McKay Orthopaedic Research Laboratory > Liu Lab > Research Image Gallery

	Liu XS, Ardeshirpour L, VanHouten JN, Shane E, and Wysolmerski JJ, Site-Specific Changes in Bone Microarchitecture, Mineralization, and Stiffness during Lactation and After Weaning in Mice, Journal of Bone and Mineral Research, doi: 10.1002/jbmr.1503       The goal of this study is to quantify site-specific changes in bone quantity and quality during and after lactation in a mouse model. We found a significant decrease in trabecular plate microarchitecture, tissue mineralization, and whole bone stiffness in lactating versus nulliparous mice at all three sites. In recovered mice, all these different aspects of bone quality were comparable to nulliparous mice at the spine. In contrast, trabecular plate microarchitecture and whole bone stiffness at the tibia and femur in recovered mice were lower than nulliparous mice, as were central trabecular tissue mineralization and cortical structure at the femur.       Figure on the left: representative 3D distribution of tissue mineral density (TMD) of surface (sTMD), central (cTMD), and intervening trabecular bone (mTMD) occupying the envelop between surface and central trabecular bone of the mouse lumbar vertebra L3. TMD increased from surface to center of trabeculae: mean sTMD (yellow), mTMD (orange), and cTMD (red) of nulliparous mice were 767, 969, and 1086 mgHg/cm3, respectively.
	Individual Trabecula Segmentation (ITS)-Based Morphological Analyses and Micro Finite Element Analysis of HR-pQCT Images Discriminate Postmenopausal Fragility Fractures Independent of DXA Measurements, Liu XS, Stein EM, Zhou B, Zhang CA, Nickolas TL, Cohen A, Thomas V, McMahon DJ, Cosman F, Nieves J, Shane E, and Guo XE, Journal of Bone and Mineral Research, doi: 10.1002/jbmr.562. Osteoporosis is typically diagnosed by dual energy x-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). In this study, we demonstrated that HR-pQCT-based ITS and µFEA measurements at the distal radius (Figure Left) and tibia (Figure Right) 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.
	Osteoprogeterin Deficiency Attenuates Strontium-Mediated Inhibition of Osteoclastogenesis and Bone Resorption, Peng SL, Liu XS, Zhou GQ, Li ZY, Keith DKL, Guo XE, and Lu WW, Journal of Bone and Mineral Research, 26(6): 1272-82, 2011       Strontium (Sr) exerts an anabolic and antiresorptive effect on bone, but the mechanism remains unknown. Osteoprotegerin (OPG) expressed by osteoblasts plays an important role in regulating bone homeostasis by inhibiting osteoclastogenesis and bone resorption. This study aims at evaluating the role of OPG in Sr-mediated inhibition of osteoclastogenesis and bone resorption. The findings demonstrate that Sr compound treatment results in greater bone volume and trabecular number than Veh treatment in WT mice. However, the anabolic response of trabecular bone to Sr treatment is attenuated in OPG-KO mice.       Figure on the left: (A) new bone formation with Goldner's trichrome staining in the L4 vertebrae. (B) double calcein labeling in the L4 vertebrae by fluorescence microscopy. There were significant difference in the bone-formation parameter osteoid surface (OS/BS) and bone-formation rate (BFR/BS) between Sr and Veh in WT mice, but not in OPG-KO mice.
	Individual Trabeculae Segmentation (ITS)-Based Morphological Analysis of Micro-Scale Images of Human Tibial Trabecular Bone at Limited Spatial Resolution, Liu XS, Shane E, McMahon DJ, and Guo XE, Journal of Bone and Mineral Research, 26 (9): 2184-93, 2011 Individual trabecula segmentation (ITS), a rigorous model-independent 3D morphological analysis, has been developed to assess trabecular plate and rod microstructure separately based on micro-computed tomographic (µCT) images. We examined the influence of the limited spatial resolution, noise, and artifact of high-resolution peripheral quantitative CT (HR-pQCT) on ITS measurements of human tibial trabecular bone and conclude that ITS measurements of HR-pQCT images are highly reflective of trabecular bone microarchitecture from a biomechanical perspective. Figure on the left shows the 3D reconstruction of whole-bone segment (left) and decomposed trabecular bone subvolume by ITS technique (right) based on registered (Top) µCT and (Bottom) HR-pQCT images of human distal tibiae. Color indicates different individual trabeculae.
