Analysis Of Bone Microarchitecture Research Articles

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. The mean age of the patients was 45.5 ± 9.3years with a lag of 8.3 ± 7.2years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

The Role of Cone-Beam Computed Tomography CT Extremity Arthrography in the Preoperative Assessment of Osteoarthritis.

Osteoarthritis (OA) is a prevalent disease and the leading cause of pain, disability, and quality of life deterioration. Our study sought to evaluate the image quality and dose of cone-beam computed tomography arthrography (CBCT-A) and compare them to digital radiography (DR) for OA diagnoses. Overall, 32 cases of CBCT-A and DR with OA met the inclusion criteria and were prospectively analyzed. The Kellgren and Lawrence classification (KLC) stage, sclerosis, osteophytes, erosions, and mean joint width (MJW) were compared between CBCT-A and DR. Image quality was excellent in all CBCT-A cases, with excellent inter-observer agreement. OA under-classification was noticed with DR for MJW (p = 0.02), osteophyte detection (<0.0001), and KLC (p < 0.0001). The Hounsfield Unit (HU) values obtained for the cone-beam computed tomography CBCT did not correspond to the values for multi-detector computed tomography (MDCT), with a greater mean deviation obtained with the MDCT HU for Modeled Based Iterative Reconstruction 1st (MBIR1) than for the 2nd generation (MBIR2). CBCT-A has been found to be more reliable for OA diagnosis than DR as revealed by our results using a three-point rating scale for the qualitative image analysis, with higher quality and an acceptable dose. Moreover, the use of this imaging technique permits the preoperative assessment of extremities in an OA diagnosis, with the upright position and bone microarchitecture analysis being two other advantages of CBCT-A.

Micro-CT-Based Bone Microarchitecture Analysis of the Murine Skull.

X-ray micro-computed tomography (micro-CT) imaging has important applications in microarchitecture analysis of cortical and trabecular bone structure. While standardized protocols exist for micro-CT-based microarchitecture assessment of long bones, specific protocols need to be developed for different types of skull bones taking into account differences in embryogenesis, organization, development, and growth compared to the rest of the body. This chapter describes the general principles of bone microarchitecture analysis of murine craniofacial skeleton to accommodate for morphological variations in different regions of interest.

Microcomputed tomographic analysis of bone microarchitecture after sinus augmentation with hyaluronic matrix: a case-control study.

The aim of this study was to analyze trabecular microarchitecture of augmented sinuses with hyaluronic matrix and xenograft by microcomputed tomography, and to investigate whether hyaluronic matrix has an effect on the newly formed bone quality. Thirteen patients undergoing maxillary sinus augmentation were included in this split-mouth study. Right and left sinus sites were randomly assigned to test and control group. In test group, the sinus was grafted with hyaluronic matrix and xenograft; in control group, only with xenograft. Four months after augmentation, bone samples were harvested during implant placement and analyzed for the following trabecular microarchitecture parameters using microcomputed tomography: bone volume (BV), total volume (TV), bone volume fraction (BV/TV), bone surface (BS), specific bone surface (BS/BV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular pattern factor (Tb.Pf), and fractal dimension (FD). There was statistically significant difference only for BS/TV parameter between two groups. BS/TV was higher in hyaluronic matrix group compared with control group. Addition of hyaluronic matrix to xenograft may enhance bone quality in terms of bone surface density. However, more research investigating the microstructural variation of augmented sinuses is needed with a greater sample.

In vivo bone microarchitecture analysis in a psoriatic arthritic patient before and after anti-TNFα treatment

In vivo bone microarchitecture analysis in a psoriatic arthritic patient before and after anti-TNFα treatment

Effects of premature contact in maxillary alveolar bone in rats: relationship between experimental analyses and a micro scale FEA computational simulation study.

The aim of the investigation was to evaluate the maxillary alveolar bone morphology, bone architecture, and bone turnover in relation to the mechanical strain distribution in rats with dental premature contact. Fifty 2-month-old male Wistar rats were used. The premature contact group (N=40) received a unilateral (right side) resin cementation on the occlusal surface of the upper first molar. The animals were distributed in 4 subgroups according to the periods of euthanasia: 7, 14, 21, and 28 days after cementation (N=10, for each period). For the control group (N=10), the teeth were kept without resin, featuring a normal occlusion. The pieces including the upper first molars, alveolar bone, and periodontal tissue were processed to histological and immunohistochemical evaluation of RANK-L and TRAP protein expression. A three-dimensional bone microarchitecture analysis was performed, where the heads of animals were scanned using microtomography and analyzed using CT-Analyser software (Bruker, Kontich, Belgium). In the computer simulation by finite element analysis, two micro-scaled three-dimensional finite element models of first molar and dentoalveolar tissues were constructed, in representation of control and premature contact groups, using Materialise MIMICS Academic Research v18 (Materialise, Leuven, Belgium). The analysis was set to simulate a maxillary molar biting during the power stroke phase. The total deformation, equivalent strain, and minimum principal strain distribution were calculated. The expression of RANK-L and TRAP presented higher positive ratio in the 7-day period compared to the control group. The three-dimensional morphometry showed decrease of bone volume in the premature contact, with significant values between the control and the 7-day and 14-day groups (P = 0.007). In FEA, the premature contact model presented a uniform compressive strain distribution in the alveolar bone crest compared to a non-uniform compressive strain distribution in the control model. The results from FEA, 3D bone microarchitecture, and histological and immunohistochemical analyses showed that a model with dental traumatic occlusion resulted in changes of alveolar bone mechanobiology and, consequently, its morphology. These results could be applied in dental treatment planning bringing biological and mechanical feedback to provide an effective mechanism to obtain physiological bone loss responses. Furthermore, this association between experimental and computational analyses will be important to figure out the alveolar bone response to mechanical stimulation in different clinical conditions.

Hip Fractures in Older Adults Are Associated With the Low Density Bone Phenotype and Heterogeneous Deterioration of Bone Microarchitecture.

Femoral neck areal bone mineral density (FN aBMD) is a key determinant of fracture risk in older adults; however, the majority of individuals who have a hip fracture are not considered osteoporotic according to their FN aBMD. This study uses novel tools to investigate the characteristics of bone microarchitecture that underpin bone fragility. Recent hip fracture patients (n= 108, 77% female) were compared with sex- and age-matched controls (n= 216) using high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of the distal radius and tibia. Standard morphological analysis of bone microarchitecture, micro-finite element analysis, and recently developed techniques to identify void spaces in bone microarchitecture were performed to evaluate differences between hip fracture patients and controls. In addition, a new approach for phenotyping bone microarchitecture was implemented to evaluate whether hip fractures in males and females occur more often in certain bone phenotypes. Overall, hip fracture patients had notable deterioration of bone microarchitecture and reduced bone mineral density compared with controls, especially at weight-bearing sites (tibia and femoral neck). Hip fracture patients were more likely to have void spaces present at either site and had void spaces that were two to four times larger on average when compared with non-fractured controls (p< 0.01). Finally, bone phenotyping revealed that hip fractures were significantly associated with the low density phenotype (p< 0.01), with the majority of patients classified in this phenotype (69%). However, female and male hip fracture populations were distributed differently across the bone phenotype continuum. These findings highlight how HR-pQCT can provide insight into the underlying mechanisms of bone fragility by using information about bone phenotypes and identification of microarchitectural defects (void spaces). The added information suggests that HR-pQCT can have a beneficial role in assessing the severity of structural deterioration in bone that is associated with osteoporotic hip fractures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Novel roles of Atrogin‐1 in cardiac disease, lipid metabolism and bone microstructure

Ubiquitination plays a critical role in controlling protein turnover via proteasomal degradation, altering subcellular localization, and regulating protein activity. Functional role(s) for the Atrogin‐1 (MAFbx) ubiquitin ligase in regulating transcription factors have been found in skeletal muscle and the heart, but not in other organs. Within the myocyte, Atrogin‐1 localizes to the sarcomere and nucleus. We have previously reported that Atrogin‐1 is a critical regulator of pathologic and physiologic cardiac hypertrophy in vivo, involving specific interaction and ubiquitination of transcription factors central the signaling pathways driving these hypertrophic responses, including FOXO1/3. Recent studies have linked cardiomyocyte Atrogin‐1 to the regulation of the extracellular matrix. With evidence that cardiomyocyte Atrogin‐1 can affect cells other than myocytes, we analyzed Atrogin‐1−/− mice for their effects on metabolism and bone. DEXA whole body analysis of Atrogin‐1−/− mice revealed significantly decreased fat mass (15.6% vs. 35.8% fat, p&lt;0.05) with a corresponding increase in lean mass (84.4% vs. 64.2%, p&lt;0.05) at the age of 11–15 months, but not at 5 months, when compared to strain‐ and age‐matched wildtype (WT) control mice. Since the Atrogin‐1−/− mice weighed significantly less than WT mice (29±3 vs. 40±2 g, p&lt;0.05), the net fat loss was 4.6 g (vs. 14.3 g in age‐matched WT) and the lean body mass identical between groups (25.7 vs. 24.6 g). Together these findings suggest Atrogin‐1’s role in regulating fat metabolism. Analysis of bone microarchitecture and mechanical properties of adult Atrogin‐1−/− mice was undertaken at 17–21 weeks of age, a time point where no phenotype has been previously observed in skeletal muscle or heart. Femurs were dissected and subsequently assessed by μCT (SkyScan 1172) for bone microarchitecture in the distal femur metaphysis (1 mm) and mid‐diaphysis region and challenged by a three‐point bending test to assess their material and structural properties. No differences in cortical or trabecular bone microarchitecture were identified and nor were any changes in mechanical properties. Together, these findings illustrate novel biological roles of Atrogin‐1 in regulating systemic fat metabolism, possibly involving crosstalk between skeletal muscle/heart and systemic fat metabolism. Our analysis provides an essential framework for the potential therapeutic targeting of ubiquitin ligases like Atrogin‐1 in the context of striated muscle and metabolic disease.Support or Funding InformationSupport: Lilly Foundation/Indiana Center for Musculoskeletal Health/ IU School of Medicine, Physician Scientist Initiative, Scientific Research Initiative

Bone microarchitectural analysis using ultra-high-resolution CT in tiger vertebra and human tibia

BackgroundTo reveal trends in bone microarchitectural parameters with increasing spatial resolution on ultra-high-resolution computed tomography (UHRCT) in vivo and to compare its performance with that of conventional-resolution CT (CRCT) and micro-CT ex vivo.MethodsWe retrospectively assessed 5 tiger vertebrae ex vivo and 16 human tibiae in vivo. Seven-pattern and four-pattern resolution imaging were performed on tiger vertebra using CRCT, UHRCT, and micro-CT, and on human tibiae using UHRCT. We measured six microarchitectural parameters: volumetric bone mineral density (vBMD), trabecular bone volume fraction (bone volume/total volume, BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and connectivity density (ConnD). Comparisons between different imaging resolutions were performed using Tukey or Dunnett T3 test.ResultsThe vBMD, BV/TV, Tb.N, and ConnD parameters showed an increasing trend, while Tb.Sp showed a decreasing trend both ex vivo and in vivo. Ex vivo, UHRCT at the two highest resolutions (1024- and 2048-matrix imaging with 0.25-mm slice thickness) and CRCT showed significant differences (p ≤ 0.047) in vBMD (51.4 mg/cm3 and 63.5 mg/cm3versus 20.8 mg/cm3), BV/TV (26.5% and 29.5% versus 13.8 %), Tb.N (1.3 l/mm and 1.48 l/mm versus 0.47 l/mm), and ConnD (0.52 l/mm3 and 0.74 l/mm3versus 0.02 l/mm3, respectively). In vivo, the 512- and 1024-matrix imaging with 0.25-mm slice thickness showed significant differences in Tb.N (0.38 l/mm versus 0.67 l/mm, respectively) and ConnD (0.06 l/mm3versus 0.22 l/mm3, respectively).ConclusionsWe observed characteristic trends in microarchitectural parameters and demonstrated the potential utility of applying UHRCT for microarchitectural analysis.

