Femoral Sections Research Articles

Morphological Measurement and Clinical Significance of Abnormal Development of Distal Femur with Hemophilia Knee Arthritis: A Consideration on the Renewal of Total Knee Prosthesis.

The knee joint of hemophiliacs may face the result of local morphological changes due to long-term irritation of synovitis. This study aims to elucidate the morphological characteristics of distal femur in hemophilic arthritis (HA) and compare the compatibility of three types of prostheses with the anteroposterior (AP) and mediolateral (ML) dimensions of the femoral osteotomy surface. This study retrospectively and randomly selected 50 patients with HA registered for treatment at our hospital from June 2016 to August 2022 as the study subjects, with an equal number of male osteoarthritis (OA) patients and healthy male individuals set as the control group. This study used medical digitalization software to simulate osteotomies on the distal femur during total knee arthroplasties (TKA) for 50 patients with HA, OA patients, and the healthy population, respectively, and measure the morphological parameters to compare with three commonly used femoral components of TKA in clinical practice. The differences between the femur resection of anteroposterior and mediolateral (FRAP, FRML) osteotomy surface and the prosthesis's BOX-AP/ML were compared in three prostheses. One-way ANOVA and multiple Kruskal-Wallis H test were used for the normal or non-normal distribution data, and pairwise comparisons between groups were conducted using the Bonferroni method, and the linear correlation analysis was utilized to assess the relationship between section femoral morphological data and prosthesis parameters. In HA patients, the morphological characteristics of the distal femur were shown as shorter than femur AP (FAP), medial and lateral condyle anterior-posterior dimension (FMCAP, FLCAP), notch width (NW), posterolateral condyle height (PLCH), posteromedial condyle width (PMCW), and posterior condylar axis length (PCAL) dimension. They had comparatively smaller femur section aspect ratios (p < 0.005). They showed longer posterolateral condyle width (PLCW), anterior condyle mediolateral dimension (FRACML), anterolateral condyle height (ALCH), and femur resection anterior condylar mediolateral (FRACML) dimension (p < 0.005). They showed larger distal femur aspect ratio and resection aspect ratio (FAR, FRAR, p < 0.005). All selected prostheses showed ML undercoverage under similar AP dimensions, and ML undersizing of Attune systems was more obvious in three femoral prostheses. The distal femur morphological change of HA patient is shown as smaller AP dimension, narrow posterior condyle spacing, lower and shallower trochlear, thinner anterior condyle, wider and lower intercondylar notch and higher posterior-lateral condyle. The selected prostheses showed ML undercoverage under similar AP dimensions. This typical morphological tendency of the distal femur seems to warrant consideration in the process of knee joint prosthesis upgrading.

Stem to prevent periprosthetic fracture after notching in total knee arthroplasty.

Improper osteotomy during total knee arthroplasty (TKA) can lead to anterior femoral notching, which increases the risk of periprosthetic fractures due to stress concentration. One potential solution is the addition of an intramedullary stem to the femoral component. However, the optimal stem length remains unclear. In this study, we aimed to determine the optimal stem length using finite element models. Finite element models of femurs were developed with unstemmed prostheses and prostheses with stem lengths of 50, 75, and 100 mm. Under squat loading conditions, the von Mises stress at the notch and stress distribution on four transversal sections of the femur were analyzed. Additionally, micromotion of the prosthesis-bone interface was evaluated to assess initial stability. The unstemmed prosthesis exhibited a von Mises stress of 191.8 MPa at the notch, which decreased to 43.1, 8.8, and 23.5 MPa for stem lengths of 50, 75, and 100 mm, respectively. The stress reduction on four selected femoral transversal sections compared with the unstemmed prosthesis was 40.0%, 84.4%, and 67.1% for stem lengths of 50, 75, and 100 mm, respectively. Micromotion analysis showed a maximum of 118.8 μm for the unstemmed prosthesis, which decreased significantly with the application of stems, particularly at the anterior flange. Intramedullary stems effectively reduced stress concentration at the femoral notch. The 50-mm stem length provided the optimal combination of reduced notch stress, minimized stress-shielding effect, and decreased micromotion at the anterior flange.

Effects of high dose aspartame-based sweetener on the gut microbiota and bone strength in young and aged mice.

