Trabecular Bone Structure Research Articles

Hypochondroplasia gain-of-function mutation in FGFR3 causes defective bone mineralization in mice.

Hypochondroplasia (HCH) is a mild dwarfism caused by missense mutations in fibroblast growth factor receptor 3 (FGFR3), with the majority of cases resulting from a heterozygous p.Asn540Lys gain-of-function mutation. Here, we report the generation and characterization of the first mouse model (Fgfr3Asn534Lys/+) of HCH to our knowledge. Fgfr3Asn534Lys/+ mice exhibited progressive dwarfism and impairment of the synchondroses of the cranial base, resulting in defective formation of the foramen magnum. The appendicular and axial skeletons were both severely affected and we demonstrated an important role of FGFR3 in regulation of cortical and trabecular bone structure. Trabecular bone mineral density (BMD) of long bones and vertebral bodies was decreased, but cortical BMD increased with age in both tibiae and femurs. These results demonstrate that bones in Fgfr3Asn534Lys/+ mice, due to FGFR3 activation, exhibit some characteristics of osteoporosis. The present findings emphasize the detrimental effect of gain-of-function mutations in the Fgfr3 gene on long bone modeling during both developmental and aging processes, with potential implications for the management of elderly patients with hypochondroplasia and osteoporosis.

Finite element analysis of the mechanical strength of a new hip Spacer

Background and objectiveAt present, the influence of the internal metallic endoskeleton of Spacer on the biomechanical strength of Spacer remains unclear. The aim of this study was to analyze the mechanical stability of a novel Spacer applying a annular skeleton that mimics the structure of trabecular bone using finite element methods.MethedsThe femur models of three healthy individuals and skeletonless Spacer, K-Spacer, and AD-Spacer were assembled to create 15 3D models. Finite element analysis was performed in an Ansys Bench2022R1. Biomechanical parameters such as stress and strain of the Spacer, internal skeleton and femur were evaluated under three loads, which were applied with the maximum force borne by the hip joint (2100 N), standing on one leg (700 N), and standing on two legs (350 N). The mechanical properties of the new hip Spacer were evaluated.ResultThe stresses on the medial and lateral surfaces of the AD-Spacer and K-Spacer were smaller than the stresses in the state without skeletal support. The maximum stresses on the medial and lateral surfaces of the AD-Spacer were smaller than those of the inserted K-Spacer, and the difference gradually increased with the increase of force intensity. When the skeleton diameter was increased from 3 to 4 mm, the stresses in the medial and lateral sides of the AD-Spacer and K-Spacer necks decreased. The stress of both skeletons was concentrated at the neck, but the stress of the annular skeleton was evenly distributed on the medial and lateral sides of the skeleton. The mean stress in the proximal femur was higher in femurs with K-Spacer than in femurs with AD-Spacer.ConclusionsAD-Spacer has lower stress and higher load-bearing capacity than K-Spacer, and the advantages of AD-Spacer are more obvious under the maximum load state of hip joint.

Nicotinamide mononucleotide supplementation mitigates osteopenia induced by modeled microgravity in rats.

Exposure to weightlessness causes severe osteopenia, resulting in raised fracture risk. The current study aimed to investigate whether nicotinamide mononucleotide (NMN) supplementation protected against the osteopenia in hindlimb unloading (HLU) rats in vivo and modeled microgravity-induced osteoblastic dysfunction in vitro. The 3-mo-old rats were exposed to HLU and intragastrically administered NMN every 3days (500mg/kg body weight) for 4weeks. NMN supplementation mitigated HLU-induced bone loss, evidenced by greater bone mass and biomechanical properties and better trabecular bone structure. NMN supplementation mitigated HLU-induced oxidative stress, evidenced by greater levels of nicotinamide adenine dinucleotide and activities of superoxide dismutase 2 and lesser malondialdehyde levels. Modeled microgravity stimulation using rotary wall vessel bioreactor in MC3T3-E1 cells inhibited osteoblast differentiation, which was reversed by NMN treatment. Furthermore, NMN treatment mitigated microgravity-induced mitochondrial impairments, evidenced by lesser reactive oxygen species generation and greater adenosine triphosphate production, mtDNA copy number, and activities of superoxide dismutase 2 and Complex I and II. Additionally, NMN promoted activation of AMP-activated protein kinase (AMPK), evidenced by greater AMPKα phosphorylation. Our research suggested that NMN supplementation attenuated osteoblastic mitochondrial impairment and mitigated osteopenia induced by modeled microgravity.

Utilising of water hammer effect for surface roughening of Ti6Al4V

There are many technological ways to activate biocompatible surfaces, but in some cases, there are not reliable for elderly patients. It has been found that surfaces created using pulsating water jets have a structure similar to trabecular bone structures. Such a similar shape to the endoprosthesis stems would enable faster fixation. The paper presents a novel way of utilizing the water hammer effect caused by forced multiple droplet impingement with a spatial frequency of 40,000 i/s on Ti6Al4V titanium alloy surface under different technological conditions. The objective was to create a structured surface with desired values of surface profile parameters Ra and Rz to increase the possible potential for implant osseointegration, fixation and stability. Pulsating water jet was generated at pressures from 20 to 100 MPa using a circular nozzle with a diameter of 1.32 mm. Two different strategies of the jet trajectory, namely linear and cross-hatch strategy, were investigated. Results were compared with grit blasted followed by plasma spray-coated femoral stem for cementless total hip arthroplasty. It has been found that variation in the input parameters results in significant changes in the surface generated. Samples whose surfaces were generated using energy intensity lower than 5 KJ/mm2 and have surface roughness in the range Ra = 4 – 8 μm were selected for surface topography and morphology analysis along with the commercial femoral stem. SEM analysis revealed the absence of foreign contamination and steeper surface heights on pulsating water jet treated samples compared to standard femoral prosthetic. The cross-section images showed the presence of sub-surface voids and craters of different sizes due to the jet's action. Surface topology is similar to trabecular shape. This indicates that roughening the surface increases the surface area and thus has potential bone tissue ingrowth during osseointegration.

Effects of Leptin and Body Weight on Inflammation and Knee Osteoarthritis Phenotypes in Female Rats.

Leptin is a proinflammatory adipokine that contributes to obesity-associated osteoarthritis (OA), especially in women. However, the extent to which leptin causes knee OA separate from the effect of increased body weight is not clear. We hypothesized that leptin is necessary to induce knee OA in obese female rats but not sufficient to induce knee OA in lean rats lacking systemic metabolic inflammation. The effect of obesity without leptin signaling was modeled by comparing female lean Zucker rats to pair fed obese Zucker rats, which possess mutant fa alleles of the leptin receptor gene. The effect of leptin without obesity was modeled in female F344BN F1 hybrid rats by systemically administering recombinant rat leptin versus saline for 23 weeks via osmotic pumps. Primary OA outcomes included cartilage histopathology and subchondral bone micro-computed tomography. Secondary outcomes included targeted cartilage proteomics, serum inflammation, and synovial fluid inflammation following an acute intra-articular challenge with interleukin-1β (IL-1β). Compared to lean Zucker rats, obese Zucker rats developed more severe tibial osteophytes and focal cartilage lesions in the medial tibial plateau, with modest changes in proximal tibial epiphysis trabecular bone structure. In contrast, exogenous leptin treatment, which increased plasma leptin sixfold without altering body weight, caused mild generalized cartilage fibrillation and reduced Safranin O staining compared to vehicle-treated animals. Leptin also significantly increased subchondral and trabecular bone volume and bone mineral density in the proximal tibia. Cartilage metabolic and antioxidant enzyme protein levels were substantially elevated with leptin deficiency and minimally suppressed with leptin treatment. In contrast, leptin treatment induced greater changes in systemic and local inflammatory mediators compared to leptin receptor deficiency, including reduced serum IL-6 and increased synovial fluid IL-1β. In conclusion, rat models that separately elevate leptin or body weight develop distinct OA-associated phenotypes, revealing how obesity increases OA pathology through both leptin-dependent and independent pathways. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Plasma Polishing as a New Polishing Option to Reduce the Surface Roughness of Porous Titanium Alloy for 3D Printing.

