| 21. |
- Vanderschueren, Dirk, et al.
(author)
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Active Vitamin D (1,25-Dihydroxyvitamin D) and Bone Health in Middle-Aged and Elderly Men: The European Male Aging Study (EMAS).
- 2013
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:3, s. 995-1005
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Journal article (peer-reviewed)abstract
- Context:There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] on bone health including turnover.Objective:The objective of the study was to determine the influence of 1,25(OH)(2)D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.Design, Setting, and Participants:Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)(2)D, 25(OH)D, and PTH were measured. 1,25(OH)(2)D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.Main Outcome Measure(s):QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.Results:A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)(2)D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)(2)D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)(2)D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)(2)D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.Conclusions:Serum 1,25(OH)(2)D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)(2)D and low 25(OH)D is associated with the poorest bone health.
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| 22. |
- Hackett, Jamie A., et al.
(author)
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Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline
- 2012
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In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 139:19, s. 3623-3632
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Journal article (peer-reviewed)abstract
- Mouse primordial germ cells (PGCs) erase global DNA methylation (5mC) as part of the comprehensive epigenetic reprogramming that occurs during PGC development. 5mC plays an important role in maintaining stable gene silencing and repression of transposable elements (TE) but it is not clear how the extensive loss of DNA methylation impacts on gene expression and TE repression in developing PGCs. Using a novel epigenetic disruption and recovery screen and genetic analyses, we identified a core set of germline-specific genes that are dependent exclusively on promoter DNA methylation for initiation and maintenance of developmental silencing. These gene promoters appear to possess a specialised chromatin environment that does not acquire any of the repressive H3K27me3, H3K9me2, H3K9me3 or H4K20me3 histone modifications when silenced by DNA methylation. Intriguingly, this methylation-dependent subset is highly enriched in genes with roles in suppressing TE activity in germ cells. We show that the mechanism for developmental regulation of the germline genome-defence genes involves DNMT3B-dependent de novo DNA methylation. These genes are then activated by lineage-specific promoter demethylation during distinct global epigenetic reprogramming events in migratory (~E8.5) and post-migratory (E10.5-11.5) PGCs. We propose that genes involved in genome defence are developmentally regulated primarily by promoter DNA methylation as a sensory mechanism that is coupled to the potential for TE activation during global 5mC erasure, thereby acting as a failsafe to ensure TE suppression and maintain genomic integrity in the germline.
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| 23. |
- Lindh, Christina, et al.
(author)
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Combination of radiographic measurement of cortical width and clinical risk index for diagnosis of osteoporosis : the OSTEDENT study
- 2006
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Conference paper (peer-reviewed)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by an Active Shape Model (ASM) method in combination with a clinical risk index, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. A questionnaire was completed for each subject to identify factors related to osteoporosis risk and calculate a clinical risk index (OSIRIS). A manually initialised ASM method was used to derive cortical width measurements from each radiograph. ROC analysis was used to identify the most effective clinical index. Logistic regression analysis was used to build a model, with the presence or absence of osteoporosis as the dichotomous dependent variable and OSIRIS and the radiographic data as independent variables. Results: ROC analysis gave an Az value for OSIRIS of 0.841 (95% CI: 0.811 to 0.868). The sensitivity and specificity of the combined radiographic-clinical risk assessment were 38.6% and 97.9% respectively. Conclusions: Combining the cortical width measurement and the clinical risk index provided a high specificity method for detection of subjects with osteoporosis, although sensitivity was modest. This model would be most suitable for use in the context of restricted availability of DXA. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 24. |
- Lindh, Christina, et al.
(author)
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Mandibular cortical index for osteoporosis diagnosis : the OSTEODENT project
- 2006
-
Conference paper (peer-reviewed)abstract
- Objectives: to determine the diagnostic validity of the mandibular cortical index (MCI) for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made an assessment of porosity of the cortex of the lower border of the mandible using MCI. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. MCI data for each observer were dichotomosed so that MCI grade 3 indicated a positive test result and grades 1 and 2 a negative test result. The sensitivities and specificties of MCI for osteoporosis diagnosis were determined: Osteoporosis at any site Osteoporosis at femoral neck Observer Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%) 1 24.8 93.3 27.3 91.3 2 23.4 93.2 24.2 91.3 3 23.4 91.5 24.2 89.8 4 20.6 99.8 22.7 91.8 5 19.1 91.1 22.7 90.3 Interobserver repeatability (using weighted Kappa) showed a range of 0.183 to 0.780, with a median value of 0.467. This median indicated moderate agreement. Conclusions: MCI had low sensitivity but high specificity for diagnosis of osteoporosis. This high specificity might prove to be more appropriate for use in primary dental care than using a different diagnostic threshold. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 25. |
- Lindh, Christina, et al.
(author)
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ROC analysis of automatically measured mandibular cortical width from panoramic radiographs for diagnosis of osteoporosis : the OSTEDENT study
- 2006
-
Conference paper (peer-reviewed)abstract
- 1School of Dentistry and 2Imaging Science and Biomedical Engineering, The University of Manchester, United Kingdom 3School of Dentistry, Oral Pathology and Maxillofacial Surgery, Oral Imaging Centre, Katholieke Universiteit Leuven, Belgium 4Oral Diagnosis and Radiology, The National and Kapodistrian University of Athens, Greece 5Oral Radiology, Malmö University, Sweden 6Oral Radiology, ACTA, Amsterdam, The Netherlands Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by Active Shape Model (ASM) methods, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Two ASM methods, one entirely automatic and one manually initialised, were used to derive measurements of mandibular cortical width. ROC analysis was used to determine the diagnostic ability of manual and ASM methods. Results: 652 subjects were examined (mean age 54.9y; sd=6.10), with 140 (21.5%) being classified as having osteoporosis. Using the manually initialized ASM method, Az values for the diagnosis of osteoporosis at any site and at femoral neck alone were 0.816 (95% CI: 0.784 to 0.845) and 0.835, (95% CI: 0.805-0.863), respectively. Using the automatically initialized ASM method, the Az values for the diagnosis of osteoporosis at any site and at the femoral neck alone were 0.759 (95% CI: 0.724-0.791) and 0.805 (95% CI: 0.773 -0.835), respectively. The difference in Az of the two methods for the diagnosis of osteoporosis at either the hip or spine was significant (p<0.001), but not significant at the femoral neck alone. Conclusions: ASM-based methods ofmandibular cortical width measurement were effective in the diagnosis of osteoporosis. The manually initialized method, involving a small amount of user interaction, performed best. Further analysis is necessary to establish the appropriate diagnostic threshold for clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 26. |
- Lindh, Christina, et al.
(author)
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ROC analysis of densitometric measurements on intraoral radiographs for detection of osteoporosis as part of the OSTEDENT study
- 2006
-
Conference paper (other academic/artistic)abstract
- Objectives: To determine the diagnostic validity of mandibular and maxillary bone density, measured between the premolars (mm Aleq) in detecting osteoporosis at the hip or lumbar spine. Methods: Female subjects between 45 and 70 years of age, were recruited from 4 European centres. They underwent dual x-ray energy absorptiometry of the hip and lumber spine, to provide a gold standard diagnosis of osteoporosis. In addition, intra-oral radiography of upper and lower right premolar region was performed, using an aluminum wedge as a densitometric reference. Jaw bone density in 4 selected regions of interest (ROI) was determined using dedicated software Osteop (Nackaerts et al 2005**). Two ROIs were determined between the upper premolar teeth and another 2 between the lower premolars. 5 observers performed the analysis. Intra- and inter-observer differences and ROC curves were analyzed. Results: Results from 660 subjects (mean age 54.8y; sd 6.19) were suitable for analysis. 136 of these subjects were classified as having osteoporosis. For ROC analysis, measurement data from all observers were averaged, since there was no significant inter-observer difference. Az values as well as 95% confidence intervals are shown in the table: Detecting osteoporosis at any site (spine, hip, femoral neck): ROI1 upper jaw Az 0.691 (0.653 to 0.726) ROI2 upper jaw Az 0.708 (0.671 to 0.743) ROI1 lower jaw Az 0.709 (0.672 o 0.745) ROI2 lower jaw Az 0.702 (0.655 to 0.738) None of the differences in Az between sites was statistically significant (p always > >0.05). Conclusions: Density of the premolar region expressed in mm Aleq is a fair indication for the presence of osteoporosis. More extensive analysis of the OSTEODENT results might reveal an even better predictive tool for osteoporosis screening. **Nackaerts O, Jacobs R, Pillen M, Engelen L, Gijbels F, Devlin H, Lindh C, Nicopolou-Karayianni K, van der Stelt P, Horner K. Accuracy and precision of a densitometric tool for jaw bone. DentoMaxilloFacial Radiology. In press This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 27. |
- Lindh, Christina, et al.
(author)
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ROC analysis of directly measured mandibular cortical width from panoramic radiogarphs for diagnosis of osteoporosis : the OSTEODENT study
- 2006
-
Conference paper (peer-reviewed)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured directly by observers, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made manual measurements of width of the mandibular lower border cortex below the mental foramina bilaterally. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. Az values are given below: Osteoporosis at any site Osteoporosis at femoral neck Observer Az (se) 95% CI Az (se) 95% CI 1 0.782 0.748-0.813 0.804 0.771-0.833 2 0.766 0.731-0.799 0.757 0.722-0.791 3 0.756 0.721-0.788 0.790 0.757-0.821 4 0.746 0.711-0.779 0.762 0.727-0.794 5 0.710 0.673-0.744 0.752 0.718-0.785 A diagnostic threshold of 3mm resulted in a sensitivity of 50.7% and a specificity of 80.4% (data for median observer, 2). Mean within-subject variance for the five observers was 0.126mm (sd = 0.355mm). Repeatability is the difference between two measurements made by any pair of observers for the same subject and was expected to be less than 0.983 mm for 95% of pairs of observations. Conclusions: Direct measurement of mandibular cortical width was diagnostically effective in diagnosis of osteoporosis. However, repeatability may be a problem in clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 28. |
- Lindh, Christina, et al.
(author)
-
Trabecular pattern in intraoral radiographs as a sign of osteoporosis : the OSTEODENT study
- 2006
-
Conference paper (peer-reviewed)abstract
- Objectives: The aim of this study was to investigate if the trabecular pattern in intraoral radiographs, assessed by five observers, could serve as an indicator of osteoporosis. Methods: Six hundred and seventy one women (45 - 70 yrs) from four European centers were included in the study and examined with intraoral radiographs in the right upper and lower premolar region. The patients also underwent examinations with central dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. Five observers assessed the trabecular pattern in the intraoral radiographs into one of three classes: dense, heterogeneous or sparse trabecular pattern. The assessments were made with the aid of reference images and the observers underwent a calibration procedure before starting their assessments. The classifications were compared with the true diagnosis of osteoporosis measured using DXA. Results: The sensitivity and specificity for five observers’ assessments of the intraoral radiographs with sparse trabecular pattern as indicative of osteoporosis at either hip or spine are given in the table below. The values are calculated for patients diagnosed as having osteoporosis at any of the examined sites. Upper jaw Lower jaw Observer Sensitivity Specificity Sensitivity Specificity 1 22.2 90.2 13.2 94.5 2 22.6 94.8 15.8 94.2 3 26.5 91.6 28.1 86.7 4 36.3 87.4 30.2 82.4 5 35.3 93.7 39.1 95.6 If the cut-off included either “heterogeneous” or “sparse” trabeculation then a higher sensitivity was achieved (90.6 – 73.7) but a lower specificity (49.4 – 26.2). Conclusion: Assessment of sparse trabecular pattern on intraoral radiographs offered a combination of low sensitivity but high specificity for osteoporosis diagnosis. If it is assumed that high specificity is preferred for osteoporosis assessment by dentists, then this method may have potential for clinical use, although inter-observer variability may be a problem. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
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| 29. |
- Nackaerts, Olivia, et al.
(author)
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Osteoporosis detection using intraoral densitometry
- 2008
-
In: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 37:5, s. 282-287
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine the diagnostic accuracy of mandibular and maxillary bone density in detecting osteoporosis using receiver operating characteristic (ROC) analysis. METHODS: 671 women between 45 years and 70 years of age underwent dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. This was the gold standard for diagnosing osteoporosis. Intraoral radiography of the upper and lower right premolar region was performed, using an aluminium wedge as a densitometric reference. Jaw bone density was determined using dedicated software. Observer differences and ROC curves were analysed. RESULTS: For detecting osteoporosis using jaw bone density, the area under the ROC curve (A(z)) was 0.705. For separate analysis of mandibular and maxillary films, sensitivity varied from 33.9% to 38.7% and specificity from 83.5% to 85.3% when using a threshold of 4.3 mm Al equivalent. CONCLUSIONS: Density of the premolar region reaches a fair diagnostic accuracy, which might improve when including additional factors in the analysis and refining the densitometric tool.
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| 30. |
- Reddington, James P, et al.
(author)
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Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes
- 2013
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:3, s. R25-
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Journal article (peer-reviewed)abstract
- BACKGROUND: DNA methylation and the Polycomb repression system are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear.RESULTS: By genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression.CONCLUSIONS: An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining Polycomb Repressive Complex 2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.
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