In a recent study examining the effects of manipulating the gut microbiome on bone, a control group of mice in which the microbiome was altered using a non-caloric, aspartame-based sweetener resulted in whole bone strength being 40% greater than expected from geometry alone, implicating enhanced bone tissue strength. However, the study was not designed to detect changes in bone in this control group and was limited to young male mice. Here we report a replication study examining how changes in the gut microbiome caused by aspartame-based sweetener influence bone. Male and female C57Bl/6J mice were untreated or treated with a high dose of sweetener (10g/L) in their drinking water from either 1 to 4mo of age (young cohort; n = 80) or 1 to 22mo of age (aged cohort; n = 52). Sweetener did not replicate the modifications to the gut microbiome observed in the initial study and did not result in an increase in bone tissue strength in either sex at either age. Aged male mice dosed with sweetener had larger bones (+17% femur section modulus, p<.001) and greater whole bone strength (+22%, p=.006) but the increased whole bone strength was explained by the associated increase in body mass (+9%, p<.001). No differences in body mass, whole bone strength, or femoral geometry were associated with sweetener dosing in males from the young cohort or females at either age. As we were unable to replicate the gut microbiota observed in the initial experiment, it remains unclear if changes in the gut microbiome can enhance bone tissue strength. Although prior work studying gut microbiome-induced changes in bone with oral antibiotics has been highly repeatable, the current study highlights the variability of nutritional manipulations of the gut microbiota in mice.

Titanium dioxide nanoparticles oral exposure induce osteoblast apoptosis, inhibit osteogenic ability and increase lipogenesis in mouse

Titanium dioxide nanoparticles (TiO2-NPs) are widely used in food, paint, coating, cosmetic, and composite orthodontic material. As a common food additive, TiO2-NPs can accumulate in various organs of human body, but the effect and underlying mechanism of bone remain unclear. Here mice were exposed to TiO2-NPs by oral gavage, and histological staining of femoral sections showed that TiO2-NPs reduced bone formation and enhanced osteoclast activity and lipogenesis, contributing to decreased trabecula bone. Transmission electron microscope (TEM) as well as biochemical and flow cytometry analysis of osteoblast exhibited that TiO2-NPs accumulated in osteoblast cytoplasm and impaired mitochondria ultrastructure with increased reactive oxygen species (ROS) and lipid hyperoxide, resulting in osteoblast apoptosis. In terms of mechanism, TiO2-NPs treatment inhibited expression of AKT and then increased pro-apoptotic protein Bax expression which was failure to form heterodimers with decreased anti-apoptotic Bcl-2, activating downstream Caspase-9 and Caspase-3 and inducing apoptosis. Additionally, TiO2-NPs suppressed Wnt3a level and then activated anti-Glycogen synthesis kinase (GSK-3β) phosphorylation, and ultimately resulted in degradation of β-catenin which down-regulated Runt-related transcription factor 2 (Runx2) and Osterix, inhibiting expression of osteogenic related proteins. Together, these results revealed that exposure of TiO2-NPs induced apoptosis and inhibited osteoblast differentiation through suppressing PI3K/AKT and Wnt/β-catenin signaling pathways, resulting in reduction of trabecula bone.

Peripheral canalicular branching is decreased in streptozotocin-induced diabetes and correlates with decreased whole-bone ultimate load and perilacunar elastic work.

Osteocytes, the most abundant cell type in bone, play a crucial role in mechanosensation and signaling for bone formation and resorption. These cells reside within a complex lacuno-canalicular network (OLCN). Osteocyte signaling is reduced under diabetic conditions, and both type 1 and type 2 diabetes lead to reduced bone turnover, perturbed bone composition, and increased fracture risk. We hypothesized that this reduced bone turnover, and altered bone composition with diabetes is associated with reduced OLCN architecture and connectivity. This study aimed to elucidate: (1) the sequence of OLCN changes with diabetes related to bone turnover and (2) whether changes to the OLCN are associated with tissue composition and mechanical properties. Twelve- to fourteen-week-old male C57BL/6 mice were administered streptozotocin at 50mg/kg for 5 consecutive days to induce hyperglycemia, sacrificed at baseline (BL), or after being diabetic for 3 (D3) and 7 (D7) wk with age-matched (C3, C7) controls (n = 10-12 per group). Mineralized femoral sections were infiltrated with rhodamine, imaged with confocal microscopy, then the OLCN morphology and topology were characterized and correlated against bone histomorphometry, as well as local and whole-bone mechanics and composition. D7 mice exhibited a lower number of peripheral branches relative to C7. The total number of canalicular intersections (nodes) was lower in D3 and D7 relative to BL (P <0.05 for all), and a reduced bone formation rate (BFR) was observed at D7 vs C7. The number of nodes explained only 15% of BFR, but 45% of Ct.BV/TV, and 31% of ultimate load. The number of branches explained 30% and 22% of the elastic work at the perilacunar and intracortical region, respectively. Collectively, the reduction in OLCN architecture and association of OLCN measures with bone turnover, mechanics, and composition highlights the relevance of the osteocyte and the OLCN and a potential therapeutic target for treating diabetic skeletal fragility.