	Better Skeletal Microstructure Helps to Explain Lower Fracture Risk among Chinese-American Women versus Caucasian Women, Liu XS, Walker MD, McMahon DJ, Udesky J, Liu G, Bilezikian JP, and Guo XE, Journal of Bone and Mineral Research, 26 (8): 1783-92, 2011       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. Bigger bone size, thinner cortex, and less dense trabecular bone volume of (Top) white compared with (Bottom) Chinese-American women was illustrated by representative 3D cortical and trabecular bone microarchitecture imaged by HR-pQCT. Plate and rod trabecular structure was illustrated by green and red, respectively. Chinese-American women have significantly more platelike trabeculae than white women. 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.
Accuracy of High-Resolution In Vivo Micro Magnetic Resonance Imaging for Measurements of Microstructural and Mechanical Properties of Human Distal Tibial Bone, Liu XS, Zhang XH, Rajapakse CS, Wald MJ, Magland J, Sekhon KK, Adam MF, Sajda P, Wehrli FW, and Guo XE, Journal of Bone Mineral Research,25(9): 2039-50, 2010 Micro magnetic resonance imaging (µMRI) is an in vivo imaging method that permits 3D quantification of cortical and trabecular bone microstructure. µMR images can also be used for building microstructural finite element (µFE) models to assess bone stiffness, which highly correlates with bone's resistance to fractures. In order for µMRI-based microstructural and µFE analyses to become standard clinical tools for assessing bone quality, validation with a current gold standard, namely, high-resolution micro computed tomography (µCT) was performed by obtaining microstructural measurements of 25 human cadaveric distal tibias for the registered µMR (Figure Bottom Row) and µCT images (Figure Top Row), respectively. We conclude that most microstructural and mechanical properties of the distal tibia can be derived efficiently from µMR images and can provide additional information regarding bone quality.
	Individual Trabeculae Segmentation (ITS)-Based Morphological Analyses of High Resolution Peripheral Quantitative Computed Tomography Images Detect Abnormal Trabecular Plate and Rod Microarchitecture in Premenopausal Women with Idiopathic Osteoporosis, Liu XS, Cohen A, Shane E, Stein E, Roger H, Kokolus SL, Yin PT, McMahon DJ, Lappe JM, Recker RR, and Guo XE, Journal of Bone and Mineral Research, 25(7): 1496-505, 2010       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. We found that women with IOP had 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. However, trabecular plate and rod thickness did not differ.
	Bone Density, Geometry, Microstructure and Stiffness: Relationships Between Peripheral and Central Skeletal Sites Assessed by DXA, HR-pQCT, and cQCT in Premenopausal Women, Liu XS, Cohen A, Shane E, Yin PT, Stein EM, Roger H, Kokolus SL, McMahon DJ, Lappe JM, Recker RR, Lang T, and Guo XE, Journal of Bone Mineral Research, 25(10): 2229-38, 2010       High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone at the distal radius and tibia. No studies have investigated the extent to which measurements of the peripheral skeleton by HR-pQCT reflect those of the spine and hip, where the most serious fractures occur. To address this research question, we performed dual-energy X-ray absorptiometry (DXA), central QCT (cQCT), HR-pQCT, and image-based finite-element analyses (FEA) on 69 premenopausal women. The top row of the left figure shows the HR-pQCT images and FEA of the distal tibia and radius; the bottom row shows the cQCT image-based FEA for assessing stiffness of the lumbar vertebra and proximal femur. Our results suggest that bone density and microstructural and mechanical properties measured by HR-pQCT of the distal radius and tibia reflect the mechanical competence of the central skeleton.<
	Effects of trabecular type and orientation on microdamage susceptibility in trabecular bone, Shi X, Liu XS, Wang X, Guo XE, and Niebur GL, Bone 46(5): 1260-6, 2010       In order to address the effects of trabecular type and orientation on trabecular bone damage mechanics, microstructural finite element modeling was used to identify the yielded tissue in ten bovine tibial trabecular bone samples compressed to 1.2% on-axis apparent strain. The yielded tissue was mapped onto individual trabeculae identified by an Individual Trabeculae Segmentation (ITS) technique, and the distribution of the predicted yielding among trabecular types and orientations was compared to the experimentally measured microdamage. Although most of the predicted yielded tissue was found in longitudinal plates (73+/-11%), the measured microcrack density was positively correlated with the proportion of the yielded tissue in longitudinal rods (R2=0.52, p=0.02), but not in rods of other directions or plates. The results suggest that bending or buckling deformations of rod-like trabeculae may make trabecular structures more susceptible to microdamage formation. Moreover, while simple strain-based tissue yield criteria may account for macroscopic yielding, they may not be suitable for identifying damage.
	Contributions of Trabecular Rods of Various Orientations in Determining the Elastic Properties of Human Vertebral Trabecular Bone, Liu XS, Zhang XH, and Guo XE, Bone 45(2): 158-63, 2009       Although trabecular rods represent only a small fraction of total bone volume, their existence has important roles in failure initiation and progression. The results suggested that the loss of transverse rods induced a significant decrease in in-plane mechanical competence, which was greater than what could be explained only by the associated bone volume loss. In contrast, the reduction in the axial Young's modulus caused by the loss of transverse rods was proportional to the bone volume decrease. Furthermore, the loss of longitudinal rods affected the axial Young's modulus through both bone volume loss and architectural change. With aging, the reduction in in-plane mechanical competence would be magnified by the preferential loss of transverse rods. The predictive ability of bone mineral density, a surrogate of BV/TV in clinical measurements, may reduce more quickly for transverse mechanical properties than for the axial mechanical properties.
Micromechanical Analyses of Vertebral Trabecular Bone Based on Individual Trabeculae Segmentation of Plates and Rods, Liu XS, Bevill G, Keaveny TM, Sajda P, and Guo XE, Journal of Biomechanics, 42(3): 249-56, 2009       A longitudinal trabecular plate (top) and a transverse trabecular rod (bottom) under 0.1%, 0.3%, 0.5%, and 0.7% apparent strain. Red indicates local failure under compression and green indicates local failure under tension. The nodal displacement was amplified by a factor of 10. From 0.3% to 1% apparent strain, significantly more longitudinal trabecular plate and transverse rod failed than other types of trabeculae. While failure initiates at rods and rods fail disproportionally to their number, plates contribute significantly to the apparent yield strength because of their larger number and tissue volume. The relative failed number and tissue fraction at apparent yield point indicate homogeneous local failure in plates and rods of different orientations.
	Dynamic Simulation of Three Dimensional Architectural and Mechanical Alterations in Human Trabecular Bone during Menopause, Liu XS, Huang AH, Zhang XH, Sajda P, and Guo XE, Bone, 43(2): 292-301, 2008       A three dimensional (3D) computational simulation of dynamic process of trabecular bone remodeling was developed with all the parameters derived from physiological and clinical data to study the trabecular bone changes during menopause. Figure on the left shows a simulation of a vertebral trabecular bone sample at a) 5 Years before and b) 0 c) 5 d) 10 years after menopause.  Note the perforation of trabeculae in the insets and the breakage and disconnection of trabeculae in the circle. The dynamic bone remodeling simulation predicted the time course of menopausal bone loss pattern of spine and femur. Microstructural plate perforation could be the primary cause of menopausal trabecular bone loss. The combined effect of trabeculae perforation, breakage, and isolated fragments resulted in fewer and smaller trabecular plates and more but thinner trabecular rods.
	Complete Volumetric Decomposition of Individual Trabecular Plates and Rods and Its Morphological Correlations with Anisotropic Elastic Moduli in Human Trabecular Bone, Liu XS, Sajda P, Saha, PK, Wehrli FW, Bevill G, Keaveny TM, and Guo XE, Journal of Bone and Mineral Research, 23(2): 223-35, 2008       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 individual trabecula segmentation (ITS)-based morphological analyses better characterize microarchitecture and help predict anisotropic mechanical properties of trabecular bone.       Figure on the left shows the results of the complete volumetric decomposition procedure on image of vertebral trabecular bone sample (. (A) An original image of a trabecular bone sample. (B) Results of skeletonization and topological classification of A. (C) Results of arc-skeletonization and topological classification of B. (D) Results of the decomposition of C. (E) Intermediate result of reconstruction to B. (F) Result of complete reconstruction to A. Colors indicate different branches in D.
	Quantification of the Roles of Trabecular Microarchitecture and Trabecular Type in Determining the Elastic Modulus of Human Trabecular Bone, Liu XS, Sajda P, Saha, PK, Wehrli FW, and Guo XE, Journal of Bone and Mineral Research, 21(10): 1608-17, 2006       A new topology preserving skeletonization and classification technique combined with micro computed tomography (µCT) image based finite element (FE) model was used to study the roles of microarchitecture and types of trabeculae in determining elastic modulus of trabecular bone The unique feature of this technique is the preservation of topological properties (rod-like and plate-like structures, connectivities and cavities) while without maintaining bone volume fraction. The results suggest that trabecular plates play an essential role in determining elastic properties of trabecular bone.