Individual trabecula segmentation (ITS) technique can decompose the trabecular bone network into individual trabecular plates and rods and is capable of quantifying the plate/rod-related microstructural characteristics of trabecular bone. This novel technique has been shown to be able to provide in-depth insights into micromechanics and failure mechanisms of human trabecular bone, as well as to distinguish the fracture status independent of area bone mineral density in clinical applications. However, the plate/rod microstructural parameters from ITS have never been correlated to experimentally determined mechanical properties of human trabecular bone. In this study, on-axis cylindrical trabecular bone samples from human proximal tibia (n=22), vertebral body (n=10), and proximal femur (n=21) were harvested, prepared, scanned using micro computed-tomography (µCT), analyzed with ITS and mechanically tested. Regression analyses showed that the plate bone volume fraction (pBV/TV) and axial bone volume fraction (aBV/TV) calculated by ITS analysis correlated the best with elastic modulus (R(2)=0.96-0.97) and yield strength (R(2)=0.95-0.96). Trabecular plate-related microstructural parameters correlated highly with elastic modulus and yield strength, while most rod-related parameters were found inversely and only moderately correlated with the mechanical properties. In addition, ITS analysis also identified that trabecular bone at human femoral neck had the highest trabecular plate-related parameters while the other sites were similar with each other in terms of plate-rod microstructure.

Trabecular bone quality includes both microstructural and intrinsic tissue mineralization properties. However, the tissue mineralization in individual trabeculae of different trabecular types and orientations has not yet been investigated. The aim of this study was to develop an individual trabecula mineralization (ITM) analysis technique to determine tissue mineral density (TMD) distributions in plate- and rod-like trabeculae, respectively, and to compare the TMD of trabeculae along various orientations in micro-computed tomography (μCT) images of trabecular bone samples from the femoral neck, greater trochanter, and proximal tibia. ITM analyses indicated that trabecular plates, on average, had significantly higher TMD than trabecular rods. In addition, the distribution of TMD in trabecular plates depended on trabecular orientation with the lowest TMD in longitudinal plates and the highest TMD in transverse plates. Conversely, there was a relatively uniform distribution of TMD among trabecular rods, with respect to trabecular orientation. Further analyses of TMD distribution revealed that trabecular plates had higher mean and peak TMD, whereas trabecular rods had a wider TMD distribution and a larger portion of low mineralized trabeculae. Comparison of apparent Young's moduli derived from micro-finite element models with and without heterogeneous TMD demonstrated that heterogeneous TMD in trabecular plates had a significant influence on the elastic mechanical property of trabecular bone. In conclusion, this study revealed differences in TMD between plate- and rod-like trabeculae and among various trabecular orientations. The observation of less mineralized longitudinal trabecular plates suggests interesting implications of these load-bearing plates in bone remodeling. The newly developed ITM analysis can be a valuable technique to assess the influence of metabolic bone diseases and their pharmaceutical treatments on not only microstructure of trabecular bone but also the microarchitectural heterogeneity of tissue mineralization.

Vertebral strength, a key etiologic factor of osteoporotic fracture, may be affected by the relative amount of vertically oriented trabeculae. To better understand this issue, we performed experimental compression testing, high-resolution micro-computed tomography (µCT), and micro-finite-element analysis on 16 elderly human thoracic ninth (T(9)) whole vertebral bodies (ages 77.5 ± 10.1 years). Individual trabeculae segmentation of the µCT images was used to classify the trabeculae by their orientation. We found that the bone volume fraction (BV/TV) of just the vertical trabeculae accounted for substantially more of the observed variation in measured vertebral strength than did the bone volume fraction of all trabeculae (r(2) = 0.83 versus 0.59, p < .005). The bone volume fraction of the oblique or horizontal trabeculae was not associated with vertebral strength. Finite-element analysis indicated that removal of the cortical shell did not appreciably alter these trends; it also revealed that the major load paths occur through parallel columns of vertically oriented bone. Taken together, these findings suggest that variation in vertebral strength across individuals is due primarily to variations in the bone volume fraction of vertical trabeculae. The vertical tissue fraction, a new bone quality parameter that we introduced to reflect these findings, was both a significant predictor of vertebral strength alone (r(2) = 0.81) and after accounting for variations in total bone volume fraction in multiple regression (total R(2) = 0.93). We conclude that the vertical tissue fraction is a potentially powerful microarchitectural determinant of vertebral strength.

The microstructure of trabecular bone is usually perceived as a collection of plate-like and rod-like trabeculae, which can be determined from the emerging high-resolution skeletal imaging modalities such as micro-computed tomography (μCT) or clinical high-resolution peripheral quantitative CT (HR-pQCT) using the individual trabecula segmentation (ITS) technique. It has been shown that the ITS-based plate and rod parameters are highly correlated with elastic modulus and yield strength of human trabecular bone. In the current study, plate-rod (PR) finite element (FE) models were constructed completely based on ITS-identified individual trabecular plates and rods. We hypothesized that PR FE can accurately and efficiently predict elastic modulus and yield strength of human trabecular bone. Human trabecular bone cores from proximal tibia (PT), femoral neck (FN) and greater trochanter (GT) were scanned by μCT. Specimen-specific ITS-based PR FE models were generated for each μCT image and corresponding voxel-based FE models were also generated in comparison. Both types of specimen-specific models were subjected to nonlinear FE analysis to predict the apparent elastic modulus and yield strength using the same trabecular bone tissue properties. Then, mechanical tests were performed to experimentally measure the apparent modulus and yield strength. Strong linear correlations for both elastic modulus (r(2) = 0.97) and yield strength (r(2) = 0.96) were found between the PR FE model predictions and experimental measures, suggesting that trabecular plate and rod morphology adequately captures three-dimensional (3D) microarchitecture of human trabecular bone. In addition, the PR FE model predictions in both elastic modulus and yield strength were highly correlated with the voxel-based FE models (r(2) = 0.99, r(2) = 0.98, respectively), resulted from the original 3D images without the PR segmentation. In conclusion, the ITS-based PR models predicted accurately both elastic modulus and yield strength determined experimentally across three distinct anatomic sites. Trabecular plates and rods accurately determine elastic modulus and yield strength of human trabecular bone.

Context

Idiopathic osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture.

Objective

The objective of the study was to compare three-dimensional volumetric BMD and bone stiffness in premenopausal women with IOP based on fracture history, those with idiopathic low BMD (Z score ≤ -2.0) and no low trauma fracture, and normal age-matched controls.

Design

We measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls.

Results

Subjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of -2.0 or less for a cQCT volumetric BMD Z score of -2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck.

Conclusion

Women with idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term osteoporosis may be appropriate in women with Z scores below -2.0, whether or not there is a history of fracture.

Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin-T, and antibodies raised against human amyloid β42. Fn produces amyloid-like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid-like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid-binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as "hooks" to crosslink neighboring FadA filaments to form a stable amyloid-like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti-amyloid therapies as possible interventions for Fn-mediated disease processes.

Context

The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation.

Objective

The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights.

Design

We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies.

Results

Body mass index (BMI) ranged from 20.1 to 39.2 kg/m(2). Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm(2)/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = -0.50; P < .01) and bone formation rate (r = -0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI.

Conclusions

At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation.