Individual Trabecula Segmentation Research Articles

Mechanical and structural properties of articular cartilage and subchondral bone in human osteoarthritic knees.

Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within the osteochondral unit may drive OA progression. Although structural-biomechanical properties of bone and cartilage have been studied, potential interaction within the osteochondral unit in the context of OA has yet to be investigated. We performed comprehensive structural and biomechanical quantification of the cartilage, subchondral bone plate (SBP), and subchondral trabecular bone (STB) using 101 osteochondral cores collected from tibial plateaus of 12 control human cadavers (CT, 5 male/7 female) and 19 patients undergoing total knee replacement (OA, 6 male/13 female). For each sample, we quantified SBP microstructure, plate-and-rod morphological properties of the STB using individual trabecula segmentation, and morphological and compositional properties of the articular cartilage. We also performed indentation testing on each compartment of the osteochondral unit to extract the respective structural-mechanical properties. Cartilage thickness was lower in moderate and severe OA regions, while Osteoarthritis Research Society International score was higher only in severe OA regions. GAG content did not change in any OA region. Aggregate and shear moduli were lower only in severe OA regions, while permeability was lower only in moderate OA regions. In the SBP, thickness and tissue mineral density were higher in moderate and severe OA regions. Tissue modulus of STB was lower in moderate OA regions despite a thicker and more mineralized SBP; this deterioration was not observed in severe OA regions. Regression analysis revealed strong correlations between cartilage and STB properties in CT; these correlations were also found in moderate OA regions but were not observed in severe OA regions. In summary, our findings comprehensively characterize the human OA osteochondral unit. Importantly, uncoupling cartilage and subchondral bone structural-mechanical properties may be a hallmark of OA.

Fractures in women with type 2 diabetes are associated with marked deficits in cortical parameters and trabecular plates.

The basis for increased fracture risk in type 2 diabetes (T2DM) is not well understood. In this multi-ethnic, population-based study (n = 565), we investigated bone microstructure, trabecular plate/rod morphology, and mineralization in women with T2DM (n = 175) with and without fracture using a second-generation HRpQCT and individual trabecula segmentation and mineralization (ITS; ITM). Covariate-adjusted aBMD was 3.0%-6.5% higher at all sites (all p<.005) in T2DM vs controls. By HRpQCT, T2DM had higher covariate-adjusted trabecular vBMD (5.3%-6.4%) and number (3.8%-5.1%) and greater cortical area at the radius and tibia. Covariate-adjusted cortical porosity was 10.0% higher at the tibia only in T2DM vs controls, but failure load did not differ. Among women with T2DM, those with adult atraumatic fracture (n = 59) had 5.2%-8.5% lower adjusted aBMD at all sites by DXA compared with those without fracture (n = 103). By HRpQCT, those with fracture had lower adjusted total vBMD and smaller cortical area (10.2%-16.1%), lower cortical thickness (10.5-15.8%) and lower cortical vBMD associated with 18.1 and 17.2% lower failure load at the radius and tibia, respectively (all p<.05); plate volume and thickness were 5.7% and 4.7% lower, respectively, (p<.05) while rod volume fraction was 12.8% higher in the fracture group at the tibia only. Sodium glucose cotransporter 2 inhibitor users (SGLT2i; n = 19), tended to have lower radial rod tissue mineral density by ITS (p=.06). GLP1 agonist users (n = 19) had trabecular deficits at both sites and higher cortical porosity and larger pores at the distal tibia. In summary, T2DM is associated with increased cortical porosity while those with T2DM and fracture have more marked cortical deficits and fewer trabecular plates associated with lower failure load.

Individual trabecula segmentation validation in first- and second-generation high-resolution peripheral computed tomography compared to micro-computed tomography in the distal radius and tibia.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has been used for in vivo 3D visualization of trabecular microstructure. Second-generation HR-pQCT (HR-pQCT II) has been shown to have good agreement with first generation HR-pQCT (HR-pQCT I). Advanced Individual Trabecula Segmentation (ITS) decomposes the trabecula network into individual plates and rods. ITS based on HR-pQCT I showed a strong correlation to ITS based on micro-computed tomography (μCT) and identified trabecular changes in metabolic bone diseases. ITS based on HR-pQCT II has new potential because of the enhanced resolution but has yet to be validated. The objective of this study was to assess the agreement between ITS based on HR-pQCT I, HR-pQCT II, and μCT to assess the capability of ITS on HR-pQCT images as a tool for studying bone structure. Freshly frozen tibia and radius bones were scanned in the distal region using HR-pQCT I at 82μm, HR-pQCT II at 60.7μm, and μCT at 37μm. Images were registered, binarized, and ITS analysis was performed. Bone volume fraction (pBV/TV, rBV/TV), number density (pTb.N, rTb.N), thickness (pTb.Th, rTb.Th), and plate-to-rod (PR) ratio (pBV/rBV) of trabecular plates and rods were obtained. Paired Student's t-tests with post hoc Bonferroni analysis were used to examine the differences. Linear regression was used to determine the correlation coefficient. The HR-pQCT I parameters were different from the μCT measurements. The HR-pQCT II parameters were different from the μCT measurements except for rTb.N, and the HR-pQCT I parameters were different from the HR-pQCT II measurements except for pTb.Th. The strong correlation between HR-pQCT II and μCT microstructural analysis (R2 = 0.55-0.94) suggests that HR-pQCT II can be used to assess changes in plate and rod microstructure and that values from HR-pQCT I can be corrected.

Ankle flexor torque, size and density are differential determinants of distal tibia trabecular plate-rod morphometry and bone strength: The Ankle Quality Study.

Greater peak torque and higher myotendinous density at the ankle are associated with a more plate-like architecture at the distal tibia. In this cross-sectional study, women and men ≥ 50years old with no metal implants, reconstructive surgery, muscular dystrophies, or tendinopathies in any leg were recruited by convenience. Isometric ankle dorsi-plantar flexion and inversion-eversion peak torques were measured using dynamometry. HR-pQCT distal tibia scans were completed. Both assessments were completed on the same day on the non-dominant leg. Integral and trabecular vBMD were derived from standard analyses, failure load (FL) was obtained from finite element analysis, plate-specific parameters were computed from individual trabecula segmentation (ITS) analysis, myotendinous density (MyD) and volume fraction (MyV/TV) were computed from soft tissue analysis. pQCT scans of the 66% mid-leg were performed (500μm at 15mm/s) to obtain muscle density (MD) and muscle cross-sectional area (MCSA). General linear models estimated how ankle muscle group torque and muscle size and density differentially related, both separately and together, to whole-bone properties (integral vBMD, FL) and trabecular morphometry (ITS plate parameters). Models were adjusted for age, sex, BMI, use of glucocorticoids, current osteoarthritis, and participation in moderate to vigorous recreational or sport activities. Among 105 participants (77% female, mean age: 63 (10) years, BMI: 25.8 (5.4) kg/m2, 25% with OA, 17% fracture history, 42% falls history), all torque measures, particularly ankle dorsiflexion and eversion, were correlates of plate-plate/rod junction density and failure load. However, muscle size and density measures were further associated with vBMD. The effect of greater ankle flexor-extensor torque on more connected bone was stronger when MyD was higher (interaction p<0.001). Strength of muscles around the ankle are correlates of plate-like trabeculae at the distal tibia, while leaner muscle and myotendinous tissues facilitates better quality bone for stronger ankle muscle torque.

Subchondral Trabecular Microstructure and Articular Cartilage Damage Variations Between Osteoarthritis and Osteoporotic Osteoarthritis: A Cross-sectional Cohort Study.

Osteoporotic osteoarthritis (OP-OA) is a specific type of OA. In this study, we aimed to assess the subchondral plate and rod microstructural differences between OA and OP-OA patients by using an individual trabeculae segmentation (ITS) system and to analyze the relationships between subchondral microstructures and cartilage damage in OA and OP-OA patients. Overall, 31 femoral heads were included in this study, which included 11 samples with OA and 13 samples with OP-OA; the normal control (NC) group contained 7 healthy femoral heads. ITS was performed to segment the subchondral trabecular bone into plate and rod trabeculae based on microcomputed tomography (micro-CT) images. We compared the plate and rod trabeculae of the subchondral trabecular bone between OA and OP-OA patients. The Osteoarthritis Research Society International (OARSI) score was employed to evaluate cartilage damage based on histological observations. Pearson's correlation coefficient and linear regression analysis were applied to analyze the relationships between subchondral microstructures and articular cartilage damage. Results showed that several microstructural parameters, including bone volume fraction (BV/TV), plate bone volume fraction (pBV/TV), rod bone volume fraction (rBV/TV), plate trabecular number (pTb.N), rod trabecular number (rTb.N), junction density between rod and plate (R-P Junc.D), and junction density between plate and plate (P-P Junc.D), were significantly decreased in patients with OP-OA compared with those in patients with OA (p < 0.05). Histological observations indicated that cartilage damage was more serious in patients with OP-OA than that in patients with OA (p < 0.05). Moreover, BV/TV, pBV/TV, pTb.N, and pTb.Th were significantly related to the OARSI score in both OA and OP-OA patients. These results indicated that there were differences in the subchondral rod and plate trabeculae between OA and OP-OA patients. Subchondral decreased plate trabeculae (pBV/TV, pTb.N, and pTb.Th) might account for cartilage damage in the progression of OP-OA. This study provided new insights to research OA when it is combined with OP.

Microstructure Determines Apparent-Level Mechanics Despite Tissue-Level Anisotropy and Heterogeneity of Individual Plates and Rods in Normal Human Trabecular Bone.

Trabecular plates and rods determine apparent elastic modulus and yield strength of trabecular bone, serving as important indicators of bone's mechanical integrity in health and disease. Although trabecular bone's apparent-level mechanical properties have been widely reported, tissue mechanical properties of individual trabeculae have not been fully characterized. We systematically measured tissue mineral density (TMD)-dependent elastic modulus of individual trabeculae using microindentation and characterized its anisotropy as a function of trabecular type (plate or rod), trabecular orientation in the global coordinate (longitudinal, oblique, or transverse along the anatomic loading axis), and indentation direction along the local trabecular coordinate (axial or lateral). Human trabecular bone samples were scanned by micro-computed tomography for TMD and microstructural measurements. Individual trabecula segmentation was used to decompose trabecular network into individual trabeculae, where trabecular type and orientation were determined. We performed precise, selective indentation of trabeculae in each category using a custom-built, microscope-coupled microindentation device. Co-localization of TMD at each indentation site was performed to obtain TMD-to-modulus correlations. We found significantly higher TMD and tissue modulus in trabecular plates than rods. Regardless of trabecular type and orientation, axial tissue modulus was consistently higher than lateral tissue modulus, with ratios ranging from 1.13 to 1.41. Correlations between TMD and tissue modulus measured from axial and lateral indentations were strong but distinct: axial correlation predicted higher tissue modulus than lateral correlation at the same TMD level. To assess the contribution of experimentally measured anisotropic tissue properties of individual trabeculae to apparent-level mechanics, we constructed non-linear micro-finite element models using a new set of trabecular bone samples and compared model predictions to mechanical testing measurements. Heterogeneous anisotropic models accurately predicted apparent elastic modulus but were no better than a simple homogeneous isotropic model. Variances in tissue-level properties may therefore contribute nominally to apparent-level mechanics in normal human trabecular bone. © 2021 American Society for Bone and Mineral Research (ASBMR).

Distributions of Microdamage Are Altered Between Trabecular Rods and Plates in Cancellous Bone From Men With Type 2 Diabetes Mellitus.

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture despite exhibiting normal to high bone mineral density (BMD). Conditions arising from T2DM, such as reduced bone turnover and alterations in microarchitecture, may contribute to skeletal fragility by influencing bone morphology and microdamage accumulation. The objectives of this study were (i) to characterize the effect of T2DM on microdamage quantity and morphology in cancellous bone, and (ii) relate the accumulation of microdamage to the cancellous microarchitecture. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n= 22, age=65 ± 9 years, glycated hemoglobin [HbA1c]=7.00% ± 0.98%; non-diabetic [non-DM]: n= 25, age=61 ± 8 years, HbA1c=5.50% ± 0.4%), compressed to 3% strain, stained with lead uranyl acetate to isolate microdamage, and scanned with micro-computed tomography (μCT). Individual trabeculae segmentation was used to isolate rod-like and plate-like trabeculae and their orientations with respect to the loading axis. The T2DM group trended toward a greater BV/TV (+27%, p= 0.07) and had a more plate-like trabecular architecture (+8% BVplates , p= 0.046) versus non-DM specimens. Rods were more damaged relative to their volume compared to plates in the non-DM group (DVrods /BVrods versus DVplates /BVplates : +49%, p< 0.0001), but this difference was absent in T2DM specimens. Longitudinal rods were more damaged in the non-DM group (DVlongitudinal rods /BVlongitudinal rods : +73% non-DM versus T2DM, p= 0.027). Total damage accumulation (DV/BV) and morphology (DS/DV) did not differ in T2DM versus non-DM specimens. These results provide evidence that cancellous microarchitecture does not explain fracture risk in T2DM, pointing to alterations in material matrix properties. In particular, cancellous bone from men with T2DM may have an attenuated ability to mitigate microdamage accumulation through sacrificial rods. © 2022 American Society for Bone and Mineral Research (ASBMR).

Bone Density and Trabecular Morphology at Least 10 Years After Gastric Bypass and Gastric Banding.

Roux-en-Y gastric bypass (RYGB) instigates high-turnover bone loss in the initial 5 years after surgery, whereas skeletal changes after adjustable gastric banding (AGB) are less pronounced. Long-term skeletal data are scarce, and the mechanisms of bone loss remain unclear. We sought to examine bone density and microarchitecture in RYGB and AGB patients a decade after surgery and to determine whether prior published reports of bone loss represent an appropriate adaptation to new postsurgical weight. In this cross-sectional study, 25 RYGB and 25 AGB subjects who had bariatric surgery ≥10 years ago were matched 1:1 with nonsurgical controls for age, sex, and current body mass index (BMI). We obtained bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), volumetric BMD and microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular morphology by individual trabecular segmentation, and metabolic bone laboratory results. As compared with BMI-matched controls, RYGB subjects had significantly lower hip BMD, and lower total volumetric BMD at the distal radius and tibia. Substantial deficits in cortical and trabecular microarchitecture were observed in the RYGB group compared to controls, with reduced trabecular plate bone volume fraction and estimated failure load at both the radius and tibia, respectively. Bone turnover markers CTX and P1NP were 99% and 77% higher in the RYGB group than controls, respectively, with no differences in serum calcium, 25-hydroxyvitamin D, or parathyroid hormone. In contrast, the AGB group did not differ from their BMI-matched controls in any measured bone density, microarchitecture, or laboratory parameter. Thus, RYGB, but not AGB, is associated with lower than expected hip and peripheral BMD for the new weight setpoint, as well as deleterious changes in bone microarchitecture. These findings suggest that pathophysiologic processes other than mechanical unloading or secondary hyperparathyroidism contribute to bone loss after RYGB, and have important clinical implications for the long-term care of RYGB patients. © 2020 American Society for Bone and Mineral Research.

Differences in subchondral trabecular bone microstructure and finite element analysis-based biomechanical properties between osteoporosis and osteoarthritis.

SummaryBackground/ObjectiveThe microstructure of the subchondral trabecular bone, including the composition and distribution of plates and rods, has an important influence on the disease progression and mechanical properties of osteoarthritis (OA) and osteoporosis (OP). We aimed to determine whether differences in plates and rods influence the variations in the quantities and qualities of the subchondral trabecular bone between OA and OP.Materials and methodsThirty-eight femoral head samples [OA, n = 13; OP, n = 17; normal control (NC), n = 8] were collected from male patients undergoing total hip arthroplasty. They were scanned using microcomputed tomography, and subchondral trabecular structures were analysed using individual trabecular segmentation. Micro-finite element analysis (μFEA) was applied to assess the mechanical property of the trabecular bone. Cartilage changes were evaluated by using histological assessment. Analysis of variance was used to compare intergroup differences in structural and mechanical properties and cartilage degradation. Pearson analysis was used to evaluate the relationship between the trabecula microstructure and biomechanical properties.ResultsCompared with the OP and NC group, there was serious cartilage damage in the OA group. With respect to the microstructure results, the OA group had the highest plate and rod trabecular microstructures including number and junction density among the three groups. For the mechanical properties detected via μFEA, the OA group had higher stiffness and failure load than did the OP group. Pearson analysis revealed that compared with OP, OA had a higher number of microstructure parameters (e.g., rod bone volume fraction and rod trabecular number) that were positively correlated with its mechanical property.ConclusionsCompared with OP, the OA subchondral bone has both increased plate and rod microarchitecture and has more microstructures positively related with its mechanical property. These differences may help explain the variation in mechanical properties between these bone diseases.The translational potential of this articleOur findings suggested that changes in the plates and rods of the subchondral trabecular bone play a critical role in OA and OP progression and that the improvement of the subchondral trabecular bone may be a promising treatment approach.

Different subchondral trabecular bone microstructure and biomechanical properties between developmental dysplasia of the hip and primary osteoarthritis

ObjectiveDevelopmental dysplasia of the hip (DDH) is recognized as a frequent cause of secondary osteoarthritis (OA). The purpose in this study was to compare structural and biomechanical properties of subchondral trabecular bone ​and its relationship with cartilage damage between patients with DDH and patients with primary hip OA. MethodsForty-three femoral head specimens obtained from patients who underwent total hip arthroplasty [DDH, n ​= ​17; primary OA, n ​= ​16; and normal control (NC), n ​= ​10] were scanned by microcomputed tomography and analyzed by individual trabecula segmentation to obtain the microstructural types of subchondral trabecular bone. The biomechanical properties were analyzed by micro–finite element analysis, and cartilage damage was evaluated by histology. The linear regression analysis was used to indicate the association between microstructures, biomechanical property, and articular cartilage. ResultsThe DDH group showed the lowest total bone volume fractions (BV/TV) and plate BV/TV in the three groups (p ​< ​0.05). There were also different discrepancies between the three groups in plate/rod trabecular number, plate/rod trabecular thickness, trabecular plate surface area/trabecular rod length, and junction density with different modes (plate–plate, rod–rod, and plate–rod junction density). The micro–finite element analysis, histology, and linear regression revealed that the subchondral trabecular bone in the DDH group had inferior biomechanical properties ​and cartilage damage of patients with DDH was more serious with different subchondral trabecular bone microstructures. ConclusionOur findings detected deteriorating subchondral trabecular bone microstructures in patients with DDH. The mass and type of subchondral trabecular bone play a key role in mechanical properties in DDH, which might be related to cartilage damage. The translational potential of this articleOur findings suggested that changes of subchondral trabecular bone play a critical role ​in DDH progression and that the improvement on subchondral trabecular bone may be a sensitive and promising way in treatment of DDH.

Dimorphism in axial and appendicular dimensions, cortical and trabecular microstructure and matrix mineral density in Chinese and Caucasian women.

Appendicular fractures are less common in Chinese than Caucasian women. Bone mineral density (BMD) is lower, not higher than in Caucasians because Chinese have smaller appendicular dimensions than Caucasians. However, smaller bones may offset the liability to fracture by being assembled with a more robust microstructure. We hypothesized that Chinese assemble an appendicular skeleton with a thicker, less porous and more mineralized cortex that is less deteriorated in advanced age than in Caucasians. We compared anthropometry in 477 Chinese and 278 Caucasian women and compared bone microstructure using high-resolution peripheral quantitative computed tomography in another cohort of 186 Chinese and 381 Caucasian women aged 18 to 86 years, all living in Melbourne, Australia. Trabecular plate (p) and rod (r) bone volume/total volume (BV/TV) were quantified using individual trabecula segmentation (ITS). Bone strength was estimated using micro-finite element analysis (μFEA). Premenopausal Chinese were shorter than Caucasian women, mainly due to shorter leg length. Distal radial total cross sectional area (CSA) was 14.8% smaller (p < 0.001). After adjusting for age and total CSA, Chinese had similar cortical and medullary areas but 0.30 SD lower cortical porosity and 0.27 SD higher matrix mineral density (both p < 0.05). Trabecular plate-to-rod ratio was 0.55 SD higher due to a 0.41 SD higher pBV/TV and 0.36 SD lower rBV/TV (p ranging 0.001 to 0.023). Chinese also had 0.36 SD greater whole bone stiffness and 0.36 SD greater failure load than Caucasians (both p < 0.05). After adjusting for age and total CSA, postmenopausal Chinese had 3.3% smaller cortical area, medullary area was 2.1% larger, cortical porosity was no lower, matrix mineral density and pBV/TV were no higher compared with Caucasians at the distal radius. Whole bone stiffness was 0.39 SD lower and failure load was 0.40 SD lower in Chinese (both p < 0.05). Chinese build a more robust skeleton than Caucasians during growth, an advantage not observed in advanced age due to greater bone loss or race-specific secular trends in bone morphology.

Regional Variations of HR-pQCT Morphological and Biomechanical Measurements of Bone Segments and Their Associations With Whole Distal Radius and Tibia Mechanical Properties

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.

Differences in Trabecular Plate and Rod Structure in Premenopausal Women Across the Weight Spectrum.

Premenopausal women with anorexia nervosa (AN) and obesity (OB) have elevated fracture risk. More plate-like and axially aligned trabecular bone, assessed by individual trabeculae segmentation (ITS), is associated with higher estimated bone strength. Trabecular plate and rod structure has not been reported across the weight spectrum. To investigate trabecular plate and rod structure in premenopausal women. Cross-sectional study. Clinical research center. A total of 105 women age 21 to 46 years: (i) women with AN (n = 46), (ii) eumenorrheic lean healthy controls (HCs) (n = 29), and (iii) eumenorrheic women with OB (n = 30). Trabecular microarchitecture by ITS. Mean age (±SD) was similar (28.9 ± 6.3 years) and body mass index differed (16.7 ± 1.8 vs 22.6 ± 1.4 vs 35.1 ± 3.3 kg/m2; P < 0.0001) across groups. Bone was less plate-like and axially aligned in AN (P ≤ 0.01) and did not differ between OB and HC. After controlling for weight, plate and axial bone volume fraction and plate number density were lower in OB vs HC; some were lower in OB than AN (P < 0.05). The relationship between weight and plate variables was quadratic (R = 0.39 to 0.70; P ≤ 0.0006) (i.e., positive associations were attenuated at high weight). Appendicular lean mass and IGF-1 levels were positively associated with plate variables (R = 0.27 to 0.67; P < 0.05). Amenorrhea was associated with lower radial plate variables than eumenorrhea in AN (P < 0.05). In women with AN, trabecular bone is less plate-like. In women with OB, trabecular plates do not adapt to high weight. This is relevant because trabecular plates are associated with greater estimated bone strength. Higher muscle mass and IGF-1 levels may mitigate some of the adverse effects of low weight or excess adiposity on bone.

OR03-6 Tibial and Radial Bone Structure as Assessed by HRpQCT May Explain Differences in Peripheral Skeletal Integrity and Fracture Risk Across the Weight Spectrum That Cannot Be Explained by Areal BMD Alone

No study has investigated tibial or radial bone structure or estimated strength by high-resolution peripheral quantitative CT (HRpQCT) in women across the weight spectrum. We studied 139 women, 17-46yo: 1) anorexia nervosa (AN n=74), 2) lean controls (HC n=33) and 3) overweight/obese (OB n=32). All HC and OB were eumenorrheic. Areal BMD (aBMD) and appendicular lean mass (ALM) were measured by DXA; cortical and trabecular volumetric BMD (vBMD), cortical thickness, cortical porosity, failure load (finite element analysis) and trabecular plate parameters (individual trabecular segmentation) at the tibia and radius by HRpQCT. Mean age was similar among groups. Mean BMI was 17.7 ± 2.1 vs 22.6 ± 1.4 vs 35.2 ± 3.2 kg/m2 (p<0.0001). Mean aBMD Z-scores were lowest in AN, intermediate in HC and highest in OB (PA spine -1.6 ± 1.3 vs -0.5 ± 0.8 vs 0.5 ± 0.8; total hip -1.0 ± 1.1 vs 0.2 ± 0.9 vs 1.0 ± 0.9; radius -0.6 ± 1.0 vs 0.1 ± 0.9 vs 0.7 ± 0.9; p<0.0001). At the tibia and radius, mean trabecular vBMD and failure load were lowest in AN, intermediate in HC and highest in OB, while mean trabecular plate bone volume fraction, plate number density and plate-plate junction density were lower in AN (p<0.05) and similar in HC and OB. Mean cortical vBMD and cortical porosity were similar among groups, but cortical thickness was lower in AN vs OB (p<0.01). There was a quadratic relationship between BMI and trabecular vBMD, failure load and all plate parameters (R=0.40-0.67, p<0.0001), such that the higher the BMI, the smaller the increase in these parameters. In contrast, ALM had a consistent positive linear relationship with these parameters (R=0.37-0.78, p<0.0001). IGF-1 levels were positively associated with tibial and radial estimated strength and trabecular structure (R=0.21-0.37, p<0.05). Duration of amenorrhea in AN was negatively associated with radial estimated strength and trabecular structure (R= -0.25- -0.37, p<0.01). Despite similar mean aBMD at all sites, those with a history of fracture (n=57) had lower mean tibial and radial trabecular vBMD and plate-plate junction density; lower mean tibial cortical vBMD, plate bone volume fraction and plate number; and higher mean tibial cortical porosity compared to those without (n=72) (p<0.05). Conclusions: Trabecular bone structure and estimated strength were generally higher with greater weight, but the incremental increase was smaller as BMI increased into the obese range. Cortical bone parameters generally did not increase with greater weight. This suggests that the skeleton in women with obesity may not be able to fully adapt to an increased weight load. Muscle mass and IGF-1 levels were positive, and duration of amenorrhea a negative, determinant of bone structure and estimated strength. Across the weight spectrum, tibial and radial bone structure by HRpQCT may explain differences in peripheral skeletal integrity and fracture risk that cannot be explained by aBMD alone.

Deteriorating subchondral bone microstructure accelerates osteoarthritis progression in developmental dysplasia of the hip than in primary osteoarthritis

Purpose: Developmental dysplasia of the hip (DDH) is recognized as a frequent cause of secondary osteoarthritis (OA). Compared with primary hip OA, DDH often causes changes in the anatomical hip structure and leads to more severe symptoms and imaging manifestations. However, the subchondral bone microstructure and biomechanical property of patients with DDH has not been previously evaluated. Thus, we aimed to analyze the subchondral bone and its association with articular cartilage damage in DDH and primary hip OA through a novel technique for microstructural observation, the individual trabecula segmentation (ITS) analysis. We hypothesized that the changes of subchondral bone in DDH could partly account for the acceleration of OA progression. Methods: Thirty-three femoral head specimens obtained from patients underwent total hip arthroplasty (DDH, n=17; primary OA, n=16) were scanned using Micro-CT, and the selected volume of interest (VOI) was processed by ITS to obtain the microstructural types of subchondral bone. The biomechanical property of VOI was analyzed by micro-finite element analysis (μFEA) and cartilage damage was evaluated by the histology. Moreover, the linear regression analysis was utilized to indicate the association between microstructures, biomechanical property and articular cartilage. Results: Compared with the OA group, the DDH group showed lower total bone volume fractions (BV/TV) and plate bone volume fractions (pBV/TV) by the ITS-based analysis (p<0.05). The plate-to-rod ratio was significantly higher in the OA group than in the DDH group (p<0.05). Remarkably, there were varying degrees of discrepancy between the two groups in pTb.N/rTb.N (plate/rod trabecular number), pTb.Th/rTb.Th (plate/rod trabecular thickness), pTb.S/rTb.L (plate surface area and rod length) and P-P Junc.D/R-R Junc.D/P-R Junc.D (junction density with different trabecular modes). Moreover, the μFEA, histology and linear regression analysis revealed that the subchondral bone in patients with DDH had inferior biomechanical property, and the cartilage damage was severer than patients with OA due to the different subchondral bone microstructures. Conclusions: In this study, our findings detected a less connected, more widely separated trabecular network and deteriorating subchondral bone microstructure in patients with DDH than those with primary OA. The mass and type changes of subchondral bone may contribute to worsening biomechanical property and cartilage damage, thus leading to the acceleration of OA progression in patients with DDH.

Accurate and Efficient Plate and Rod Microfinite Element Models for Whole Bone Segments Based on High-Resolution Peripheral Computed Tomography

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.

Chinese Women in Both the United States and Hong Kong Have Cortical Microstructural Advantages and More Trabecular Plates Compared With White Women.

We cross-sectionally compared racial differences in bone quality between Chinese women in the United States (US) and Hong Kong (HK) with white women. A total of 514 women were included. We measured bone geometry, mass, microstructure, and stiffness by high-resolution peripheral quantitative computed tomography (HR-pQCT), individual trabecula segmentation (ITS), and microfinite element analysis (μFEA). After adjustment for age and body mass index (BMI), premenopausal Chinese women in the US and HK had smaller bone area but greater radial cortical (Ct.) thickness and Ct. and trabecular (Tb.) volumetric bone mineral density (vBMD) versus white women but did not differ from each other. At the radius, Tb. number was lower and spacing greater in Chinese women from HK and the US versus white women, whereas Chinese women did not differ from each other. Tb. thickness was highest in Chinese women from HK, intermediate in Chinese-Americans, and lowest in white women. Chinese women had more trabecular plates versus white women, leading to greater age- and BMI-adjusted stiffness for premenopausal Chinese women in HK and the US (both p < 0.05) versus white women. Tibial differences were similar in premenopausal women; analogous trends in microstructure were present in postmenopausal women at the tibia, although stiffness did not differ. In contrast, at the radius, cortical, plate-to-rod ratio, and stiffness were similar between postmenopausal HK and white women. Adjusting for age, weight, and height rather than age and BMI tended to reduce differences in bone size and Tb. parameters but accentuate cortical differences such that Chinese premenopausal women in both locations and postmenopausal women from HK had higher stiffness at both skeletal sites compared with white women. Compared with white women, Chinese women in the US and HK have vBMD and microstructural advantages leading to higher or similar mechanical competence in pre- and postmenopausal women, respectively, despite smaller bone size.

Trabecular microstructure is influenced by race and sex in Black and White young adults.

Lower fracture rates in Black men and women compared to their White counterparts may be explained by favorable bone microstructure in Black individuals. Individual trabecular segmentation (ITS) analysis, which characterizes the alignment and plate- and rod-like nature of trabecular bone using high-resolution peripheral quantitative computed tomography (HR-pQCT), may provide insight into trabecular differences by race/ethnic origin. We determined differences in trabecular bone microarchitecture, connectivity, and alignment according to race/ethnic origin and sex in young adults. We analyzed HR-pQCT scans of 184 adult (24.2 ± 3.4years) women (n = 51 Black, n = 50 White) and men (n = 34 Black, n = 49 White). We used ANCOVA to compare bone outcomes, and adjusted for age, height, and weight. Overall, the effect of race on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race. After adjusting for covariates, Black participants and men of both races had greater trabecular plate volume fraction, plate thickness, plate number density, plate surface area, and greater axial alignment of trabeculae, leading to higher trabecular bone stiffness compared to White participants and women, respectively (p < 0.05 for all). These findings demonstrate that more favorable bone microarchitecture in Black individuals compared to White individuals and in men compared to women is not unique to the cortical bone compartment. Enhanced plate-like morphology and greater trabecular axial alignment, established in young adulthood, may contribute to the improved bone strength and lower fracture risk in Black versus White individuals and in men compared to women.

Sexual Dimorphism in Cortical and Trabecular Bone Microstructure Appears During Puberty in Chinese Children.

Distal forearm fractures during growth are more common in males than females. Because metaphyseal cortical bone is formed by coalescence of trabeculae emerging from the periphery of the growth plate, we hypothesized that the later onset of puberty in males produces a longer delay in trabecular bone formation and coalescence, which leaves a transient phase of high cortical porosity, low matrix mineral density, and high trabecular density relative to females. We quantified the nondominant distal radial microstructure using high-resolution peripheral quantitative computed tomography in 214 healthy Chinese boys and 219 Chinese girls aged between 7 and 17 years living in Hong Kong. Measurements of 110 slices (9.02 mm) were acquired 5 mm proximal to the growth plate of the nondominant distal radius. Porosity was measured using StrAx1.0 (Straxcorp, Melbourne, VIC, Australia) and trabecular plate and rod structure were measured using individual trabecula segmentation (ITS). Mechanical properties were estimated using finite element analysis (FEA). Results were adjusted for age, total bone cross-sectional area (CSA), dietary calcium intake, and physical activity. In boys, total bone CSA was 17.2% to 22.9% larger throughout puberty, cortical/total bone CSA was 5.1% smaller in Tanner stage 2 only, cortical porosity was 9.4% to 17.5% higher, and matrix mineral density was 1.0% to 2.5% lower in Tanner stage 2 to 5, than girls. Boys had higher trabecular rod BV/TV in Tanner stage 3 and 4, but higher trabecular plate BV/TV and plate to rod ratio in Tanner stage 5, than girls. Boys had 17.0% lower apparent modulus than girls in Tanner stage 2. A transient phase of higher porosity due to dissociation between bone mineral accrual and linear growth may contribute to higher distal radial bone fragility in Chinese boys compared to girls. © 2018 American Society for Bone and Mineral Research.

Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images.

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.