Trabecular Bone Microarchitecture Research Articles

Tibial cartilage, subchondral bone plate and trabecular bone microarchitecture in varus-and valgus-osteoarthritis versus controls.

This preliminary study quantified tibia cartilage thickness (Cart.Th), subchondral bone plate thickness (SBPl.Th)and subchondral trabecular bone (STB) microarchitecture in subjects with varus- or valgus- malaligned knees diagnosed with end-stage knee osteoarthritis (OA) and compared them to controls (non-OA). Tibial plateaus from 25 subjects with knee-OA (undergoing knee arthroplasty) and 15 cadavers (controls) were micro-CT scanned (17 µm/voxel). Joint alignment was classified radiographically for OA subjects (varus-aligned n = 18, valgus-aligned n = 7). Cart.Th, SBPl.Th, STB bone volume fraction (BV/TV) and their medial-to-lateral ratios were analyzed in anteromedial, anterolateral, posteromedial and posterolateral subregions. Varus-OA and valgus-OA were compared to controls. Compared to controls (1.19-1.54 mm), Cart.Th in varus-OA was significantly lower anteromedially (0.58 mm, -59%) and higher laterally (2.19-2.47 mm,+60-63%); in valgus-OA, Cart.Th was significantly higher posteromedially (1.86 mm,+56%). Control medial-to-lateral Cart.Th ratios were around unity (0.8-1.1), in varus-OA significantly below (0.2-0.6) and in valgus-OA slightly above (1.0-1.3) controls. SBPl.Th and BV/TV were significantly higher medially in varus-OA (0.58-0.72 mm and 37-44%, respectively) and laterally in valgus-OA (0.60-0.61 mm and 32-37%), compared to controls (0.26-0.47 mm and 18-37%). In varus-OA, the medial-to-lateral SBPl.Th and BV/TV ratios were above unity (1.4-2.4) and controls (0.8-2.1); in valgus-OA they were closer to unity (0.8-1.1) and below controls. Varus- and valgus-OA tibia differ significantly from controls in Cart.Th, SBPl.Thand STB microarchitecture depending on joint alignment, suggesting structural changes in OA may reflect differences in medial-to-lateral load distribution upon the tibial plateau. Here we identified an inverse relationship between cartilage thickness and underlying subchondral bone, suggesting a whole-joint response in OA to daily stimuli.

Identification of Novel Genetic Variants Related to Trabecular Bone Score in Community-Dwelling Older Adults.

BackgroundAs the genetic variants of trabecular bone microarchitecture are not well-understood, we performed a genome-wide association study to identify genetic determinants of bone microarchitecture analyzed by trabecular bone score (TBS).MethodsTBS-associated genes were discovered in the Ansung cohort (discovery cohort), a community-based rural cohort in Korea, and then validated in the Gene-Environment Interaction and Phenotype (GENIE) cohort (validation cohort), consisting of subjects who underwent health check-up programs. In the discovery cohort, 2,451 participants were investigated for 1.42 million genotyped and imputed markers.ResultsIn the validation cohort, identified as significant variants were evaluated in 2,733 participants. An intronic variant in iroquois homeobox 3 (IRX3), rs1815994, was significantly associated with TBS in men (P=3.74E-05 in the discovery cohort, P=0.027 in the validation cohort). Another intronic variant in mitogen-activated protein kinase kinase 5 (MAP2K5), rs11630730, was significantly associated with TBS in women (P=3.05E-09 in the discovery cohort, P=0.041 in the validation cohort). Men with the rs1815994 variant and women with the rs11630730 variant had lower TBS and lumbar spine bone mineral density. The detrimental effects of the rs1815994 variant in men and rs11630730 variant in women were also identified in association analysis (β=−0.0281, β=−0.0465, respectively).ConclusionIn this study, the rs1815994 near IRX3 in men and rs11630730 near MAP2K5 in women were associated with deterioration of the bone microarchitecture. It is the first study to determine the association of genetic variants with TBS. Further studies are needed to confirm our findings and identify additional variants contributing to the trabecular bone microarchitecture.

The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development.

N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.

Cadmium exposure negatively affects the microarchitecture of trabecular bone and decreases the density of a subset of sympathetic nerve fibers innervating the developing rat femur.

Cadmium (Cd) is toxic to the skeletal system resulting in bone loss and pain. We aimed at determining the effect of chronic Cd exposure on bone density and microarchitecture along with changes in the density of a subset of sensory and sympathetic nerve fibers innervating the developing rat femur. Newborn male Wistar rats were injected daily for 49 days with CdCl2 (1mg/kg i.p.) or saline solution (control group). At the day of sacrifice, levels of Cd in the right femur, liver and kidney were determined by atomic absorption spectrophotometry. Additionally, microCT followed by immunohistochemical analyses were performed in the left femur. Results showed Cd accumulation in trabecular bone neared levels seen in liver and kidney. Cd concentration in cortical bone was significantly lower versus trabecular bone. MicroCT analysis revealed that Cd-exposed rats had a significant decrease in trabecular bone parameters at the distal femoral metaphysis; however, most of the cortical bone parameters were not significantly affected. Cd-exposed rats showed a significant loss of TH+ sympathetic nerve fibers, but not of CGRP+ sensory nerve fibers, at the level of bone marrow of the femoral diaphysis as compared to control rats. This study shows that Cd negatively affects bone density and microarchitecture of trabecular bone and decreases the density of sympathetic nerve fibers innervating rat femur. Future studies are warranted to determine the toxigenic mechanisms of Cd on sympathetic nerves and how sympathetic denervation influences bone loss in animals exposed to Cd.

Pulsed Electromagnetic Fields Ameliorate Skeletal Deterioration in Bone Mass, Microarchitecture, and Strength by Enhancing Canonical Wnt Signaling-Mediated Bone Formation in Rats with Spinal Cord Injury.

Spinal cord injury (SCI) leads to extensive bone loss and high incidence of low-energy fractures. Pulsed electromagnetic fields (PEMF) treatment, as a non-invasive biophysical technique, has proven to be efficient in promoting osteogenesis. The potential osteoprotective effect and mechanism of PEMF on SCI-related bone deterioration, however, remain unknown. The spinal cord of rats was transected at vertebral level T12 to induce SCI. Thirty rats were assigned to the control, SCI, and SCI+PEMF groups (n = 10). One week after surgery, the SCI+PEMF rats were subjected to PEMF (2.0 mT, 15 Hz, 2 h/day) for eight weeks. Micro-computed tomography results showed that PEMF significantly ameliorated trabecular and cortical bone microarchitecture deterioration induced by SCI. Three-point bending and nanoindentation assays revealed that PEMF significantly improved bone mechanical properties in SCI rats. Serum biomarker and bone histomorphometric analyses demonstrated that PEMF enhanced bone formation, as evidenced by significant increase in serum osteocalcin and P1NP, mineral apposition rate, and osteoblast number on bone surface. The PEMF had no impact, however, on serum bone-resorbing cytokines (TRACP 5b and CTX-1) or osteoclast number on bone surface. The PEMF also attenuated SCI-induced negative changes in osteocyte morphology and osteocyte survival. Moreover, PEMF significantly increased skeletal expression of canonical Wnt ligands (Wnt1 and Wnt10b) and stimulated their downstream p-GSK3β and β-catenin expression in SCI rats. This study demonstrates that PEMF can mitigate the detrimental consequence of SCI on bone quantity/quality, which might be associated with canonical Wnt signaling-mediated bone formation, and reveals that PEMF may be a promising biophysical approach for resisting osteopenia/osteoporosis after SCI in clinics.

Mesenchyme-specific loss of Dot1L histone methyltransferase leads to skeletal dysplasia phenotype in mice.

Chromatin modifying enzymes play essential roles in skeletal development and bone maintenance, and deregulation of epigenetic mechanisms can lead to skeletal growth and malformation disorders. Here, we report a novel skeletal dysplasia phenotype in mice with conditional loss of Disruptor of telomeric silencing 1-like (Dot1L) histone methyltransferase in limb mesenchymal progenitors and downstream descendants. Phenotypic characterizations of mice with Dot1L inactivation by Prrx1-Cre (Dot1L-cKOPrrx1) revealed limb shortening, abnormal bone morphologies, and forelimb dislocations. Our in vivo and in vitro data support a crucial role for Dot1L in regulating growth plate chondrocyte proliferation and differentiation, extracellular matrix production, and secondary ossification center formation. Micro-computed tomography analysis of femurs revealed that partial loss of Dot1L expression is sufficient to impair trabecular bone formation and microarchitecture in young mice. Moreover, RNAseq analysis of Dot1L deficient chondrocytes implicated Dot1L in the regulation of key genes and pathways necessary to promote cell cycle regulation and skeletal growth. Collectively, our data show that early expression of Dot1L in limb mesenchyme provides essential regulatory control of endochondral bone morphology, growth, and stability.

Acrylamide-Induced Prenatal Programming of Bone Structure in Mammal Model

Abstract Acrylamide (AA) is a chemical substance with a potentially carcinogenic effect. Its presence in food or animal food arises from its thermal processing. The experiment was conducted to evaluate the effect of AA exposure (3.0 mg/kg. b.w./day) of pregnant dams during the second half of the pregnancy on bone development in offspring. As an model animal, guinea pig was used. While term body weight of newborns was not influenced by maternal AA treatment, shorter bones with reduced bone diaphysis cross-sectional area were observed in experimental group. Numerous negative, offspring sex-dependent effects of maternal AA exposure were observed in femoral epiphysis and metaphysis as well as the articular and growth plate cartilages. These effects resulted from the AA-induced alterations in bone metabolism, as indicated by the changes in the expression of numerous proteins involved in bone development: receptor activator of nuclear factor kappa-Β ligand (RANKL), tissue inhibitor of metalloproteinases 2 (TIMP-2), bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), and cartilage oligomeric matrix protein (COMP), all of whose expression was measured as well as distribution of immature collagen fibres was determined. Based on the results, it can be concluded that the exposure of pregnant dams to AA negatively affected the structure of compact bone in bone diaphysis, microarchitecture of trabecular bone in metaphysis and epiphysis as well as the structure of the articular and growth plate cartilages in their offspring. The AA-induced bone impairment increased osteoclast differentiation, as observed through the change in the RANKL/OPG ratio, which in turn inhibited osteoblast function by decreasing the expression of other proteins. The data of the present study suggests that maternal AA exposure can result in insufficient bone gain and even bone loss after the birth.

Trabecular bone microarchitecture: A comparative analysis between high field, ultra high field MRI and X-ray micro CT in humans anatomical samples

Trabecular bone microarchitecture: A comparative analysis between high field, ultra high field MRI and X-ray micro CT in humans anatomical samples

Recombinant Human Bone Morphogenetic Protein–2 Improves Spine Fusion in a Vitamin D–Deficient Rat Model

The effects of vitamin D deficiency on spinal fusion are not well studied, nor are approaches to overcoming deficiency-related detrimental effects. The purpose of this study was to (1) evaluate the effects of vitamin D deficiency on spine fusion in a rat model, and (2) determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can improve outcomes in deficient rats. Sprague-Dawley rats were assigned to a vitamin D group: vitamin D sufficient (14), vitamin D deficient (16), vitamin D postoperative rescue (15). Posterolateral fusion was performed at L3-4 and L5-6, with one level receiving rhBMP-2 and the other allograft. Following 6 weeks, the spines were harvested for micro-computed tomography (micro-CT) and histological analyses. Fusion was assessed via manual palpation and micro-CT assessment. Micro-CT images were analyzed for bone microarchitecture in intact L5 vertebral bodies and within fused bone masses treated with rhBMP-2. There were no significant effects of vitamin D status on fusion assessments. However, the microarchitecture of native bone in the intact L5 vertebral bodies of vitamin D-sufficient rats showed significantly greater trabecular thickness (P < .001) and bone volume fraction (P < .001), with decreased trabecular spacing (P < .001), than that of vitamin D-deficient rats. Fusion masses of rhBMP-2 levels also showed significant effects of vitamin D supplementation on both bone volume fraction and trabecular thickness. Histological analysis confirmed that robust bone formation was observed in rhBMP-2-treated fusions, but not in fusion levels treated with allograft. Overall, vitamin D deficiency decreased trabecular bone microarchitecture, and treatment with rhBMP-2 improved outcomes across all vitamin D groups. Given the prevalence of vitamin D deficiency in spine surgery patients, vitamin D supplementation may be a cost-effective method for reducing the risk of pseudoarthrosis.

Beneficial effect of 2’-acetylacteoside on ovariectomized mice via modulating the function of bone resorption

2’-Acetylacteoside-(2’-AA), a bioactive constituent isolated from Cistanche deserticola, has been proven to possess a variety of important pharmacological effects, thus brought an increased amount of scientists’ attention. As the extract of C. deserticola exhibited significant anti-osteoporotic bioactivity in our previous study, we proposed that 2’-AA maybe one of the responsibilities. As a result, 2’-AA (10, 20 and 40 mg/kg body weight/day) exhibited significant anti-osteoporotic effects on ovariectomized (OVX) mice after 12 weeks of oral administration, confirmed by the increased bone mineral density, enhanced bone strength and improved trabecular bone micro-architecture including bone mineral content, tissue mineral content, trabecular number, and trabecular separation of OVX mice. Moreover, the properties of bone resorption markers including cathepsin K, TRAP and deoxypyridinoline were significantly suppressed, whereas the activities of bone formation index like ALP and BGP as well as the weights of the body, uterus, and vagina were seemingly not influenced by 2’-AA intervention. Mechanistically, the above therapeutic effect of 2’-AA on bone resorption of OVX mice operated maybe mainly through RANKL/RANK/TRAF6-mediated NF-κB/NFATc1 pathway, which was confirmed by the down-regulated expressions of RANK, TRAF6, IκB kinase β, NF-κB and NFATc1. Summarily, 2’-AA exhibited significant anti-osteoporotic activity and may be regarded as a promising anti-osteoporotic candidate for future clinical trial.

Optimizing DXA to Assess Skeletal Health: Key Concepts for Clinicians

The diagnosis of osteoporosis and assessment of fracture risk prior to a sentinel fracture was transformed by the widespread clinical use of dual-energy X-ray absorptiometry (DXA) for the assessment of bone mineral density (BMD). This review is based on a collection of primary and review literature gathered from a PubMed search of "dual energy X-ray absorptiometry," "trabecular bone score," and "atypical femur fracture" among other keywords. PubMed searches were supplemented by the authors' prior knowledge of the subject. While uncertainty exists for some aspects of osteoporosis care, patient and clinician familiarity with BMD assessment for screening and monitoring is firmly established. Beyond BMD, lateral spine images obtained with DXA can diagnose osteoporosis and refine fracture risk through the detection of unrecognized vertebral fractures. In addition, analysis of DXA lumbar spine images can reflect changes in trabecular bone microarchitecture, a component of bone "quality" that predicts risk of fracture independent of BMD. Finally, monitoring of bone health by DXA may be extended to include assessment of the femoral cortices for rare but serious adverse effects associated with antiresorptive therapies. Increasing technologic sophistication requires additional consideration for how DXA imaging is performed, interpreted and applied to patient care. As with any test, clinicians must be familiar with DXA performance, pitfalls in analysis, and interpretation within each clinical context in which DXA is applied. With this perspective, care providers will be well positioned to contribute to continuous improvement of DXA performance and, in turn, quality of osteoporosis care.

Pregnancy and Lactation Impair Subchondral Bone Leading to Reduced Rat Supraspinatus Tendon-to-Bone Insertion Site Failure Properties.

Pregnant women experience weight gain, gait changes, and biochemical fluctuations that impair joint function and alter the maternal skeleton. Hormonal changes increase pelvic ligament laxity in preparation for childbirth and affect peripheral joint laxity. Calcium demands also rise during pregnancy and lactation, resulting in reduced bone mineral density (BMD) and maternal bone loss. Altered tendon properties and bone loss during pregnancy and lactation may impact tendon insertion sites, such as rotator cuff tendons where insertion site ruptures are common. However, the effects of pregnancy and lactation at the tendon-to-bone interface have not been investigated. Therefore, the objective of this study was to evaluate supraspinatus tendon mechanical properties and insertion site microstructure during pregnancy, lactation, and postweaning recovery in female rats. We hypothesized that pregnancy and lactation would compromise supraspinatus tendon mechanical properties and subchondral bone microstructure. Female rats were divided into virgin, pregnancy, lactation, and recovery groups, and supraspinatus tendons were mechanically evaluated. Surprisingly, tendon mechanics was unaffected by pregnancy and lactation. However, tendon modulus decreased two-weeks postweaning. Additionally, tendons failed by bony avulsion at the insertion site, and the lactation group exhibited reduced failure properties corresponding to decreased subchondral bone mineralization. Lactation also resulted in dramatic bone loss at the epiphysis, but trabecular bone microarchitecture recovered postweaning. In conclusion, lactation following pregnancy impaired trabecular bone microstructure and subchondral bone mineralization, leading to reduced supraspinatus tendon-to-bone insertion site failure properties. These findings will contribute toward understanding the pathogenesis of tendon-to-bone disorders.

Association between knee alignment, osteoarthritis disease severity, and subchondral trabecular bone microarchitecture in patients with knee osteoarthritis: a cross-sectional study

BackgroundKnee osteoarthritis (OA) is a common disabling disease involving the entire joint tissue, and its onset and progression are affected by many factors. However, the current number of studies investigating the relationship between subchondral trabecular bone (STB), knee alignment, and OA severity is limited. We aimed to investigate the variation in tibial plateau STB microarchitecture in end-stage knee OA patients and their association with knee alignment (hip-knee-ankle, HKA, angle) and OA severity.MethodsSeventy-one knee OA patients scheduled for total knee arthroplasty (TKA) underwent preoperative radiography to measure the HKA angle and Kellgren-Lawrence grade. Tibial plateaus collected from TKA were scanned using micro-computed tomography to analyze the STB microarchitecture. Histological sections were used to assess cartilage degeneration (OARSI score). Correlations between the HKA angle, OA severity (OARSI score, Kellgren-Lawrence grade), and STB microarchitecture were evaluated. Differences in STB microstructural parameters between varus and valgus alignment groups based on the HKA angle were examined.ResultsThe HKA angle was significantly correlated with all STB microarchitecture parameters (p < 0.01). The HKA angle was more correlated with the medial-to-lateral ratios of the microarchitecture parameters than with the medial or lateral tibia plateaus. The HKA angle and all STB microarchitecture parameters are significantly correlated with both the OARSI score and Kellgren-Lawrence grade (p < 0.01).ConclusionsThe STB microarchitecture is associated with the HKA angle and OA severity. With the increase of the knee alignment deviation and OA severity, the STB of the affected side tibial plateau increased in bone volume, trabecular number, and trabecular thickness and decreased in trabecular separation.

Relationship between Skeletal Muscle Mass, Bone Mineral Density, and Trabecular Bone Score in Osteoporotic Vertebral Compression Fractures.

