Trabecular Bone Microarchitecture Research Articles

Ontogenetic Patterning of Human Subchondral Bone Microarchitecture in the Proximal Tibia.

Simple SummaryThe objective of this study is to explain the subchondral trabecular and the cortical ontogenetic changes that occur in the proximal tibia in both the medial and lateral condylar regions due to differential loadings associated with changing knee joint kinetics and body mass. The differential response of subchondral bone to changing mechanical loads during growth and development serves as a powerful tool to evaluate the significance of mechanical loading on subchondral bone morphology and joint development, and can offer insight into adult morphological variation for joint health.High-resolution computed tomography images were acquired for 31 proximal human tibiae, age 8 to 37.5 years, from Norris Farms #36 cemetery site (A.D. 1300). Morphometric analysis of subchondral cortical and trabecular bone architecture was performed between and within the tibial condyles. Kruskal–Wallis and Wilcoxon signed-rank tests were used to examine the association between region, age, body mass, and each morphometric parameter. The findings indicate that age-related changes in mechanical loading have varied effects on subchondral bone morphology. With age, trabecular microstructure increased in bone volume fraction (p = 0.033) and degree of anisotropy (p = 0.012), and decreased in connectivity density (p = 0.001). In the subchondral cortical plate, there was an increase in thickness (p < 0.001). When comparing condylar regions, only degree of anisotropy differed (p = 0.004) between the medial and lateral condyles. Trabeculae in the medial condyle were more anisotropic than in the lateral region. This research represents an innovative approach to quantifying both cortical and trabecular subchondral bone microarchitecture in archaeological remains.

Utility of micro-CT for dating post-cranial fractures of known post-traumatic ages through 3D measurements of the trabecular inner morphology

Fracture dating is an issue at the forefront of forensic sciences. While dating fracture is crucial to understanding and verifying the chronology of events in cases of abuse and violent death, its application is the subject of considerable discussion in the scientific community, filled with limitations and difficulties. Current methods for fracture dating are mainly based on a qualitative assessment through macroscopy, microscopy, and imaging and subject to variations depending on the experience of the observer. In this paper, we investigated the potential of quantifiable micro-CT analysis for fracture dating. Five histomorphometric parameters commonly used for the study of the 3D bone trabecular microarchitecture with micro-CT were calculated based on nine fractures of known post-traumatic ages, including the degree of anisotropy, connectivity density, bone volume fraction, trabecular thickness, and trabecular separation. As a result, trends in the evolution of the microarchitecture of the bone relative to age of the callus could be identified, in particular concerning anisotropy, trabecular separation and connectivity density, consistent with the healing bone process. The findings obtained in this pilot study encourage further research in quantifiable parameters of the bone microarchitecture as they could represent useful features for the construction of objective models for fracture dating.

Relationships between QUS and HR-pQCT, DXA, and bone turnover markers.

Relationship of quantitative ultrasound (QUS) with high-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers was analyzed. The subjects were 480 individuals. Speed of sound (SOS) was measured by calcaneal QUS. Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical bone in the distal radius and tibia were assessed by HR-pQCT. Areal bone mineral density (aBMD) in the lumbar spine and proximal femur were measured by DXA. TRACP-5b, P1NP, 25 (OH) vitamin D, and pentosidine were evaluated by biochemical tests. The correlation of each parameter was analyzed for all subjects and by sex and age group. QUS was moderately correlated with Tb.vBMD and Tb.BV/TV in the radius and tibia. No correlation was seen with Ct.vBMD or cortical porosity (Ct.Po). Although a correlation was seen with cortical thickness (Ct.Th) in the tibia in all subjects, no correlation was seen in women aged ≥ 60years. QUS showed moderate correlations with aBMD in the proximal femur. Although moderate correlation was seen with aBMD in the lumbar spine in all subjects, no correlation was seen in subjects aged ≥ 60years. No significant correlations were seen between QUS and biochemical markers. Moderate correlations were seen between QUS and Tb.vBMD and microarchitecture in the radius and tibia and aBMD of the proximal femur. On the other hand, practically no correlations were seen with Ct.vBMD or Ct.Po and the bone-related biochemical markers. Only in middle age, moderate correlations were seen with Ct.Th in the tibia and with aBMD of the lumbar spine.

Effects of Total Flavonoids of Epimedium on Bone Marrow Adipose Tissue in Ovariectomized Rats.

Bone marrow adipose tissue has brown fat characteristics. Several studies have demonstrated that total flavonoids of Epimedium (TFE) could prevent bone loss and reduce the white adiposity in bone marrow induced by ovariectomy (OVX) in rats. However, the effects of TFE on marrow brown fat in OVX rats remain unclear. In this word, we addressed this question expected to provide a new target for preventing and treating osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were equally divided into Sham controls, OVX controls, and OVX treated with TFE. Chemical shift coding magnetic resonance was performed to detect marrow fat fraction at the left femur at baseline, 6 and 12 weeks post-OVX. Bone mineral density at the lumbar spine and femur was measured by dual-energy x-ray absorptiometry. Serum bone biomarkers by ELISA, trabecular bone microarchitecture at the proximal tibia by micro-CT, quantitative parameters of marrow adipocyte by hematoxylin, and eosin staining were evaluated. The marrow adipocyte gene and protein expressions profile were determined by real-time quantitative PCR and immunostaining in whole tibiae. We found that TFE treatment could decrease bone turnover rate and improved bone mineral density and trabecular microarchitecture in OVX rats. OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARγ2 and FABP4. These pathological changes induced by estrogen deficiency were restored by TFE treatment. TFE also increased brown adipocyte expressions of the transcription factor Ucp1 and Prdm16 in whole tibiae. There was no detectible protein expression of brown adipocyte markers in the proximal tibia. Taken together, TFE regulation of bone marrow adiposity in OVX rats is mediated, at least in part, via maintaining the reciprocity of white and brown adipose tissue.

S-allylmercapto-N-acetylcysteine protects bone cells from oxidation and improves femur microarchitecture in healthy and diabetic mice.

Oxidative stress is involved in the deterioration of bone quality and mechanical strength in both diabetic and aging adults. Therefore, we studied the ability of the antioxidant compound, S-allylmercapto-N-acetylcysteine (ASSNAC) to protect bone marrow stromal cells (BMSCs) from advanced glycation end-products (AGEs) cytotoxicity and improve bone microarchitecture of adult healthy and obese/diabetic (db/db) female mice. ASSNAC effect on AGEs-treated cultured rat BMSCs was evaluated by Neutral Red and XTT cell survival and reactive oxygen species (ROS) level assays. Its effect on healthy (C57BL/6) and obese/diabetic (C57BLKS/J Leprdb+/+; db/db) female mice femur parameters, such as (1) number of adherent BMSCs, (2) percentage of CD73+/CD45- cells in bone marrow (BM), (3) glutathione level in BM cells, and (4) femur microarchitecture parameters by microcomputed tomography, was studied. ASSNAC treatment protected BMSCs by significantly decreasing AGEs-induced ROS production and increasing their cellular resistance to the cytotoxic effect of AGEs. ASSNAC treatment of healthy female mice (50 mg/kg/day; i.p.; age 12-20 weeks) significantly increased the number of BMSCs (+60%), CD73+/CD45- cells (+134%), and glutathione level (+110%) in the femur bone marrow. Furthermore, it increased the femur length (+3%), cortical diameter (+3%), and cortical areal moment of inertia (Ct.MOI; +10%) a surrogate for biomechanical strength. In db/db mice that demonstrated a compromised trabecular bone and growth plate microarchitecture, ASSNAC treatment restored the trabecular number (Tb.N, +29%), bone volume fraction (Tb.BV/TV, +130%), and growth plate primary spongiosa volumetric bone mineral density (PS-vBMD, +7%) and thickness (PS-Th, +18%). In conclusion, this study demonstrates that ASSNAC protects bone marrow cells from oxidative stress and may improve bone microarchitecture in adult healthy and diabetic female mice.

Moderate-Intensity Exercise Preserves Bone Mineral Density and Improves Femoral Trabecular Bone Microarchitecture in Middle-Aged Mice.

BackgroundAging leads to significant bone loss and elevated osteoporosis risk. Exercise slows age-related bone loss; however, the effects of various moderate-intensity exercise training volumes on bone metabolism remain unclear. This study aimed to determine the degree to which different volumes of moderate-intensity aerobic exercise training influence bone mineral density (BMD), bone mineral content (BMC), femoral trabecular bone microarchitecture, and cortical bone in middle-aged mice.MethodsTwenty middle-aged male C57BL/6 mice were randomly assigned 8 weeks of either (1) non-exercise (CON); (2) moderate-intensity with high-volume exercise (EX_MHV); or (3) moderate-intensity with low-volume exercise (EX_MLV) (N=6–7, respectively). Femoral BMD and BMC were evaluated using dual energy X-ray absorptiometry, and trabecular and cortical bone were measured using micro-computed tomography.ResultsFemoral BMD in EX_MHV but not EX_MLV was significantly higher (P<0.05) than in CON. The distal femoral fractional trabecular bone volume/tissue volume (BV/TV, %) was significantly higher (P<0.05) in both EX_MHV and EX_MLV than in CON mice. Increased BV/TV was induced by significantly increased trabecular thickness (mm) and tended to be higher (P<0.10) in BV (mm3) and lower in trabecular separation (mm) in EX_MHV and EX_MLV than in CON. The femoral mid-diaphysis cortical bone was stronger in EX_MLV than EX_MHV.ConclusionsLong-term moderate-intensity aerobic exercise with low to high volumes can be thought to have a positive effect on hindlimb BMD and attenuate age-associated trabecular bone loss in the femur. Moderate-intensity aerobic exercise may be an effective and applicable exercise regimen to prevent age-related loss of BMD and BV.

Effects of Korean red ginseng on three-dimensional trabecular bone microarchitecture and strength in growing rats: Comparison with changes due to jump exercise.

The preventive effects of Korean red ginseng (KRG) on bone loss and microarchitectural deterioration have been extensively studied in animal models. However, few results have been reported for the effects of KRG on the trabecular microarchitecture as compared to changes resulting from physiological stimuli such as exercise load. We compared the effects of KRG and jump exercise on improvements in trabecular microarchitecture and strength of the distal femoral metaphysis in rats. Eleven-week-old male Wistar rats were divided into sedentary (CON), KRG-administered (KRG), and jump-exercised (JUM) groups. Rats were orally administered KRG extract (200 mg/kg body weight/day) once a day for 6 weeks. The jump exercise protocol comprised 10 jumps/day, 5 days/week at a jump height of 40 cm. We used microcomputed tomography to assess the microarchitecture, volumetric bone mineral density (vBMD), and fracture load as predicted by finite element analysis at the right distal femoral metaphysis. The left femur was used for the quantitative bone histomorphometry measurements. Although KRG produced significantly higher trabecular bone volume (BV/TV) than CON, BV/TV was even higher in JUM than in KRG, and differences in vBMD and fracture load were only significant between JUM and CON. In terms of trabecular microarchitecture, KRG increased trabecular number and connectivity, whereas the JUM group showed increased trabecular thickness. Bone resorption showed significant decrease by JUM and KRG group. In contrast, bone formation showed significant increase by JUM group. These data show that KRG has weak but significant positive effects on bone mass and suggest that the effects on trabecular microarchitecture differ from those of jump exercise. The effects of combined KRG and jump exercise on trabecular bone mass and strength should be investigated.

The Influence of Low Energy Availability on Bone Mineral Density and Trabecular Bone Microarchitecture of Pubescent Female Athletes: A Preliminary Study.

The influence of low energy availability (LEA) on bone mineral density (BMD) and trabecular bone microarchitecture in pubescent female athletes is unclear. This study aimed to investigate the influence of LEA on BMD and trabecular bone microarchitecture in 21 pubescent female athletes (age, 12–15 years; 11 track and field athletes, 10 gymnasts). We used two indices to assess LEA: energy availability and the percent of ideal body weight. Dual-energy X-ray absorptiometry was used to obtain total body less head, lumbar spine BMD Z-scores, and lumbar trabecular bone scores (TBS). Pearson’s or Spearman’s correlation coefficients were used to assess the relationship among EA, percent of ideal body weight, and bone parameters. The threshold for statistical significance was set at p < 0.05. The percent of ideal body weight was significantly correlated with the BMD Z-scores of the total body less head (r = 0.61; p < 0.01), lumbar spine (r = 0.55; p < 0.01), and lumbar TBS (r = 0.47; p = 0.03). However, energy availability was not correlated with bone parameters. These findings suggest that screening for low ideal body weight may be a useful predictor of low BMD and insufficient trabecular bone microarchitecture in pubescent female athletes.

Probability-based approach for characterization of microarchitecture and its effect on elastic properties of trabecular bone

Trabecular bone is a random cellular solid with an interconnected network of plate-like and rod-like components. However, the structural randomness and complexity have hindered rigorous mathematical modeling of trabecular bone microarchitecture. Recent advancements in imaging processing techniques have enabled us to define the size, orientation, and spatial location of individual trabecular plates and rods in trabecular bone. Based on the essential information, this study proposed a probability-based approach to define the size, orientation, and spatial distributions of trabecular plates and rods for trabecular bone cubes (N = 547) acquired from six human cadaver proximal femurs. Using two groups of probability-based parameters, it was attempted to capture microarchitectural details, which could not be captured by the existing histomorphometric parameters, but crucial to the elastic properties of trabecular bone. The elastic properties of the trabecular bone cubes in three principal axes were estimated using microCT based finite element (FE) simulations. Based on the results of multivariate multiple regression modeling, the efficacy of the two groups of probability-based parameters in prediction of the elastic properties was verified in comparison with that of the existing histomorphometric parameters (BV/TV, Tb.Th, Tb.Sp, DA, EF.Med, and Conn.D). The results indicated that the regression models trained using the probability-based parameters had a comparable and even better accuracy (rMSE = 0.621 and 0.548) than that of the histomorphometric parameters (rMSE = 0.647). More importantly, the probability-based parameters could provide more insights into some unexplored microarchitectural features, such as individual trabecular size, orientation, and spatial distributions, which are also critical to the elastic properties of trabecular bone.

Trabecular Bone Structural Variation of the Human Distal Tibia, Talus, and Calcaneus

Based on the principles of bone functional adaptation, bone structure has been interpreted as reflective, at least in part, of the mechanical loading environment experienced by an individual during their lifetime. However, the extent to which reduced skeletal robusticity in modern humans over the last 10,000 years is the result of reduced activity and increasing reliance on agricultural subsistence strategies, rather than genetic or environmental factors known to influence skeletal phenotype, is not well understood. The objective of this study is to investigate how bone structure varies between human groups with distinct subsistence strategies, and thus different levels of physical activity and mechanical loading. Here we compare trabecular bone structure in the distal tibia, talus, and calcaneus of three archaeological groups from central and southern Illinois with varying levels of mobility from relatively low mobility mixed strategy agriculturalists to relatively high mobility hunter‐gatherers. High‐resolution CT image data of the distal tibia, talus, and calcaneus was used to quantify trabecular bone microarchitecture variables including bone volume fraction and degree of anisotropy. Bone structural variables are compared between subsistence groups using registered point clouds and Bayesian multilevel modeling to test whether bone structure differs between groups with different inferred mobility and activity levels, but similar population history and environmental context. Results indicate that variation in trabecular bone structure for the distal tibia, talus, and calcaneus support the hypothesis that more highly mobile subsistence groups have greater trabecular robusticity. Investigating the relationship between bone structure variation and differences in activity and mobility is important for understanding the role of behavioral, ecological, and biological factors in determining human skeletal phenotype.

People living with HIV have low trabecular bone mineral density, high bone marrow adiposity, and poor trabecular bone microarchitecture at the proximal femur.

People living with HIV (PLWH) have increased risk of osteoporosis and fractures. However, studies assessing the main determinants of bone strength in the proximal femur exclude this vulnerable population. We assessed the proximal femur of 40 PLWH and 26 age-matched seronegative controls using quantitative computed tomography and magnetic resonance imaging. We examined cortical volumetric bone mineral density (Ct.vBMD), trabecular vBMD (Tb.vBMD), cortical thickness (Ct.Th), bone marrow adiposity (BMA), and trabecular number, separation, and bone volume fraction. Parametric comparisons between the two groups were made for the femoral head, femoral neck, trochanter, and total hip using linear regression adjusting for several covariates, including metrics of body composition. In addition, we investigated the associations of BMA with Tb.vBMD and trabecular microarchitecture with Spearman's rank partial correlations. PLWH had lower Tb.vBMD and deteriorated trabecular microarchitecture in the femoral neck, trochanter and total hip, and elevated BMA in the femoral head, femoral neck, and total hip. Ct.vBMD and Ct.Th were not significantly different between the two groups. BMA was significantly associated with lower Tb.vBMD and deteriorated trabecular microarchitecture in both groups albeit at different femoral regions. Our findings suggest that the trabecular, and not the cortical, compartment is compromised in the proximal femur of PLWH. The observed impairments in fracture-prone regions in PLWH indicate lower femoral strength and suggest higher fracture risk. The inverse associations of BMA with trabecular bone density and microarchitecture quality agree with findings at other anatomic sites and in other populations, suggesting that excess BMA possibly due to a switch from the osteoblast to the adipocyte lineage may be implicated in the pathogenesis of bone fragility at the femur in PLWH.

Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance.

Metabolic bone diseases, such as osteoporosis, typically reflect an increase in the number and activity of bone-resorbing osteoclasts that result in a loss of bone mass. Inflammatory mediators have been identified as drivers of both osteoclast formation and activity. The IL-17 family of inflammatory cytokines has gained attention as important contributors to both bone formation and resorption. The majority of IL-17 cytokines signal through receptor complexes containing IL-17a receptor (IL-17ra); however, the role of IL-17ra signaling in osteoclasts remains elusive. In this study, we conditionally deleted Il17ra in osteoclast precursors using LysM-Cre and evaluated the phenotypes of skeletally mature male and female conditional knockout and control mice. The conditional knockout mice displayed an increase in trabecular bone microarchitecture in both the appendicular and axial skeleton. Assessment of osteoclast formation in vitro revealed that deletion of Il17ra decreased osteoclast number, which was confirmed in vivo using histomorphometry. This phenotype was likely driven by a lower abundance of osteoclast precursors in IL-17ra conditional knockout mice. This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss.

Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study.

Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments. HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs. SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR. The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.

Ethanolic extract from the root and leaf of Sida cordifolia promotes osteoblast activity and prevents ovariectomy-induced bone loss in mice

BackgroundSida cordifolia is traditionally found in the Indian system of medicine, well known for its medicinal and nutritional properties among local natives. PurposeThe present study aims to investigate the osteo-protective effect of root and leaf ethanolic extract of S. cordifolia (RE and LE) and its underlying mechanism. MethodsAntioxidant activity of RE and LE was assessed. Total phenolic and flavonoid content were determined. HPLC profiling of RE and LE was performed to examine the polyphenol content. The effect of RE and LE on osteoblast cells proliferation, differentiation, mineralization, and expression of the protein associated with osteogenesis were evaluated using primary calvarial osteoblast culture. Skeletal effects of RE and LE of S. cordifolia were investigated in C57BL/6J ovariectomized mice. Micro CT was employed to evaluate the alteration in trabecular and cortical bone microarchitecture. Histology studies were performed on the isolated vertebra. qPCR analysis and western blotting was done to check the key bone markers. ResultsRE and LE showed a potent antioxidant activity, owing to a notable polyphenol content. Both RE and LE did not alter the cell viability but significantly increased the osteoblast cell proliferation, differentiation, and mineralization. Moreover, they enhanced the mRNA expression of osteogenic genes. Both RE and LE stimulated the activation of ERK, AKT, and CREB. Both RE and LE had no direct effect on osteoclastogenesis, but both increased Opg/Rankl ratio expression in osteoblast cells. Both RE and LE at 750 mg/kg/day significantly improved the trabecular and cortical microarchitecture of femur and tibia by increasing bone mineral density, bone volume fraction, trabecular number, and trabecular thickness, and decreasing trabecular separation and structural model index in ovariectomized mice. Furthermore, vertebral histology of lumbar vertebrae revealed that RE and LE significantly enhance the vertebral bone mass and exert osteo-protective effects by stimulating osteoblast function and inhibiting osteoclast function. ConclusionIn conclusion, both RE and LE stimulate osteoblast differentiation through activating ERK, AKT, and CREB signalling pathways and indirectly inhibits osteoclast differentiation. RE and LE also improve the trabecular and cortical microarchitecture of ovariectomized mice, making it a promising agent to prevent postmenopausal bone loss.

Trabecular Bone Microarchitecture Improvement Is Associated With Skeletal Nerve Increase Following Aerobic Exercise Training in Middle-Aged Mice.

Advancing age is associated with bone loss and an increased risk of osteoporosis. Exercise training improves bone metabolism and peripheral nerve regeneration, and may play a critical role in osteogenesis and increase in skeletal nerve fiber density. In this study, the potential positive role of aerobic exercise training in bone metabolism and skeletal nerve regeneration was comprehensively evaluated in 14-month-old male C57BL/6 mice. The mice were divided into two groups: no exercise (non-exercise group) and 8-weeks of aerobic exercise training (exercise group), with six mice in each group. Dual-energy X-ray absorptiometry and micro-computed tomography showed that femoral and tibial bone parameters improved after aerobic exercise training. Greater skeletal nerve fiber density was also observed in the distal femoral and proximal tibial periostea, measured and analyzed by immunofluorescence staining and confocal microscopy. Pearson correlation analysis revealed a significant association between skeletal nerve densities and trabecular bone volume/total volume ratios (distal femur; R2 = 0.82, p < 0.05, proximal tibia; R2 = 0.59, p = 0.07) in the exercise group; while in the non-exercise group no significant correlation was found (distal femur; R2 = 0.10, p = 0.54, proximal tibia; R2 = 0.12, p = 0.51). Analysis of archival microarray database confirmed that aerobic exercise training changed the microRNA profiles in the mice femora. The differentially expressed microRNAs reinforce the role of aerobic exercise training in the osteogenic and neurogenic potential of femora and tibiae. In conclusion, 8-weeks of aerobic exercise training positively regulate bone metabolism, an effect that paralleled a significant increase in skeletal nerve fiber density. These findings suggest that aerobic exercise training may have dual utility, both as a direct stimulator of bone remodeling and a positive regulator of skeletal nerve regeneration.

Contemporary kidney transplantation has a limited impact on bone microarchitecture

Bone microarchitecture is an important component of bone quality and disturbances may reduce bone strength and resistance to trauma. Kidney transplant recipients have an excess risk of fractures, and bone loss affecting both trabecular and cortical bone compartments have been demonstrated after kidney transplantation. The primary aim of this study was to investigate the impact of kidney transplantation on trabecular and cortical bone microarchitecture, assessed by histomorphometry and micro computed tomography (μCT). Iliac crest bone biopsies, analyzed by bone histomorphometry and μCT, were performed at time of kidney transplantation and 12 months post-transplantation in an unselected cohort of 30 patients. Biochemical markers of mineral metabolism and bone turnover were measured at both time-points. At 12 months post-transplantation, bone turnover was low in 5 (17%) and normal in 25 (83%) patients. By histomorphometry, bone remodeling normalized, with decreases in eroded perimeters (4.0 to 2.1%, p = 0.02) and number of patients with marrow fibrosis (41 to 0%, p < 0.001). By μCT, trabecular thickness (134 to 125 μM, p = 0.003) decreased slightly. Other parameters of bone volume and microarchitecture, including cortical thickness (729 to 713 μm, p = 0.73) and porosity (10.2 to 9.5%, p = 0.15), remained stable. We conclude that kidney transplantation with current immunosuppressive protocols has a limited impact on bone microarchitecture.

Effects of teriparatide and low-intensity aerobic exercise on osteopenia in type 2 diabetes mellitus rats.

In patients with type 2 diabetes mellitus (T2DM), bone fragility increases fracture risk. Teriparatide (TPTD) improves bone strength, and exercise therapy suppresses blood glucose levels in T2DM. In this study, the combined effects of TPTD and exercise therapy on trabecular and cortical bone were examined in advanced T2DM model rats. Thirty-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into four groups (n = 9-10 in each group at two time points): Cont group (vehicle-treated control), TPTD group (TPTD 30μg/kg injected subcutaneously, 3 times/week), Exe group (treadmill exercise, 10m/min, 60min/day, 5 times/week), and Comb group (TPTD-treated and treadmill exercise combined). Five and 10weeks after treatment, bone mineral density (BMD), bone strength, and bone micro-architecture were measured. TPTD and combined treatment significantly increased BMDs of the lumbar spine and femur compared to the Cont group (p < 0.05 to p < 0.01). In the three-point bending test of the femur, only combined treatment increased the maximum load at 5weeks compared with the Cont and Exe groups (p < 0.01). In the compression test of the distal femoral metaphysis, both TPTD and combined treatment increased the trabecular bone strength compared with the Cont and Exe groups (p < 0.05 to p < 0.01). Although TPTD and combined treatment improved the micro-architecture of trabecular bone (p < 0.05 to p < 0.01), only combined treatment improved the micro-structures of cortical bone from 5weeks of treatment (p < 0.05 to p < 0.01). The combination of TPTD and treadmill exercise increased BMD and trabecular and cortical bone strength of the femur with improved micro-architecture in T2DM model rats.

Investigation of distal femur microarchitecture and factors influencing its deterioration: An ex vivo high-resolution peripheral quantitative computed tomography study.

While fractures of the distal femur are often considered as fragility fractures, detailed knowledge of the bone microarchitecture at this skeletal site is largely unavailable. Initial evaluation of a patient cohort with distal femur fractures showed a markedly increased occurrence in elderly women. The purpose of this study was to determine the extent to which demographic characteristics of distal femur fractures are reflected by general age- and sex-specific variations in local microarchitectural parameters. Fifty cadaveric femora were collected from 25 subjects (12 females, 13 males, age 25-97 years). A volume of interest within 3 cm proximal to the condyles was analyzed using high-resolution peripheral quantitative computed tomography (HR-pQCT), which revealed impaired trabecular and cortical bone microarchitecture in women compared to men as well as in osteoporotic compared to normal or osteopenic subjects, as classified by dual-energy X-ray absorptiometry (DXA) T-score. Linear regression analyzes showed negative associations between age and HR-pQCT parameters in women (e.g., cortical thickness -14 µm/year, 95% CI: -21 to -7 µm/year), but not in men (e.g., cortical thickness 1 µm/year, 95% CI: -12 to 14 µm/year). HR-pQCT parameters showed strong positive associations with areal bone mineral density (aBMD) determined by DXA at the hip in both sexes. Taken together, our findings suggest that female sex, advanced age, and low aBMD represent major risk factors for impaired microarchitecture at the distal femur. Both the diagnostic value of DXA for predicting distal femur fractures and the efficacy of bone-specific agents on fracture risk reduction should be investigated in the future.

Radiografia panorâmica digital como ferramenta de análise da qualidade da microarquitetura óssea trabecular

Abstract Introduction Osteoporosis is a metabolic disease characterized by reduced bone mineral density, often accompanied by loss of quality of trabecular bone microarchitecture. Objective To assess the quality or degradation of trabecular bone microarchitecture in digital panoramic radiography to better predict the risk of fragility fractures. Material and method The sample included 68 female patients, age-matched, and divided into three groups according to densitometric results. Trabecular Bone Score values were measured and digital panoramic radiographs were taken. Fractal analysis with box counting was conducted in the region of premolars and angle of the mandible, with regions of interest measuring 64×64 and 80×120 pixels. In the statistical analysis, Pearson’s correlation was applied between the Trabecular Bone Score and fractal analysis results obtained in each group, using age as a control variable and assigning individualized age ranges within groups. Result A moderate correlation was identified in the regions of interest of 64×64 and 80×120 pixels at the angle of the mandible in the osteoporosis group and in the normal group. A moderate correlation was also obtained using age as a control variable in the 64x64 pixel regions of interest in the premolar region. Considering age range, the within-group analysis presented a strong correlation in the osteoporosis group and moderate correlation in the osteopenia and normal groups. Conclusion Fractal analysis in digital panoramic radiographs was shown to be a promising predictive instrument of bone microarchitecture quality.

Zuogui Wan improves trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats by regulating orexin-A and orexin receptor.

To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model. Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17β-estradiol (E2, 50 μg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17β-estrogen (17β-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis. Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17β-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01). ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.