Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.
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SUBMITTER: Alonso N
PROVIDER: S-EPMC5912156 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.
Alonso Nerea N Estrada Karol K Albagha Omar M E OME Herrera Lizbeth L Reppe Sjur S Olstad Ole K OK Gautvik Kaare M KM Ryan Niamh M NM Evans Kathryn L KL Nielson Carrie M CM Hsu Yi-Hsiang YH Kiel Douglas P DP Markozannes George G Ntzani Evangelia E EE Evangelou Evangelos E Feenstra Bjarke B Liu Xueping X Melbye Mads M Masi Laura L Brandi Maria Luisa ML Riches Philip P Daroszewska Anna A Olmos José Manuel JM Valero Carmen C Castillo Jesús J Riancho José A JA Husted Lise B LB Langdahl Bente L BL Brown Matthew A MA Duncan Emma L EL Kaptoge Stephen S Khaw Kay-Tee KT Usategui-Martín Ricardo R Del Pino-Montes Javier J González-Sarmiento Rogelio R Lewis Joshua R JR Prince Richard L RL D'Amelio Patrizia P García-Giralt Natalia N Nogués Xavier X Nogués Xavier X Mencej-Bedrac Simona S Marc Janja J Wolstein Orit O Eisman John A JA Oei Ling L Medina-Gómez Carolina C Schraut Katharina E KE Navarro Pau P Wilson James F JF Davies Gail G Starr John J Deary Ian I Tanaka Toshiko T Ferrucci Luigi L Gianfrancesco Fernando F Gennari Luigi L Lucas Gavin G Elosua Roberto R Uitterlinden André G AG Rivadeneira Fernando F Ralston Stuart H SH
Annals of the rheumatic diseases 20171123 3
<h4>Objectives</h4>To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis.<h4>Methods</h4>Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and ...[more]
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Project description:In a population-based study, we found that computed tomography (CT)-based bone density and strength measures from the thoracic spine predicted new vertebral fracture as well as measures from the lumbar spine, suggesting that CT scans at either the thorax or abdominal regions are useful to assess vertebral fracture risk.IntroductionPrior studies have shown that computed tomography (CT)-based lumbar bone density and strength measurements predict incident vertebral fracture. This study investigated whether CT-based bone density and strength measurements from the thoracic spine predict incident vertebral fracture and compared the performance of thoracic and lumbar bone measurements to predict incident vertebral fracture.MethodsThis case-control study of community-based men and women (age 74.6 ± 6.6) included 135 cases with incident vertebral fracture at any level and 266 age- and sex-matched controls. We used baseline CT scans to measure integral and trabecular volumetric bone mineral density (vBMD) and vertebral strength (via finite element analysis, FEA) at the T8 and L2 levels. Association between these measurements and vertebral fracture was determined by using conditional logistic regression. Sensitivity and specificity for predicting incident vertebral fracture were determined for lumbar spine and thoracic bone measurements.ResultsBone measurements from T8 and L2 predicted incident vertebral fracture equally well, regardless of fracture location. Specifically, for predicting vertebral fracture at any level, the odds ratio (per 1-SD decrease) for the vBMD and strength measurements at L2 and T8 ranged from 2.0 to 2.7 (p < 0.0001) and 1.8 to 2.8 (p < 0.0001), respectively. Results were similar when predicting fracture only in the thoracic versus the thoracolumbar spine. Lumbar and thoracic spine bone measurements had similar sensitivity and specificity for predicting incident vertebral fracture.ConclusionThese findings indicated that like those from the lumbar spine, CT-based bone density and strength measurements from the thoracic spine may be useful for identifying individuals at high risk for vertebral fracture.
