The bone bridge significantly affects the decrease in bone mineral density measured with quantitative computed tomography in ankylosing spondylitis.
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ABSTRACT: Introduction and objective
Ankylosing spondylitis (AS) has characteristics of spinal bone bridge and fusion. Although BMD reduction in AS may be presumed to be due to spinal inflammation, this study was designed to confirm whether immobilization of the spine due to syndesmophytes is related to BMD reduction, as immobilization itself is a risk factor for BMD reduction.Methods
Among male patients diagnosed with AS according to the modified New York criteria, those who underwent bone density tests with quantitative computed tomography (QCT) were retrospectively analyzed through a chart review. The correlation between the presence or absence of bone bridges for each vertebral body level of the L spine confirmed with radiography and BMD confirmed with QCT was analyzed.Results
A total of 47 male patients with AS were enrolled. The mean patient age was 46.8 ± 8.2 years, and the mean disease duration was 7.9 ± 6.4 years. The trabecular BMD of the lumbar spine (L1-L4) ranged from 23.1 to 158.45 mg/cm3 (mean 102.2 ± 37 mg/cm3), as measured with QCT. The lumbar BMD measurements showed that 30 patients (63.8%) had osteopenia or osteoporosis. Bone bridge formation showed a negative correlation with BMD. Low BMD was significantly correlated with bone bridge in the vertebral body (p < 0.05). Positive correlations were observed between bone bridge score and BASMI flexion score, whereas significant negative correlations were found between BMD and BASMI flexion score (p < 0.05).Conclusion
Decreased mobility of the vertebrae due to bone bridge formation affects the decrease in BMD in patients with AS.
SUBMITTER: Lee SY
PROVIDER: S-EPMC8051772 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionRheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides.MethodsForty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined.ResultsWe did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD.ConclusionsBMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.
| S-EPMC8461899 | biostudies-literature
Project description:BackgroundAnkylosing spondylitis (AS) is a common chronic progressive rheumatic disease. The aim of this study was to explore factors influencing abnormal bone mineral density (BMD) in young and middle-aged patients with AS.MethodsFrom July 2014 to August 2018, hospitalized patients with AS and health examinees in the health examination center of our clinics, ranging in age from 20 to 50 years, were monitored. The BMD of the lumbar spine and femoral neck of AS patients and those of a healthy control group were measured using dual-energy X-ray absorption. The BMDs of AS patients were compared with respect to age, course of disease, iritis, smoking habits, sex, height, weight, body mass index (BMI), medication use, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet volume, platelet count, uric acid (UA), alkaline phosphatase (AKP), and calcium ion levels. Single-nucleotide polymorphisms (SNPs) related to BMD were screened using genome-wide association analysis.ResultsThere was no statistical difference in the proportion of abnormal bone masses between the different body parts. The BMD of all bones in AS patients was lower than that in healthy controls (P < 0.05). Additionally, BMD was correlated with serum calcium and CRP in AS patients (P < 0.05), but not with age, platelet volume, platelet count, ESR, UA, AKP, height, weight, and BMI. The incidence of abnormal bone mass in AS patients was correlated with sex (P < 0.05), but not with medication use, iritis, or smoking. BMD of the lumbar spine in AS patients did not correlate linearly with the course of the disease, but BMD of the femoral neck correlated linearly with the course of the disease (P < 0.05). BMD was correlated with multiple SNPs in patients with AS. Lumbar BMD was correlated with rs7025373 and rs7848078. Femoral head BMD was correlated with 3:102157365, 3:102157417, rs1252202, rs1681355, rs3891857, rs7842614, and rs9870734, suggesting that genetic factors play a role in BMD in patients with AS.ConclusionsThe proportion of abnormal bone mass in AS patients was higher than that in healthy individuals of the same age. The factors related to BMD in patients with AS are gender, CRP, and blood calcium. The BMD of the femoral neck of AS patients decreases with the course of the disease, but BMD of the lumbar spine is not related to the course of the disease. BMD in AS patients is associated with multiple SNPs.