Study DesignA retrospective observational study was performed.PurposeWe investigated the relationships between skeletal muscle mass, bone mineral density (BMD), and trabecular bone score (TBS) in patients with osteoporotic vertebral compression fractures (VCFs).Overview of LiteratureThe TBS has attracted attention as a measurement of trabecular bone microarchitecture. It is derived from data obtained using dual-energy X-ray absorptiometry (DXA) and is a reported indicator of VCFs, and its addition to the Fracture Risk Assessment Tool increases the accuracy of fracture prediction.MethodsBMD, skeletal muscle mass, and TBS were measured in 142 patients who visited Shimoshizu National Hospital from April to August 2019. Patients were divided into a VCF group and a non-VCF group. Whole-body DXA scans were performed to analyze body composition, including appendicular skeletal muscle mass index (SMI; lean mass [kg]/height [m2]) and BMD. The diagnostic criteria for sarcopenia was an appendicular SMI <5.46 kg/m2. A logistic regression analysis was conducted to identify the risk factors for VCFs.ResultsThe significant (p<0.05) findings (VCF group vs. non-VCF group, respectively) included age (79 vs. 70 years), femoral BMD (0.50 vs. 0.58 g/cm2), TBS (1.25 vs. 1.29), and lower limb muscle mass (8.6 vs. 9.9 kg). The VCF group was significantly older and had a lower femur BMD and decreased leg muscle mass than the non-VCF group. Based on the multiple logistic regression analysis, lower femoral BMD and decreased leg muscle mass were identified as risk factors for vertebral fracture independent of age, but the TBS was not.ConclusionsPatients with VCFs had low BMD, a low TBS, and low skeletal muscle mass. Lower femoral BMD and decreased leg muscle mass were identified as risk factors for VCFs independent of age, whereas the TBS was not identified as a risk factor for VCFs.

Associations between bone mineral density, trabecular bone score, and body mass index in postmenopausal females

ObjectivesBone mineral density (BMD), as a gold standard determinant of osteoporosis, assesses only one of many characteristics contributing to the bone. Trabecular bone score (TBS) is applied to evaluate the microarchitecture of trabecular bone. A high body mass index (BMI) has been reported to have a positive correlation with BMD. However, the relation between BMI and TBS has remained unclear. Therefore, the aim of this study is to shed light on the associations between BMI, T-score, and TBS in postmenopausal women without a diagnosed underlying disease. MethodsIn this cross-sectional study, 1054 postmenopausal women were randomly recruited from the Department of Radiology, Isfahan University of Medical Sciences. Demographic characteristics and medical history of all subjects were collected from documents. TBS measurements for L1-L4 vertebrae were retrospectively performed by the TBS iNsight software using the dual X-ray absorptiometry (DXA) from the same region of spine of the subjects. The analysis was done to detect the correlation between TBS and BMI. ResultsA statistically significant negative correlation was found between TBS and BMI in patients with osteoporosis and low bone mass. In patients with normal T-scores, BMI was not significantly correlated to TBS (P > 0.05). Furthermore, there was a significant positive association between T-score and BMI. ConclusionsAlthough a higher BMI had a protective effect against osteoporosis, higher BMI was associated with a lower TBS in patients with an abnormal T-score. However, BMI did not have a significant effect on TBS in patients with normal T-scores.

Bone geometry and microarchitecture deficits in children with Alagille syndrome.

Alagille syndrome (ALGS) is an autosomal dominant disorder attributed to mutations in the Notch signaling pathway. Children with ALGS are at increased risk for fragility fracture of unknown etiology. Our objective was to characterize bone mass, geometry, and microarchitecture in children with ALGS. This was a cross-sectional study of 10 children (9 females), ages 8-18years, with a clinical diagnosis of ALGS. Bone density was assessed via DXA (Hologic Discovery A) at several skeletal regions. Tibia trabecular and cortical bone was assessed via pQCT (Stratec XCT 2000) at the distal 3% and 38% sites, respectively. Tibia bone microarchitecture was assessed via HR-pQCT (Scanco XtremeCT II) at an ultradistal site located at 4% of tibia length and a cortical site at 30% of tibia length. Z-scores were calculated for DXA and pQCT measures. In the absence of XtremeCT II HR-pQCT reference data, these outcome measures were descriptively compared to a sample of healthy children ages 5-20years (n=247). Anthropometrics and labs were also collected. Based on one-sample t-tests, mean Z-scores for height and weight (both p<.05), were significantly less than zero. DXA bone Z-scores were not significantly different from zero, but were highly variable. For pQCT bone measures, Z-scores for total bone mineral content at the distal 3% site and cortical bone mineral content, cortical area, and cortical thickness at the distal 38% site were significantly less than zero (all p<.05). There was good correspondence between pQCT measures of cortical thickness Z-scores and DXA Z-scores for aBMD at the whole body less head, 1/3 radius, and femoral neck (all p<.05). Compared to healthy children, those with ALGS generally had lower trabecular number and greater trabecular separation despite having greater trabecular thickness (measured via HR-pQCT). Bilirubin and bile acids, markers of hepatic cholestasis, were associated with poorer bone measures. For example, greater bilirubin was associated with lower trabecular number (Spearman's rho [ρ]=-0.82, p=.023) and greater trabecular separation (ρ=0.82, p=.023) measured via HR-pQCT, and greater bile acids were associated with lower cortical area measured via pQCT (ρ=-0.78, p=.041) and lower serum insulin-like growth factor-1 (ρ=-0.86, p=.002). In summary, deficits in cortical bone size and trabecular bone microarchitecture were evident in children with ALGS. Further investigation is needed to understand the factors contributing to these skeletal inadequacies, and the manner in which these deficits contribute to increased fracture risk.

Bone Health in Rheumatoid Arthritis: What Can Studies of Bone Microarchitecture Tell Us?

Introduction: Rheumatoid arthritis (RA) is associated with changes in skeletal health, including increased risk of fracture. This study used a novel technique, high-resolution quantitative CT (HRpQCT), to assess bone microarchitecture in patients with RA. Methods: There were 59 patients (female: 41; male: 18) with RA recruited. They underwent dual energy X-ray absorptiometry and HRpQCT of the radius and tibia. The questionnaire information included age, sex, BMI, disease duration, comorbidities, medication use, smoking and alcohol consumption, rheumatoid factor (RF) or cyclic citrullinated peptide (CCP) status, and disease activity. HRpQCT results were compared with published estimated age and sex-specific values. Results: There were 55 patients (female: 39; male: 16) who had either radial or tibial scans available. The mean age was 55.8 (standard deviation [SD]: 12.6) years and median disease duration was 11.4 years (interquartile range [IQR]: 6.3–19.4). Mean BMI was 27.2 (SD: 5.8). Forty-nine (90.7%) participants were RF or CCP positive, with disease severity ranked as severe in 33 (61.1%) patients and moderate in 20 (37.0%). Fifteen participants (27.8%) had previously taken steroids and 47 (85.5%) were receiving tumour necrosis factor inhibitor (TNF-i) medication. Radial trabecular number and density were lower than expected, and trabecular separation was greater than expected (p&lt;0.05), though tibial results were similar (p&lt;0.10 for trabecular number and separation). No difference in cortical values reached statistical significance in this sample. Previous use of steroids was associated with greater radial periosteal circumference (p&lt;0.05, adjusted for sex) and use of TNF-i agents was associated with lower radial total and trabecular area (p&lt;0.05, adjusted for sex). Conclusion: Trabecular bone microarchitecture differences were observed among patients with RA. Further studies with larger numbers of participants are needed.

The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis.

Recent studies showed an increased incidence of vertebral fractures in alcoholic liver cirrhosis (ALC) patients, while data about vertebral micro-structure are still limited. The aim of this study was to compare trabecular and cortical micro-architecture of lumbar vertebrae between ALC patients and healthy age- and sex-matched controls. Our study included lumbar vertebral samples of male cadaveric donors, divided into ALC (n = 20, age: 59 ± 6years) and control group (n = 20, age: 59 ± 8years). Following pathohistological verification of liver cirrhosis, trabecular and cortical bone micro-architecture was analyzed by micro-computed tomography(micro-CT). Micro-CT evaluation of the trabecular bone in lumbar vertebrae showed a significant decrease in bone volume fraction, trabecular thickness, trabecular number, and connectivity (p < 0.01). In contrast to trabecular deterioration, prominent alteration in cortical parameters was not observed in lumbar vertebrae of ALC patients (p > 0.05). Our data indicate that susceptibility to non-traumatic fractures in ALC patients could be explained by alterations in trabecular bone micro-architecture. Thus, we genuinely recommend osteological screening of the lumbar spine for all ALC patients in order to evaluate individual fracture risk. Graphical abstract.

The effect of age on the microarchitecture and profile of gene expression in femoral head and neck bone from patients with osteoarthritis

Ageing of the skeleton is characterised by decreased bone mineral density, reduced strength, and increased risk of fracture. Although it is known that these changes are determined by the activities of bone cells through the processes of bone modelling and remodelling, details of the molecular mechanisms that underlie age-related changes in bone are still missing. Here, we analysed age-related changes in bone microarchitecture along with global gene expression in samples obtained from patients with osteoarthritis (OA). We hypothesised that changes would be evident in both microarchitecture and gene expression and aimed to identify novel molecular mechanisms that underlie ageing processes in bone. Samples of femoral head and neck were obtained from patients undergoing hip arthroplasty for OA, who were either ≤60 years or ≥70 years of age. Bone microarchitecture was analysed in cores of trabecular bone from the femoral head (17 from the younger group and 18 from the older), and cortical bone from the femoral neck (25 younger/22 older), using a Skyscan 1172 microCT scanner (Bruker). Gene expression was compared between the two age groups in 20 trabecular samples from each group, and 10 cortical samples from each group, using Clariom S Human microarrays (ThermoFisher Scientific). We found no significant changes between the two age groups in indices of trabecular or cortical bone microarchitecture. Gene expression analysis identified seven genes that had higher expression in the older group, including the transcription factor EGR1 and the glucose transporter SLC2A3 (GLUT3), and 21 differentially expressed genes in cortical bone samples (P<0.05, fold change>2). However, none of the comparisons of gene expression had false discovery rate-adjusted P<0.1. In contrast to our working hypothesis, we found only minor differences in gene expression and no differences in bone microarchitecture between the two age-groups. It is possible that pathological processes related to OA provide protection against age-related changes in bone. Our study suggests that in patients with OA, the bone properties measured here in femoral head and neck do not deteriorate significantly from the sixth to the eighth decade of life.

Effect of Scanning Resolution on the Prediction of Trabecular Bone Microarchitectures Using Dental Cone Beam Computed Tomography.

Assessing bone quality and quantity at the location of dental implants before dental implantation is crucial. In recent years, dental cone-beam computed tomography (dental CBCT) has often been used to assess bone quality and quantity prior to dental implant. However, the effect of scanning resolution on the prediction of trabecular bone microarchitectural parameters (TBMPs) remains unclear. The objective of this study was to examine how dental CBCT with various scanning resolution differs with regard to predicting TBMPs. This study used micro-computed tomography (micro-CT) with 18 μm resolution and dental CBCT with 100 μm and 150 μm resolutions on 28 fresh bovine vertebrae cancellous bone specimens. Subsequently, all images were input into the ImageJ software to measure four TBMPs: bone volume total volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp). One-way analysis of variance and Tukey’s test were subsequently used to assess the differences between three scanning modes for the four TBMPs. In addition, correlations between measurement results obtained from micro-CT and dental CBCT with two resolutions were measured. The experimental results indicated that significant differences in four TBMPs were observed between micro-CT and dental CBCT (p < 0.05). The correlation coefficients between BV/TV, Tb.N, and Tb.Sp obtained from micro-CT and from dental CBCT with 100 μm resolution (0.840, 0.739, and 0.820, respectively) were greater than the correlation coefficients between BV/TV, Tb.N, and Tb.Sp obtained from micro-CT and from dental CBCT with 150 μm resolution (0.758, 0.367, and 0.724, respectively). The experimental results revealed that the TBMPs measured with dental CBCT with two resolutions differed from ideal values, but a higher resolution could provide more accurate prediction results, particularly for BV/TV, Tb.N, and Tb.Sp.