MicroRNA levels in bone and blood change during bisphosphonate and teriparatide therapy in an animal model of postmenopausal osteoporosis.

MicroRNAs control the activity of a variety of genes that are pivotal to bone metabolism. Therefore, the clinical utility of miRNAs as biomarkers and drug targets for bone diseases certainly merits further investigation. This study describes the use of an animal model of postmenopausal osteoporosis to generate a comprehensive dataset on miRNA regulation in bone tissue and peripheral blood during bone loss and specifically anti-resorptive and osteo-anabolic treatment. Forty-two Sprague-Dawley rats were randomized to SHAM surgery (n=10) or ovariectomy (OVX, n=32). Eight weeks after surgery, OVX animals were further randomized to anti-resorptive treatment with zoledronate (n=11), osteo-anabolic treatment with teriparatide (n=11), or vehicle treatment (n=10). After 12 weeks of treatment, bone and serum samples were used for microRNA analysis using next-generation sequencing (NGS), mRNA levels using RT-qPCR, and bone microarchitecture analysis using nanoCT. Ovariectomy resulted in loss of trabecular bone, which was fully rescued using osteo-anabolic treatment, and partially rescued using anti-resorptive treatment. NGS revealed that both, anti-resorptive and anabolic treatment had a significant impact on miRNA levels in bone tissue and serum: out of 426 detected miRNAs, 46 miRNAs were regulated by teriparatide treatment an d 10 by zoledronate treatment (p-adj.<0.1). Interestingly, teriparatide and zoledronate treatment were able to revert miRNA changes in tissue and serum of untreated OVX animals, such as the up-regulation of miR-203a-3p, a known osteo-inhibitory miRNA. We confirmed previously established mechanisms of miR-203a by analyzing its direct target Dlx5 in femoral head. Our data reveal a significant effect of ovariectomy-induced bone loss, as well as the two major types of anti-osteoporotic treatment on miRNA transcription in femoral head tissue. These changes are associated with altered activity of target genes relevant to bone formation, such as Dlx5. The observed effects of bone loss and treatment response on miRNA levels in bone are also reflected in the peripheral blood, suggesting the possibility of minimally-invasive monitoring of bone-derived miRNAs using liquid biopsies.

Monosodium Glutamate Supplementation Improves Bone Status in Mice Under Moderate Protein Restriction.

ABSTRACTAdequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later. Using a mild protein restriction model in Balb/C mice consuming 6% of their total energy intake as soy protein (LP‐SOY)—for which we observed a significantly lower femoral cortical thickness, bone volume, trabecular number, and thickness reduction—we evaluated the effects of monosodium glutamate (MSG) supplementation at different concentrations (0.5, 1, 5, 10, and 20 g/kg of diet) on bone characteristics in LP‐SOY‐fed mice. After 6 and 12 weeks, LP‐SOY‐fed mice had lower BMD and reduced body weight related to lower lean mass, which was associated with a reduced IGF‐1 level. The negative effect of the LP‐SOY diet on BMD correlated with impaired bone formation. MSG supplementation, at 5, 10, and 20 g/kg of diet, and PTH injection, used as a positive control, were able to improve BMD and to increase osteoblast activity markers (P1NP and osteocalcin), as well as glutamine plasma concentration. An analysis of bone microarchitecture found that cortical bone was less sensitive to protein restriction than trabecular bone, and that MSG ingestion was able to preserve bone quality through an increase of collagen synthesis, although it did not allow normal bone growth. Our study reinforces the view that glutamate can act as a functional amino acid for bone physiology and support clinical investigation of glutamate supplementation in adults characterized by poor bone status, notably as a result of insufficient protein intake. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Impact of micro-computed tomography reconstruction protocols on bone microarchitecture analysis

The aim of this study was to assess the influence of reconstruction protocols of micro-computed tomography (micro-CT) images on analyses of bone microarchitecture. Micro-CT images of the maxillae of 5 Wistar rats were reconstructed with different protocols by varying the levels of the following tools: smoothing filter (SF; 2-6); ring artifact correction (RAC; 5-15); and beam hardening correction (BHC; 15%-60%). A control protocol (P0; without any correction tool) and a standard protocol (SP; according to the manufacturer's recommendation: SF = 2; RAC = 5; BHC = 45%) were also obtained. For each protocol, 8 bone microarchitecture parameters were calculated (bone volume/total volume [BV/TV], bone surface/total volume [BS/TV], trabecular number [Tb.N], trabecular thickness [Tb.Th], trabecular separation [Tb.Sp], degree of anisotropy [DA], connectivity density [Conn.D], and total porosity [Po-tot]) by using CTAn software. Test protocols were compared with the SP by using 1-way analysis of variance and the Dunnet post hoc test (α = 0.05). An inverse relationship was observed between BHC tool levels and all microarchitecture parameters except BV/TV and Tb.Th. The combination of BHC and SF significantly influenced all microarchitecture parameters except for DA, for which all protocols were similar to the SP (P > .05). Calculation of bone microarchitecture parameters is influenced by the applied levels of artifact correction tools, mainly BHC and SF. It is necessary to standardize such tool levels for correct data interpretation.

FGF-2 targets sclerostin in bone and myostatin in skeletal muscle to mitigate the deleterious effects of glucocorticoid on musculoskeletal degradation

AimMyokines are associated with regulation of bone and muscle mass. However, limited information is available regarding the impact of myokines on glucocorticoid (GC) mediated adverse effects on the musculoskeletal system. This study investigates the role of myokine fibroblast growth factor-2 (FGF-2) in regulating GC-induced deleterious effects on bone and skeletal muscle. MethodsPrimary osteoblast cells and C2C12 myoblast cell line were treated with FGF-2 and then exposed to dexamethasone (GC). FGF-2 mediated attenuation of the inhibitory effect of GC on osteoblast and myoblast differentiation and muscle atrophy was assessed through quantitative PCR and western blot analysis. Further, FGF-2 was administered subcutaneously to dexamethasone treated mice to collect bone and skeletal muscle tissue for in vivo analysis of bone microarchitecture, mechanical strength, histomorphometry and for histological alterations in treated tissue samples. Key findingsFGF-2 abrogated the dexamethasone induced inhibitory effect on osteoblast differentiation by modulating BMP-2 pathway and inhibiting Wnt antagonist sclerostin. Further, dexamethasone induced atrophy in C2C12 cells was mitigated by FGF-2 as evident from down regulation of atrogenes expression. FGF-2 prevented GC-induced impairment of mineral density, biomechanical strength, trabecular bone volume, cortical thickness and bone formation rate in mice. Additionally, skeletal muscle tissue from GC treated mice displayed weak myostatin immunostaining and reduced expression of atrogenes following FGF-2 treatment. SignificanceFGF-2 mitigated GC induced effects through inhibition of sclerostin and myostatin expression in bone and muscle respectively. Taken together, this study exhibited the role of exogenous FGF-2 in sustaining osteoblastogenesis and inhibiting muscle atrophy in presence of glucocorticoid.

Runx2 overexpression compromises bone quality in acromegalic patients.

Acromegalic patients, characterized by excessive secretion of GH and IGF-1, show a high fracture risk but bone mineral density is a poor predictor for bone fractures in these patients. The effects of an excess of GH/IGF1 on skeleton as well as on osteogenic progenitors, i.e. mesenchymal stem cells, have not been investigated in these patients. We aimed to elucidate the skeletal conditions of acromegalic patients by means of bone microarchitecture analysis and evaluation of MSCs osteogenic commitment. In particular, we performed histomorphometric analyses, and we quantified the expression levels of the osteogenic transcription factor RUNX2 in circulating MSCs. Our results showed an abnormal microarchitecture and demonstrated that bone impairment in acromegalic patients is associated with the upregulation of RUNX2 expression. Furthermore, osteoblastic activity was significantly reduced in patients under pharmacological treatment, compared to untreated patients. In conclusion, this study demonstrates the key role of RUNX2 gene overexpression in causing bone impairment in acromegalic patients. It also suggests a therapeutic approach for the improvement of bone quality, focused on the osteoblastic lineage rather than the inhibition of osteoclastic activity.

Fractal analysis of subchondral bone changes of the hand in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder. Conventional radiography, a widely available and cost-effective examination method, remains the standard of reference for the detection and quantification of joint involvement in RA. Fractal dimension (FD) of the trabecular bone structure has been proven to correlate with the bone's physical properties. The present study was designed to use fractal analysis to validate radiograph changes in the hand of RA patients.This study retrospectively evaluated the hand radiographs of 108 subjects. Fifty-four patients were suffering from RA, of which 18 were men and 36 were women. Their ages ranged from 25 to 90 years. The hand radiographs of 54 healthy patients, 18 men and 36 women (age range 23–88 years), were used as the control group. Bone structure value (BSV) is a critical parameter for the assessment and analysis of bone microarchitecture. The BSVs were calculated over the fractal dimension using the Brownian motion.The BSV calculated for ROI showed a significant difference in ROI5 (0.210 ± 0.045), ROI6 (0.186 ± 0.066), and ROI11 (0.201 ± 0.056) in patients with RA, in comparison to the CG (P < 0.05). A significant correlation was observed between anti-CCP and ROI4, ROI5, ROI6, ROI9, and ROI12 in seropositive RA patients (post hoc test (Bonferroni) P <0.001).This study demonstrates that the bone textural image analysis technique can be used to quantify the radiographic changes in RA hands, based on comparisons of FDs.

The effects of Labisia pumila extracts on bone microarchitecture of ovariectomized-induced osteoporosis rats: A micro-CT analysis.

Labisia pumila (LP) is a popular herb used by women over the past few decades. This herb has shown potentials as an alternative agent for treatment and prevention of postmenopausal osteoporosis. It was observed in previous studies that supplementation to ovariectomized rats were associated with increased bone antioxidative enzymes and reduced lipid peroxidation activity. It had also improved bone formation markers in ovariectomized rats. This study aimed to evaluate the effects of giving different forms of LP extracts on the trabecular bone microarchitecture of ovariectomised rats. Forty-eight female Sprague-Dawley rats were randomly divided into sham-operated (Sham), ovariectomized control (OVX), ovariectomized and given estrogen at 64.5 μg/kg (ERT), ovariectomized and given LP aqueous extract (LPaq), LP methanol extract (LPmet) and LP ethanol extract (LPet) at 100 mg/kg, respectively. Treatments were given daily via oral gavages for nine weeks. Following sacrifice, femora were dissected out for bone microarchitectural analysis using an in vitro micro-CT, which provided three dimensional informations on bone microarchitecture. LPaq was the most effective extract found to improve the bone microarchitectural paramaters which comprised ofBone volume fraction (BV/TV), Trabecular separation (Tb.Sp), Trabecular number (Tb.N), Connective density (Conn.dens), Structure model index (SMI) and Degree of anisotropy (DA). LPaq was effective in protecting the bone of postmenopausal osteoporosis rat model against microarchitectural deterioration.

High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures.

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25-72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25-68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and formineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p < 0.05) lower bone volume/trabecular volumeratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volumeratio (p = 0.003) and mean trabecular thickness (p < 0.001) and greater mean trabecular separation (p = 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstructure.

Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT.

ObjectivesThis study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats.MethodsThe mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software.ResultsThere were highly significant correlations between undecalcified histological sections and micro-CT for all parameters (bone volume density (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp))in the mandible and tibia. Bone histomorphometric parameters analysed by both methods exhibited significant differences among sham, OVX, and OVX-ZOL groups. There were significant correlations between mandible and tibia in BV/TV, BS/BV, and Tb.Sp.ConclusionsMicro-CT is a complementary tool to histological sections in basic research that could improve our understanding of bone histomorphometry. The mandible can be used as an effective site to assess bone morphometry of OVX or metabolic bone disease rat models.Cite this article: H. Liu, W. Li, Y. S. Liu, Y. S. Zhou. Bone micro-architectural analysis of mandible and tibia in ovariectomised rats: A quantitative structural comparison between undecalcified histological sections and micro-CT. Bone Joint Res 2016;5:253–262.

Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. “Cluster 1” contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. “Cluster 2” contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone.

TU-AB-204-02: Advances in C-Arm CBCT for Cardiac Interventions

This symposium highlights advanced cone-beam CT (CBCT) technologies in four areas of emerging application in diagnostic imaging and image-guided interventions. Each area includes research that extends the spatial, temporal, and/or contrast resolution characteristics of CBCT beyond conventional limits through advances in scanner technology, acquisition protocols, and 3D image reconstruction techniques. Dr. G. Chen (University of Wisconsin) will present on the topic: Advances in C-arm CBCT for Brain Perfusion Imaging. Stroke is a leading cause of death and disability, and a fraction of people having an acute ischemic stroke are suitable candidates for endovascular therapy. Critical factors that affect both the likelihood of successful revascularization and good clinical outcome are: 1) the time between stroke onset and revascularization; and 2) the ability to distinguish patients who have a small volume of irreversibly injured brain (ischemic core) and a large volume of ischemic but salvageable brain (penumbra) from patients with a large ischemic core and little or no penumbra. Therefore, “time is brain” in the care of the stroke patients. C-arm CBCT systems widely available in angiography suites have the potential to generate non-contrast-enhanced CBCT images to exclude the presence of hemorrhage, time-resolved CBCT angiography to evaluate the site of occlusion and collaterals, and CBCT perfusion parametric images to assess the extent of the ischemic core and penumbra, thereby fulfilling the imaging requirements of a “one-stop-shop” in the angiography suite to reduce the time between onset and revascularization therapy. The challenges and opportunities to advance CBCT technology to fully enable the one-stop-shop C-arm CBCT platform for brain imaging will be discussed. Dr. R. Fahrig (Stanford University) will present on the topic: Advances in C-arm CBCT for Cardiac Interventions. With the goal of providing functional information during cardiac interventions, significant effort has been expended to improve the quantitative accuracy of C-arm CBCT reconstructions. The challenge is to improve image quality while providing very short turnaround between data acquisition and volume data visualization. Corrections for x-ray scatter, view aliasing and patient motion that require no more than 2 iterations keep processing time short while reducing artifact. Fast, multi-sweep acquisitions can be used to permit assessment of left ventricular function, and visualization of radiofrequency lesions created to treat arrhythmias. Workflows for each imaging goal have been developed and validated against gold standard clinical CT or histology. The challenges, opportunities, and limitations of the new functional C-arm CBCT imaging techniques will be discussed. Dr. W. Zbijewski (Johns Hopkins University) will present on the topic: Advances in CBCT for Orthopaedics and Bone Health Imaging. Cone-beam CT is particularly well suited for imaging of musculoskeletal extremities. Owing to the high spatial resolution of flat-panel detectors, CBCT can surpass conventional CT in imaging tasks involving bone visualization, quantitative analysis of subchondral trabecular structure, and visualization and monitoring of subtle fractures that are common in orthopedic radiology. A dedicated CBCT platform has been developed that offers flexibility in system design and provides not only a compact configuration with improved logistics for extremities imaging but also enables novel diagnostic capabilities such as imaging of weight-bearing lower extremities in a natural stance. The design, development and clinical performance of dedicated extremities CBCT systems will be presented. Advanced capabilities for quantitative volumetric assessment of joint space morphology, dual-energy image-based quantification of bone composition, and in-vivo analysis of bone microarchitecture will be discussed, along with emerging applications in the diagnosis of arthritis and osteoporosis and assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: 1. Brain perfusion imaging, including assessment of ischemic stroke 2. Cardiac imaging for functional assessment in cardiac interventions 3. Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis 4. Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone).