Skeletal Structure in Postmenopausal Women With Osteopenia and Fractures Is Characterized by Abnormal Trabecular Plates and Cortical Thinning

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity. Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius. In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls, despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia. © 2014 American Society for Bone and Mineral Research.     

Distinct Tissue Mineral Density in Plate‐ and Rod‐like Trabeculae of Human Trabecular Bone

Trabecular bone quality includes both microstructural and intrinsic tissue mineralization properties. However, the tissue mineralization in individual trabeculae of different trabecular types and orientations has not yet been investigated. The aim of this study was to develop an individual trabecula mineralization (ITM) analysis technique to determine tissue mineral density (TMD) distributions in plate‐ and rod‐like trabeculae, respectively, and to compare the TMD of trabeculae along various orientations in micro–computed tomography (μCT) images of trabecular bone samples from the femoral neck, greater trochanter, and proximal tibia. ITM analyses indicated that trabecular plates, on average, had significantly higher TMD than trabecular rods. In addition, the distribution of TMD in trabecular plates depended on trabecular orientation with the lowest TMD in longitudinal plates and the highest TMD in transverse plates. Conversely, there was a relatively uniform distribution of TMD among trabecular rods, with respect to trabecular orientation. Further analyses of TMD distribution revealed that trabecular plates had higher mean and peak TMD, whereas trabecular rods had a wider TMD distribution and a larger portion of low mineralized trabeculae. Comparison of apparent Young's moduli derived from micro–finite element models with and without heterogeneous TMD demonstrated that heterogeneous TMD in trabecular plates had a significant influence on the elastic mechanical property of trabecular bone. In conclusion, this study revealed differences in TMD between plate‐ and rod‐like trabeculae and among various trabecular orientations. The observation of less mineralized longitudinal trabecular plates suggests interesting implications of these load‐bearing plates in bone remodeling. The newly developed ITM analysis can be a valuable technique to assess the influence of metabolic bone diseases and their pharmaceutical treatments on not only microstructure of trabecular bone but also the microarchitectural heterogeneity of tissue mineralization. © 2015 American Society for Bone and Mineral Research.     

Differences in Macro‐ and Microarchitecture of the Appendicular Skeleton in Young Chinese and White Women

To identify the racial differences in macro‐ and microstructure of the distal radius and tibia that may account for the lower fracture rates in Asians than whites, we studied 61 healthy premenopausal Chinese and 111 white women 18–45 yr of age using high‐resolution pQCT (HR‐pQCT). The Chinese were shorter and leaner. Distal radius total cross‐sectional area (CSA) was 14.3% smaller in Chinese because of an 18.0% smaller trabecular area (p < 0.001). Cortical thickness was 8.8% greater in the Chinese, but cortical area was no different. Total volumetric BMD (vBMD) was 10.3% higher in the Chinese because of the 8.8% higher cortical thickness and 2.8% greater cortical density (all p < 0.01). Trabecular vBMD and bone volume/tissue volume (BV/TV) did not differ by race because trabeculae were 7.0% fewer but 10.8% thicker in Chinese than whites (both p < 0.01). Similar results were found at the distal tibia. Lower fracture risk in Chinese women may be partly caused by thicker cortices and trabeculae in a smaller bone‐more bone within the bone than in whites.     

Better skeletal microstructure confers greater mechanical advantages in Chinese‐American women versus white women

Despite lower areal bone mineral density (aBMD), Chinese‐American women have fewer fractures than white women. We hypothesized that better skeletal microstructure in Chinese‐American women in part could account for this paradox. Individual trabecula segmentation (ITS), a novel image‐analysis technique, and micro–finite‐element analysis (µFEA) were applied to high‐resolution peripheral quantitative computed tomography (HR‐pQCT) images to determine bone microarchitecture and strength in premenopausal Chinese‐American and white women. Chinese‐American women had 95% and 80% higher plate bone volume fraction at the distal radius and tibia, respectively, as well as 20% and 18% higher plate number density compared with white women (p < .001). With similar rodlike characteristics, the plate‐to‐rod ratio was twice as high in the Chinese‐American than in white trabecular bone (p < .001). Plate‐rod junction density, a parameter indicating trabecular network connections, was 37% and 29% greater at the distal radius and tibia, respectively, in Chinese‐American women (p < .002). Moreover, the orientation of the trabecular bone network was more axially aligned in Chinese‐American women because axial bone volume fraction was 51% and 32% higher at the distal radius and tibia, respectively, than in white women (p < .001). These striking differences in trabecular bone microstructure translated into 55% to 68% (distal radius, p < .001) and 29% to 43% (distal tibia, p < .01) greater trabecular bone strength, as assessed by Young's moduli, in the Chinese‐American versus the white group. The observation that Chinese‐American women have a major microstructural advantage over white women may help to explain why their risk of fracture is lower despite their lower BMD. © 2011 American Society for Bone and Mineral Research     

Premenopausal and postmenopausal differences in bone microstructure and mechanical competence in Chinese‐American and white women

Compared to white women, premenopausal Chinese‐American women have more plate‐like trabecular (Tb) bone. It is unclear whether these findings are relevant to postmenopausal women and if there are racial differences in the deterioration of bone microarchitecture with aging. We applied individual trabecula segmentation and finite element analysis to high‐resolution peripheral quantitative computed tomography images in premenopausal and postmenopausal Chinese‐American and white women to quantify within‐race age‐related differences in Tb plate‐versus‐rod microarchitecture and bone stiffness. Race–menopause status interactions were assessed. Comparisons between races within menopause status were adjusted for age, height and weight. Comparisons between premenopausal and postmenopausal women were adjusted for height and weight. Adjusted analyses at the radius indicated that premenopausal Chinese‐Americans had a higher plate bone volume fraction (pBV/TV), Tb plate‐to‐rod ratio (P‐R ratio), and greater plate‐plate junction densities (P‐P Junc.D) versus white women (all p < 0.01), resulting in 27% higher Tb stiffness (p < 0.05). Greater cortical thickness and density (Ct.Th and Dcort) and more Tb plates led to 19% greater whole bone stiffness (p < 0.05). Postmenopausal Chinese‐Americans had similar pBV/TV and P‐P Junc.D, yet a higher P‐R ratio versus white women. Postmenopausal Chinese‐American versus white women had greater Ct.Th, Dcort, and relatively intact Tb plates, resulting in similar Tb stiffness but 12% greater whole bone stiffness (p < 0.05). In both races, Ct.Th and Dcort were lower in postmenopausal versus premenopausal women and there were no differences between races. Tb plate parameters were also lower in postmenopausal versus premenopausal women, but age‐related differences in pBV/TV, P‐R ratio, and P‐P Junc D were greater (p < 0.05) in Chinese‐Americans versus white women. There are advantages in cortical and Tb bone in premenopausal Chinese‐American women. Within‐race cross‐sectional differences between premenopausal and postmenopausal women suggest greater loss of plate‐like Tb bone with aging in Chinese‐Americans, though thicker cortices and more plate‐like Tb bone persists.     

Individual trabeculae segmentation (ITS)–based morphological analysis of high‐resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis

Idiopathic osteoporosis (IOP) in premenopausal women is a poorly understood entity in which otherwise healthy women have low‐trauma fracture or very low bone mineral density (BMD). In this study, we applied individual trabeculae segmentation (ITS)–based morphological analysis to high‐resolution peripheral quantitative computed tomography (HR‐pQCT) images of the distal radius and distal tibia to gain greater insight into skeletal microarchitecture in premenopausal women with IOP. HR‐pQCT scans were performed for 26 normal control individuals and 31 women with IOP. A cubic subvolume was extracted from the trabecular bone compartment and subjected to ITS‐based analysis. Three Young's moduli and three shear moduli were calculated by micro–finite element (µFE) analysis. ITS‐based morphological analysis of HR‐pQCT images detected significantly decreased trabecular plate and rod bone volume fraction and number, decreased axial bone volume fraction in the longitudinal axis, increased rod length, and decreased rod‐to‐rod, plate‐to‐rod, and plate‐to‐plate junction densities at the distal radius and distal tibia in women with IOP. However, trabecular plate and rod thickness did not differ. A more rod‐like trabecular microstructure was found in the distal radius, but not in the distal tibia. Most ITS measurements contributed significantly to the elastic moduli of trabecular bone independent of bone volume fraction (BV/TV). At a fixed BV/TV, plate‐like trabeculae contributed positively to the mechanical properties of trabecular bone. The results suggest that ITS‐based morphological analysis of HR‐pQCT images is a sensitive and promising clinical tool for the investigation of trabecular bone microstructure in human studies of osteoporosis. © 2010 American Society for Bone and Mineral Research     

Race and ethnic variation in proximal femur structure and BMD among older men.

Femoral neck dimensions and vBMD from QCT were compared among 3,305 black, Asian, Hispanic, and white men >or=65 yr of age. All had similar stature-adjusted mean femoral neck volume, but black and Asian men had thicker cortices and higher trabecular vBMD, which may increase bone strength. INTRODUCTION: Hip fracture rates among elderly U.S. black and Asian men are lower than rates among white men. Structural characteristics or volumetric BMD (vBMD), which confer advantages for femoral neck bone strength, may vary by race/ethnicity. However, this topic has not been studied in detail. MATERIALS AND METHODS: In a cross-sectional study, dimensions and vBMD in the femoral neck and shaft were obtained from QCT scans among 3,305 men >or=65 yr of age in the Osteoporotic Fractures in Men (MrOS) study. Femoral neck measures were cross-sectional area; integral, cortical, and medullary volumes and integral, cortical, and trabecular vBMD. Shaft measures were cross-sectional, cortical, and medullary areas and cortical vBMD. Self-reported race/ethnicity was classified as black, Asian, Hispanic, or white. We used multivariable linear regression models with adjustment for age, height, and body mass index to compare means of the outcome measures in black, Asian, and Hispanic men to those in whites. RESULTS: All groups had similar femoral neck integral volume. Among black and Asian men, mean cortical volume as a percent of integral volume was 6% greater, integral vBMD was 6-10% greater, and trabecular vBMD was 33-36% greater than means among whites. Shaft cross-sectional area was similar among blacks, but smaller among Asians, compared with whites. However, mean shaft cortical area was greater among blacks but similar among Asians and whites, resulting in mean cortical thickness being 5% greater among black and Asian men. Blacks also had greater mean cortical vBMD in both the femoral neck and shaft. CONCLUSIONS: Black and Asian men >or=65 yr of age have features in the proximal femur that may confer advantages for bone strength. Specifically, greater cortical thickness and higher trabecular vBMD among black and Asian men could help explain the lower hip fracture rates in these populations. Discerning the mechanisms underlying these differences could provide advances for the prevention and treatment of osteoporosis.     

Trabecular bone deficits among Vietnamese immigrants

Summary  

Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels.     

Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements

Osteoporosis is typically diagnosed by dual-energy X-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabecula segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by microfinite element analysis (μFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip, and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number, and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number, and connectivity were directly associated with bone stiffness. In contrast, rod volume, number, and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and μFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and μFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women.     

Differences in bone microarchitecture between postmenopausal Chinese‐American and white women

Chinese‐American women have lower rates of hip and forearm fracture than white women despite lower areal bone density (aBMD) by dual X‐ray absorptiometry (DXA). We recently reported higher trabecular (D_trab) and cortical (D_comp) bone density as well as greater trabecular (Tb.Th) and cortical thickness (C.Th) but smaller bone area (CSA), as measured by high‐resolution peripheral quantitative computed tomography (HR‐pQCT), in premenopausal Chinese‐American compared with white women. These findings may help to account for the lower fracture rate among Chinese‐American women but were limited to measurements in premenopausal women. This study was designed to extend these investigations to postmenopausal Chinese‐American (n = 29) and white (n = 68) women. Radius CSA was 10% smaller in the Chinese‐American versus the white group (p = .008), whereas their C.Th and D_comp values were 18% and 6% greater (p < .001 for both). Tibial HR‐pQCT results for cortical bone were similar to the radius, but Tb.Th was 11% greater in Chinese‐American versus white women (p = .007). Tibial trabecular number and spacing were 17% lower and 20% greater, respectively, in Chinese‐American women (p < .0001 for both). There were no differences in trabecular or whole‐bone stiffness estimated by microstructural finite‐element analysis, but Chinese‐American women had a greater percentage of load carried by the cortical bone compartment at the distal radius and tibia. There was no difference in load distribution at the proximal radius or tibia. Whole‐bone finite‐element analysis may indicate that the thicker, more dense cortical bone and thicker trabeculae in postmenopausal Chinese‐American women compensate for fewer trabeculae and smaller bone size. © 2011 American Society for Bone and Mineral Research.     

Differences in skeletal microarchitecture and strength in African‐American and white women

African‐American women have a lower risk of fracture than white women, and this difference is only partially explained by differences in dual‐energy X‐ray absorptiometry (DXA) areal bone mineral density (aBMD). Little is known about racial differences in skeletal microarchitecture and the consequences for bone strength. To evaluate potential factors underlying this racial difference in fracture rates, we used high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to assess cortical and trabecular bone microarchitecture and estimate bone strength using micro–finite element analysis (µFEA) in African‐American (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation (SWAN). African‐American women had larger and denser bones than whites, with greater total area, aBMD, and total volumetric BMD (vBMD) at the radius and tibia metaphysis (p < 0.05 for all). African‐Americans had greater trabecular vBMD at the radius, but higher cortical vBMD at the tibia. Cortical microarchitecture tended to show the most pronounced racial differences, with higher cortical area, thickness, and volumes in African‐Americans at both skeletal sites (p < 0.05 for all), and lower cortical porosity in African‐Americans at the tibia (p < 0.05). African‐American women also had greater estimated bone stiffness and failure load at both the radius and tibia. Differences in skeletal microarchitecture and estimated stiffness and failure load persisted even after adjustment for DXA aBMD. The densitometric and microarchitectural predictors of failure load at the radius and tibia were the same in African‐American and white women. In conclusion, differences in bone microarchitecture and density contribute to greater estimated bone strength in African‐Americans and probably explain, at least in part, the lower fracture risk of African‐American women. © 2013 American Society for Bone and Mineral Research.     

Trabecular bone is more deteriorated in spinal cord injured versus estrogen-free postmenopausal women

The prevalence of osteoporosis is high among postmenopausal women and individuals sustaining a spinal cord injury (SCI). We assessed the effects of estrogen loss and unloading on the trabecular bone of the knee in women. Pre- and postmenopausal ambulatory women (n=17) were compared to pre- and postmenopausal women with SCI (n=20). High-resolution magnetic resonance imaging was used to compare groups on apparent measures of trabecular bone volume, trabecular number, trabecular spacing, and trabecular thickness in the distal femur and proximal tibia, regions with a high proportion of trabecular bone and the most common fracture site for SCI patients. Trabecular bone was deteriorated in women with SCI compared to ambulatory women. SCI groups had fewer, (–19 and –26% less) and thinner trabeculae (–6%) that were spaced further apart (40% and 62% more space between structures) resulting in less trabecular bone volume (–22% and –33%) compared to the ambulatory groups (tibia and femur, respectively). Postmenopausal women with SCI also had 34% greater trabecular spacing in the tibia compared to the 40-year-old premenopausal women with SCI, showing an interaction between unloading and estrogen loss. Middle-aged postmenopausal, ambulatory women, not taking estrogen or medications that affect bone, did not show the deteriorated trabeculae that were evident in women with SCI, nor did they show differences in distal femur and proximal tibia trabeculae compared to a premenopausal group. We conclude that the effect of unloading on bone architecture is greater than that of estrogen loss in middle-aged women.     

Comparisons of trabecular and cortical bone in late adolescent black and white females

Few childhood studies have investigated racial differences in volumetric bone mineral density (vBMD), bone geometry, and bone strength indices measured by three-dimensional bone imaging. The purpose of this study was to compare trabecular and cortical bone parameters at the radius and tibia between late adolescent white and black females using peripheral quantitative computed tomography (QCT). White (n = 25) and black females (n = 25), 18–19 years of age, were pair-matched for age, height, and fat-free soft tissue mass. Peripheral QCT scans were obtained at the 4% (trabecular bone), 20% (cortical bone), and 66% [muscle cross-sectional area (CSA)] sites from the distal metaphyses. Bone strength was determined from vBMD and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength–strain index (SSI; cortical site). Radial SSI was not different between groups; however, blacks had greater radial BSI (P = 0.02) than whites. After adjustment for the longer forearm in blacks, the greater radial BSI in blacks no longer remained. At the tibia, blacks versus whites had greater bone strength at the trabecular and cortical bone sites (BSI, P = 0.03; SSI, P = 0.04, respectively). When controlling for differences in tibial length and muscle CSA, the higher estimates of bone strength persisted in blacks versus whites (BSI, P = 0.01; SSI, P = 0.02). Our data suggest that when differences in body size are considered, late adolescent black versus white females have a stronger bone profile, due to greater bone geometry and vBMD, at the trabecular and cortical regions of the tibia but not at the radius.     

Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women

Typically, in the milder form of primary hyperparathyroidism (PHPT), now seen in most countries, bone density by dual‐energy X‐ray absorptiometry (DXA) and detailed analyses of iliac crest bone biopsies by histomorphometry and micro–computed tomography (µCT) show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and nonvertebral sites is increased in PHPT. Emerging technologies, such as high‐resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro–finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate‐like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate‐rod and plate‐plate junctions at the radius and tibia, and rod‐rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole‐bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment, which may help to account for increased global fracture risk in PHPT. © 2013 American Society for Bone and Mineral Research.     

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

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

Age‐ and Sex‐Related Changes in Bone Microarchitecture and Estimated Strength: A Three‐Year Prospective Study Using HRpQCT

Although projections from cross‐sectional studies have shown that bone loss leading to osteoporosis begins around menopause in women and later in life in men, this has not been examined longitudinally in population‐based studies using high‐resolution technology capable of distinguishing cortical (Ct) and trabecular (Tb) bone microarchitecture. The aim of this 3‐year prospective study was to investigate age‐ and sex‐related changes in bone compartment–specific geometry, volumetric bone mineral density (vBMD), microarchitecture, and estimated strength. The distal radius and tibia were imaged at baseline and after 3 years (median 3.0; range, 2.7 to 3.9 years) using high‐resolution peripheral computed tomography (HRpCT) in an age‐ and sex‐stratified, population‐based, random sample of white men and women (n = 260) aged 21 to 82 years. In general, at the radius and tibia there was a moderate annual increase in cortical thickness (Ct.Th) that seemed to offset the increase in cortical porosity (Ct.Po), resulting in net annual increase in cortical vBMD (Ct.vBMD) in premenopausal women and young men. With advancing age, postmenopausal women displayed significant bone loss with decreased trabecular vBMD (Tb.vBMD) (due to loss of entire trabeculae) and Ct.vBMD (manifested as increase in Ct.Po and decrease in Ct.Th) at the radius, and a decline in Ct.vBMD (with increasing Ct.Po) at the tibia, resulting in loss of estimated bone strength. In contrast, men had a lower rate of bone loss with advancing age with smaller increases in Ct.Po at both the skeletal sites. In summary, the pattern of bone loss in men and women was discrepant, with women losing more bone than men with aging, although with a dominance of cortical over trabecular bone loss at the peripheral sites in both sexes. This conforms to epidemiological evidence that most fractures occurring in old age are predominantly at cortical peripheral sites, with women having a higher incidence of fractures than men at any given age. © 2016 American Society for Bone and Mineral Research.     

Trabecular Plate Loss and Deteriorating Elastic Modulus of Femoral Trabecular Bone in Intertrochanteric Hip Fractures

Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (μCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major microstructural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (μFE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis.     

Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures

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.     

Trabecular and Cortical Microstructure and Fragility of the Distal Radius in Women

Fragility fractures commonly involve metaphyses. The distal radius is assembled with a thin cortex formed by fusion (corticalization) of trabeculae arising from the periphery of the growth plate. Centrally positioned trabeculae reinforce the thin cortex and transfer loads from the joint to the proximal thicker cortical bone. We hypothesized that growth‐ and age‐related deficits in trabecular bone disrupt this frugally assembled microarchitecture, producing bone fragility. The microarchitecture of the distal radius was measured using high‐resolution peripheral quantitative computed tomography in 135 females with distal radial fractures, including 32 girls (aged 7 to 18 years), 35 premenopausal women (aged 18 to 44 years), and 68 postmenopausal women (aged 50 to 76 years). We also studied 240 fracture‐free controls of comparable age and 47 healthy fracture‐free premenopausal mother‐daughter pairs (aged 30 to 55 and 7 to 20 years, respectively). In fracture‐free girls and pre‐ and postmenopausal women, fewer or thinner trabeculae were associated with a smaller and more porous cortical area (r = 0.25 to 0.71 after age, height, and weight adjustment, all p < 0.05). Fewer and thinner trabeculae in daughters were associated with higher cortical porosity in their mothers (r = 0.30 to 0.47, all p < 0.05). Girls and premenopausal and postmenopausal women with forearm fractures had 0.3 to 0.7 standard deviations (SD) fewer or thinner trabeculae and higher cortical porosity than controls in one or more compartment; one SD trait difference conferred odds ratio (95% confidence interval) for fracture ranging from 1.56 (1.01–2.44) to 4.76 (2.86–7.69). Impaired trabecular corticalization during growth, and cortical and trabecular fragmentation during aging, may contribute to the fragility of the distal radius. © 2014 American Society for Bone and Mineral Research.     

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).