Trabecular Bone Region Research Articles

Characterization and selection of a skull surrogate for the development of a biofidelic head model

This research paper explores the advancement of physical models simulating the human skull-brain complex, focusing on applications in simulating mild Traumatic Brain Injury (mTBI). Existing models, especially head forms, lack biofidelity in accurately representing the native structures of the skull, limiting the understanding of intracranial injury parameters beyond kinematic head accelerations. This study addresses this gap by investigating the use of additive manufacturing (AM) techniques to develop biofidelic skull surrogates. Materials such as Polylactic Acid (PLA), a bone-simulant PLA variant, and Hydroxyapatite-coated Poly(methyl methacrylate) (PMMA) were used to create models tested for their flexural modulus and strength. The trabecular bone regions were simulated by adjusting infill densities (30%, 50%, 80%) and print raster directions, optimizing manufacturing parameters for biofidelic performance. Among the tested materials, PLA and its bone-simulating variant printed at 80% infill density with a side (tangential) print orientation demonstrated the closest approximation to the mechanical properties of cranial bone, yielding a mean flexural modulus of 1337.2 MPa and a mean ultimate strength of 56.9 MPa. Statistical analyses showed that infill density significantly influenced the moduli and strength of the printed simulants. Digital Image Correlation (DIC) corroborated the comparable performance of the simulants, showing similar strain and displacement behaviors to native skull bone. Notably, the performance of the manufactured cortical and trabecular regions underscored their crucial role in achieving biofidelity, with the trabecular structure providing critical dampening effects when the native bone is loaded. This study establishes PLA, particularly its bone-simulant variant, as an optimal candidate for cranial bone simulants, offering significant potential for developing more accurate biofidelic head models in mTBI research.

Histological and Histopathological Features of the Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove in Thoroughbred Horses with Racing History.

Information regarding the histopathology of the proximal phalanx (P1) sagittal groove in racehorses is limited. Twenty-nine cadaver limbs from nine Thoroughbred racehorses in racing/race-training underwent histological examination. Histological specimens of the third metacarpal/metatarsal (MC3/MT3) parasagittal grooves and P1 sagittal grooves were graded for histopathological findings in hyaline cartilage (HC), calcified cartilage (CC), and subchondral plate and trabecular bone (SCB/TB) regions. Histopathological grades were compared between (1) fissure and non-fissure locations observed in a previous study and (2) dorsal, middle, and palmar/plantar aspects. (1) HC, CC, and SCB/TB grades were more severe in fissure than non-fissure locations in the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades were more severe in fissure than non-fissure locations in the P1 sagittal groove (p < 0.001). (2) HC, CC, and SCB/TB grades including SCB collapse were more severe in the palmar/plantar than the middle aspect of the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades including SCB collapse were more severe in the dorsal and middle than the palmar/plantar aspect of the P1 sagittal groove (p < 0.001). Histopathology in the SCB/TB region including bone fatigue injury was related to fissure locations, the palmar/plantar MC3/MT3 parasagittal groove, and the dorsal P1 sagittal groove.

Accuracy of Volumetric Bone Mineral Density Measurement in Weight Bearing, Cone Beam Computed Tomography

Background: Weight bearing computed tomography (WBCT) utilizes cone beam CT technology to provide assessments of lower limb joint structures while they are functionally loaded. Grey-scale values indicative of X-ray attenuation that are output from cone beam CT are challenging to calibrate, and their use for bone mineral density (BMD) measurement remains debatable. To determine whether WBCT can be reliably used for cortical and trabecular BMD assessment, we sought to establish the accuracy of BMD measurements at the knee using modern WBCT by comparing them to measurements from conventional CT.Methods: A hydroxyapatite phantom with three inserts of varying densities was used to systematically quantify signal uniformity and BMD accuracy across the acquisition volume. We evaluated BMD in vivo (n = 5, female) using synchronous and asynchronous calibration techniques in WBCT and CT. To account for variation in attenuation along the height (z-axis) of acquisition volumes, we tested a height-dependent calibration approach for both WBCT and CT images.Results: Phantom BMD measurement error in WBCT was as high as 15.3% and consistently larger than CT (up to 5.6%). Phantom BMD measures made under synchronous conditions in WBCT improved measurement accuracy by up to 3% but introduced more variability in measured BMD. We found strong correlations (R = 0.96) as well as wide limits of agreement (-324 mgHA/cm3 to 183 mgHA/cm3) from Bland-Altman analysis between WBCT and CT measures in vivo that were not improved by height-dependent calibration.Conclusion: Whilst BMD accuracy from WBCT was found to be dependent on apparent density, accuracy was independent of the calibration technique (synchronous or asynchronous) and the location of the measurement site within the field of view. Overall, we found strong correlations between BMD measures from WBCT and CT and in vivo measures to be more accurate in trabecular bone regions. Importantly, WBCT can be used to distinguish between anatomically relevant differences in BMD, however future work is necessary to determine the repeatability and sensitivity of BMD measures in WBCT.

ATP6AP2, a regulator of LRP6/β-catenin protein trafficking, promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types, including osteoblast (OB) differentiation and function. Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive. ATP6AP2, an accessory subunit of V-ATPase, plays important roles in multiple cell types/organs and multiple signaling pathways. However, little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation. Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions. Conditionally knocking out (CKO) ATP6AP2 in the OB-lineage cells (Atp6ap2Ocn-Cre) reduced trabecular, but not cortical, bone formation and bone mass. Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs, but not osteocytes. Additional in vitro and in vivo studies revealed impaired β-catenin signaling in ATP6AP2-KO BMSCs and OBs, but not osteocytes, under both basal and Wnt stimulated conditions, although LRP5 was decreased in ATP6AP2-KO osteocytes, but not BMSCs. Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression of β-catenin phosphorylation, but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane, thus preventing their degradation. Expression of active β-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs. Taken together, these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability, and thus regulating β-catenin levels, demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

Mitochondria-specific antioxidant MitoTEMPO alleviates senescence of bone marrow mesenchymal stem cells in ovariectomized rats.

Senescence in bone marrow mesenchymal stem cells (BMSCs), triggered by excessive oxidative stress, plays a crucial role in the onset of postmenopausal osteoporosis. Recent studies underscore the importance of mitochondrial rehabilitation and quality control as key determinants in the modulation of oxidative stress and cellular senescence. MitoTEMPO, a mitochondria-targeted antioxidant, has been shown to mitigate the heightened levels of reactive oxygen species (ROS). In our research, we observed that BMSCs from ovariectomized (OVX) rats displayed premature senescence, which was attributed to combined mitochondrial and lysosomal dysfunction, a condition that worsens with extended estrogen deprivation. Treatment with MitoTEMPO effectively reversed these effects, reinstating lysosomal functionality and suppressing the mitochondrial unfolded protein response (UPRmt). Subsequent in vivo experiments corroborated these observations, revealing that MitoTEMPO administration in OVX rats curtailed trabecular bone loss and reduced the expression of p53, HSP60, and CLPP in the trabecular bone region of the proximal tibia. Overall, our findings suggest that MitoTEMPO holds promise as a therapeutic agent to counteract senescence in OVX-BMSCs, offering a potential strategy for treating postmenopausal osteoporosis.

Finite element study on post-screw removal stress in toy poodle radius with different plate designs and screw arrangements.

The study employs finite element analysis to investigate stress distribution in the radius of toy poodles after screw removal. The examination focuses on the biomechanical implications of varied screw hole configurations using 1.5 and 2.0-mm locking compression plates (LCPs) with notched head T-Plates. To provide a noninvasive approach to analyzing the immediate consequences of screw removal from the radius bone in toy poodles. Specifically, it explores the impact of varied plate designs and screw arrangements on stress distribution within the forelimb bones. The study constructs a three-dimensional bone model of the toy poodle's forelimb based on computed tomography (CT) images. Simulations were designed to replicate jumping and landing from a 40 cm height, comparing stress distribution in the radius post-screw removal. The analysis reveals significant variations in stress distribution patterns between the two LCPs. The radius implanted with the 2.0-mm LCP displays a uniform stress distribution, contrasting with the 1.5-mm plates. Localized stress concentration is observed around the screw holes, while trabecular bone regions near the screw holes exhibit lower stress levels. The study highlights the plate designs and screw configurations that affect bone stress in toy poodle forelimbs post-screw removal. The findings provide valuable insights for veterinarians, aiding informed decisions in veterinary orthopedic practices.

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging

Introduction Rare non-hematopoietic cells in the bone marrow make essential contributions to hematopoiesis. Despite tremendous progress in understanding the mouse bone marrow microenvironment, the precise identity of human non-hematopoietic bone marrow cells and their spatial organization remain largely uncharacterized. Here, we performed single cell transcriptomics and spatial proteomics, assembling the first comprehensive atlas of human bone marrow cellular composition and organization. Methods Using fresh femoral head samples obtained from orthopedic hip replacement surgeries, we first performed single-cell RNA sequencing (scRNA-Seq) to create a comprehensive human bone marrow atlas profiling 29,325 enriched non-hematopoietic cells as well as 53,417 hematopoietic cells from enzymatically digested femoral heads from 12 individuals. We next employed Co-Detection by Indexing (CODEX) multiplexed imaging of 18 bone marrow samples, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. Results Our transcriptional analysis revealed nine distinct non-hematopoietic bone marrow cell types including mesenchymal stromal cell (MSC) subsets, osteolineage cells, vascular smooth muscle cells, and both sinusoidal and arterial endothelial cells (Figure 1A). We found that MSCs were heterogeneous and hierarchically organized. One specific cell cluster, which we termed Fibro-MSCs, corresponded to previous descriptions of mesenchymal stem cells and was both computationally and functionally shown to be the most stem/progenitor-like. Next, we performed computational cellular communication analysis which revealed that two MSC subsets, Adipo and THY1+ MSCs, provided the majority of canonical hematopoietic supportive factors such as CXCL12, KITLG, IL7, and PTN. Next, we used CODEX to systematically study spatial relationships between these cells. Consistent with the scRNA-Seq cellular communication analysis, we found that Adipo and THY1+ MSCs were in the bone marrow interacting with hematopoietic cells, while osteolineage cells and Fibro-MSCs were found within the trabecular bone region. We then performed unsupervised neighborhood analysis to analyze the distinct niches of the bone marrow. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, where early myeloid progenitors were characterized by very low levels of HIF1α, in contrast to HIF1α hi neutrophils which were found largely residing near sinusoids. We also employed point pattern statistics and permutation tests to analyze the proximity of cell types to manually identified structures in the bone marrow. This analysis revealed that CD34+ hematopoietic stem and progenitor cells (HSPCs) were frequently contacting adipocytes (Figure 1B), but not sinusoids or bone. Collectively, these results led us to propose a data-driven working model for how human myelopoiesis is spatially organized, with the earliest myeloid progenitors being specified from HSPCs near adipocytes, then migrating to the peri-arteriolar/peri-endosteal early myeloid progenitor niche, and then finally localizing near sinusoids which facilitates bone marrow egress as they mature to neutrophils. To evaluate if our CODEX atlas could be used to study disease states, we mapped new bone marrow images from acute myeloid leukemia (AML) patients and controls to our reference. We used machine learning to identify true mutant cells based on NPM1c expression patterns. We discovered Adipo and THY1+ MSC expansion in AML patients compared to controls, with expanded MSCs spatially associated with leukemic blasts. Our results highlight the potential of our CODEX atlas to contextualize new datasets and study bone marrow organization in disease states, and provide further rationale to study MSC-AML blast interactions. Conclusions Taken together, our scRNA-Seq and CODEX data act in concert, demonstrating the diversity of non-hematopoietic stromal elements, establishing the source of hematopoietic cytokines, and defining the spatial organization in healthy human bone marrow. We envision our multiomic, spatially resolved atlas of human bone marrow will serve as a critical resource for future study of the bone marrow microenvironment in both healthy and disease states.

Microvascular Disease Associates with Larger Osteocyte Lacunae in Cortical Bone in Type 2 Diabetes Mellitus.

Clinical studies indicate that microvascular disease (MVD) affects bone microstructure and decreases bone strength in type 2 diabetes mellitus (T2D). Osteocytes are housed in small voids within the bone matrix and lacunae and act as sensors of mechanical forces in bone. These cells regulate osteoclastic bone resorption and osteoblastic bone formation as well as osteocytic perilacunar remodeling. We hypothesized that MVD changes morphometric osteocyte lacunar parameters in individuals with T2D. We collected iliac crest bone biopsies from 35 individuals (10 female, 25 male) with T2D with MVD (15%) or without MVD (21%) with a median age of 67 years (interquartile range [IQR] 62-72 years). The participants were included based on c-peptide levels >700 pmol L-1, absence of anti-GAD65 antibodies, and glycated hemoglobin (HbA1c) levels between 40 and 82 mmol mol-1 or 5.8% and 9.7%, respectively. We assessed osteocyte lacunar morphometric parameters in trabecular and cortical bone regions using micro-computed tomography (micro-CT) at a nominal resolution of 1.2 μm voxel size. The cortical osteocyte lacunar volume (Lc.V) was 7.7% larger (p = 0.05) and more spherical (Lc.Sr, p < 0.01) in the T2D + MVD group. Using linear regression, we found that lacunar density (Lc.N/BV) in trabecular but not cortical bone was associated with HbA1c (p < 0.05, R 2 = 0.067) independently of MVD. Furthermore, Lc.V was larger and Lc.Sr higher in the center than in the periphery of the trabecular and cortical bone regions (p < 0.05). In conclusion, these data imply that MVD may impair skeletal integrity, possibly contributing to increased skeletal fragility in T2D complicated by MVD. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The Synergistic Effect of Zuogui Pill and Eldecalcitol on Improving Bone Mass and Osteogenesis in Type 2 Diabetic Osteoporosis.

Background and Objectives: The incidence of diabetic osteoporosis, an important complication of diabetes mellitus, is increasing gradually. This study investigated the combined effect of the Zuogui pill (ZGP) and eldecalcitol (ED-71), a novel vitamin D analog, on type 2 diabetic osteoporosis (T2DOP) and explored their action mechanism. Materials and Methods: Blood glucose levels were routinely monitored in db/db mice while inducing T2DOP. We used hematoxylin and eosin staining, Masson staining, micro-computed tomography, and serum biochemical analysis to evaluate changes in the bone mass and blood calcium and phosphate levels of mice. Immunohistochemical staining was performed to assess the osteoblast and osteoclast statuses. The MC3T3-E1 cell line was cultured in vitro under a high glucose concentration and induced to undergo osteogenic differentiation. Quantitative real-time polymerase chain reaction, Western blot, immunofluorescence, ALP, and alizarin red staining were carried out to detect osteogenic differentiation and PI3K-AKT signaling pathway activity. Results: ZGP and ED-71 led to a dramatic decrease in blood glucose levels and an increase in bone mass in the db/db mice. The effect was strongest when both were used together. ZGP combined with ED-71 promoted osteoblast activity and inhibited osteoclast activity in the trabecular bone region. The in vitro results revealed that ZGP and ED-71 synergistically promoted osteogenic differentiation and activated the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 or AKT inhibitor ARQ092 altered the synergistic action of both on osteogenic differentiation. Conclusions: The combined use of ZGP and ED-71 reduced blood glucose levels in diabetic mice and promoted osteogenic differentiation through the PI3K-AKT signaling pathway, resulting in improved bone mass. Our study suggests that the abovementioned combination constitutes an effective treatment for T2DOP.

Biomechanical Performance of a Novel Implant Design in Simulated Extraction Sites and Sinuslift Procedures

With increasing experience and in an attempt to shorten overall treatment times, implant placement in combination with tooth extractions and sinus lift procedures has become popular. In both cases, primary stability has to be achieved by either engaging apical and oral regions of trabecular bone or by engaging residual host bone beneath the sinus cavity. Extraction sites were formed by pressing a root analog into homogeneous low density polyurethane foam which was used as bone surrogate while a 3 mm thick sheet of medium density foam was used for mimicking a sinus lift situation. Two types (n = 10) of bone level implants with a conventional tapered design and a cervical back taper (NobelActive; control) and a novel design characterized by a shift in core diameter and thread geometry (AlfaGate; test) were placed in these models following conventional osteotomy preparation. Insertion torque was measured using a surgical motor and primary stability was determined by resonance frequency analysis. Statistical analysis was based on Welch two sample t tests with the level of significance set at α = 0.05. In sinuslifting, NobelActive implants required significantly higher insertion torques as compared to AlfaGate (p = 0.000) but did not achieve greater implant stability (p = 0.076). In extraction sites, AlfaGate implants showed both, significantly higher insertion torques (p = 0.004) and significantly greater implant stability (p = 0.000). The novel implant design allowed for greater primary stability when being placed in simulated extraction sockets and sinuslift situations. While in extraction sockets the position of condensing threads in combination with an increase in core diameter is beneficial, the deep cervical threads of the novel implant lead to superior performance in sinuslift situations.

Interaction Phenomena between Dental Implants and Bone Tissue in Case of Misfit: A Pilot Study

The biomechanical response of cortical and trabecular bone tissues represents a fundamental aspect for the interpretation of the functional response of dental implants. In the case of misfit, the interaction phenomena occurring within the surgical and the subsequent healing phases must be interpreted primarily in the light of the response of bone tissue. This is influenced by the specific loadings induced, characterized by intensity and variable trends. The pilot study reported, which intentionally refers to a simple case of a two-implants frame, is addressed to define the method to approach the biomechanical investigation of the problem and to attest the necessity to integrate clinical competences with biomechanical analysis for interpreting different aspects of osseointegration. The action induced in cortical and trabecular bone regions depending on the implant frame conformation, the surgical procedure adopted, the varying condition at the bone–implant interface and the evolutionary trend of healing are the principal aspects to be considered to evaluate the osseointegration process. The biomechanical reliability of the specific implant frame is investigated in terms of bone–implant interaction by means of numerical models. This approach can offer valid information and support clinical practice under the fundamental condition that bone biomechanical behavior is properly characterized and represented in the model, in spite of the complex formulation to be adopted.

Rapid trabecular bone growth in puberty associated with stiffer arteries in adulthood - longitudinal study on healthy young males.

Our aim was to assess the relationships between arterial parameters in adulthood and bone parameters in several locations longitudinally from puberty to 18-years and cross-sectionally at 18-years. 102 healthy male data from a 7-year follow-up study was used to analyse total body (TB), femoral neck (FN) and lumbar spine (LS) mineral content and density by DXA, carotid intima-media thickness (cIMT) by ultrasound, carotid-femoral pulse wave velocity (cfPWV) and heart rate adjusted augmentation index (AIxHR75) by applanation tonometry. Linear regression analysis revealed negative associations between LS bone mineral density (BMD) and cfPWV [ß=-1.861, CI -3.589, -0.132, p=0.035] which remained significant [ß=-2.679, CI -4.837, -0.522, p=0.016] after adjustment to smoking, lean mass, weight category, pubertal stage, physical fitness, and activity. For AIxHR75 similar results were present [ß=-0.286, CI -0.553, -0.020, p=0.035], but were dependent on confounders. Analysis on pubertal bone growth speed showed independent positive associations to AIxHR75 between Δ FN bone mineral apparent density (BMAD) [ß=672.50, CI 348.07, 996.93, p<0.001] and Δ LS BMAD [ß=700.40, CI 57.384, 1343.423, p=0.033]. Further analysis combining pubertal bone growth and adulthood BMC revealed that the relationships of AIxHR75 with LS BMC and ΔFN BMAD were independent of each other. Trabecular bone regions like lumbar spine and femoral neck, showed stronger relationships with arterial stiffness. Rapid bone growth in puberty is related to arterial stiffening, while final bone mineral content relates to decreased arterial stiffness. These results could indicate that bone metabolism is independently associated with arterial stiffness rather than bone and arteries just having common traits of growth and maturation.

Age- and sex-specific normative values of bone mineral density in the adult glenoid.

The objective of this study was to determine the normative bone mineral density (BMD) of cortical and trabecular bone regions in the adult glenoid and its dependence on the subject's age and sex. We analyzed computed tomography (CT) scans of 441 shoulders (310 males, 18-69 years) without any signs of glenohumeral joint pathology. Glenoid BMD was automatically quantified in six volumes of interest (VOIs): cortical bone (CO), subchondral cortical plate (SC), subchondral trabecular bone (ST), and three adjacent layers of trabecular bone (T1, T2, and T3). BMDwas measured in Hounsfield unit (HU). We evaluated the association between glenoid BMD and sex and age with the Student's t test and Pearson's correlation coefficient (r), respectively. The lambda-mu-sigma method was used to determine age- and sex-specific normative values of glenoid BMD in cortical (CO and SC) and trabecular (ST, T1, T2, and T3) bone. Glenoid BMDwas higher in males than females, in most age groups and most VOIs. Before 40 years old, the effect of age on BMD was very weak in both males and females. After 40 years old, BMD declined over time in all VOIs. This BMDdecline with age was greater in females (cortical: r = -0.45, trabecular: r = -0.41) than in males (cortical: r = -0.30; trabecular: r = -0.32). These normative glenoid BMD values could prove clinically relevant in the diagnosis and management of patients with various shoulder disorders, in particular glenohumeral osteoarthritis and shoulder arthroplasty or shoulder instability, as well as in related research.

A Micro-computed Tomography Database and Reference Implementation for Parallel Computations of Trabecular Thickness and Spacing

We provide a well-defined accurate brute force implementation without approximations as a reference to support future development of correct and fast algorithms to measure the trabecular thickness and spacing. Using artificial ellipsoid examples, the systematic error is shown to be related to the voxelization, which can be reduced by upsampling. Furthermore, we collected a database of 40 three-dimensional micro-computed tomography images of trabecular bone regions of a sheep femur. With the coverage of a broad range of trabecular thickness and spacing, the database is suitable for assessing the correctness of algorithms for the measurements of trabecular thickness and spacing. The bone data is shared publicly in the online repository ‘Figshare’ and the brute force code is freely available in Code Ocean. Scientists are encouraged to implement faster algorithms, e.g., graphic processing unit-accelerated, with accurate or controlled approximate behaviour to compute trabecular thickness and spacing. Especially, the provided data can be re-employed together with the reference algorithm to evaluate their accuracies.

A Shrewd Inspection of Vertebral Regionalization in Large Shrews (Soricidae: Crocidurinae).

SynopsisThe regionalization of the mammalian spinal column is an important evolutionary, developmental, and functional hallmark of the clade. Vertebral column regions are usually defined using transitions in external bone morphology, such as the presence of transverse foraminae or rib facets, or measurements of vertebral shape. Yet the internal structure of vertebrae, specifically the trabecular (spongy) bone, plays an important role in vertebral function, and is subject to the same variety of selective, functional, and developmental influences as external bone morphology. Here, we investigated regionalization of external and trabecular bone morphology in the vertebral column of a group of shrews (family Soricidae). The primary goals of this study were to: (1) determine if vertebral trabecular bone morphology is regionalized in large shrews, and if so, in what configuration relative to external morphology; (2) assess correlations between trabecular bone regionalization and functional or developmental influences; and (3) determine if external and trabecular bone regionalization patterns provide clues about the function of the highly modified spinal column of the hero shrew Scutisorex. Trabecular bone is regionalized along the soricid vertebral column, but the configuration of trabecular bone regions does not match that of the external vertebral morphology, and is less consistent across individuals and species. The cervical region has the most distinct and consistent trabecular bone morphology, with dense trabeculae indicative of the ability to withstand forces in a variety of directions. Scutisorex exhibits an additional external morphology region compared to unmodified shrews, but this region does not correspond to a change in trabecular architecture. Although trabecular bone architecture is regionalized along the soricid vertebral column, and this regionalization is potentially related to bone functional adaptation, there are likely aspects of vertebral functional regionalization that are not detectable using trabecular bone morphology. For example, the external morphology of the Scutisorex lumbar spine shows signs of an extra functional region that is not apparent in trabecular bone analyses. It is possible that body size and locomotor mode affect the degree to which function is manifest in trabecular bone, and broader study across mammalian size and ecology is warranted to understand the relationship between trabecular bone morphology and other measures of vertebral function such as intervertebral range of motion.

3D strain analysis of trabecular bone within the osteoarthritic humeral head subjected to stepwise compressive loads

Understanding the local mechanical properties of trabecular bone at the humeral head-neck junction is essential for the safe design of stemless humeral head implants. Recent advancements in mechanical testing coupled with volumetric imaging have allowed for the ability to quantify full-field strain distributions throughout trabecular bone. Within this study, digital volume correlation (DVC) was applied to micro-computed tomography images to investigate the local load carrying characteristics of trabecular bone within osteoarthritic (OA) humeral heads subjected to stepwise loading. A multi-pegged indenter was used to transfer loads from a custom-fabricated loading apparatus to trabecular bone on the resection surface of OA humeral head osteotomies retrieved from patients undergoing total shoulder arthroplasty (TSA). In regions of trabecular bone that eventually fractured, third principal strains were significantly higher (95th percentile third principal strain = −12,558 μstrain, p < 0.001) compared to regions that did not fracture (95th percentile third principal strain = −7,806 μstrain). As well, bone volume fraction (p = 0.012), trabecular separation (p = 0.014), and trabecular number (p = 0.007) were found to influence the likelihood of trabecular bone fracture. Collectively, this work has led to a deeper understanding of the local load carrying characteristics of trabecular bone specific to patients receiving TSA for osteoarthritis.

Types of vertebral fractures could influence the selection of clinical bone mineral measures to predict biomechanical properties

Areal and volumetric BMD (aBMD and vBMD) measured by DXA and quantitative CT (QCT), respectively, are usually employed to predict vertebral fracture risks. In this study, we induced compression and wedge vertebral fractures to test if the types of fracture could influence the selection of bone mineral measures to predict biomechanical properties of vertebral bodies. DXA and QCT were employed to scan twenty-four male cadaveric vertebral bodies of humans for bone mineral content (BMC) and aBMD measures, and vBMD measures, respectively. We computed vBMD measures from three kinds of volumes of interest: intact structures (vertebral body, cortical compartment, and trabecular core), axially middle sections (1.250–1.875 cm height) of the intact structures, and clinically used elliptical regions of trabecular bone. We loaded vertebral bodies to failure for properties of strength (Pu), failure displacement (δu), and stiffness (K). Thirteen vertebral bodies sustained compression fractures and the remaining sustained wedge fractures. Linear and power regression models were used to test bone mineral predictions for Pu, δu, and K. We also did equality tests of correlation coefficients. Our results showed aBMD, BMC, and vBMD of the middle section of trabecular bone had the strongest correlations with Pu (R2 = 0.6420, p < 0.001), δu (R2 = 0.4619, p < 0.001), and K (R2 = 0.5992, p < 0.001) in power regression models, respectively when compression and wedge fractures were mixed. Considering compression fractures only, vBMD of the intact vertebral body displayed the strongest correlations with both Pu (R2 = 0.6529, p < 0.001) and K (R2 = 0.6354, p < 0.001) while BMC showed the strongest correlation with δu (R2 = 0.4376, p < 0.001) in linear regression models. When only wedge fractures were analyzed, vBMD of the elliptical regions of trabecular bone exhibited the strongest correlations with both Pu (R2 = 0.5845, p < 0.001) and K (R2 = 0.6420, p < 0.001) in power regression models, however, no bone mineral measure could significantly correlate with δu. These results may suggest the type of fracture could influence the determination of bone mineral measures to predict biomechanical properties of vertebral bodies.

TRABECULAR AND CORTICAL MANDIBULAR BONE STRUCTURE IN FAMILIAL ADENOMATOUS POLYPOSIS: A PANORAMIC RADIOGRAPHIC STUDY

<h3>BACKGROUND</h3> Colorectal cancer (CRC) is the third leading cause of cancer-associated deaths worldwide and is responsible for almost 9% of all deaths. Familial adenomatous polyposis (FAP) is an autosomal dominant disorder presenting with dento-osseous manifestations. <h3>OBJECTIVE(S)</h3> To analyze the mandibular cortical and trabecular bone pattern in patients with FAP through dental panoramic radiomorphometric indices and fractal dimension (FD). <h3>STUDY DESIGN</h3> Dental panoramic radiographs (DPRs) were obtained from patients with FAP and paired controls. The parameters analyzed were FD of the trabecular bone in 4 different regions of interest (ROIs), mandibular cortical index (MCI), and mandibular cortical width (MCW). Blinded evaluators were trained until they reached an adequate intra- and interobserver reliability calculated via the intraclass correlation coefficient (ICC). FD for each area, MCI and MCW were compared between groups by parametric Student <i>t</i> tests and the chi-square statistic. <h3>RESULTS</h3> Sixty panoramic radiographs of dentate patients, including patients with FAP (n = 15) and matched controls (n = 45), were investigated. The ICC showed an excellent agreement, FD ICC = 100%, MCI = 0.967 (confidence interval [CI], 0.945-0.980), MCW(R) = 0.995 (CI, 0.991-0.997), and MCW(L) = 0.983 (CI, 0.972-0.990). The FD values were lower for the FAP group compared with the non-FAP controls. Statistically significant differences were shown in ROI-2 and ROI-3 anteriorly to the mental foramen bilaterally (<i>P</i> = .001 and <i>P</i> = .006, respectively). ROI-1 and ROI-4, at the mandibular angle trabecular bone region, indicated statistical significance on the right side (<i>P</i> = .036) and no difference on the left side (<i>P</i> = .091). There was no significant difference in MCI and MCW between the groups, with MCW (L) <i>P</i> = .247 and MCW (R) <i>P</i> = .070. <h3>DISCUSSION/CONCLUSIONS</h3> Fractal dimension values of mandibular trabecular bone of patients with FAP were lower than those in healthy controls. The radiomorphometric indices MCI and MCW were not useful for the analysis of the cortical bone pattern. Therefore, FD is a promising tool for bone structure evaluation in dental panoramic radiographs and for supporting the appropriate referral of patients with FAP.

Assessing biases in the analysis of trabecular bone microarchitecture of non-adult individuals

Micro-computed tomography (µCT) is a non-destructive x-ray technique that can provide high-resolution images of skeletal material, making it an attractive option for analysing archaeological human remains. However, µCT data acquisition, image segmentation and 3D reconstruction may bias the quantification of trabecular bone microarchitecture (TBMA) parameters. Some biases have been evaluated in previous studies, but never in non-adult individuals at different stages of development. Five non-pathological humeral metaphyses from known-age individuals of various developmental stages were µCT-scanned at a high resolution based on bone size. First, repeatability and reproducibility of the volume of interest selection protocol (VOI, trabecular bone region analysed) have been evaluated and found to produce non-significant variations of the TBMA parameters. Then, each bone was assessed for biasing effects related to image resolution and segmentation, as well as the size and position of the VOI. According to the bias tested, individuals of different developmental stages and parameters are differentially affected. By progressing through the stages of development, the TBMA parameters seem less sensitive to the variation introduced by the bias tests. Perinatal stage and mature adolescent stage distinctly differ from others depending on the tests and parameters measured. Bone volume fraction, trabecular thickness and trabecular number are the most sensitive and correlated parameters to the biases tested. We therefore propose specific recommendations to assure homologous VOI selection and reliable and comparable results for non-adult TBMA analyses.

Gli1+ progenitors mediate bone anabolic function of teriparatide via Hh and Igf signaling.

SUMMARYTeriparatide is the most widely prescribed bone anabolic drug in the world, but its cellular targets remain incompletely defined. The Gli1+ metaphyseal mesenchymal progenitors (MMPs) are a main source for osteoblasts in postnatal growing mice, but their potential response to teriparatide is unknown. Here, by lineage tracing, we show that teriparatide stimulates both proliferation and osteoblast differentiation of MMPs. Single-cell RNA sequencing reveals heterogeneity among MMPs, including an unexpected chondrocyte-like osteoprogenitor (COP). COP expresses the highest level of Hedgehog (Hh) target genes and the insulin-like growth factor 1 receptor (Igf1r) among all cell clusters. COP also expresses Pth1r and further upregulates Igf1r upon teriparatide treatment. Inhibition of Hh signaling or deletion of Igf1r from MMPs diminishes the proliferative and osteogenic effects of teriparatide. The study therefore identifies COP as a teriparatide target wherein Hh and insulin-like growth factor (Igf) signaling are critical for the osteoanabolic response in growing mice.