Trabecular Bone Structure Analysis in the Osteoporotic Spine Using a Clinical In Vivo Setup for 64‐Slice MDCT Imaging: Comparison to μCT Imaging and μFE Modeling

Assessment of trabecular microarchitecture may improve estimation of biomechanical strength, but visualization of trabecular bone structure in vivo is challenging. We tested the feasibility of assessing trabecular microarchitecture in the spine using multidetector CT (MDCT) on intact human cadavers in an experimental in vivo–like setup. BMD, bone structure (e.g., bone volume/total volume = BV/TV; trabecular thickness = Tb.Th; structure model index = SMI) and bone texture parameters were evaluated in 45 lumbar vertebral bodies using MDCT (mean in‐plane pixel size, 274 μm²; slice thickness, 500 μm). These measures were correlated with structure measures assessed with μCT at an isotropic spatial resolution of 16 μm and to microfinite element models (μFE) of apparent modulus and stiffness. MDCT‐derived BMD and structure measures showed significant correlations to the density and structure obtained by μCT (BMD, R² = 0.86, p < 0.0001; BV/TV, R² = 0.64, p < 0.0001; Tb.Th, R² = 0.36, p < 0.01). When comparing μCT‐derived measures with μFE models, the following correlations (p < 0.001) were found for apparent modulus and stiffness, respectively: BMD (R² = 0.58 and 0.66), BV/TV (R² = 0.44 and 0.58), and SMI (R² = 0.44 and 0.49). However, the overall highest correlation (p < 0.001) with μFE app. modulus (R² = 0.75) and stiffness (R² = 0.76) was achieved by the combination of QCT‐derived BMD with the bone texture measure Minkowski Dimension. In summary, although still limited by its spatial resolution, trabecular bone structure assessment using MDCT is overall feasible. However, when comparing with μFE‐derived bone properties, BMD is superior compared with single parameters for microarchitecture, and correlations further improve when combining with texture measures.     

The interrelation of trabecular microstructural parameters of the greater tubercle measured for different species

In the present study the trabecular microstructural parameters (bone volume fraction, trabecular thickness, trabecular separation, trabecular number, connectivity density, degree of anisotropy, and structure model index) of the greater tubercle of the humeral head were measured for human healthy, human osteopenic, ovine, bovine, and porcine bones using micro‐computed tomography. Except for trabecular thickness and degree of anisotropy the values of the trabecular microstructural parameters generally differed significantly between species. Thus, only the species for which the implant is designed should be used for in vitro mechanical tests on the stability of implants in trabecular bone. Multivariate regression analysis showed that the microstructural parameters have similar principal interrelations in all species. The most significant relations were found between trabecular thickness and bone volume fraction (median (over all species) p < 0.001), trabecular number and bone volume fraction (p = 0.001), the structural change from plates to rods and bone volume fraction (p < 0.001) as well as between connectivity density and trabecular number (p < 0.001). Trabecular thickness, trabecular number, and the structural change from plates to rods each contributed to the bone volume fraction approximately to the same extent. Based on the similar principal interrelations of the trabecular microstructural parameters found in all investigated species the design of trabecular microstructure in the greater tubercle follows similar phenomenological mechanisms in all species. Thus, in vivo experiments on trabecular bone healing and osteoporosis research for application in humans can be conducted in ovine, bovine, or porcine species. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:429–434, 2012     

Ultrasound Velocity and Attenuation in Cancellous Bone Samples from Lumbar Vertebra and Calcaneus