Porous titanium alloy implants with simulated trabecular bone fabricated by 3D printing technology have broad prospects. However, due to the fact that some powder adheres to the surface of the workpiece during the manufacturing process, the surface roughness in direct printing pieces is relatively high. At the same time, since the internal pores of the porous structure cannot be polished by conventional mechanical polishing, an alternative method needs to be found. As a surface technology, plasma polishing technology is especially suitable for parts with complex shapes that are difficult to polish mechanically. It can effectively remove particles and fine splash residues attached to the surface of 3D printed porous titanium alloy workpieces. Therefore, it can reduce surface roughness. Firstly, titanium alloy powder is used to print the porous structure of the simulated trabecular bone with a metal 3D printer. After printing, heat treatment, removal of the supporting structure, and ultrasonic cleaning is carried out. Then, plasma polishing is performed, consisting of adding a polishing electrolyte with the pH set to 5.7, preheating the machine to 101.6 °C, fixing the workpiece on the polishing fixture, and setting the voltage (313 V), current (59 A), and polishing time (3 min). After polishing, the surface of the porous titanium alloy workpiece is analyzed by a confocal microscope, and the surface roughness is measured. Scanning electron microscopy is used to characterize the surface condition of porous titanium. The results show that the surface roughness of the whole porous titanium alloy workpiece changed from Ra (average roughness) = 126.9 µm to Ra = 56.28 µm, and the surface roughness of the trabecular structure changed from Ra = 42.61 µm to Ra = 26.25 µm. Meanwhile, semi-molten powders and ablative oxide layers are removed, and surface quality is improved.

A New Microarchitecture-Based Parameter to Predict the Micromechanical Properties of Bone Allografts.

Scaffolds are an essential component of bone tissue engineering. They provide support and create a physiological environment for cells to proliferate and differentiate. Bone allografts extracted from human donors are promising scaffolds due to their mechanical and structural characteristics. Bone microarchitecture is well known to be an important determinant of macroscopic mechanical properties, but its role at the microscopic, i.e., the trabeculae level is still poorly understood. The present study investigated linear correlations between microarchitectural parameters obtained from X-ray computed tomography (micro-CT) images of bone allografts, such as bone volume fraction (BV/TV), degree of anisotropy (DA), or ellipsoid factor (EF), and micromechanical parameters derived from micro-finite element calculations, such as mean axial strain (εz) and strain energy density (We). DAEF, a new parameter based on a linear combination of the two microarchitectural parameters DA and EF, showed a strong linear correlation with the bone mechanical characteristics at the microscopic scale. Our results concluded that the spatial distribution and the plate-and-rod structure of trabecular bone are the main determinants of the mechanical properties of bone at the microscopic level. The DAEF parameter could, therefore, be used as a tool to predict the level of mechanical stimulation at the local scale, a key parameter to better understand and optimize the mechanism of osteogenesis in bone tissue engineering.

Collagen X Is Dispensable for Hypertrophic Differentiation and Endochondral Ossification of Human iPSC-Derived Chondrocytes.

Collagen X is a non-fibril collagen produced by hypertrophic chondrocytes and was believed to associate with the calcification process of growth plate cartilage. The homozygous loss of Col10a1 gene in mice, however, demonstrated no remarkable effects on growth plate formation or skeletal development. To investigate the role of collagen X in human chondrocytes, we established human induced pluripotent stem cells (hiPSCs) with heterozygous (COL10A1 +/-) or homozygous (COL10A1 -/-) deletions of COL10A1 gene using the dual sgRNA CRISPR/Cas9 system. Several mutant clones were established and differentiated into hypertrophic chondrocytes by a previously reported 3D induction method. No remarkable differences were observed during the differentiation process between parental and mutant cell lines, which differentiated into cells with features of hypertrophic chondrocytes, indicating that collagen X is dispensable for the hypertrophic differentiation of human chondrocytes in vitro. To investigate the effects of collagen X deficiency in vivo, chondrocyte pellets at the proliferating or prehypertrophic stage were transplanted into immunodeficient mice. Proliferating pellet-derived tissues demonstrated the zonal distribution of chondrocytes with the transition to bone tissues mimicking growth plates, and the proportion of bone tended to be larger in COL10A1 -/- tissues. Prehypertrophic pellet-derived tissues produced trabecular bone structures with features of endochondral ossification, and there was no clear difference between parental- and mutant-derived tissues. A transcriptome analysis of chondrocyte pellets at the hypertrophic phase showed a lower expression of proliferating-phase genes and a higher expression of calcification-phase genes in COL10A1 -/- pellets compared with parental cell pellets. These in vitro and in vivo data suggested that collagen X is dispensable for the hypertrophic differentiation and endochondral ossification of human iPSC-derived chondrocytes, though it may facilitate the differentiation process. Thus, COL10A1 -/- iPSC lines are useful for investigating the physiological role of collagen X in chondrocyte differentiation. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Photon-counting CT of elbow joint fractures: image quality in a simulated post-trauma setting with off-center positioning

BackgroundPhoton-counting detector computed tomography (PCD-CT) has the potential to provide superior image quality compared to energy-integrating detector computed tomography (EID-CT). We compared the two systems for elbow imaging in off-center arm positioning, 90° flexion, and cast fixation in a simulated post-trauma setting.MethodsThe institutional review board approved the study protocol. In a cadaver study, an olecranon fracture was artificially created in ten whole arm specimens. Two different scanning positions were evaluated: (a) arm overhead; and (b) arm on top of the abdomen of a whole-body phantom. The ultra-high resolution mode with three dose protocols and two reconstruction kernels was applied. Two blinded radiologists independently evaluated fracture and trabecular bone delineation. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and cortical sharpness measurements were performed. Cohen κ correlations, Mann-Whitney U and Wilcoxon signed rank tests were used. A p value lower than 0.05 was considered statistically significant.ResultsDose-equivalent PCD-CT scans were rated better for fracture and trabecular bone evaluation (p < 0.001). SNR, CNR, and cortical sharpness were higher for all diagnostic (Br76) PCD-CT images (p < 0.001). The arm position had less effect on image quality in the PCD-CT compared to the EID-CT. The use of a sharp bone kernel (Br89) improved image quality ratings for PCD-CT. In the low-dose scan mode, PCD-CT resulted in more diagnostic scans (75%) compared to EID-CT (19%).ConclusionsPCD-CT provided superior objective and subjective image quality for fracture and trabecular bone structures delineation of the elbow compared to EID-CT in a typical post-trauma setting.Key points• Photon-counting detector computed tomography (PCD-CT) preserved high image quality in elbow imaging with off-center positions.• PCD-CT was advantageous for bone evaluation in trauma elbows.• PCD-CT ultra-high-resolution mode and very sharp reconstruction kernels facilitated higher image quality.

Comparative evaluation of trabecular bone structures of bruxist and non-bruxist individuals with bone apposition in the mandible angle region by fractal analysis.

This study aimed to compare the trabecular internal structure of different regions of the mandible according to the grades of appositional classification in the mandible angle region in probable bruxist individuals and non-bruxist G0(Convex course of the basal cortex, no directional change, no bone apposition) individuals by measuring fractal dimension (FD) on panoramic radiographs. 200 sample jaws, bilaterally, of 80 probable bruxists and 20 non-bruxist G0 individuals were included in the study. According to the classification in the literature, each mandible angle apposition severity was classified as G0-G1-G2-G3. FD was calculated by selecting the region of interest (ROI) area of 7 regions from each sample. Gender differences in changes between ROIs in radiographs and independent samples t-test were evaluated. Relation between categorical variables was determined by chi-square test (p < .05). In the comparison of the probable bruxist and non-bruxist G0 groups, FD was found to be statistically significantly higher in the mandible angle (p=0.013) and cortical bone (p=0.000) regions in the probable bruxist group than in the non-bruxist G0 group. There is a statistically significant difference between probable bruxist G0 and non-bruxist G0 grades in terms of FD averages in cortical bone (p < 0.001). A statistically significant difference was found in the relationship of ROIs with gender in canine apex (p=0.021) and canine distal (p=0.041) regions. FD was found to be higher in the mandibular angle region and cortical bone in probable bruxist individuals than in non-bruxist G0 individuals. Morphological changes seen in the mandible angulus region may be a finding that may raise suspicion for bruxism for clinicians.

Accuracy of osseointegrated screw-bone construct stiffness and peri-implant loading predicted by homogenized FE models relative to micro-FE models

Computational predictions of stiffness and peri-implant loading of screw-bone constructs are highly relevant to investigate and improve bone fracture fixations. Homogenized finite element (hFE) models have been used for this purpose in the past, but their accuracy has been questioned given the numerous simplifications, such as neglecting screw threads and modelling the trabecular bone structure as a continuum. This study aimed to investigate the accuracy of hFE models of an osseointegrated screw-bone construct when compared to micro-FE models considering the simplified screw geometry and different trabecular bone material models.Micro-FE and hFE models were created from 15 cylindrical bone samples with a virtually inserted, osseointegrated screw (fully bonded interface). Micro-FE models were created including the screw with threads (=reference models) and without threads to quantify the error due to screw geometry simplification. In the hFE models, the screws were modelled without threads and four different trabecular bone material models were used, including orthotropic and isotropic material derived from homogenization with kinematic uniform boundary conditions (KUBC), as well as from periodicity-compatible mixed uniform boundary conditions (PMUBC). Three load cases were simulated (pullout, shear in two directions) and errors in the construct stiffness and the volume average strain energy density (SED) in the peri-implant region were evaluated relative to the micro-FE model with a threaded screw.The pooled error caused by only omitting screw threads was low (max: 8.0%) compared to the pooled error additionally including homogenized trabecular bone material (max: 92.2%). Stiffness was predicted most accurately using PMUBC-derived orthotropic material (error: -0.7 ± 8.0%) and least accurately using KUBC-derived isotropic material (error: +23.1 ± 24.4%). Peri-implant SED averages were generally well correlated (R2 ≥ 0.76), but slightly over- or underestimated by the hFE models and SED distributions were qualitatively different between hFE and micro-FE models.This study suggests that osseointegrated screw-bone construct stiffness can be predicted accurately using hFE models when compared to micro-FE models and that volume average peri-implant SEDs are well correlated. However, the hFE models are highly sensitive to the choice of trabecular bone material properties. PMUBC-derived isotropic material properties represented the best trade-off between model accuracy and complexity in this study.

Differential bone adaptation to mechanical unloading and reloading in young, old, and osteocyte deficient mice.

Mechanical unloading causes rapid loss of bone structure and strength, which gradually recovers after resuming normal loading. However, it is not well established how this adaptation to unloading and reloading changes with age. Clinically, elderly patients are more prone to musculoskeletal injury and longer periods of bedrest, therefore it is important to understand how periods of disuse will affect overall skeletal health of aged subjects. Bone also undergoes an age-related decrease in osteocyte density, which may impair mechanoresponsiveness. In this study, we examined bone adaptation during unloading and subsequent reloading in mice. Specifically, we examined the differences in bone adaptation between young mice (3-month-old), old mice (18-month-old), and transgenic mice that exhibit diminished osteocyte density at a young age (3-month-old BCL-2 transgenic mice). Mice underwent 14days of hindlimb unloading followed by up to 14days of reloading. We analyzed trabecular and cortical bone structure in the femur, mechanical properties of the femoral cortical diaphysis, osteocyte density and cell death in cortical bone, and serum levels of inflammatory cytokines. We found that young mice lost ~10% cortical bone volume and 27-42% trabecular bone volume during unloading and early reloading, with modest recovery of metaphyseal trabecular bone and near total recovery of epiphyseal trabecular bone, but no recovery of cortical bone after 14days of reloading. Old mice lost 12-14% cortical bone volume and 35-50% trabecular bone volume during unloading and early reloading but had diminished recovery of trabecular bone during reloading and no recovery of cortical bone. In BCL-2 transgenic mice, no cortical bone loss was observed during unloading or reloading, but 28-31% trabecular bone loss occurred during unloading and early reloading, with little to no recovery during reloading. No significant differences in circulating inflammatory cytokine levels were observed due to unloading and reloading in any of the experimental groups. These results illustrate important differences in bone adaptation in older and osteocyte deficient mice, suggesting a possible period of vulnerability in skeletal health in older subjects during and following a period of disuse that may affect skeletal health in elderly patients.

Effects of obesity on talar micro- and macro-morphology.

The addition of information regarding obesity status to the forensic anthropological biological profile could significantly contribute to the identification of human skeletal remains since over 40% of the U.S. adult population is currently obese. This study examines the differences in talar shape and trabecular bone structure between obese and non-obese individuals. A sample of 20 obese and 20 non-obese divided evenly by sex was selected from the Texas State University Donated Skeletal Collection. Tali were imaged using x-ray computed tomography (voxel size: 28-38.7μm). Image stacks were processed to produce binary images as well as trabecular thickness and spacing maps. Landmark-based geometric morphometric analyses were conducted to quantify shape variation. Shape coordinates were used to locate 100 geometrically homologous volumes of interest within each talus. Bone volume fraction, trabecular thickness, and trabecular spacing were extracted at each volume of interest. Within each sex, a one-way ANCOVA was used to determine if significant differences exist between obese and non-obese individuals in trabecular bone after controlling for age. The size of the talus as well as subtle aspects of shape were found to distinguish the sexes. The results further indicate that bone volume fraction significantly differs between obese and non-obese males. In females, bone volume fraction is correlated with age but does not differ between obese and non-obese. The study demonstrates that bone microstructure is a promising approach to estimating body mass or body mass index category but age effects diminish the potential for the talus to be used alone.

Capacitive stimulation-sensing system for instrumented bone implants: Finite element model to predict the electric stimuli delivered to the interface

BackgroundPrevalence of orthopaedic replacements are increasing around the world. The main cause of revision remains associated to the interface loosening. In this work, a computational study using the Finite element method was developed to predict the electric field stimuli delivered to trabecular bone structures, as well as to predict the sensing ability to detect different bone-implant interface scenarios. MethodsThree finite element models were developed: two simplified models, including a Gyroid TMP structure, and a realistic model based on microCT scan of a trabecular bone from sheep vertebra. Simulations were performed using a co-surface capacitive technology for stimulating and sensing bone-implant interfaces. Different fixation scenarios were considered, namely by establishing bone-stimulator gap sizes up to 1 mm (from fixation to massive loosening scenario). Electrodes were excited with sinusoidal and square electric signals up to 10V voltage and 64kHz frequency. ResultsSimplification of bone geometry resulted in significant electric stimuli differences compared to the realistic bone geometry. Realistic modelling allowed to observe that, in the fixation scenario, the electric field stimuli decreased 85% from the sensor interface to a parallel plane 2 mm apart from such interface. A significant influence of the bone-stimulator distance on the electric stimuli was found: the electric stimuli magnitudes varied in the range between 0.38 V/mm (fixation scenario) and 4.8 mV/mm (massive loosening scenario) for voltages up to 10V. Strong frequency-dependent behaviours were also observed in the electric stimuli: their magnitudes can reach 106-fold decreases when the excitation frequency is decreased from 32 kHz to 14 Hz ConclusionThis study points out the inability of our two simplified models to predict the electric stimulation provided to different bone-implant interface scenarios. Results highlight that co-surface stimulators can deliver osteogenic electric stimuli along trabecular bone structures, ensuring low electric power excitations. Moreover, realistic models strongly enhance the sensing predictability of the bone-implant fixation states. These new and significant evidences provide a strong support to integrate co-surface capacitive into bioelectronic implants for both therapeutic and sensing operations.

The influence of image processing of μ-CT images on mechanical behavior of mandibular trabecular bone structure using micro finite element method

Computational modeling plays an important role in assessment of biomaterial structures, living tissue and their mechanical properties. Microstructure investigation of bone tissue needs high-level computational models based on μ-CT images. A crucial factor when creating a computational model is image processing using tissue segmentation. The most common method for segmentation is thresholding. Threshold value can influence the geometry model and mechanical response in the bone tissue. One of the aims of the work is to determine and analyze the apparent mechanical behavior of mandibular trabecular bone structure based on different threshold value. Another aim of this study is to assess its influence on strain intensity from a local point of view, namely on one specific trabeculae. Fifty-four computational models including detailed trabecular structure of mandible were created based on μ-CT images. The thresholding was observed to have a significant effect on mechanical behavior of the trabecular bone structure.

Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice.

This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma. CCRF S-180II cells (2-4×105 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed. Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS. The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.

A Fractal Dimension Analysis to Evaluate the Change in the Alveolar Osseous Structure of Mandibular Incisors after Orthodontic Treatment: A Retrospective Study

Introduction: As bone traces tooth movement during orthodontic treatment, leading to biological response of the surrounding tissues of the teeth resulting in remodelling of the socket, favourable bone response is expected after incisor retraction. Orthodontic treatment causing changes in alveolar bone can be evaluated using Fractal dimension (FD) analysis, a mathematical method of information processing, where the input data is in the form of an image and generated information is displayed as numbers. Aim: To evaluate changes in the trabecular structure of alveolar bone after incisor retraction in the mandibular symphysis region in adult patients using fractal analysis. Materials and Methods: This retrospective study was conducted with digital Orthopantomogram (OPG) of 30 patients with class I and class II malocclusion with mandibular incisor protrusion treated with extraction and retraction of anterior teeth were taken with standard protocols at the three different periods, before orthodontic treatment (T0), before retraction (T1) and after retraction of anterior teeth (T2) included in the study. Regions of interest were located between the apices of mandibular incisors. FD was calculated using ImageJ software. Statistical Analysis was carried out by repeated Analysis of Variance (ANOVA) test and post-hoc test. Results: Total of 30 cases were selected, out of which 15 were males and 15 females with the mean age of 21±2 years. FD values of the alveolar bone of mandibular incisors at T0 were 1.470±0.09 which reduced to 1.390±0.09 at T1 and to 1.350±0.08 at T2. This overall changes in FD values were significant (p-value=0.001). Conclusion: Fractal dimension analysis demonstrate significant changes in bone trabeculation of the mandibular symphysis region before and after orthodontic treatment. It has valuable impact in the cases of fenestration, dehiscence’s, and osteoporosis.

Evaluation of trabecular bone in individuals with periodontitis using fractal analysis: An observational cross-sectional study.

It is very difficult to objectively evaluate the negative changes in bone structure due to periodontitis. The present study was aimed to evaluate the trabecular bone structure between healthy individuals and periodontitis patients by fractal analysis (FA) on digital panoramic radiographs. The study included 50 periodontally healthy individuals (control group), 50 individuals with Stage 1 periodontitis (S1-P group), 50 individuals with Stage 2 periodontitis (S2-P), and 50 individuals with Stage 3 periodontitis (S3-P), a total of 200 individuals were included. The fractal dimension (FD) value of the trabecular bone in the interdental space between mandibular first molar and second premolar tooth roots was evaluated using Image J program. The mean FD values of the two regions were calculated by box counting method. There was a statistically significant difference between the groups in terms of all periodontal parameter values (p<0.05). The mean FD values of individuals diagnosed with periodontitis were 1.36±0.08 in the S1-P group, 1.35±0.07 in the S2-P group, 1.28±0.15 in the S3-P group, and 1.44±0.06 in the control group. When the FD values between the groups were examined, it was seen that there was a statistically significant difference between the control and individuals with periodontitis, and the mean FD values were significantly higher in the healthy group (p<0.05). The best receiver operator curve was identified for periodontitis at the ≤1.409 cut-off FD value (area under the curve: 0.828; 95% CI: 0.758-0.899); p=0.000, p<0.001). FD evaluation can give an objective result about the effect of periodontitis on alveolar bone. The FD values of trabecular bone are different in healthy individuals and individuals with different stages of periodontitis. The findings suggested that a negative correlation between the periodontal data with the sites in which FD was measured and as the periodontitis stage progresses, FD decreases. Key words:Diagnosis, Periodontal Diseases, Radiographic Evaluation.

The effect of Hyperhomocysteinemia on the Osteoclasts activity in Male New Zealand White Rabbits

Methionine is a specific amino acid which contains sulfur, and can be used to make proteins, found in fish, meat, and dairy products, the excess intake of L-methionine lead to elevated homocysteine (Hcy) level that known as Hyperhomocysteinemia (HHcy). Increased Hcy plasma may represent an independent risk factor for osteoporotic fractures, and therefore may also negatively affect bone metabolism. This study was designed to examine the impact of Hcy on osteoclast activity in Male Rabbits, following methionine overload. To achieve this study's aims, we recruiting (20) males of New Zealand white rabbits that were divided into (10/group) control group and a group treated with methionine. Then after the intubation of methionine overload, we measured the "Receptor Activator of Nuclear factor Kappa-b" (RANK) and "Receptor Activator of Nuclear factor Kappa-b ligand" (RANK-L) levels in the blood, in addition to histological examination of the trabecular structure of femur bone. The results show a significant (p≤0.001) increase in serum RANK and RANK-L levels of methionine treated group in comparison with the control group. The histological examination of the trabecular structure of femur bone shows an increase in osteoclasts percentage, activity, and large resorption pits in the methionine treated group. The HHcy that was induced by methionine overload, caused an increase in osteoclast activity and numbers in male rabbits suggested a mechanistic role for bone resorption by Hcy. Future research clarifying the mechanistic function of elevated concentrations of Hcy in osteoporosis may have important therapeutic implications.

Trabecular bone ontogeny tracks neural development and life history among humans and non-human primates

Trabecular bone-the spongy bone inside marrow cavities-adapts to its mechanical environment during growth and development. Trabecular structure can therefore be interpreted as a functional record of locomotor behavior in extinct vertebrates. In this paper, we expand upon traditional links between form and function by situating ontogenetic trajectories of trabecular bone in four primate species into the broader developmental context of neural development, locomotor control, and ultimately life history. Our aim is to show that trabecular bone structure provides insights into ontogenetic variation in locomotor loading conditions as the product of interactions between increases in body mass and neuromuscular maturation.Our results demonstrate that age-related changes in trabecular bone volume fraction (BV/TV) are strongly and linearly associated with ontogenetic changes in locomotor kinetics. Age-related variation in locomotor kinetics and BV/TV is in turn strongly associated with brain and body size growth in all species. These results imply that age-related variation in BV/TV is a strong proxy for both locomotor kinetics and neuromuscular maturation. Finally, we show that distinct changes in the slope of age-related variation in bone volume fraction correspond to the age of the onset of locomotion and the age of locomotor maturity.Our findings compliment previous studies linking bone development to locomotor mechanics by providing a fundamental link to brain development and life history. This implies that trabecular structure of fossil subadults can be a proxy for the rate of neuromuscular maturation and major life history events like locomotor onset and the achievement of adult-like locomotor repertoires.