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Project description:Changes in the bone mineral density distribution (BMDD), due to disease or drugs, can alter whole bone mechanical properties such as strength, stiffness and toughness. The methods currently available for assessing BMDD are destructive and two-dimensional. Micro-computed tomography (?CT) has been used extensively to quantify the three-dimensional geometry of bone and to measure the mean degree of mineralization, commonly called the tissue mineral density (TMD). The TMD measurement has been validated to ash density; however parameters describing the frequency distribution of TMD have not yet been validated. In the current study we tested the ability of ?CT to estimate six BMDD parameters: mean, heterogeneity (assessed by the full-width-at-half-maximum (FWHM) and the coefficient of variation (CoV)), the upper and lower 5% cutoffs of the frequency distribution, and peak mineralization) in rat sized femoral cortical bone samples. We used backscatter scanning electron microscopy (bSEM) as the standard. Aluminum and hydroxyapatite phantoms were used to identify optimal scanner settings (70kVp, and 57?A, with a 1500ms integration time). When using hydroxyapatite samples that spanned a broad range of mineralization levels, high correlations were found between ?CT and bSEM for all BMDD parameters (R2?0.92, p<0.010). When using cortical bone samples from rats and various species machined to mimic rat cortical bone geometry, significant correlations between ?CT and bSEM were found for mean mineralization (R2=0.65, p<0.001), peak mineralization (R2=0.61, p<0.001) the lower 5% cutoff (R2=0.62, p<0.001) and the upper 5% cutoff (R2=0.33, p=0.021), but not for heterogeneity, measured by FWHM (R2=0.05, p=0.412) and CoV (R2=0.04, p=0.469). Thus, while mean mineralization and most parameters used to characterize the BMDD can be assessed with ?CT in rat sized cortical bone samples, caution should be used when reporting the heterogeneity.
| S-EPMC5481667 | biostudies-literature
Project description:ObjectiveTo examine the relationship between vertebral trabecular bone mineral density (tBMD), vertebral strength, and syndesmophytes in patients with ankylosing spondylitis (AS) using quantitative computed tomography (QCT).MethodsWe performed QCT of the spine to measure syndesmophytes and tBMD in 5 vertebrae (T11-L3) in 61 patients with AS. Finite element analysis was performed to measure vertebral strength in compressive overload, including in trabecular and cortical compartments. In cross-sectional analyses, we examined associations of syndesmophyte height with tBMD and vertebral strength in each vertebra. In 33 patients followed up for 2 years, we investigated whether baseline tBMD and vertebral strength predicted syndesmophyte growth in the same vertebra, and vice versa.ResultsIn the cross-sectional analyses, 126 vertebrae had bridging, 77 vertebrae had nonbridging syndesmophytes, and 83 vertebrae had no syndesmophytes. There were strong inverse associations between syndesmophyte height and tBMD, total strength, and trabecular strength only among bridged vertebrae. In the longitudinal analysis, nonbridged vertebrae with low tBMD (adjusted β = -0.01 [95% confidence interval (95% CI) -0.019, -0.0012]) and low strength (adjusted β = -0.0003 [95% CI -0.0004, -0.0002]) had more syndesmophyte growth over time. Similar associations were absent among bridged vertebrae. Conversely, vertebrae with bridging at baseline had a significant loss in percent tBMD over time (adjusted β = -0.001 [95% CI -0.0017, -0.0004]).ConclusionAssociations between syndesmophytes and vertebral density and strength in AS differ between bridged and nonbridged vertebrae. Among nonbridged vertebrae, low tBMD and strength are associated with syndesmophyte growth. Bridging is associated with large subsequent losses in tBMD, possibly due to mechanical offloading.
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Project description:This study aimed to assess the relationship between bone marrow edema (BME) on magnetic resonance imaging (MRI) and bone mineral density (BMD) in patients with ankylosing spondylitis (AS).The study included 333 patients with AS who underwent BMD measurements and axial MRI. Additionally, 106 normal controls were included. The modified New York criteria were used as the classification criteria of AS. Clinical, laboratory, and imaging data were collected and analyzed. Lumbar spine and proximal femur BMD were assessed using dual-energy X-ray absorptiometry. Low BMD was defined by a Z-score ?-2. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index was used to assess inflammation at the sacroiliac joint (SIJ) and spine.Among the 333 patients, the male:female ratio was 4.6:1, mean patient age was 28.5±10.6 years, and mean disease duration was 7.3±6.8 years. The prevalences of low BMD, osteopenia, and osteoporosis were significantly higher among AS patients than among controls (19.8%, 62.8%, and 5.7% vs. 4.7%, 33.0%, and 0%, respectively, P = 0.000). The BMD values were significantly lower and prevalences of low BMD at both the spine and femur were significantly higher among patients with BME on MRI than among those without BME. Multivariate logistic regression analysis showed that male sex (OR 3.87, 95% CI 1.21-7.36, P = 0.023), high ASDAS-CRP score (OR 2.83, 95% CI 1.36-4.76, P = 0.015), the presence of BME on sacroiliac MRI (OR 2.83, 95% CI 1.77-6.23, P = 0.000) and spinal MRI (OR 4.06, 95% CI 1.96-8.46, P = 0.000), and high grade of sacroiliitis (OR 2.93, 95% CI 1.82-4.45, P = 0.002) were risk factors for low BMD (any site). The SPARCC scores of the SIJ were negatively correlated with femoral BMD (r = -0.22, 95% CI -0.33 to -0.10, P = 0.000). Additionally, the SPARCC scores of the spine were negatively correlated with BMD values (r = -0.23, 95% CI -0.36 to -0.09, P = 0.003) and Z-scores (r = -0.24, 95% CI -0.36 to -0.12, P = 0.001) at the spine.Low BMD is common in AS patients. BME on MRI is highly associated with low BMD at both the spine and femur.
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Project description:Study objectivesClinical studies have investigated whether obstructive sleep apnea (OSA) can modulate bone metabolism but data are conflicting. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is the standard technique for quantifying bone strength but has limitations in overweight patients (body mass index [BMI] ? 25 kg/m(2)). The aim of this study was to examine the association between OSA and BMD by examining CT images that allow true volumetric measurements of the bone regardless of BMI.MethodsLumbar vertebrae BMD was evaluated in 234 persons (180 males and 54 females) by CT scan. The method was calibrated by a phantom containing a known concentration of hydroxyapatite.ResultsBMD was lower in male patients with severe OSA (apnea-hypopnea index [AHI] ? 30/h) than non OSA (AHI < 5; p < 0.05), while OSA and BMD had no association in females. Linear and multiple regression analyses revealed that age (p < 0.0001, ? = -0.52), hypertension (p = 0.0068, ? = -0.17), and the alveolar-arterial oxygen pressure difference (A-aDO2) (p = 0.012, ? = -0.15) in males were associated with BMD, while only age (p < 0.0001, ? = -0.68) was associated with BMD in females.ConclusionMales with severe OSA had a significantly lower BMD than non OSA participants. Age, hypertension, and elevation of A-aDO2 were significant factors for BMD by CT imaging. The usefulness of measuring BMD in OSA patients by CT scanning should be studied in future.
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Project description:Background and Objectives: Women with gynecological cancers constitute a high-risk cohort for loss of bone density. International guidance stipulates women undergoing cancer treatments associated with bone loss should have a quantitative assessment of bone density. Access to Dual-energy X-ray Absorptiometry (DXA) is limited. This study aimed to assess the accuracy of opportunistic bone density measurement on staging computed tomography (CT) scans for gynaecological malignancies, in comparison to the gold standard DXA. Materials and Methods: Women with a staging CT scan of the abdomen and pelvis for a new diagnosis of gynecological cancer were recruited. DXA was performed within 6 weeks of treatment for gynaecological cancer. Lumbar bone density was measured by CT attenuation values, in Hounsfield units (HU), of the anterior trabecular region. Correlations between CT and DXA parameters were analysed. Receiver Operating Characteristic(ROC) curves for diagnosis of low bone density and osteoporosis were analysed. Results: Final cohort included 48 of 50 women recruited. There was good diagnostic accuracy for abnormal bone density and osteoporosis, with areas under the ROC curve at L1 of 0.77 (p = 0.002) and 0.80 (p = 0.020) respectively. CT-HU of 170-190 yielded sensitivities of 87-90%, positive predictive values of 75-84% and negative predictive values of 71-75% for the diagnosis of low bone mineral density. CT-HU of 90-110 yielded specificities of 85-93% for the diagnosis of osteoporosis. Moderate correlations were found between CT-HU and both DXA T-scores and diagnostic categories. Conclusions: This is the first study to assess the opportunistic application of CT in the assessment of bone health in women with gynaecological cancer, a cohort at high-risk of osteoporosis. The correlation between bone density assessment in CT-HU and DXA, and strong AUC values for the diagnosis of low bone density (0.77) and osteoporosis (0.80) support this pragmatic solution in resolving the care-gap in cancer treatment-induced bone loss, often associated with poor access to DXA.
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Project description:BackgroundThe update in technology may impact the accuracy in measuring bone mineral density (BMD). However, the application of the new fast kilovoltage (kV)-switching dual-energy computed tomography (DECT) for BMD measurement has not yet been reported. This study aimed to examine the accuracy and precision of the new fast kV-switching DECT in measuring BMD and to evaluate its applicability in clinical BMD measurement.MethodsForty sets of the new fast kV-switching DECT scans and one quantitative computed tomography (QCT) scan were performed on the European Spine Phantom. Their relative errors and relative standard deviations were compared. A retrospective analysis was performed on patients who underwent chest plain DECT and abdominal monoenergetic plain CT at the same time. The relationship between hydroxyapatite-water and hydroxyapatite-fat measured using DECT and BMD measured using QCT was analyzed by multivariate regression analysis.ResultsThe relative errors of the new fast kV-switching DECT with low tube speeds (0.8 and 1.0 s/r) were all less than 6% and were less than those of QCT, except for those at 515 mA. The relative standard deviation values with high tube rotation speeds (0.5 and 0.6 s/r) were higher than those with low tube speeds (0.8 and 1.0 s/r) under most tube current conditions. The new fast kV-switching DECT-derived BMD values corrected by multiple linear regression (predicted hydroxyapatite) were significantly positively correlated with the QCT-based BMD values (R2=0.912; P<0.001). The results of the Bland-Altman analysis demonstrated high consistency between the 2 measurement methods.ConclusionsResults of the phantom measurements indicated that the new fast kV-switching DECT could measure BMD with relatively high accuracy and precision. The results of a subsequent clinical in vivo experiment demonstrated that vertebral BMD measurements derived from DECT and QCT were mostly consistent and highly accurate. Therefore, patients who undergo DECT for other clinical indications can simultaneously have their BMD determined.
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Project description:Excessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment.Twelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks.At baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints (mean SUVAUC -1.2; P = 0.03) in contrast to non-responders.18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment.
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Project description:The aim of the present study was to extract potential sub?pathway biomarkers for spondyloarthropathy (SpA)/ankylosing spondylitis (AS) using a sub?pathway strategy. SpA/AS?relevant data, reference pathways and long non?coding (lnc)RNA?micro (mi)RNA?mRNA interactions were downloaded. The seed pathways based on Kyoto Encyclopedia of Genes and Genomes pathways and the mRNAs in the co?expressed lncRNA?mRNA interactions were extracted. Sub?pathways regulated by lncRNA were selected after establishing condition?specific lncRNA competitively regulated pathways (LCRP) network. Significant sub?pathways were further identified using the attract method. These significant sub?pathways were evaluated in the other independent published AS microarray data (E?GEOD?25101) using in silico validation. In addition, to uncover SpA/AS?relevant lncRNAs, the degree analysis for all nodes in the LCRP network was conducted. A total of 35 lncRNAs, 131 mRNAs and 145 co?expressed interactions were identified. When entering these 131 mRNAs into the reference pathways, 82 seed pathways were extracted, which were transformed into undirected graphs, and the 35 lncRNAs were mapped to the pathway graphs to further establish the condition?specific LCRP network. Based on degree analysis, four hub lncRNAs were selected, including C14orf169, LINC00242, LINC00116 and LINC00482. It was identified that 35 lncRNAs competitively regulating sub?pathways were involved in 56 complete pathways. Among these, the top three sub?pathways were path: 04010_1, which was a subregion of the mitogen?activated protein kinase (MAPK) signaling pathway; path: 04062?1, an important subregion in the chemokine signaling pathway; and path: 04066_2, was a part of HIF?1 signaling pathway. Furthermore, it was validated consistently in the separate microarray data set E?GEOD?25101. Cancer?associated pathways and hub node C14orf169 were identified in validation. Sub?pathways, including the MAPK signaling pathway and chemokine signaling pathway, and hub lncRNA (C14orf169) may serve important roles in SpA/AS.
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