Search

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a promising imaging modality that provides an in vivo three-dimensional (3D) assessment of bone microstructure by scanning fixed regions of the distal radius and tibia. However, how microstructural parameters and mechanical analysis based on these segment scans correlate to whole distal radius and tibia mechanics are not well-characterized. On 26 sets of cadaveric radius and tibia, HR-pQCT scans were performed on the standard scan segment, a segment distal to the standard segment, and a segment proximal to the standard segment. Whole distal radius and tibia stiffness were determined through mechanical testing. Segment bone stiffness was estimated using linear finite element (FE) analysis based on segment scans. Standard morphological and individual trabecula segmentation (ITS) analyses were used to estimate microstructural properties. Significant variations in microstructural parameters were observed among segments at both sites. Correlation to whole distal radius and tibia stiffness was moderate for microstructural parameters at the standard segment, but correlation was significantly increased for FE-predicted segment bone stiffness based on standard segment scans. Similar correlation strengths were found between FE-predicted segment bone stiffness and whole distal radius and tibia stiffness. Additionally, microstructural parameters at the distal segment had higher correlation to whole distal radius and tibia stiffness than at standard or proximal segments. Our results suggest that FE-predicted segment stiffness is a better predictor of whole distal radius and tibia stiffness for clinical HR-pQCT analysis and that microstructural parameters at the distal segment are more highly correlated with whole distal radius and tibia stiffness than at the standard or proximal segments., (Copyright © 2019 by ASME.)

The high-resolution peripheral quantitative computed tomography (HR-pQCT) provides unprecedented visualization of bone microstructure and the basis for constructing patient-specific microfinite element (μFE) models. Based on HR-pQCT images, we have developed a plate-and-rod μFE (PR μFE) method for whole bone segments using individual trabecula segmentation (ITS) and an adaptive cortical meshing technique. In contrast to the conventional voxel approach, the complex microarchitecture of the trabecular compartment is simplified into shell and beam elements based on the trabecular plate-and-rod configuration. In comparison to voxel-based μFE models of μCT and measurements from mechanical testing, the computational and experimental gold standards, nonlinear analyses of stiffness and yield strength using the HR-pQCT-based PR μFE models demonstrated high correlation and accuracy. These results indicated that the combination of segmented trabecular plate-rod morphology and adjusted cortical mesh adequately captures mechanics of the whole bone segment. Meanwhile, the PR μFE modeling approach reduced model size by nearly 300-fold and shortened computation time for nonlinear analysis from days to within hours, permitting broader clinical application of HR-pQCT-based nonlinear μFE modeling. Furthermore, the presented approach was tested using a subset of radius and tibia HR-pQCT scans of patients with prior vertebral fracture in a previously published study. Results indicated that yield strength for radius and tibia whole bone segments predicted by the PR μFE model was effective in discriminating vertebral fracture subjects from nonfractured controls. In conclusion, the PR μFE model of HR-pQCT images accurately predicted mechanics for whole bone segments and can serve as a valuable clinical tool to evaluate musculoskeletal diseases., (Copyright © 2019 by ASME.)

The second name of the ninth author, X.E. Guo, was incorrectly coded as part of his surname. The publisher apologises for the inconvenience caused.