We report a study of ultrasound velocity and broadband ultrasound attenuation (BUA) in human cancellous bone samples. The influence of density and microarchitecture on ultrasound propagation in cancellous bone was examined. A total of 20 samples from vertebra L1 and 21 from calcanei were studied. The direction of ultrasound propagation was anteroposterior in the vertebra and lateromedial in the calcaneus. The relationships between ultrasonic parameters and density of bone samples, apparent ash density, trabecular bone volume (BV/TV) and trabecular thickness (Tb.Th) were analyzed using a simple linear model and a multiple regression model. Velocity of ultrasound and BUA were positively correlated with density and morphometric parameters, in both vertebra and calcaneus. The best correlation was found between velocity and bone sample density in vertebra (r= 0.961, p < 0.0001) and the worst between velocity and trabecular thickness in calcaneus (r= 0.632, p= 0.002). The best correlation for BUA was with BV/TV in vertebra (r= 0.960, p < 0.0001). Using the stepwise regression procedure, BV/TV only was selected as significant for BUA and apparent ash density with Tb.Th for velocity, in both vertebra and in calcaneus. The possible influence of trabecular configuration on ultrasonic parameters is discussed, emphasizing the different slopes of regression lines obtained for vertebra and calcaneus, sites with different architecture of trabecular bone. Received: 9 April 1997 / Accepted: 27 April 1998     

Impaired Bone Microarchitecture Improves After One Year On Gluten‐Free Diet: A Prospective Longitudinal HRpQCT Study in Women With Celiac Disease

We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high‐resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten‐free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone‐specific parameters and CD serology) at both time points. Secondary, we compared 1‐year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow‐up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.     

Microstructural adaptation in trapezial bone due to subluxation of the thumb

Although the thumb saddle is one of the most common sites of degenerative osteoarthritis in the hand, little is known about the altered microstructure in osteoarthritic trapezial bones. External forces resulting from subluxation of the carpometacarpal joint of the thumb (CMC I) should provoke microstructural changes in the trapezium. The purpose of this study was to compare the regional differences of the microstructure between osteoarthritic and healthy trapezial bones. Fifteen trapezia harvested from female patients with radiologically and clinically diagnosed saddle joint osteoarthritis (OA) were compared with 15 unaffected controls. Microstructural parameters, such as bone volume ratio (BV/TV), three‐dimensional connectivity (Conn.D), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were studied using a microcomputed tomography (microCT) system. While the trapezial height in OA was 22% less, the sclerotic subchondral bone layer thickness was 50% higher in OA compared with the control group (p < 0.001). In the OA group there was a 42% higher bone volume ratio (p ≤ 0.001), an 18% increase in Tb.Th (p = 0.006), and a 10% greater Tb.N (p = 0.034) compared with the control group. Although in both groups BV/TV was significantly lower in the radial region, the radial column showed the highest relative increase in bone volume and structure compared with the control group (+67% BV/TV, +20% Tb.Th, +23% Tb.N). The reinforcement of the bony microstructure in CMC I OA, especially at the radial side, is a sign for bone adaptation reacting to radially shifted joint forces. This has to be considered during the development of new prosthetic alternatives. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:208–216, 2008     

Effects of Parathyroid Hormone Administration on Bone Strength in Hypoparathyroidism

The microstructural skeletal phenotype of hypoparathyroidism (HypoPT), a disorder of inadequate parathyroid hormone secretion, is altered trabecular microarchitecture with increased trabecular bone volume and thickness. Using 2‐D histomorphometric analysis, we previously found that 2 years of PTH(1‐84) in HypoPT is associated with reduced trabecular thickness (Tb.Th) and an increase in trabecular number (Tb.N). We have now utilized direct 3‐D microstructural analysis to determine the extent to which these changes may be related to bone strength. Iliac crest bone biopsies from HypoPT subjects (n = 58) were analyzed by microcomputed tomography (μCT) and by microfinite element (μFE) analysis. Biopsies were performed at baseline and at 1 or 2 years of recombinant human PTH(1‐84) [rhPTH(1‐84)]. In a subset of subjects (n = 13) at 3 months, we demonstrated a reduction in trabecular separation (Tb.Sp, 0.64 ± 0.1 to 0.56 ± 0.1 mm; p = 0.005) and in the variance of trabecular separation (Tb.SD, 0.19 ± 0.1 to 0.17 ± 0.1 mm; p = 0.01), along with an increase in bone volume/total volume (BV/TV, 26.76 ± 10.1 to 32.83 ± 13.5%; p = 0.02), bone surface/total volume (BS/TV, 3.85 ± 0.7 to 4.49 ± 1.0 mm²/mm³; p = 0.005), Tb.N (1.84 ± 0.5 versus 2.36 ± 1.3 mm^?1; p = 0.02) and Young's modulus (649.38 ± 460.7 to 1044.81 ± 1090.5 N/mm²; p = 0.049). After 1 year of rhPTH(1‐84), Force increased (144.08 ± 102.4 to 241.13 ± 189.1 N; p = 0.04) and Young's modulus tended to increase (662.15 ± 478.2 to 1050.80 ± 824.1 N/m²; p = 0.06). The 1‐year change in cancellous mineralizing surface (MS/BS) predicted 1‐year changes in μCT variables. The biopsies obtained after 2 years of rhPTH(1‐84) showed no change from baseline. These data suggest that administration of rhPTH(1‐84) in HypoPT is associated with transient changes in key parameters associated with bone strength. The results indicate that rhPTH(1‐84) improves skeletal quality in HypoPT early in treatment. © 2016 American Society for Bone and Mineral Research.     

Complete Volumetric Decomposition of Individual Trabecular Plates and Rods and Its Morphological Correlations With Anisotropic Elastic Moduli in Human Trabecular Bone

Trabecular plates and rods are important microarchitectural features in determining mechanical properties of trabecular bone. A complete volumetric decomposition of individual trabecular plates and rods was used to assess the orientation and morphology of 71 human trabecular bone samples. The ITS‐based morphological analyses better characterize microarchitecture and help predict anisotropic mechanical properties of trabecular bone. Introduction: Standard morphological analyses of trabecular architecture lack explicit segmentations of individual trabecular plates and rods. In this study, a complete volumetric decomposition technique was developed to segment trabecular bone microstructure into individual plates and rods. Contributions of trabecular type‐associated morphological parameters to the anisotropic elastic moduli of trabecular bone were studied. Materials and Methods: Seventy‐one human trabecular bone samples from the femoral neck (FN), tibia, and vertebral body (VB) were imaged using μCT or serial milling. Complete volumetric decomposition was applied to segment trabecular bone microstructure into individual plates and rods. The orientation of each individual trabecula was determined, and the axial bone volume fractions (aBV/TV), axially aligned bone volume fraction along each orthotropic axis, were correlated with the elastic moduli. The microstructural type‐associated morphological parameters were derived and compared with standard morphological parameters. Their contributions to the anisotropic elastic moduli, calculated by finite element analysis (FEA), were evaluated and compared. Results: The distribution of trabecular orientation suggested that longitudinal plates and transverse rods dominate at all three anatomic sites. aBV/TV along each axis, in general, showed a better correlation with the axial elastic modulus (r² = 0.95～0.99) compared with BV/TV (r² = 0.93～0.94). The plate‐associated morphological parameters generally showed higher correlations with the corresponding standard morphological parameters than the rod‐associated parameters. Multiple linear regression models of six elastic moduli with individual trabeculae segmentation (ITS)‐based morphological parameters (adjusted r² = 0.95～0.98) performed equally well as those with standard morphological parameters (adjusted r² = 0.94～0.97) but revealed specific contributions from individual trabecular plates or rods. Conclusions: The ITS‐based morphological analyses provide a better characterization of the morphology and trabecular orientation of trabecular bone. The axial loading of trabecular bone is mainly sustained by the axially aligned trabecular bone volume. Results suggest that trabecular plates dominate the overall elastic properties of trabecular bone.     

High Resolution Magnetic Resonance Imaging of the Calcaneus: Age-Related Changes in Trabecular Structure and Comparison with Dual X-Ray Absorptiometry Measurements

A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 ± 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1–2% and 3–6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r ²= 33.7%, P < 0.0037), I.Th (r ²= 26.6%, P < 0.0118), I.Sp (r ²= 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (− 0.52%/year), I.Th (−0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure. Received: 11 March 1996 / Accepted: 9 July 1996     

Comparison of the radiographic vertebral trabecular pattern with the vertebral fracture prevalence and spinal bone density

Spinal bone densitometry allows accurate and precise measurement of the severity of bone loss. Where densitometry is not yet available medical practitioners have to continue to rely on clinical radiography. Since the grey levels of the radiographic image are highly inaccurate we studied the radiographic vertebral trabecular pattern for its suitability as a semiquantitative assessment of vertebral bone loss. We defined four vertebral trabecular pattern indices (VTPI 4=normal, VTPI 1=severe bone loss) and tested these for correlations with the prevalence of vertebral fractures, and with spinal and hip bone mineral density measured by dual-energy X-ray absorptiometry (DXA). We found negative correlations between VTPI and the percentage of patients with vertebral fractures (p=0.0001), between VTPI and the number of vertebral fractures per patient (r=0.606,p=0.001) and between VTPI and the severity of vertebral fractures, and a positive correlation between VTPI and spinal (r ²=0.556,p=0.0001) and hip DXA values (r ²=0.315,p=0.0001). We conclude that the vertebral trabecular pattern index can be used to assess the severity of spinal bone loss when a bone densitometer is not available.     

In Vivo Magnetic Resonance Detects Rapid Remodeling Changes in the Topology of the Trabecular Bone Network After Menopause and the Protective Effect of Estradiol

Introduction : Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the μMRI‐based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network. Materials and Methods : Subjects studied were early postmenopausal women, 45–55 yr of age (N = 65), of whom 32 were on estrogen (estradiol group), and the remainder were not (control group). Early menopause was defined by amenorrhea for 6–24 mo and elevated serum follicle‐stimulating hormone (FSH) concentration. The subjects were evaluated with three imaging modalities at baseline and 12 and 24 mo to determine the temporal changes in trabecular and cortical architecture and density. μMRI of the distal radius and tibia was performed at 137 × 137 × 410‐μm³ voxel size. The resulting bone volume fraction maps were Fourier interpolated to a final voxel size of 45.7 × 45.7 × 136.7 μm³, binarized, skeletonized, and subjected to 3D digital topological analysis (DTA). Skeletonization converts trabecular rods to curves and plates to surfaces. Parameters quantifying scale included BV/TV, whereas DTA parameters included the volume densities of curves (C) and surface (S)‐type voxels, as well as composite parameters: the surface/curve ratio (S/C), and erosion index (EI, ratio of the sum of parameters expected to increase with osteoclastic resorption divided by the sum of those expected to decrease). For comparison, pQCT of the same peripheral locations was conducted, and trabecular density and cortical structural parameters were measured. Areal BMD of the lumbar vertebrae and hip was also measured. Results : Substantial changes in trabecular architecture of the distal tibia, in particular as they relate to topology of the network, were detected after 12 mo in the control group. S/C decreased 5.6% (p < 0.0005), and EI increased 7.1% (p < 0.0005). Most curve‐ and profile‐type voxels (representative of trabecular struts), increased significantly (p < 0.001). Curve and profile edges resulting from disconnection of rod‐like trabeculae increased by 9.8% and 5.1% (p = 0.0001 and <0.001, respectively). Similarly, DXA BMD in the spine and hip decreased 2.6% and 1.3% (p < 0.0001 and <0.005, respectively), and pQCT cortical area decreased 3.6% (p = 0.0001). However, neither trabecular density nor BV/TV changed. Furthermore, none of the parameters measured in the estradiol group were significantly different after 12 mo. Substantial differences in the mean changes from baseline between the estradiol treatment and control groups, in particular after 24 mo, were observed, with relative group differences as large as 13% (S/C, p = 0.005), and the relative changes in the two groups had the opposite sign for most parameters. The observed temporal alterations in architecture are consistent with remodeling changes that involve gradual conversion of plate‐like to rod‐like trabecular bone along with disconnection of trabecular elements, even in the absence of a net loss of trabecular bone. The high‐resolution 3D rendered images provide direct evidence of the above remodeling changes in individual subjects. The radius structural data indicated similar trends but offered no definitive conclusions. Conclusions : The short‐term temporal changes in trabecular architecture after menopause, and the protective effects of estradiol ensuring maintenance of a more plate‐like TB architecture, reported here, have not previously been observed in vivo. This work suggests that MRI‐based in vivo micromorphometry of trabecular bone has promise as a tool for monitoring osteoporosis treatment.     

Limitations of Global Morphometry in Predicting Trabecular Bone Failure

Efforts in finding independent measures for accurate and reliable prediction of trabecular bone failure have led to the development of a number of morphometric indices characterizing trabecular bone microstructure. Generally, these indices assume a high homogeneity within the bone specimen. However, in the present study we found that the variance in bone volume fraction (BV/TV) in a single bone specimen can be relatively large (CV = 9.07% to 28.23%). To assess the limitations of morphometric indices in the prediction of bone failure for specimens in which the assumption of homogeneity is not met, we harvested 13 cadaveric samples from a single human spine. We tested these cylindrical samples using image‐guided failure assessment (IGFA), a technique combining stepwise microcompression and time‐lapsed micro–computed tomography (µCT). Additionally, we computed morphometric indices for the entire sample as well as for 10 equal subregions along the anatomical axis. We found that ultimate strength was equally well predicted by BV/TV of the entire sample (R² = 0.55) and BV/TV of the weakest subregion (R² = 0.57). Investigating three‐dimensional animations of structural bone failure, we showed that two main failure mechanisms determine the competence of trabecular bone samples; in homogeneous, isotropic trabecular bone samples, competence is determined by a whole set of trabecular elements, whereas in inhomogeneous, anisotropic bone samples a single or a missing trabeculae may induce catastrophic failure. The latter failure mechanism cannot be described by conventional morphometry, indicating the need for novel morphometric indices also applicable to the prediction of failure in inhomogeneous bone samples. © 2014 American Society for Bone and Mineral Research.     

A non-invasive in vitro technique for the three-dimensional quantification of microdamage in trabecular bone

An accurate analysis and quantification of microdamage is critical to understand how microdamage affects the mechanics and biology of bone fragility. In this study we demonstrate the development and validation of a novel in vitro micro-computed tomography (microCT) method that employs lead-uranyl acetate as a radio-opaque contrast agent for automated quantification of microdamage in trabecular bone. Human trabecular bone cores were extracted from the femoral neck, scanned via microCT, loaded in unconfined compression to a range of apparent strains (0.5% to 2.25%), stained in lead-uranyl acetate, and subsequently re-scanned via microCT. An investigation of the regions containing microdamage using the backscatter mode of a scanning electron microscope (BSEM) showed that the lead-uranyl sulfide complex was an effective contrast agent for microdamage in bone. Damaged volume fraction (DV/BV), as determined by microCT, increased exponentially with respect to applied strains and proportionately to mechanically determined modulus reduction (p<0.001). Furthermore, the formation of microdamage was observed to occur before any apparent stiffness loss, suggesting that the localized tissue yielding occurs prior to the structural yielding of trabecular bone. This non-invasive in vitro technique for the detection of microdamage using microCT may serve as a valuable complement to existing morphometric analyses of bone.     

Application of High‐Resolution Skeletal Imaging to Measurements of Volumetric BMD and Skeletal Microarchitecture in Chinese‐American and White Women: Explanation of a Paradox

Asian women have lower rates of hip and forearm fractures despite lower areal BMD (aBMD) by DXA compared with white women and other racial groups. We hypothesized that the lower fracture rates may be explained by more favorable measurements of volumetric BMD (vBMD) and microarchitectural properties, despite lower areal BMD. To address this hypothesis, we used high‐resolution pQCT (HRpQCT), a new method that can provide this information noninvasively. We studied 63 premenopausal Chinese‐American (n = 31) and white (n = 32) women with DXA and HRpQCT. aBMD by DXA did not differ between groups for the lumbar spine (1.017 ± 0.108 versus 1.028 ± 0.152 g/cm²; p = 0.7), total hip (0.910 ± 0.093 versus 0.932 ± 0.134 g/cm²; p = 0.5), femoral neck (0.788 ± 0.083 versus 0.809 ± 0.129 g/cm²; p = 0.4), or one‐third radius (0.691 ± 0.052 versus 0.708 ± 0.047 g/cm²; p = 0.2). HRpQCT at the radius indicated greater trabecular (168 ± 41 versus 137 ± 33 mg HA/cm³; p = <0.01) and cortical (963 ± 46 versus 915 ± 42 mg HA/cm³; p < 0.0001) density; trabecular bone to tissue volume (0.140 ± 0.034 versus 0.114 ± 0.028; p = <0.01); trabecular (0.075 ± 0.013 versus 0.062 ± 0.009 mm; p < 0.0001) and cortical thickness (0.98 ± 0.16 versus 0.80 ± 0.14 mm; p < 0.0001); and lower total bone area (197 ± 34 versus 232 ± 33 mm²; p = <0.001) in the Chinese versus white women and no difference in trabecular number, spacing, or inhomogeneity before adjustment for covariates. Similar results were observed at the weight‐bearing tibia. At the radius, adjustment for covariates did not change the direction or significance of differences except for bone, which became similar between the groups. However, at the tibia, adjustment for covariates attenuated differences in cortical BMD and bone area and accentuated differences in trabecular microarchitecture such that Chinese women additionally had higher trabecular number and lower trabecular spacing, as well as inhomogeneity after adjustment. Using the high‐resolution technology, the results provide a mechanistic explanation for why Chinese women have fewer hip and forearm fractures than white women.     

Gender differences in trabecular bone architecture of the distal radius assessed with magnetic resonance imaging and implications for mechanical competence

High-resolution magnetic resonance imaging (hrMRI) has recently made it possible to evaluate trabecular bone structure in vivo. Despite obvious gender differences in fracture incidence at the distal radius, little is known about gender differences in trabecular bone microarchitecture and its relationship to the structural strength of the forearm. The aim of this study was to determine trabecular bone structure in the distal radius of elderly women and men and its correlation with failure loads of the distal radius as determined in a fall configuration. Specifically, we tested the hypotheses that structural indices differ between women and men and that they offer information that is independent from BMD for predicting structural strength. Intact right arms were obtained from 73 formalin-fixed cadavers (age 80±11 years, 43 women, 30 men). Trabecular structural indices (apparent bone volume fraction [app. BV/TV], trabecular number [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app. Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis, using hrMRI with 156 µm in-plane resolution and proprietary digital image analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women displayed significantly lower BMD (–29.8%, p <0.001), app. BV/TV (–8.2%, p <0.05) and app. Tb.Th (–10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and fractal dimension did not differ significantly. Structural parameters differed between normal and osteopenic women (BV/TV: –11%, p <0.01; Tb.Th: –8%, p <0.001) and between normal and osteoporotic women BV/TV: –21%, p <0.001; Tb.Th: –16%, p <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information independent from BMD in the prediction of radial failure loads in multiple regression models. These findings imply that it should be of clinical interest to monitor both bone mass and trabecular microstructure for predicting osteoporotic fracture risk.     

Implant stability is affected by local bone microstructural quality

It is known that low bone quality, caused for instance by osteoporosis, not only increases the risk of fractures, but also decreases the performance of fracture implants; yet the specific mechanisms behind this phenomenon are still largely unknown. We hypothesized that especially peri-implant bone microstructure affects implant stability in trabecular bone, to a greater degree than more distant bone. To test this hypothesis we performed a computational study on implant stability in trabecular bone. Twelve humeral heads were measured using micro-computed tomography. Screws were inserted digitally into these heads at 25 positions. In addition, at each screw location, a virtual biopsy was taken. Bone structural quality was quantified by morphometric parameters. The stiffness of the 300 screw-bone constructs was quantified as a measure of implant stability. Global bone density correlated moderately with screw-bone stiffness (r2=0.52), whereas local bone density was a very good predictor (r2=0.91). The best correlation with screw-bone stiffness was found for local bone apparent Young's modulus (r2=0.97), revealing that not only bone mass but also its arrangement in the trabecular microarchitecture are important for implant stability. In conclusion, we confirmed our hypothesis that implant stability is affected by the microstructural bone quality of the trabecular bone in the direct vicinity of the implant. Local bone density was the best single morphometric predictor of implant stability. The best predictability was provided by the mechanical competence of the peri-implant bone. A clinical implication of this work is that apparently good bone stock, such as assessed by DXA, does not guarantee good local bone quality, and hence does not guarantee good implant stability. New tools that could quantify the structural or mechanical quality of the peri-implant bone may help improve the surgical intervention in reaching better clinical outcomes for screw fixation.     

Decreased Quantity and Quality of the Periarticular and Nonperiarticular Bone in Patients With Rheumatoid Arthritis: A Cross‐Sectional HR‐pQCT Study

Rheumatoid arthritis (RA) is a highly bone destructive disease. Although it is well established that RA leads to bone loss and increased fracture risk, current knowledge on the microstructural changes of bone in RA is still limited. The purpose of this study was to assess the microstructure of periarticular and nonperiarticular bone in female and male RA patients and compare it with respective healthy controls. We performed two high‐resolution peripheral quantitative computed tomography (HR‐pQCT; Xtreme‐CT) scans, one of the distal radius and one of the ultradistal radius in 90 patients with RA (60 females, 30 males) and 70 healthy controls (40 females, 30 males) matched for sex, age, and body mass index. Volumetric bone mineral density (vBMD), bone geometry, and bone microstructure including trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th) and cortical porosity (Ct.Po) were assessed. At the distal and ultradistal radius, trabecular (p = 0.005 and p < 0.001) and cortical BMD (p < 0.001 and p < 0.001) were significantly decreased in male and female patients with RA, respectively. BV/TV was also decreased at both sites, based on lower Tb.N in female RA (p < 0.001 for both sites) and lower Tb.Th (p = 0.034 and p = 0.005) in male RA patients compared with respective healthy controls. Cortical thinning (p = 0.018 and p = 0.002) but not Ct.Po (p = 0.070 and p = 0.275) was pronounced in male and female RA patients at the distal radius. Cortical perimeter was increased in male and female RA patients at both sites. Multiple regression models showed that bone geometry (cortical perimeter) is predominantly influenced by age of the RA patient, cortical thickness by both age and disease duration, and trabecular microstructure predominantly by the disease duration. In summary, these data show profound deterioration of bone microstructure in the appendicular skeleton of RA patients at both periarticular and nonperiarticular sites. © 2014 American Society for Bone and Mineral Research.     

Articular cartilage calcification of the humeral head is highly prevalent and associated with osteoarthritis in the general population

Articular cartilage calcification is considered a pathological albeit incompletely understood process which is known to be associated with osteoarthritis of the knee and hip. The goal of this study was to determine the prevalence of articular cartilage calcification of the shoulder as a non‐weight‐bearing joint and to analyze the interrelationship of calcification with age and histological severity of shoulder osteoarthritis in the general population. In a cross‐sectional study of 180 humeral heads from 90 donors (n = 49 male, n = 41 female; mean age 62.7 years [20–93]), cartilage calcification of the humeral head was quantified by digital contact radiography (DCR). Histological OA grade (OARSI) was determined and structural equation modeling (SEM) was used to analyze the interrelationship of cartilage calcification, OARSI and age. The prevalence of articular cartilage calcification was 98.9% (95%CI: [93.96%, 99.97%]) and was independent of gender (p = 0.55). Cartilage calcification of one shoulder correlated significantly with that of the contralateral side (r = 0.61, 95%CI: [0.46, 0.73], p < 0.001). SEM demonstrated significant associations between histological OA grade and cartilage calcification (r = 0.55, p = 0.039), between histological OA grade and age (β = 0.59, p < 0.001) but not between age and cartilage calcification (β = 0.24, p = 0.116). In conclusion, the prevalence of shoulder cartilage calcification in the general population is higher than anticipated. The high prevalence, its concomitant bilateral manifestation and the association between the amount of cartilage calcification and OA severity, but not age, suggest that cartilage calcification is a systemically driven process with early onset in life and may be a causative factor in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1984–1990, 2016.     

Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Smoking is associated with impaired bone mass development in young adult men: A 5-year longitudinal study

It has previously been shown that smoking is associated with reduced bone mass and increased fracture risk, but no longitudinal studies have been published investigating altered smoking behavior at the time of bone mass acquisition. The aim of this study was to investigate the development of bone density and geometry according to alterations in smoking behavior in a 5‐year, longitudinal, population‐based study of 833 young men, age 18 to 20 years (baseline). Furthermore, we aimed to examine the cross‐sectional, associations between current smoking and parameters of trabecular microarchitecture of the radius and tibia, using high‐resolution peripheral quantitative computed tomography (HR‐pQCT), in young men aged 23 to 25 years (5‐year follow‐up). Men who had started to smoke since baseline had considerably smaller increases in areal bone mineral density (aBMD) at the total body (mean ± SD, 0.020 ± 0.047 mg/cm² versus 0.043 ± 0.040 mg/cm², p < 0.01) and lumbar spine (0.027 ± 0.062 mg/cm² versus 0.052 ± 0.065 mg/cm², p = 0.04), and substantially greater decreases in aBMD at the total hip (?0.055 ± 0.058 mg/cm² versus ?0.021 ± 0.062 mg/cm², p < 0.01) and femoral neck (?0.077 ± 0.059 mg/cm² versus ?0.042 ± 0.070 mg/cm², p < 0.01) than men who were nonsmokers at both the baseline and follow‐up visits. At the tibia, subjects who had started to smoke had a smaller increment of the cortical cross‐sectional area (CSA) than nonsmokers (8.1 ± 4.3 mm² versus 11.5 ± 8.9 mm², p = 0.03), and a larger decrement of trabecular volumetric BMD (vBMD) than nonsmokers (?13.9 ± 20.5 mg/mm³ versus ?4.1 ± 13.9 mg/mm³, p < 0.001). In the cross‐sectional analysis at follow‐up (23–25 years of age), smokers had significantly lower trabecular vBMD at the tibia (7.0%, p < 0.01) due to reduced trabecular thickness (8.9%, p < 0.001), as assessed using HR‐pQCT, than nonsmokers. In conclusion, this study is the first to report that men who start to smoke in young adulthood have poorer development of their aBMD at clinically important sites such as the spine and hip than nonsmokers, possibly due to augmented loss of trabecular density and impaired growth of cortical cross‐sectional area. © 2012 American Society for Bone and Mineral Research.     

Trabecular plates and rods determine elastic modulus and yield strength of human trabecular bone

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 (r² = 0.97) and yield strength (r² = 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 (r² = 0.99, r² = 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.