Regenerative effect of microcarrier form of acellular dermal matrix versus bone matrix bio-scaffolds loaded with adipose stem cells on rat bone defect

BackgroundBone defects lead to dramatic changes in the quality of life. Acellular dermal matrix (ADM) and decellularized bone matrix (DBM) are natural scaffolds for tissue regeneration. The microcarrier scaffolds enable better vascularization and cell proliferation. This study compared the effect of microcarrier forms of DBM and ADM-loaded with adipose stem cells (ASCs) in the repair of compact bone defect in-vivo. MethodsFifty-four male rats were divided into 4 groups; (i) Group (Gp) I: sham control; (ii) GpII: underwent femur bone defect induction and left to heal spontaneously; (iii) GpIII (ADM-Gp): included 2 subgroups; IIIa and IIIb: the bone defects were filled with non-loaded ADM and ADM-loaded with ASCs, respectively; (iv) GpIV (DBM-Gp): included 2 subgroups; IVa and IVb: the bone defects were filled with non-loaded DBM and DBM-loaded with ASCs, respectively. Animals were euthanized after 1, 2 and 3 months and their femur sections were stained with H&E, Masson's trichrome and immunohistochemistry for CD31, osteopontin and osteocalcin. ResultsHistological analysis illustrated limited bone regeneration in the cortical defect of GpII after 3 months. The histomorphometric analysis showed significant delayed mature collagen deposition as well as CD31, osteopontin and osteocalcin expression. Superior capacity of new bone regeneration was detected with bio-scaffold micro-carriers; loaded or non-loaded with ASCs. However, DBM-loaded with ASCs displayed enhanced regeneration properties confirmed by the apparently normal architecture of the new bone and accelerated expression of CD31, osteopontin and osteocalcin in the regenerated bone after 3 months. ConclusionsWe concluded that decellularized scaffolds significantly improved compact bone regeneration with superiority of ASCs seeded-bone scaffolds.

Comparison of the prophylactic use of ibandronate and its use in early-stage osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head.

The aim of this study was to investigate the effects of ibandronate before and after the onset of osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head. A total of 24 female Sprague-Dawley rats were used in this study. Three groups were formed with eight rats in each group. The first group was the prophylactic group that received ibandronate treatment before and after the onset of osteonecrosis (Group PT). The second group received ibandronate treatment three weeks after the development of osteonecrosis (Group TAO). The third group was the control group in which osteonecrosis was created, but only normal saline (NS) was given. At the end of the study, all rats were sacrificed, and their right femoral heads were removed, fixed with formalin, and sent for micro-computed tomography. Hematoxylin-eosin (H&E) and immunohistochemical examinations of the right femoral head sections were performed. In the PT group, the trabecular thickness was significantly higher compared to those of the TAO and control groups (p<0.05). The trabecular thickness did not significantly differ between the TAO and control groups. The trabecular bone pattern factor was significantly higher in the PT group compared to the control and TAO groups (p<0.05); however, it showed no significant difference between the TAO and control groups. The incidence of type 2 osteonecrosis in the PT and TAO groups was significantly lower than that in the control group (p<0.05). The incidence of tissue-non-specific alkaline phosphatase (TNAPase) immunoreactivity of osteoblast positivity was significantly higher in the PT and TAO groups compared to the control group (p<0.05), whereas the incidence of TRAPase immunoreactivity of osteoclastic positivity was significantly lower in the PT and TAO groups compared to the control group (p<0.05). Intravenous administration of ibandronate before the onset of the disease was more effective in the treatment of osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head.

Quantitative and large-format histochemistry to characterize peripheral artery compositional gradients.

The femoropopliteal artery (FPA) is a long, flexible vessel that travels down the anteromedial compartment of the thigh as the femoral artery andthen behind the kneecap as the popliteal artery. This artery undergoes various degrees of flexion, extension, and torsion during normal walking movements. The FPA is also the most susceptible peripheral artery to atherosclerosis and is where peripheral artery disease manifests in 80% of cases. The connection between peripheral artery location, its mechanical flexion, and its physiological or pathological biochemistry has been investigated for decades; however, histochemical methods remain poorly leveraged in their ability to spatially correlate normal or abnormal extracellular matrix and cells with regions of mechanical flexion. This study generates new histological image processing pipelines to quantitate tissue composition across high-resolution FPA regions-of-interest or low-resolution whole-section cross-sections in relation to their anatomical locations and flexions during normal movement. Comparing healthy ovine femoral, popliteal, and cranial-tibial artery sections as a pilot, substantial arterial contortion was observed in the distal popliteal and cranial tibial regions of the FPA which correlated with increased vascular smooth muscle cells and decreased elastin content. These methods aim to aid in the quantitative characterization of the spatial distribution of extracellular matrix and cells in large heterogeneous tissue sections such as the FPA. RESEARCH HIGHLIGHTS: Large-format histology preserves artery architecture. Elastin and smooth muscle content is correlated with distance from heart and contortion during flexion. Cell and protein analyses are sensitive to sectioning plane and image magnification.

Association Between Femoral Anteversion and Distal Femoral Morphology in Patients With Patellar Dislocation and Trochlear Dysplasia.

Increased femoral anteversion (FA) is reportedly associated with patellar dislocation (PD) and trochlear dysplasia (TD), and the increase in FA may occur at different segments of the femur. In addition, TD is associated with dysplasia of the posterior femoral condyle. Among patients with PD, whether FA is greater with or without TD remains unclear. To explore differences in FA and torsion distribution at different femoral sections among patients with PD and TD, patients with PD and no TD, and sex- and age-matched controls and to investigate the association between FA and distal femoral morphology. Cross-sectional study; Level of evidence, 3. This study involved 132 knees: 44 knees with PD and TD, 44 knees with PD but no TD, and 44 control knees. FA, proximal torsion (PT), middle torsion (MT), distal torsion (DT), and distal femoral morphology were measured. Differences were investigated by 1-way analysis of variance. Pearson correlation analysis was conducted to explore the association between FA and each parameter. FA was significantly larger in the PD with TD group (25.4° ± 4.7°) than in the other groups (controls: 18.9° ± 5.6°; PD without TD: 19.9° ± 4.8°) (P < .01). DT was significantly larger in the PD with TD group (15.8° ± 2.9°) than in the other groups (controls: 9.0° ± 4.3°; PD without TD: 8.8° ± 3.9°) (P < .01). In all 3 groups, FA was strongly positively correlated with DT (control, PD without TD, and PD with TD, respectively: r = 0.76, 0.80, and 0.88; P < .01), strongly positively correlated with the posteromedial condylar length (r = 0.48, 0.48, and 0.70; P < .01) and negatively correlated with the posterolateral condylar length (r = -0.30, -0.35, and -0.78, respectively; P < .05). The increased FA in knees with TD was due mainly to DT rather than PT or MT, which may provide a reference for choosing the optimal position for femoral derotation osteotomy.

Polystyrene nanoplastics induce haematotoxicity with cell oxeiptosis and senescence involved in C57BL/6J mice.

Nanoplastics (NPs) has become a worrying serious environmental problem. However, the toxicological effects and mechanisms of NPs on hematopoiesis are still unknown. To this end, male C57BL/6J mice were directly exposed to the serial concentration gradient of polystyrene NPs (PSNPs, 0, 30, 60, and 120 μg d), respectively, for 42 days by intragastric administration. Results show that PSNPs were clearly visible in bone tissues, meanwhile, induced the count of major blood indicators (WBC, RBC, and LYM) decreased. H&E staining displayed that exposed to PSNPs can cause hematopoietic damage of BM and extramedullary hematopoiesis in spleen. Flow cytometry result show that the proportion of LSK represented a dose-dependent significantly decreased after PSNPs exposure. Further research found that PSNPs can cause the systemic oxidative stress occurs manifested as MDA accumulated. In addition, as the dose of PSNPs increased, the fluorescence intensity of Keap1 and p53 in femur sections gradually increased, meanwhile, the expression of cell oxeiptosis signal pathway Keap1/PGAM5/AIFM1 and the cell senescence signal pathway p53/p21 was all increased, markedly. Overall, our study demonstrated that PSNPs exposure caused oxidative stress, potentially resulting in cell oxeiptosis and senescence to develop haematotoxicity in C57BL/6J mice.

D-β-Hydroxybutyrate Dehydrogenase Mitigates Diabetes-Induced Atherosclerosis through the Activation of Nrf2.

We aimed to investigate the role and mechanism of β-hydroxybutyrate dehydrogenase 1 (Bdh1) in regulating macrophage oxidative stress in diabetes-induced atherosclerosis (AS). We performed immunohistochemical analysis of femoral artery sections to determine differences in Bdh1 expression between normal participants, AS patients, and patients with diabetes-induced AS. Diabetic Apoe-/- mice and high-glucose (HG)-treated Raw264.7 macrophages were used to replicate the diabetes-induced AS model. The role of Bdh1 in this disease model was determined by adeno-associated virus (AAV)-mediated overexpression of Bdh1 or overexpression or silencing of Bdh1. We observed reduced expression of Bdh1 in patients with diabetes-induced AS, HG-treated macrophages, and diabetic Apoe-/- mice. AAV-mediated Bdh1 overexpression attenuated aortic plaque formation in diabetic Apoe-/- mice. Silencing of Bdh1 resulted in increased reactive oxygen species (ROS) production and an inflammatory response in macrophages, which were reversed by the ROS scavenger N-acetylcysteine. Overexpression of Bdh1 protected Raw264.7 cells from HG-induced cytotoxicity by inhibiting ROS overproduction. In addition, Bdh1 induced oxidative stress through nuclear factor erythroid-related factor 2 (Nrf2) activation by fumarate acid. Bdh1 attenuates AS in Apoe-/- mice with type 2 diabetes, accelerates lipid degradation, and reduces lipid levels by promoting ketone body metabolism. Moreover, it activates the Nrf2 pathway of Raw264.7 by regulating the metabolic flux of fumarate, which inhibits oxidative stress and leads to a decrease in ROS and inflammatory factor production.

D-mannose reduces adipogenesis by inhibiting the PI3K/AKT signaling pathway.

To explore the effects and potential mechanisms of D-mannose on adipogenic differentiation of two kinds of representative mesenchymal stem cells (MSCs). We cultured two kinds of representative MSCs, human adipose tissue-derived stromal cells (hADSCs) as well as human bone marrow mesenchymal stem cells (hBMSCs), with adipogenic-induced medium containing D-mannose or D-fructose as the control. Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to detect whether D-mannose had effects on adipogenic differentiation of MSCs. RNA sequencing (RNA-seq) transcriptomic analysis was further used to explore the potential mechanisms of D-mannose on adipogenic differentiation of MSCs. After that, qRT-PCR and WB were used to verify the results of RNA-seq. Last, we removed bilateral ovaries of female rats to establish an estrogen deficiency obesity model, and gave D-mannose intragastric administration. One month later, the femurs of rats were sliced for oil red O staining, and the inhibitory effect of D-mannose on lipid formation in vivo was studied. Oil red O staining, qRT-PCR and WB in vitro demonstrated that D-mannose inhibited the adipogenic differentiation of both hADSCs and hBMSCs. Oil red O staining of femur sections proved that D-mannose was able to reduce in vivo adipogenesis. The results of RNA-seq transcriptomic analysis revealed that the adipogenesis-inhibition effects of D-mannose were performed by antagonizing the PI3K/AKT signaling pathway. Besides, qRT-PCR and WB further verified the results of RNA-seq. Our study indicated that D-mannose was able to reduce adipogenic differentiation of both hADSCs and hBMSCs by antagonizing the PI3K/AKT signaling pathway. D-mannose is expected to be a safe and effective treatment strategy for obesity.

The Diagenetic Alterations of Historic Skeletons from the Crown Mines Cemetery, South Africa

Human skeletons associated with early gold mining in Johannesburg, South Africa are investigated. An unmarked cemetery was buried beneath a mine dump which resulted in macroscopically stained and poorly preserved bones. Histological assessments were conducted to understand the postmortem treatment of the remains, determine the extent of bone degradation, and understand how this environment affected the bone's microstructure. Various diagenetic alterations and the general histological index were assessed using normal and polarized light microscopy of thin anterior midshaft femur sections (n = 50). Degradation was identified in the periosteal and endosteal regions, while the intra-cortical region remained well-preserved. Bacterial bioerosion, microcracks, infiltrations, inclusions, and staining were found throughout the sample. Numerous non-Wedl micro-foci of destruction were observed, filled with exogenous material. The degradation suggested that the remains were buried in neutral soil that was subsequently covered by acidic mine dumps which resulted in a corrosive environment. Although the skeletons were poorly preserved, their histological integrity was more promising, especially the intra-cortical area. This is important for future investigations of archaeological bone, as this area can lead to more accurate descriptions of skeletal assemblages. Targeted sampling of this region could produce promising estimates of age, descriptions of pathology, and biomolecular results, which require further study.

Profilin 1 deficiency drives mitotic defects and reduces genome stability

Profilin 1—encoded by PFN1—is a small actin-binding protein with a tumour suppressive role in various adenocarcinomas and pagetic osteosarcomas. However, its contribution to tumour development is not fully understood. Using fix and live cell imaging, we report that Profilin 1 inactivation results in multiple mitotic defects, manifested prominently by anaphase bridges, multipolar spindles, misaligned and lagging chromosomes, and cytokinesis failures. Accordingly, next-generation sequencing technologies highlighted that Profilin 1 knock-out cells display extensive copy-number alterations, which are associated with complex genome rearrangements and chromothripsis events in primary pagetic osteosarcomas with Profilin 1 inactivation. Mechanistically, we show that Profilin 1 is recruited to the spindle midzone at anaphase, and its deficiency reduces the supply of actin filaments to the cleavage furrow during cytokinesis. The mitotic defects are also observed in mouse embryonic fibroblasts and mesenchymal cells deriving from a newly generated knock-in mouse model harbouring a Pfn1 loss-of-function mutation. Furthermore, nuclear atypia is also detected in histological sections of mutant femurs. Thus, our results indicate that Profilin 1 has a role in regulating cell division, and its inactivation triggers mitotic defects, one of the major mechanisms through which tumour cells acquire chromosomal instability.

Registration based assessment of femoral torsion for rotational osteotomies based on the contralateral anatomy

BackgroundComputer-assisted techniques for surgical treatment of femoral deformities have become increasingly important. In state-of-the-art 3D deformity assessments, the contralateral side is used as template for correction as it commonly represents normal anatomy. Contributing to this, an iterative closest point (ICP) algorithm is used for registration. However, the anatomical sections of the femur with idiosyncratic features, which allow for a consistent deformity assessment with ICP algorithms being unknown. Furthermore, if there is a side-to-side difference, this is not considered in error quantification.The aim of this study was to analyze the influence and value of the different sections of the femur in 3D assessment of femoral deformities based on the contralateral anatomy.Material and methods3D triangular surface models were created from CT of 100 paired femurs (50 cadavers) without pathological anatomy. The femurs were divided into sections of eponymous anatomy of a predefined percentage of the whole femoral length. A surface registration algorithm was applied to superimpose the ipsilateral on the contralateral side. We evaluated 3D femoral contralateral registration (FCR) errors, defined as difference in 3D rotation of the respective femoral section before and after registration to the contralateral side. To compare this method, we quantified the landmark-based femoral torsion (LB FT). This was defined as the intra-individual difference in overall femoral torsion using with a landmark-based method.ResultsContralateral rotational deviation ranged from 0° to 9.3° of the assessed femoral sections, depending on the section. Among the sections, the FCR error using the proximal diaphyseal area for registration was larger than any other sectional error. A combination of the lesser trochanter and the proximal diaphyseal area showed the smallest error. The LB FT error was significantly larger than any sectional error (p < 0.001).ConclusionWe demonstrated that if the contralateral femur is used as reconstruction template, the built-in errors with the registration-based approach are smaller than the intraindividual difference of the femoral torsion between both sides. The errors are depending on the section and their idiosyncratic features used for registration. For rotational osteotomies a combination of the lesser trochanter and the proximal diaphyseal area sections seems to allow for a reconstruction with a minimal error.

Substantiating microCT for diagnosing bioerosion in archaeological bone using a new Virtual Histological Index (VHI)

Recent technological advances have broadened the application of palaeoradiology for non-destructive investigation of ancient remains. X-ray microtomography (microCT) in particular is increasingly used as an alternative to histological bone sections for interpreting pathological alterations, trauma, microstructure, and, more recently, bioerosion with direct or ancillary use of histological indices. However, no systematic attempt has been made to confirm the reliability of microCT for histotaphonomic analysis of archaeological bone. The objective of this study is therefore to compare thin sections of human femora rated with the Oxford Histological Index to microCT sections using the newly developed Virtual Histological Index in order to provide an accessible methodology for the evaluation of bioerosion in archaeological bone. We provide detailed descriptions of virtual sections and assess the efficacy of the method on cranial and postcranial elements, cremated long bones, and faunal samples. The traditional histological and virtual methods showed a strong correlation, providing the first systematic data substantiating lab-based microCT as a suitable alternative tool for reconstructing post-mortem history in the archaeological record, and for the reliable, non-destructive screening of samples for further analyses.

A Simple Method to Improve Detection of Femoral Nail Abutment in the Distal Femur: A Computer Modeling Study.

Proximal femur fractures are more frequently treated with long femoral nails. Lateral radiographs are used to assess the nail position in the distal femur. However, because of the asymmetric shape of the distal femur, standard lateral radiographs alone are suboptimal for assessing anteriorly positioned nails in the distal femur. Consequently, instances of nail abutment or even perforation might be missed intraoperatively. Using a three-dimensional (3D) modelling approach, we asked: When the nail is in the anterior fifth of the canal, will rotating the femur to align the simulated x-ray beam with the anterior femoral condyles instead of the posterior femoral condyles increase the diagnostic accuracy of detecting nail perforation of the anterior cortex? 3D models of 42 unilateral femora from a population sample representative of patients with hip fractures (mean age of 76 ± 7 years, 10 males and 32 females, and 16 left and 26 right femora) were used. The patients had a mean height of 158 ± 9 cm; 27 femora were from Asians and 15 were from Caucasians. Clinically appropriately sized nails had already been virtually implanted previously as part of a quantitative nail fit assessment study. In a preliminary step, the mean angles of inclination of the distal anterior supracondylar region were quantified using four axial sections of the distal femur. For the femora with the nail tip in the anterior fifth of the canal, projections representing a lateral radiograph were generated along with rotated projections at mean angle (5°, 8°) rotations, with the anterior femoral condyles aligned, and anterior femoral condyle alignment followed by internal and external rotation to detect maximum nail perforation. The distance from the nail to the distal anterior cortex was measured for each rotational projection and used to detect anterior nail perforation. The accuracy of detection was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) analysis. Rotating the 3D models by aligning the x-ray beam with the anterior femoral condyles improves the diagnostic ability of detecting anterior nail perforation compared with standard lateral radiographs. The AUC increased with rotation from 0.50 (95% confidence interval 0.50 to 0.50) on the lateral projection to 0.73 (95% CI 0.57 to 0.88, difference = -0.23; p = 0.004) at 5° of rotation, 0.77 (95% CI 0.62 to 0.93, difference = -0.27; p = 0.001) at both 8° of rotation and with the anterior femoral condyles aligned, and to 0.82 (95% CI 0.67 to 0.97, difference = -0.32; p < 0.001) with internal/external rotations past the anterior femoral condyles. There were no differences in accuracy between the four methods of rotation. This study shows that rotating the femur to align the anterior femoral condyles on a lateral radiograph and then internally/externally rotating it, improves the accuracy assessed via the AUC of detecting anterior perforation when long nails are positioned in the anterior fifth of the distal femur. This approach can easily be used in a clinical setting. Intraoperatively, the image intensifier can be rotated around the leg to produce an image with the anterior femoral condyle aligned, providing surgeons with an opportunity to identify and improve the nail's position or exchange the nail while the patient is still under anesthesia.