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p < 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of <10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Developing effective treatment for osteoarthritis (OA), a prevalent and disabling disease, has remained a challenge, primarily because of limited understanding of its pathogenesis and late diagnosis. In the subchondral bone, rapid bone loss after traumatic injuries and bone sclerosis at the advanced stage of OA are well-recognized hallmarks of the disease. Recent studies have further demonstrated the crucial contribution of subchondral bone in the development of OA. However, the microstructural basis of these bone changes has not been examined thoroughly, and the paradox of how abnormal resorption can eventually lead to bone sclerosis remains unanswered. By applying a novel microstructural analysis technique, individual trabecula segmentation (ITS), to micro-computed tomography (μCT) images of human OA knees, we have identified a drastic loss of rod-like trabeculae and thickening of plate-like trabeculae that persisted in all regions of the tibial plateau, underneath both severely damaged and still intact cartilage. The simultaneous reduction in trabecular rods and thickening of trabecular plates provide important insights to the dynamic and paradoxical subchondral bone changes observed in OA. Furthermore, using an established guinea pig model of spontaneous OA, we discovered similar trabecular rod loss and plate thickening that preceded cartilage degradation. Thus, our study suggests that rod-and-plate microstructural changes in the subchondral trabecular bone may play an important role in the development of OA and that advanced microstructural analysis techniques such as ITS are necessary in detecting these early but subtle changes. With emerging high-resolution skeletal imaging modalities such as the high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular rod loss identified by ITS could potentially be used as a marker in assessing the progression of OA in future longitudinal studies or clinical diagnosis. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Individuals with cystic fibrosis (CF) have lower bone mineral density (BMD) by DXA and are at higher risk of fracture than healthy controls. However, the 2-dimensional measurement of areal BMD (aBMD) provided by DXA is influenced by bone size and the true extent of the bone deficit is unclear. Our objective was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) and individual trabecula segmentation (ITS) analysis to compare volumetric BMD (vBMD), microarchitecture and estimated strength at the distal radius and tibia in 26 young adults with CF and 26 controls matched for age, gender, and race. To assess the effect of limb length and minimize the confounding effects of size on HR-pQCT outcomes, we scanned participants at both the standard fixed HR-pQCT measurement sites and at a subject-specific relative site that varied according to limb length. CF participants did not differ significantly in age, height, weight, or BMI from controls. Ulnar and tibial lengths were 9mm shorter in CF patients, though differences were not significant. CF patients had significantly lower BMI-adjusted aBMD by DXA at the lumbar spine (8.9%, p<0.01), total hip (11.5%, p<0.01) and femoral neck (14.5%, p<0.01), but not at the forearm. At the fixed radius site, thickness of trabecular plates and torsional stiffness were significantly lower in CF participants than controls. At the relative radius site, only torsional stiffness was significantly lower in CF participants. At the tibia, total, trabecular and cortical vBMD were significantly lower at both fixed and relative sites in CF participants, with fewer, more widely-spaced trabecular plates, lower trabecular connectivity, and lower axial and torsional stiffness. Our results confirm that aBMD is lower at the spine and hip in young adults with CF, independent of BMI and body size. We also conclude that vBMD and stiffness are lower at the weight-bearing tibia. The pathogenesis of these differences in bone density and strength at the tibia appear to be related to trabecular drop-out and reduced trabecular connectivity and to be independent of differences in limb length, as assessed by scanning participants at both standard and relative sites. We concluded that significant deficits in bone structure and strength persist in young adults with CF, despite advances in care that permit them to attain relatively normal height and weight., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In postmenopausal osteoporosis, switching from teriparatide to denosumab results in continued bone mineral density (BMD) gains whereas switching from denosumab to teriparatide results in BMD loss. To assess the effects of these transitions on bone microarchitecture and strength, we performed high-resolution peripheral QCT (HR-pQCT) at the distal tibia and radius in postmenopausal osteoporotic women who received 24 months of teriparatide 20 μg daily followed by 24 months of denosumab 60 mg every 6 months, 24 months of denosumab followed by 24 months of teriparatide, or 24 months of both medications followed by 24 months of denosumab. The 77 women who completed at least one post-switch visit are included in this analysis. Tibial cortical volumetric BMD (vBMD) increased between months 24 and 48 in the teriparatide-to-denosumab (net 48-month change -0.8% ± 2.4%) and combination-to-denosumab groups (net 48-month changes +2.4% ± 4.1%) but decreased in the denosumab-to-teriparatide group (net 48-month change -3.4% ± 3.2%, p < 0.001 for all between-group comparisons). Changes in total vBMD, cortical thickness, and estimated stiffness (by micro-finite element analysis [µFEA]) followed a similar pattern, as did changes at the radius. Conversely, tibial cortical porosity remained stable between months 24 and 48 in the teriparatide-to-denosumab and combination-to-denosumab groups (net 48-month changes +7.2% ± 14.8% and -3.4% ± 12.1%, respectively) but increased in the denosumab-to-teriparatide group (net 48-month change +16.2% ± 11.5%, p < 0.05 versus other groups). Trabecular vBMD changes did not differ among groups. Together, these findings demonstrate that in women treated with denosumab, switching to teriparatide is associated with a reduction in total and cortical vBMD, cortical thickness, and estimated strength, whereas switching to denosumab from teriparatide or combination therapy results in improvements in these parameters with the greatest improvements observed in women treated with combined therapy followed by denosumab. These findings strongly suggest that the use of teriparatide after denosumab should be avoided and that the use of combined teriparatide/denosumab followed by denosumab alone may be a useful treatment strategy in those with severe osteoporosis. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Dual energy X-ray absorptiometry (DXA) is the standard for assessing fragility fracture risk using areal bone mineral density (aBMD), but only explains 60-70% of the variation in bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides 3D-measures of bone microarchitecture and volumetric bone mineral density (vBMD), but only at the wrist and ankle. Finite element (FE) models can estimate bone strength with 86-95% precision. The purpose of this study is to determine how well vBMD and FE bone strength at the wrist and ankle relate to fracture strength at the hip and spine, and to compare these relationships with DXA measured directly at those axial sites. Cadaveric samples (radius, tibia, femur and L4 vertebra) were compared within the same body. The radius and tibia specimens were assessed using HR-pQCT to determine vBMD and FE failure load. aBMD from DXA was measured at the femur and L4 vertebra. The femur and L4 vertebra specimens were biomechanically tested to determine failure load. aBMD measures of the axial skeletal sites strongly correlated with the biomechanical strength for the L4 vertebra (r=0.77) and proximal femur (r=0.89). The radius correlated significantly with biomechanical strength of the L4 vertebra for vBMD (r=0.85) and FE-derived strength (r=0.72), but not with femur strength. vBMD at the tibia correlated significantly with femoral biomechanical strength (r=0.74) and FE-estimated strength (r=0.83), and vertebral biomechanical strength for vBMD (r=0.97) and FE-estimated strength (r=0.91). The higher correlations at the tibia compared to radius are likely due to the tibia's weight-bearing function., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Objectives: Studies using high-resolution peripheral quantitative computed tomography showed progressive abnormalities in cortical and trabecular microarchitecture and biomechanical competence over the first year after kidney transplantation. However, high-resolution peripheral computed tomography is a research tool lacking wide availability. In contrast, the trabecular bone score is a novel and widely available tool that uses gray-scale variograms of the spine image from dual-energy x-ray absorptiometry to assess trabecular quality. There are no studies assessing whether trabecular bone score characterizes bone quality in kidney transplant recipients., Design, Settings, Participants, & Measurements: Between 2009 and 2010, we conducted a study to assess changes in peripheral skeletal microarchitecture, measured by high-resolution peripheral computed tomography, during the first year after transplantation in 47 patients managed with early corticosteroid-withdrawal immunosuppression. All adult first-time transplant candidates were eligible. Patients underwent imaging with high-resolution peripheral computed tomography and dual-energy x-ray absorptiometry pretransplantation and 3, 6, and 12 months post-transplantation. We now test if, during the first year after transplantation, trabecular bone score assesses the evolution of bone microarchitecture and biomechanical competence as determined by high-resolution peripheral computed tomography., Results: At baseline and follow-up, among the 72% and 78%, respectively, of patients having normal bone mineral density by dual-energy x-ray absorptiometry, 53% and 50%, respectively, were classified by trabecular bone score as having high fracture risk. At baseline, trabecular bone score correlated with spine, hip, and ultradistal radius bone mineral density by dual-energy x-ray absorptiometry and cortical area, density, thickness, and porosity; trabecular density, thickness, separation, and heterogeneity; and stiffness and failure load by high-resolution peripheral computed tomography. Longitudinally, each percentage increase in trabecular bone score was associated with increases in trabecular number (0.35%±1.4%); decreases in trabecular thickness (-0.45%±0.15%), separation (-0.40%±0.15%), and network heterogeneity (-0.48%±0.20%); and increases in failure load (0.22%±0.09%) by high-resolution peripheral computed tomography (all P <0.05)., Conclusions: Trabecular bone score may be a useful method to assess and monitor bone quality and strength and classify fracture risk in kidney transplant recipients., (Copyright © 2017 by the American Society of Nephrology.)

This is a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years. We found that Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but stiffness did not differ between groups., Introduction: We conducted a cross-sectional study to assess differences in bone quality in young Asian and Caucasian (n = 30/group) men between 25 and 35 years., Methods: We measured bone mineral density (BMD) at the spine, total hip (TH), femoral neck (FN), and forearm by dual energy X-ray absorptiometry (DXA), and bone geometry, density, microarchitecture, and mechanical competence at the radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) with application of individual trabecula segmentation (ITS) and trabecular and whole bone finite element analysis (FEA). We measured load-to-strength ratio to account for differences in bone size and height, respectively. We used Wilcoxon rank sum and generalized linear models adjusted for height, weight, and their interaction for comparisons., Results: Asians were 3.9 % shorter and weighed 6.5 % less than Caucasians. In adjusted models: by DXA, there were no significant race-based differences in areal BMD; by HR-pQCT, at the radius, Asians had smaller total and trabecular area (p = 0.003 for both), and denser (p = 0.01) and thicker (p = 0.04) cortices at the radius; by ITS, at the radius Asians, had more plate-like than rod-like trabeculae (PR ratio p = 0.01), greater plate trabecular surface (p = 0.009) and longer rod length (p = 0.002). There were no significant race-based differences in FEA or the load-to-strength ratio., Conclusions: Asians had smaller bones, thicker and denser cortices, and more plate-like trabeculae, but biomechanical estimates of bone strength did not differ between groups. Studies are needed to determine whether these differences persist later in life.

Chronic immune activation associated with human immunodeficiency virus (HIV) infection may have negative consequences on bone acquisition in individuals infected with HIV early in life. Bone mineral density (BMD) and microarchitecture were characterized in 38 HIV-infected men on antiretroviral therapy (18 perinatally-infected, 20 adolescence-infected) and 20 uninfected men age 20 to 25 years by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT). Flow cytometry was utilized to measure CD4+/CD8+ activation (HLADR+CD38+) and senescence (CD28-CD57+) and to quantify circulating osteogenic precursor (COP) cells in peripheral blood mononuclear cells using antibodies to RUNX2 and osteocalcin (OCN). Telomere lengths were measured in sorted COP cells using qPCR. DXA-derived areal BMD Z-scores and HRpQCT-derived volumetric BMD (vBMD) measures were lower in HIV-infected than uninfected men. Proportion of activated and senescent CD4+ and CD8+ T cells were higher in HIV-infected than uninfected men. The percentage of COP cells (mean ± SE) was lower in HIV-infected than uninfected (0.19% ± 0.02% versus 0.43% ± 0.06%; p < 0.0001) men, and also lower in perinatally-infected than adolescence-infected men (0.15% ± 0.02% versus 0.22% ± 0.03%; p < 0.04). A higher proportion of COP cells correlated with higher bone stiffness, a measure of bone strength, whereas a higher proportion of activated CD4+ T cells correlated with lower BMD and stiffness and lower proportion of COP cells. T cell activation with HIV-infection was associated with decreased numbers of osteogenic precursors as well as lower peak bone mass and bone strength. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Unlabelled: Bone strength is dependent on bone density and microstructure. High-resolution peripheral quantitative computed tomography (HR-pQCT) can measure microstructure but is somewhat limited due to its resolution. We compared a new HR-pQCT scanner to existing technology and found very good agreement for most parameters. This study will be important when interpreting results from different devices., Introduction: Recently, a second-generation HR-pQCT scanner (XCT2) has been developed with a higher nominal isotropic resolution (61 μm) compared to the first-generation device (XCT1, 82 μm). It is unclear how in vivo measurements from these two devices compare. In this study, we obtained and analyzed in vivo XCT1 and XCT2 measurements of bone microarchitecture and estimated strength., Methods: We scanned 51 adults (16 men and 35 women, age 44.8 ± 16.0) on both XCT2 and XCT1 on the same day. We first compared XCT1 and XCT2 measurements obtained using their respective standard patient protocols. In XCT1, microarchitecture parameters were derived, while XCT2 measurements were directly measured. We also compared XCT2-D with XCT1 by finding the overlapping regions of interest and using the standard patient protocol for XCT1., Results: We obtained excellent agreement between XCT1 and XCT2 for most of the volumetric bone mineral density (vBMD), trabecular and cortical measurements (All R (2) > 0.820) except for cortical porosity at the radius (R (2) = 0.638), trabecular number (R (2) = 0.694, 0.787) and trabecular thickness (R (2) = 0.569, 0.527) at both radius and tibia, respectively. XCT1 and XCT2-D measurements also had excellent agreement for most of the measurements (all R (2) > 0.870) except trabecular number (R (2) = 0.524, 0.706), trabecular thickness (R (2) = 0.758, 0.734) at both radius and tibia, respectively, and trabecular separation (R (2) = 0.656) at the radius., Conclusion: While some caution should be exercised for parameters that are more dependent on image resolution, results from our study indicate that second-generation scans can be compared to more widely available first-generation data and may be beneficial for multicenter and longitudinal studies using both scanner generations.

Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower whole bone and trabecular bone stiffness at the radius and tibia. Our results suggest that abnormalities in trabecular plate and rod microstructure may be important mechanisms of vertebral fracture in postmenopausal women., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Trabecular plate and rod microstructure plays a dominant role in the apparent mechanical properties of trabecular bone. With high-resolution computed tomography (CT) images, digital topological analysis (DTA) including skeletonization and topological classification was applied to transform the trabecular three-dimensional (3D) network into surface and curve skeletons. Using the DTA-based topological analysis and a new reconstruction/recovery scheme, individual trabecula segmentation (ITS) was developed to segment individual trabecular plates and rods and quantify the trabecular plate- and rod-related morphological parameters. High-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging in vivo imaging technique to visualize 3D bone microstructure. Based on HR-pQCT images, ITS was applied to various HR-pQCT datasets to examine trabecular plate- and rod-related microstructure and has demonstrated great potential in cross-sectional and longitudinal clinical applications. However, the reproducibility of ITS has not been fully determined. The aim of the current study is to quantify the precision errors of ITS plate-rod microstructural parameters. In addition, we utilized three different frequently used contour techniques to separate trabecular and cortical bone and to evaluate their effect on ITS measurements. Overall, good reproducibility was found for the standard HR-pQCT parameters with precision errors for volumetric BMD and bone size between 0.2%-2.0%, and trabecular bone microstructure between 4.9%-6.7% at the radius and tibia. High reproducibility was also achieved for ITS measurements using all three different contour techniques. For example, using automatic contour technology, low precision errors were found for plate and rod trabecular number (pTb.N, rTb.N, 0.9% and 3.6%), plate and rod trabecular thickness (pTb.Th, rTb.Th, 0.6% and 1.7%), plate trabecular surface (pTb.S, 3.4%), rod trabecular length (rTb.ℓ, 0.8%), and plate-plate junction density (P-P Junc.D, 2.3%) at the tibia. The precision errors at the radius were similar to those at the tibia. In addition, precision errors were affected by the contour technique. At the tibia, precision error by the manual contour method was significantly different from automatic and standard contour methods for pTb.N, rTb.N and rTb.Th. Precision error using the manual contour method was also significantly different from the standard contour method for rod trabecular number (rTb.N), rod trabecular thickness (rTb.Th), rod-rod and plate-rod junction densities (R-R Junc.D and P-R Junc.D) at the tibia. At the radius, the precision error was similar between the three different contour methods. Image quality was also found to significantly affect the ITS reproducibility. We concluded that ITS parameters are highly reproducible, giving assurance that future cross-sectional and longitudinal clinical HR-pQCT studies are feasible in the context of limited sample sizes.

Context: Skeletal deterioration, leading to an increased risk of fracture, is a known complication of type 2 diabetes mellitus (T2D). Yet plausible mechanisms to account for skeletal fragility in T2D have not been clearly established., Objective: The objective of the study was to determine whether bone material properties, as measured by reference point indentation, and advanced glycation endproducts (AGEs), as determined by skin autofluorescence (SAF), are related in patients with T2D., Design: This was a cross-sectional study., Setting: The study was conducted at a tertiary medical center., Patients: Sixteen postmenopausal women with T2D and 19 matched controls participated in the study., Main Outcome Measures: Bone material strength index (BMSi) by in vivo reference point indentation, AGE accumulation by SAF, and circulating bone turnover markers were measured., Results: BMSi was reduced by 9.2% in T2D (P = .02) and was inversely associated with the duration of T2D (r = -0.68, P = .004). Increased SAF was associated with reduced BMSi (r = -0.65, P = .006) and lower bone formation marker procollagen type 1 amino-terminal propeptide (r = -0.63, P = .01) in T2D, whereas no associations were seen in controls. SAF accounted for 26% of the age-adjusted variance in BMSi in T2D (P = .03)., Conclusions: Bone material properties are impaired in postmenopausal women with T2D as determined by reference point indentation. The results suggest a role for the accumulation of AGEs to account for inferior BMSi in T2D.

High-resolution peripheral quantitative computed tomography (HR-pQCT) provides in vivo three-dimensional (3D) imaging at the distal radius and tibia and has been increasingly used to characterize cortical and trabecular bone morphology in clinical studies. In this study, we comprehensively examined the accuracy of HR-pQCT and HR-pQCT based micro finite element (μFE) analysis predicted bone elastic stiffness and strength through comparisons with gold-standard micro computed tomography (μCT) based morphological/μFE measures and direct mechanical testing results. Twenty-six sets of human cadaveric distal radius and tibia segments were imaged by HR-pQCT and μCT. Microstructural analyses were performed for the registered HR-pQCT and μCT images. Bone stiffness and yield strength were determined by both HR-pQCT and μCT based linear and nonlinear μFE predictions and mechanical testing. Our results suggested that strong and significant correlations existed between the HR-pQCT standard, model-independent and corresponding μCT measurements. HR-pQCT based nonlinear μFE overestimated stiffness and yield strength while the linear μFE underestimated yield strength, but both were strongly correlated with those predicted by μCT μFE and measured by mechanical testing at both radius and tibia (R(2)>0.9). The microstructural differences between HR-pQCT and μCT were also examined by the Bland-Altman plots. Our results showed HR-pQCT morphological measurements of BV/TV(d), Tb.Th, and Tb.Sp, can be adjusted by correction values to approach true values measured by gold-standard μCT. In addition, we observed moderate correlations of HR-pQCT biomechanical and microstructural parameters between the distal radius and tibia. We concluded that morphological and mechanical properties of human radius and tibia bone can be assessed by HR-pQCT based measures., (Copyright © 2016. Published by Elsevier Inc.)

Context: Patients with 25-hydroxyvitamin D deficiency (25OHD <20 ng/ml) and primary hyperparathyroidism (PHPT) have more severe disease reflected by higher serum PTH levels compared to those with vitamin D levels in the insufficient (20-29 ng/ml) or replete range (≥ 30 ng/ml)., Objective: To study the effect of low vitamin D in PHPT on volumetric bone mineral density (vBMD), bone microarchitecture, and bone strength., Design, Setting, and Participants: This is a cross-sectional analysis of 99 PHPT patients with and without 25OHD insufficiency and deficiency from a university hospital., Outcome Measures: Bone microarchitecture and strength were assessed with high-resolution peripheral quantitative computed tomography (HRpQCT), microfinite element analysis, and individual trabecula segmentation., Results: In this cohort, 25OHD levels were deficient in 18.1%, insufficient in 35.4% and replete in 46.5%. Those with lower 25OHD levels had higher PTH (P < .0001), were younger (P = .001) and tended to weigh more (P = .053). There were no age-, weight- and sex-adjusted between-group differences (<20 vs 20-29 vs ≥ 30 ng/ml) in any HRpQCT, microfinite element analysis, or individual trabecula segmentation indices. Because few participants had 25OHD below 20 ng/ml, we also compared those with 25OHD below 30 vs at least 30 ng/ml and found only a trend toward lower adjusted cortical vBMD (3.1%, P = .08) and higher cortical porosity (least squares mean ± SEM 7.5 ± 0.3 vs 6.6 ± 0.3%, P = .07) at the tibia but not the radius. Stiffness did not differ at either site. In multiple regression analysis, 25OHD accounted for only three of the 49.2% known variance in cortical vBMD; 25OHD was not significant in the model for cortical porosity at the tibia., Conclusion: Low 25OHD levels are associated with higher PTH levels in PHPT, but contrary to our hypothesis, these differences did not significantly affect vBMD or microarchitecture, nor did they result in lower stiffness. Low vitamin D in PHPT using current 25OHD thresholds for insufficiency and deficiency did not significantly affect skeletal integrity as assessed by HRpQCT.

In hypoparathyroidism, areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is above average, and skeletal indices by bone biopsy are abnormal. We used high-resolution peripheral quantitative computed tomography (HRpQCT) and finite element analyses (FEA) to further investigate skeletal microstructure and estimated bone strength. We studied 60 hypoparathyroid subjects on conventional therapy using DXA, HRpQCT, and FEA of the distal radius and tibia compared with normative controls from the Canadian Multicentre Osteoporosis Study. In hypoparathyroid women and men, areal BMD was above average at the lumbar spine and hip sites by DXA; radial BMD was also above average in hypoparathyroid women. Using HRpQCT, cortical volumetric BMD was increased in the hypoparathyroid cohort compared with controls at both the radius and tibia. Cortical porosity was reduced at both sites in pre- and postmenopausal women and at the tibia in young men with a downward trend at the radius in men. At the tibia, trabecular number was increased in premenopausal women and men and trabecular thickness was lower in women. Ultimate stress and failure load at both sites for the hypoparathyroid subjects were similar to controls. Using a linear regression model, at both radius and tibia, each increment in age decreased ultimate stress and failure load, whereas each increment in duration of hypoparathyroidism increased these same indices. These results provide additional evidence for the critical role of parathyroid hormone in regulating skeletal microstructure. Longer disease duration may mitigate the adverse effects of age on estimated bone strength in hypoparathyroidism., (© 2015 American Society for Bone and Mineral Research.)

Patients with chronic kidney disease (CKD) who undergo kidney transplantation experience bone loss and increased risk of fracture. However, the mechanisms of this bone loss are unclear. Our objective was to use image registration to define the cortex to assess changes in cortical porosity (Ct.Po) in patients undergoing first-time kidney transplantation. We obtained serial measurements of parathyroid hormone (PTH) and bone turnover markers and used high-resolution peripheral quantitative computed tomography (HR-pQCT) to scan the distal radius and tibia in 31 patients (21 men, 10 women; aged 51.9 ± 13.4 years) at transplant and after 1 year. Baseline and 1-year images were aligned using a fully automated, intensity-based image registration framework. We compared three methods to define the cortical region of interest (ROI) and quantify the changes: 1) cortical bone was independently defined in baseline and follow-up scans; 2) cortical bone was defined as the common cortical ROI; and 3) the cortical ROI at baseline was carried forward to 1-year follow-up (baseline-indexed). By the independently defined ROI, Ct.Po increased 11.7% at the radius and 9.1% at the tibia, whereas by the common ROI, Ct.Po increased 14.6% at the radius and 9.1% at the tibia. By the baseline-indexed ROI, which provides insight into changes at the endocortical region, Ct.Po increased 63.4% at the radius and 17.6% at the tibia. We found significant relationships between changes in Ct.Po and bone formation and resorption markers at the radius. The strongest associations were found between markers and Ct.Po using the baseline-index method. We conclude that Ct.Po increases throughout the cortex after kidney transplant, and this increase is particularly marked at the endocortical surface. These methods may prove useful for all HR-pQCT longitudinal studies, particularly when changes are expected at the endocortical region., (© 2014 American Society for Bone and Mineral Research.)

Understanding proximal femur fracture may yield new targets for fracture prevention screening and treatment. The goal of this study was to characterize force-displacement and failure behaviours in the proximal femur between displacement control and impact loading fall simulations. Twenty-one human proximal femurs were tested in two ways, first to a sub-failure load at a constant displacement rate, then to fracture in an impact fall simulator. Comparisons of sub-failure energy and stiffness were made between the tests at the same compressive force. Additionally, the impact failure tests were compared with previous, constant displacement rate failure tests (at 2 and 100mm/s) in terms of energy, yield force, and stiffness. Loading and displacement rates were characterized and related to specimen stiffness in the impact tests. No differences were observed between the sub-failure constant displacement and impact tests in the aforementioned metrics. Comparisons between failure tests showed that the impact group had the lowest absorbed energy, 24% lower maximum force and 160% higher stiffness than the 100mm/s group (p<0.01 for all), but suffered from low statistical power to differentiate the donor age and specimen BMD. Loading and displacement rates for the specimens tested using impact varied during each test and between specimens and did not show appreciable viscoelasticity. These results indicate that constant displacement rate testing may help understand sub-failure mechanical behaviour, but may not elucidate failure behaviours. The differences between the impact and constant displacement rate fall simulations have important ramifications for interpreting the results of previous experiments., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Context: The mechanisms by which glucocorticoids (GCs) increase skeletal fragility are not well understood., Objective: The objective of the study was to evaluate the microarchitecture, trabecular morphology, and biomechanical properties of bone in postmenopausal women treated with GCs., Design: This was a case-control study., Setting: The study was conducted at a university hospital outpatient facility., Patients: Postmenopausal women treated with oral GCs for longer than 3 months (n = 30) and age/race-matched controls (n = 60) participated in the study., Main Outcome Measures: Areal bone mineral density aBMD (BMD) by dual-energy x-ray absorptiometry (DXA) was measured. Trabecular and cortical volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia were also measured. Whole-bone stiffness was estimated by finite element analysis. A novel technique, individual trabecula segmentation, was used to evaluate trabecular type (as plate or rod), orientation, and connectivity., Results: DXA T-scores did not differ significantly at any site. GC subjects had significantly lower total, cortical, and trabecular vBMD and thinner cortices, fewer, thinner, more widely, and irregularly spaced trabeculae. They had fewer trabecular plates, fewer axially aligned trabeculae, and lower trabecular connectivity. Differences ranged from 4% to 65% for these trabecular measures and 5% to 17% for the cortical measures. Whole-bone stiffness was significantly lower (11%-16%) in GC subjects. Markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and resorption (C-telopeptide) were lower in the GC subjects., Conclusions: Despite similar areal BMD by DXA, GC-treated women had abnormal cortical and trabecular vBMD and microarchitecture at both the radius and tibia, including fewer trabecular plates, a less axially aligned trabecular network, lower trabecular connectivity, thinner cortices, and lower whole-bone stiffness. Further research into these abnormalities as mechanisms for fracture in GC-treated women is warranted.

Finite element (FE) models of bone derived from quantitative computed tomography (QCT) rely on realistic material properties to accurately predict bone strength. QCT cannot resolve bone microarchitecture, therefore QCT-based FE models lack the anisotropy apparent within the underlying bone tissue. This study proposes a method for mapping femoral anisotropy using high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of human cadaver specimens. Femur HR-pQCT images were sub-divided into numerous overlapping cubic sub-volumes and the local anisotropy was quantified using a 'direct-mechanics' method. The resulting directionality reflected all the major stress lines visible within the trabecular lattice, and provided a realistic estimate of the alignment of Harvesian systems within the cortical compartment. QCT-based FE models of the proximal femur were constructed with isotropic and anisotropic material properties, with directionality interpolated from the map of anisotropy. Models were loaded in a sideways fall configuration and the resulting whole bone stiffness was compared to experimental stiffness and ultimate strength. Anisotropic models were consistently less stiff, but no statistically significant differences in correlation were observed between material models against experimental data. The mean difference in whole bone stiffness between model types was approximately 26%, suggesting that anisotropy can still effect considerable change in the mechanics of proximal femur models. The under prediction of whole bone stiffness in anisotropic models suggests that the orthotropic elastic constants require further investigation. The ability to map mechanical anisotropy from high-resolution images and interpolate information into clinical-resolution models will allow testing of new anisotropic material mapping strategies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Hispanic Americans of Caribbean origin are a fast-growing subset of the US population, but there are no studies on bone density, microstructure and biomechanical integrity in this minority group. In this study, we aimed to compare Caucasian and Caribbean Hispanic postmenopausal American women with respect to these characteristics. Thirty-three Caribbean Hispanics were age-matched to thirty-three Caucasian postmenopausal women. At the lumbar spine, the Hispanic women had significantly lower areal bone mineral density (aBMD). At the radius by high-resolution peripheral quantitative computed tomography (HR-pQCT), there were minimal differences between Hispanic and Caucasian women. At the tibia, Hispanic women had lower trabecular volumetric bone density and trabecular number, and higher trabecular separation. Individual trabecula segmentation (ITS) analyses indicated that at the tibia, Hispanic women not only had significantly lower bone volume fraction, but also had significantly lower rod bone volume fraction, plate trabecular number, rod trabecular number and lower plate-plate, plate-rod and rod-rod junction densities compared to Caucasian women. The differences in bone quantity and quality contributed to lower whole bone stiffness at the radius, and both whole bone and trabecular bone stiffness at the tibia in Hispanic women. In conclusion, Hispanic women had poorer bone mechanical and microarchitectural properties than Caucasian women, especially at the load-bearing distal tibia.

Context: In premenopausal women with idiopathic osteoporosis (IOP), treatment with teriparatide leads to substantial improvement in bone density and quality at central skeletal sites. The effects of teriparatide may differ on cortical and trabecular bone and also at the central and the peripheral skeleton., Objective: The objective of the study was to determine whether teriparatide was associated with improvements in compartmental volumetric bone mineral density (BMD), bone microarchitecture, and estimated bone strength of the distal radius and tibia as assessed by high-resolution peripheral quantitative computed tomography., Design, Setting, and Participants: Premenopausal women (n = 20, age 41 ± 5 y) with IOP (low trauma fractures and/or Z-scores ≤ -2.0) were scanned with high-resolution peripheral quantitative computed tomography at baseline and after 18 months of teriparatide treatment. Cortical and trabecular volumetric BMD and microarchitecture were measured by both standard and advanced techniques, including individual trabecula segmentation, and bone strength was estimated by finite element analysis., Main Outcome Measures: The total volumetric BMD and homogeneous bone stiffness were measured., Results: Trabecular volumetric BMD increased significantly by 2.6% (1.8, 6.2) [median (interquartile range)] at the radius and 2.5% (1.1, 3.6) at the tibia. In addition, trabecular plate bone volume fraction increased by 9.1% (2.1, 17.1) at the radius and 7.6% (1.0, 9.7) at the tibia. Cortical thickness and volumetric density did not change; however, cortical porosity increased at the radius but not at the tibia. Despite these changes, whole-bone stiffness and failure load estimated by finite element analysis increased at both the radius and tibia., Conclusions: In premenopausal women with IOP, 18 months of teriparatide was associated with increases in trabecular volumetric BMD, improved trabecular microarchitecture, and estimated bone strength at both the radius and tibia.

The use of early corticosteroid withdrawal (ECSW) protocols after kidney transplantation has become common, but the effects on fracture risk and bone quality are unclear. We enrolled 47 first-time adult transplant recipients managed with ECSW into a 1-year study to evaluate changes in bone mass, microarchitecture, biomechanical competence, and remodeling with dual energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), parathyroid hormone (PTH) levels, and bone turnover markers obtained at baseline and 3, 6, and 12 months post-transplantation. Compared with baseline, 12-month areal bone mineral density by DXA did not change significantly at the spine and hip, but it declined significantly at the 1/3 and ultradistal radii (2.2% and 2.9%, respectively; both P<0.001). HRpQCT of the distal radius revealed declines in cortical area, density, and thickness (3.9%, 2.1%, and 3.1%, respectively; all P<0.001), trabecular density (4.4%; P<0.001), and stiffness and failure load (3.1% and 3.5%, respectively; both P<0.05). Findings were similar at the tibia. Increasing severity of hyperparathyroidism was associated with increased cortical losses. However, loss of trabecular bone and bone strength were most severe at the lowest and highest PTH levels. In summary, ECSW was associated with preservation of bone mineral density at the central skeleton; however, it was also associated with progressive declines in cortical and trabecular bone density at the peripheral skeleton. Cortical decreases related directly to PTH levels, whereas the relationship between PTH and trabecular bone decreases was bimodal. Studies are needed to determine whether pharmacologic agents that suppress PTH will prevent cortical and trabecular losses and post-transplant fractures., (Copyright © 2014 by the American Society of Nephrology.)

Unlabelled: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk., Introduction: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture., Methods: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from -30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture., Results: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9 %) and when analyzed separately by femoral neck fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4 %), Conclusions: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture.

Introduction: HIV infection and antiretroviral therapy (ART) early in life may interfere with acquisition of peak bone mass, thereby increasing fracture risk in adulthood., Methods: We conducted a cross-sectional study of dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) in 30 HIV-infected African-American or Hispanic Tanner stage 5 men aged 20-25 on ART (15 perinatally infected and 15 infected during adolescence) and 15 HIV-uninfected controls., Results: HIV-infected men were similar in age and BMI, but were more likely to be African-American (P = 0.01) than uninfected men. DXA-derived areal bone mineral density (aBMD) Z-scores were 0.4-1.2 lower in HIV-infected men at the spine, hip, and radius (all P < 0.05). At the radius and tibia, total and trabecular volumetric BMD (vBMD), and cortical and trabecular thickness were between 6 and 19% lower in HIV-infected than uninfected men (P <0.05). HIV-infected men had dramatic deficiencies in plate-related parameters by individual trabeculae segmentation (ITS) analyses and 14-17% lower bone stiffness by finite element analysis. Differences in most HR-pQCT parameters remained significant after adjustment for race/ethnicity. No DXA or HR-pQCT parameters differed between men infected perinatally or during adolescence., Conclusion: At an age by which young men have typically acquired peak bone mass, HIV-infected men on ART have lower BMD, markedly abnormal trabecular plate and cortical microarchitecture, and decreased whole bone stiffness, whether infected perinatally or during adolescence. Reduced bone strength in young adults infected with HIV early in life may place them at higher risk for fractures as they age.

Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates., (Copyright © 2013 American Society for Bone and Mineral Research.)

Osteoporosis, a disease characterized by loss of bone mass and structural deterioration, is currently diagnosed by dual-energy x-ray absorptiometry (DXA). However, DXA does not provide information about bone microstructure, which is a key determinant of bone strength. Recent advances in imaging permit the assessment of bone microstructure in vivo using high-resolution peripheral quantitative computed tomography (HR-pQCT). From these data, novel image processing techniques can be applied to characterize bone quality and strength. To date, most HR-pQCT studies are cross-sectional comparing subjects with and without fracture. These studies have shown that HR-pQCT is capable of discriminating fracture status independent of DXA. Recent longitudinal studies present new challenges in terms of analyzing the same region of interest and multisite calibrations. Careful application of analysis techniques and educated clinical interpretation of HR-pQCT results have improved our understanding of various bone-related diseases and will no doubt continue to do so in the future.

Unlabelled: High-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of distal radius and tibia bone microarchitecture and finite element (FE) estimates of bone strength performed well at classifying postmenopausal women with and without previous fracture. The HR-pQCT measurements outperformed dual energy x-ray absorptiometry (DXA) at classifying forearm fractures and fractures at other skeletal sites., Introduction: Areal bone mineral density (aBMD) is the primary measurement used to assess osteoporosis and fracture risk; however, it does not take into account bone microarchitecture, which also contributes to bone strength. Thus, our objective was to determine if bone microarchitecture measured with HR-pQCT and FE estimates of bone strength could classify women with and without low-trauma fractures., Methods: We used HR-pQCT to assess bone microarchitecture at the distal radius and tibia in 44 postmenopausal women with a history of low-trauma fracture and 88 age-matched controls from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos) study. We estimated bone strength using FE analysis and simulated distal radius aBMD from the HR-pQCT scans. Femoral neck (FN) and lumbar spine (LS) aBMD were measured with DXA. We used support vector machines (SVM) and a tenfold cross-validation to classify the fracture cases and controls and to determine accuracy., Results: The combination of HR-pQCT measures of microarchitecture and FE estimates of bone strength had the highest area under the receiver operating characteristic (ROC) curve of 0.82 when classifying forearm fractures compared to an area under the curve (AUC) of 0.71 from DXA-derived aBMD of the forearm and 0.63 from FN and spine DXA. For all fracture types, FE estimates of bone strength at the forearm alone resulted in an AUC of 0.69., Conclusion: Models based on HR-pQCT measurements of bone microarchitecture and estimates of bone strength performed better than DXA-derived aBMD at classifying women with and without prior fracture. In future, these models may improve prediction of individuals at risk of low-trauma fracture.

Finite element (FE) analysis based on quantitative computed tomography (QCT) images is an emerging tool to estimate bone strength in a specific patient or specimen; however, it is limited by the computational power required and the associated time required to generate and solve the models. Thus, our objective was to develop a fast, validated method to estimate whole bone structural stiffness and failure load in addition to a sensitivity analysis of varying boundary conditions. We performed QCT scans on twenty fresh-frozen proximal femurs (age: 77±13 years) and mechanically tested the femurs in a configuration that simulated a sideways fall on the hip. We used custom software to generate the FE models with boundary conditions corresponding to the mechanical tests and solved the linear models to estimate bone structural stiffness and estimated failure load. For the sensitivity analysis, we varied the internal rotation angle of the femoral neck from -30° to 45° at 15° intervals and estimated structural stiffness at each angle. We found both the FE estimates of structural stiffness (R(2)=0.89, p<0.01) and failure load (R(2)=0.81, p<0.01) to be in high agreement with the values found by mechanical testing. An important advantage of these methods was that the models of approximately 500,000 elements took less than 11 min to solve using a standard desktop workstation. In this study we developed and validated a method to quickly and accurately estimate proximal femur structural stiffness and failure load using QCT-driven FE methods., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the sex- and maturity-related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high-resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years (n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri- and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (-118% and -56%, respectively) compared with peri- and postpubertal boys (all p < 0.001). Peri- and postpubertal boys had higher trabecular bone volume ratios (p < 0.001) and larger cortical cross-sectional areas (p < 0.05, p < 0.001) when compared with girls. Based upon the load-to-strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po (p < 0.01) and failure load (p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri-, and postpubertal groups and boys in peri- and postpubertal groups had higher estimates of bone strength compared with their same-sex prepubertal peers (p < 0.001). These results provide insight into the sex- and maturity-related differences in bone microstructure and estimated bone strength.

In addition to bone mineral density (BMD), bone microstructure is a major contributor to bone strength. With recently developed technologies we are able to assess bone microstructure in vivo . These technologies include high-resolution peripheral quantitative computed tomography (HR-pQCT), multi-detector computer tomography (MDCT), and high-resolution magnetic resonance imaging (HR-MRI). Using HR-pQCT both cortical and trabecular microstructure can be assessed with a voxel size of 82μm. While MDCT and HR-MRI have lower spatial resolution than HR-pQCT, they have the main advantage of imaging central sites such as the proximal femur. Using these technologies a variety of parameters can be measured including bone volume ratio, trabecular thickness and number, cortical thickness, and cortical porosity. In vivo microstructure measurements are associated with fracture risk and these measurements can be combined with finite element modeling to estimate bone strength. While limitations exist, such as measurement of only peripheral sites and motion artifacts, the assessment of microstructure is promising and provides clinically relevant information. The techniques may help to better predict fracture risk and determine the efficacy of treatments for metabolic bone diseases.

Unlabelled: We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to monitor changes in bone microarchitecture and strength at the distal radius and tibia associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Despite treatment-associated declines in total and cortical BMD, trabecular thinning and reduced trabecular bone volume, bone strength did not change significantly from baseline., Introduction: Teriparatide is an established anabolic therapy for osteoporosis; however, treatment effects at the distal radius are unclear. Therefore, we aimed to monitor changes in bone microarchitecture and estimated strength at the distal radius and tibia in osteoporotic postmenopausal women., Methods: We used high-resolution peripheral quantitative computed tomography (Scanco Medical, Switzerland) to perform a standard three-dimensional morphological analysis of the distal radius and tibia in 11 osteoporotic postmenopausal women (mean age, 68.7 ± 12.7 years) at baseline, 6, 12, and 18 months after initiation of 20 μg/day of teriparatide. Ten of the women received bisphosphonate therapy prior to starting on teriparatide. In addition to the standard analysis, we quantified cortical bone mineral density (BMD), porosity, and thickness using an automated segmentation procedure and estimated bone strength (ultimate stress) using finite element analysis., Results: After 18 months, we observed a decrease in total BMD (p = 0.03) at the distal radius and a decrease in cortical BMD at the distal radius (p = 0.05) and tibia (p = 0.01). The declines in cortical BMD were associated with trends for increased cortical porosity at both sites. At the distal radius, 18 months of teriparatide treatment was also associated with trabecular thinning (p = 0.009) and reduced trabecular bone volume ratio (p = 0.08). We observed similar trends at the distal tibia. Despite these changes in bone quality, bone strength was maintained over the 18-month follow-up., Conclusions: The observed changes in cortical bone structure are consistent with the effects of parathyroid hormone on intracortical bone remodeling. Controlled trials involving larger sample sizes are required to confirm the effects of teriparatide therapy on trabecular and cortical microarchitecture in the peripheral skeleton.

In this cross-sectional study, we aimed to predict age-related changes in bone microarchitecture and strength at the distal radius (DR) and distal tibia (DT) in 644 Canadian adults (n = 442 women and 202 men) aged 20 to 99 years. We performed a standard morphologic analysis of the DR and DT with high-resolution peripheral quantitative computed tomography (pQCT) and used finite-element analysis (FEA) to estimate bone strength (failure load) and the load distribution. We also calculated a DR load-to-strength ratio as an estimate of forearm fracture risk. Total bone area, which was 33% larger in young men at both sites, changed similarly with age in women and men at the DT but increased 17% more in men than in women at the DR (p < .001). Trabecular number and thickness (Tb.Th) were 7% to 20% higher in young men than in young women at both sites, and with the exception of Tb.Th at the DR, which declined more with age in men (-16%) than in women (-2%, p < .01), the age-related decline in these outcomes was similar in women and in men. In the cortex, porosity (Ct.Po) was 31% to 44% lower in young women than in young men but increased 92% to 176% more with age in women than in men (p < .001). The DR cortex carried 14% more load in young women than in young men, and the percentage of load carried by the DR cortex did not change with age in women but declined by 17% in men (p < .01). FEA-estimated bone strength was 34% to 47% greater in young men, but the predicted change with age was similar in both sexes. In contrast, the load-to-strength ratio increased 27% more in women than in men with age (p < .01). These results highlight important site- and sex-specific differences in patterns of age-related bone loss. In particular, the trends for less periosteal expansion, more porous cortices, and a greater percentage of load carried by the DR cortex in women may underpin sex differences in forearm fracture risk., (© 2011 American Society for Bone and Mineral Research.)

Increases in cortical porosity (Ct.Po) and decreases in cortical thickness (Ct.Th) are associated with increased bone fragility. The purpose of this study was to validate an autosegmentation method for high-resolution peripheral quantitative computed tomography (HR-pQCT) scans to measure Ct.Po and Ct.Th and use it to compare Ct.Po and Ct.Th between pre- and postmenopausal women with normal, osteopenic, and osteoporotic areal bone mineral density (aBMD). The Ct.Po and Ct.Th measurements were validated using cadaver forearms (n = 10) and micro-computed tomography (microCT) as the gold standard. The analysis was applied to distal radius and tibia HR-pQCT scans from a subset of participants from the Calgary, Alberta, cohort of the Canadian Multicentre Osteoporosis Study (n = 280, 18 to 90 years). Analysis of covariance compared Ct.Po and Ct.Th outcomes between 63 normal premenopausal (dual-energy X-ray absorptiometry femoral neck T-score > -1), 87 normal postmenopausal, 121 osteopenic postmenopausal, and 9 osteoporotic postmenopausal women. Linear regression analysis and Bland-Altman plots were used to assess the agreement between the HR-pQCT and microCT measurements, resulting in r(2) values of 0.80 for Ct.Po and 0.98 for Ct.Th. At both sites, Ct.Po was higher in postmenopausal (all groups) than in premenopausal women (3.2% to 12.9%, p < .001). Ct.Th was not significantly different between normal premenopausal and postmenopausal women at either site; however, both osteopenic and osteoporotic women had thinner (-12.8% to -30.3%, p < .01), more porous (2.1% to 8.1%, p < .001) cortices than normal postmenopausal women. Our method offers promise as a valuable tool to measure Ct.Po and Ct.Th in vivo and investigate associations among cortical bone structure, age, and disease status., (Copyright 2010 American Society for Bone and Mineral Research.)

In vivo micro-computed tomography (microCT) is a new method to monitor longitudinal changes of bone micro-architecture. Common animal models of bone diseases are mice and rats, and it is important to know the reproducibility of the bone measurements in order to correctly interpret results. When performing baseline and follow-up acquisitions, variation in the scan region will influence the parameters, and it has yet to be investigated if three-dimensional (3D) registration can improve the reproducibility. Two typical breeds of mice and one typical breed of rats were scanned four times each using microCT and standard bone morphological and density measurements were calculated. Image registration was used to find the overlapping regions between the scans within each series of animal data and only overlapping regions were analyzed for the bone parameters. Reproducibility was determined for each animal both pre- and post-registration. For the rats, results included a bone volume ratio (BV/TV) precision error of 5.46%, cortical thickness (Ct.Th) error of 1.97%, and tissue mineral density (TMD) of 2.00%. For the BL6 mice, precision errors were 3.00% (BV/TV), 0.95% (Ct.Th), and 0.94% (TMD), and for the C3H mice 2.68% (BV/TV), 1.52% (Ct.Th), and 1.72% (TMD). After image registration there was a significant improvement in reproducibility in most parameters for the rats. In general, metric parameters such as bone volume ratio had better reproducibility than the non-metric parameters connectivity density and structure model index. With 3D registration, reproducibility improved the results obtained by the experienced operators in this study. Registration may serve to equalize reproducibility of operators with different skill levels and across laboratories. It also improves efficiency by reducing the amount of hand-contouring required. This reproducibility data will be important for the interpretation of current and future longitudinal microCT studies., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)