| S-EPMC8265597 | biostudies-literature
Project description:Purpose To create and validate a computer system with which to detect, localize, and classify compression fractures and measure bone density of thoracic and lumbar vertebral bodies on computed tomographic (CT) images. Materials and Methods Institutional review board approval was obtained, and informed consent was waived in this HIPAA-compliant retrospective study. A CT study set of 150 patients (mean age, 73 years; age range, 55-96 years; 92 women, 58 men) with (n = 75) and without (n = 75) compression fractures was assembled. All case patients were age and sex matched with control subjects. A total of 210 thoracic and lumbar vertebrae showed compression fractures and were electronically marked and classified by a radiologist. Prototype fully automated spinal segmentation and fracture detection software were then used to analyze the study set. System performance was evaluated with free-response receiver operating characteristic analysis. Results Sensitivity for detection or localization of compression fractures was 95.7% (201 of 210; 95% confidence interval [CI]: 87.0%, 98.9%), with a false-positive rate of 0.29 per patient. Additionally, sensitivity was 98.7% and specificity was 77.3% at case-based receiver operating characteristic curve analysis. Accuracy for classification by Genant type (anterior, middle, or posterior height loss) was 0.95 (107 of 113; 95% CI: 0.89, 0.98), with weighted κ of 0.90 (95% CI: 0.81, 0.99). Accuracy for categorization by Genant height loss grade was 0.68 (77 of 113; 95% CI: 0.59, 0.76), with a weighted κ of 0.59 (95% CI: 0.47, 0.71). The average bone attenuation for T12-L4 vertebrae was 146 HU ± 29 (standard deviation) in case patients and 173 HU ± 42 in control patients; this difference was statistically significant (P < .001). Conclusion An automated machine learning computer system was created to detect, anatomically localize, and categorize vertebral compression fractures at high sensitivity and with a low false-positive rate, as well as to calculate vertebral bone density, on CT images. © RSNA, 2017 Online supplemental material is available for this article.
| S-EPMC5584647 | biostudies-literature
Project description:RationaleFormer smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.ObjectivesTo demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.MethodsCharacteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use.Measurements and main resultsvBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures.ConclusionsMale smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population.
| S-EPMC4418341 | biostudies-literature
Project description:BACKGROUND:Observational studies have indicated a high but heterogeneous prevalence of low bone mineral density (BMD) and vertebral fractures (VF) in patients with systemic lupus erythematosus (SLE). Therefore, the objectives of this systematic review and meta-regression were: 1) to compare BMD between SLE patients and healthy controls and 2) to evaluate the relationship between BMD and glucocorticoid therapy and VF in SLE patients. METHODS AND FINDINGS:Articles were identified from electronic databases (PubMed, Embase, VHL, SciELO and the Cochrane Library). Prospective longitudinal and cross-sectional studies were considered for review. We evaluated the quality of the evidence included using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. In total, 38 articles were identified and analyzed (3442 SLE cases and 6198 controls) in the analysis of BMD (9232 women and 408 men). There were significant differences in mean BMD between SLE patients and controls. BMD mean difference in cases/controls: -0.0566 95% CI (-0.071, -0.0439; p = < 0.0001). When only SLE patients were analyzed, the BMD did not significantly differ between patients who had or had not received glucocorticoid (GCT) therapy. 694 SLE patients were included in the analysis of VF (189 with VF vs. 505 without VF). Patients with VF had lower BMD than patients without VF (BMD mean difference without VF/with VF: 0.033 (95%CI: 0.006-0.060); p-value: 0.0156). CONCLUSIONS:Patients with SLE had lower BMD than healthy controls. Moreover, SLE patients with VF had lower BMD than patients without VF. However, our data did not show that GCT therapy had an impact on BMD.
| S-EPMC5999233 | biostudies-literature
Project description:BACKGROUND:Vitamin D deficiency has long been studied as a risk factor for osteoporosis. However, the association between serum vitamin D status, bone mineral density (BMD) and the incidence of vertebral fractures (OVFs) remain controversial. It is believed that free portion of the circulating vitamin D carries the metabolic activities of vitamin D. Therefore, the aim of the present study is to analyse if free vitamin D correlates with BMD and osteoporotic fragile vertebral fractures in the elderly population. METHODS:A total of 90 consecutive patients, including 81 female and 9 male patients, aged >?48?years, were included in this cross sectional study between March and July of 2018. Total vitamin D (total 25(OH)D), free vitamin D (free 25(OH)D), calcium and phosphorus were measured. BMD was measured using dual energy X-ray absorptiometry (DEXA) and osteoporotic vertebral fracture was assessed using plain radiograph. Multiple linear regression was performed to find out the association between total vitamin D, free vitamin D and BMD at various sites. To evaluate the association with osteoporotic vertebral multivariate logistic regression model was used. RESULTS:The mean total vitamin D and free vitamin D were 25.1?±?10.2 and 6.1?±?1.7 respectively. Free vitamin D had a linear correlation with total vitamin D (R2?=?0.69). While free vitamin D had a positive correlation with lumbar BMD roles (p?<?0.05), total vitamin D didn't have any association with BMD at any site. Of the total patients, 62 patients (68.9%) had thoracolumbar junction OVFs. Free vitamin D level correlated with the prevalence of OVFs as well as lumbar osteoporosis (p?<?0.05). However, there was no statistical correlation between serum vitamin D status and the OVFs. CONCLUSIONS:Free vitamin D was significantly related to the occurrence of thoracolumbar junction OVFs and lumbar BMD, which assumed to be a positive predictor for fracture and osteoporosis prevention. However, total serum vitamin D levels did not have any association with BMD at different sites as well as fragile vertebral fracture. TRIAL REGISTRATION:The study is registered at clinicaltrials.gov NCT03605173.
| S-EPMC7069188 | biostudies-literature
Project description:Because osteoporosis is under-recognized in patients with vertebral fractures, we evaluated characteristics associated with osteoporosis identification. Most patients with vertebral fractures did not receive evaluation or treatment for osteoporosis. Black, younger, and male participants were particularly unlikely to have had recognized osteoporosis, which could increase their risk of negative outcomes.IntroductionVertebral fractures may be identified on imaging but fail to prompt evaluation for osteoporosis. Our objective was to evaluate characteristics associated with clinical osteoporosis recognition in patients who had vertebral fractures detected on their thoracolumbar spine imaging reports.MethodsWe prospectively identified individuals who received imaging of the lower spine at primary care clinics in 4 large healthcare systems who were eligible for osteoporosis screening and lacked indications of osteoporosis diagnoses or treatments in the prior year. We evaluated characteristics of participants with identified vertebral fractures that were associated with recognition of osteoporosis (diagnosis code in the health record; receipt of bone mineral density scans; and/or prescriptions for anti-osteoporotic medications). We used mixed models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 114,005 participants (47% female; mean age 65 (interquartile range: 57-72) years) were evaluated. Of the 8579 (7%) participants with vertebral fractures identified, 3784 (44%) had recognition of osteoporosis within the subsequent year. In adjusted regressions, Black participants (OR (95% CI): 0.74 (0.57, 0.97)), younger participants (age 50-60: 0.48 (0.42, 0.54); age 61-64: 0.70 (0.60, 0.81)), and males (0.39 (0.35, 0.43)) were less likely to have recognized osteoporosis compared to white participants, adults aged 65 + years, or females.ConclusionIndividuals with identified vertebral fractures commonly did not have recognition of osteoporosis within a year, particularly those who were younger, Black, or male. Providers and healthcare systems should consider efforts to improve evaluation of osteoporosis in patients with vertebral fractures.
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Project description:The Systemic Lupus International Clinics (SLICC)-Frailty Index (FI) is associated with adverse outcomes in systemic lupus erythematosus (SLE). However, to our knowledge, its association with bone mineral density (BMD) and vertebral fractures (VF), has not been investigated using a standardized methods. Our aim was to evaluate the relationship between frailty assessed by SLICC-FI, and BMD and VF in Mestizo women with SLE. Adult women were included in this cross-sectional study. Information concerning the risk factors for VF and BMD in the lumbar spine and total hip was acquired. SLICC-FI was assessed at baseline. A semi-quantitative method was utilized to evaluate the prevalence of VF on lateral thoracolumbar radiographs. Univariate and multivariate regression analyses were performed adjusting for age, body mass index (BMI), SLE duration, cumulative glucocorticoid dose, bisphosphonate use, and BMD measurements. We included 202 women with SLE (mean age [SD] = 43.3 [13.6] years). The mean (SD) SLICC-FI value was 0.14 (0.09). Eleven (5.4%) patients were categorized as robust, 62 (30.7%) as relatively less fit, 84 (41.6%) as least fit, and 45 (22.3%) as frail. Both univariate and multivariate models showed associations between frailty (defined as SLICC-FI > 0.21) and prevalent VF in the entire population (OR 5.76, 95% CI 2.53-13.12; P < 0.001) and in the premenopausal group (OR 4.29, 95% CI; P = 0.047). We also found an association between the SLICC-FI and low BMD. In conclusion, frailty assessed by SLICC-FI might be associated with VF and low BMD in mestizo females with SLE.
| S-EPMC10618373 | biostudies-literature
Project description:Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| S-EPMC9299688 | biostudies-literature
Project description:This study aimed to better define the role of heel-QUS in fracture prediction. Our results showed that heel-QUS predicts fracture independently of FRAX, BMD, and TBS. This corroborates its use as a case finding/pre-screening tool in osteoporosis management.IntroductionQuantitative ultrasound (QUS) characterizes bone tissue based on the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Heel-QUS predicts osteoporotic fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). We aimed to investigate whether (1) heel-QUS parameters predict major osteoporotic fractures (MOF) independently of the trabecular bone score (TBS) and (2) the change of heel-QUS parameters over 2.5 years is associated with fracture risk.MethodsOne thousand three hundred forty-five postmenopausal women from the OsteoLaus cohort were followed up for 7 years. Heel-QUS (SOS, BUA, and stiffness index (SI)), DXA (BMD and TBS), and MOF were assessed every 2.5 years. Pearson's correlation and multivariable regression analyses were used to determine associations between QUS and DXA parameters and fracture incidence.ResultsDuring a mean follow-up of 6.7 years, 200 MOF were recorded. Fractured women were older, more treated with anti-osteoporosis medication; had lower QUS, BMD, and TBS; higher FRAX-CRF risk; and more prevalent fractures. TBS was significantly correlated with SOS (0.409) and SI (0.472). A decrease of one SD in SI, BUA or SOS increased the MOF risk by (OR(95%CI)) 1.43 (1.18-1.75), 1.19 (0.99-1.43), and 1.52 (1.26-1.84), respectively, after adjustment for FRAX-CRF, treatment, BMD, and TBS. We found no association between the change of QUS parameters in 2.5 years and incident MOF.ConclusionHeel-QUS predicts fracture independently of FRAX, BMD, and TBS. Thus, QUS represents an important case finding/pre-screening tool in osteoporosis management. The change in QUS over time was not associated with future fractures, making it inappropriate for patient monitoring.
| S-EPMC10382398 | biostudies-literature
Project description:Vertebral fracture (VF) locations are bimodally distributed in the spine. The association between VF and bone attenuation (BA) measured on chest CT scans varied according to the location of VFs, indicating that other factors than only BA play a role in the bimodal distribution of VFs.IntroductionVertebral fractures (VFs) are associated with low bone mineral density but are not equally distributed throughout the spine and occur most commonly at T7-T8 and T11-T12 ("cVFs") and less commonly at T4-T6 and T9-T10 ("lcVF"). We aimed to determine whether associations between bone attenuation (BA) and VFs vary between subjects with cVFs only, with lcVFs only and with both cVFs and lcVFs.MethodsChest CT images of T4-T12 in 1237 smokers with and without COPD were analysed for prevalent VFs according to the method described by Genant (11,133 vertebrae). BA (expressed in Hounsfield units) was measured in all non-fractured vertebrae (available for 10,489 vertebrae). Linear regression was used to compare mean BA, and logistic regression was used to estimate the association of BA with prevalent VFs (adjusted for age and sex).ResultsOn vertebral level, the proportion of cVFs was significantly higher than of lcVF (5.6% vs 2.0%). Compared to subjects without VFs, BA was 15% lower in subjects with cVFs (p < 0.0001), 25% lower in subjects with lcVFs (p < 0.0001) and lowest in subjects with cVFs and lcVFs (- 32%, p < 0.0001). The highest ORs for presence of VFs per - 1SD BA per vertebra were found in subjects with both cVFs and lcVFs (3.8 to 4.6).ConclusionsThe association between VFs and BA differed according to VF location. ORs increased from subjects with cVFs to subjects with lcVFs and were highest in subjects with cVFs and lcVFs, indicating that other factors than only BA play a role in the bimodal VF distribution.Trial registrationClinicaltrials.gov identifier: NCT00292552.
| S-EPMC8387252 | biostudies-literature