Pulsed electromagnetic fields attenuate glucocorticoid-induced bone loss by targeting senescent LepR+ bone marrow mesenchymal stromal cells

Glucocorticoids induce cellular senescence, including of stem/progenitor cells in the bone marrow of growing long bone, which leads to bone loss in glucocorticoid–induced osteoporosis. There is no specific drug available to treat this disease. Clearance of senescent cells has been reported to be an effective therapy for osteoporosis. LepR+ cells in the bone marrow are the key kind of stem/progenitor cells conducive to bone remodeling in adulthood. Here, we show that glucocorticoids induce cellular senescence, demonstrated by increased activity of senescence-associated β-galactosidase (SA-βGal+) cells and simultaneous upregulation of coimmunofluorescence staining of p16INK4a with LepR in longitudinal femoral sections. We applied pulsed electromagnetic fields (PEMFs), which alleviated bone loss in glucocorticoid-induced osteoporosis mice. We found the increased accumulation of senescent LepR+ cells in the bone marrow of adult mice after glucocorticoid treatment, and this could be counteracted by PEMFs. Moreover, PEMFs maintained type H vessel formation and osteogenesis. This process was modulated by the polycomb histone methyltransferase enhancer of zeste homolog 2 (EZH2) and its trimethylation of histone H3 on lysine 27 (H3K27me3). These results provide evidence that PEMFs alleviate bone loss induced by glucocorticoids by eliminating senescent cells, maintaining angiogenesis-osteogenesis coupling, and shedding light on the mechanisms, providing a potential method to treat glucocorticoid-induced osteoporosis.

Promotion of Platelet Production by Co-Transplantation of Mesenchymal Stem Cells in Bone Marrow Transplantation.

Therapeutic strategies that can promote platelet production are in demand to enhance clinical outcomes of bone marrow transplantation (BMT). Our research group has studied human tonsil-derived mesenchymal stem cells (T-MSCs) and their effectiveness in promoting bone marrow (BM) engraftment. Here, we analyzed the effects of T-MSCs on platelet production and hemostasis. Donor BM cells (BMCs) were isolated from C57BL/6 mice and transplanted with or without T-MSCs to BALB/c recipient mice. Mice were sacrificed and blood cells were counted using an Auto Hematology Analyzer. Femur sections were stained with CD41 antibody to analyze megakaryocytes in the BM. Growth factor secretion from MSCs was analyzed using the Quantibody Array. Effects of T-MSC conditioned medium (CM) on megakaryopoiesis were investigated using the MegaCult assay. In a mouse model of BMT, T-MSC CM was injected with or without anti-placental growth factor (α-PlGF) blocking antibody, and blood cell numbers and coagulation were analyzed. T-MSC co-transplantation increased percent survival of BMT mice. Platelet numbers were significantly lower in the BMC-only group, whereas T-MSC co-transplantation restored circulating platelets to levels similar to those of the control group. Significantly reduced numbers of CD41 + megakaryocytes in Bu-Cy and BMC groups were increased by T-MSC co-transplantation. PlGF secretion from T-MSCs were detected and enhanced megakaryopoiesis, platelet production, and coagulation by T-MCS CM were disrupted in the presence of the α-PlGF blocking antibody. We demonstrated the effectiveness of T-MSC co-transplantation in promoting platelet production and coagulation after BMT. These findings highlight the potential therapeutic relevance of T-MSCs for preventing thrombocytopenia after BMT.

Implantation of heat treatment Ti6al4v alloys in femoral bone of Wistar rats

Two heat treatments were carried out at below (Ti6Al4V800) and above (Ti6Al4V1050) the beta-phase transformation temperature (TTRANSUS = 980 °C), to study the effect of microstructural changes on osseointegration. The alloys were implanted in the femurs of hind legs of Wistar rats for 15, 30, and 60 days. Histology of the femur sections obtained for the first 15 days showed inflammatory tissue surrounding the implants and tissue contraction, which prevented osseointegration in early stages. After 30 days, trabecular bone, reduction of inflammatory tissue around the implants, and osseointegration were observed in Ti6Al4V as received and Ti6Al4V1050 alloys, while osseointegration was detected for the three alloys after 60 days. These results were supported through morphometric studies based on the analysis of Bone Implant Contact (BIC), where there was a larger bone contact after 60 days for the Ti6Al4V1050 alloy; indicating that microstructural features of the Ti6Al4V alloys influence their osseointegration, with the lamellar microstructure (Ti6Al4V1050), being the most responsive.Graphical abstract