1) pQCT data at 2% of tibia length (from the proximal joint line) using a Stratec XCT3000 scanner at 0.2 × 0.2 mm in plane resolution; and (2) indices of joint loading, specifically external joint moment, at the indexed knee during walking gait. Joint moments were calculated from motion capture and ground reaction force data. pQCT scans were performed immediately prior to gait analysis. A sub-group of 9 participants attended a second scanning session to establish the reproducibility of the pQCT workflow. vBMD was extracted for four sub-regions (anteromedial, anterolateral, posteromedial and posterolateral). Reproducibility of the pQCT workflow was good to excellent (ICCs 0.832-0.985) with minimal detectable differences ranging from 2.3-39.5 mg HA/cm3. Significant independent correlations were identified between the external rotation moment and the medial-to-lateral (r = 0.517), posteromedial-to-posterolateral (r = 0.627) and posteromedial-to-anterolateral (r = 0.518) vBMD ratios, and between the knee adduction moment and the medial-to-lateral (r = -0.476) and posteromedial-to-posterolateral (r = -0.497) vBMD ratios. There appear to be significant relationships between measures of vBMD from pQCT and indices of joint loading in healthy people. These data are the first to combine imaging at the resolution available with pQCT and indices of joint loading in the same cohort.