| 1. |
- Adam, A, et al.
(author)
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Abstracts from Hydrocephalus 2016.
- 2017
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In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Journal article (peer-reviewed)
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| 7. |
- Akdemir, KC, et al.
(author)
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Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
- 2020
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 294-
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Journal article (peer-reviewed)abstract
- Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.
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| 8. |
- Bale, S. D., et al.
(author)
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The FIELDS Instrument Suite for Solar Probe Plus
- 2016
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 204:1-4, s. 49-82
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Research review (peer-reviewed)abstract
- NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
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| 10. |
- Tran, Thao Thanh, et al.
(author)
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Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
- 2022
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In: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 18:1
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Journal article (peer-reviewed)abstract
- A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.
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| 11. |
- Kanis, J. A., et al.
(author)
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Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures
- 2020
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31, s. 1-12
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Journal article (peer-reviewed)abstract
- Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods Clinical perspective and updated literature search. Results The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.
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| 13. |
- Chandran, M., et al.
(author)
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Impact of osteoporosis and osteoporosis medications on fracture healing : a narrative review
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In: Osteoporosis International. - 0937-941X.
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Research review (peer-reviewed)abstract
- Summary: Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. Background: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. Methods: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). Results: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. Conclusion: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.
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| 15. |
- Lems, W., et al.
(author)
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Vertebral fracture : epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services
- 2021
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32:3, s. 399-411
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Journal article (peer-reviewed)abstract
- Summary: Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. Summary points: • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.
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| 16. |
- Arul, A.J, et al.
(author)
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Reliability analysis of safety grade decay heat removal system of Indian prototype fast breeder reactor
- 2006
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In: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549. ; 33:2, s. 180-188
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Journal article (peer-reviewed)abstract
- The 500MW Indian pool type Prototype Fast Breeder Reactor (PFBR), is provided with two independent and diverse Decay Heat Removal (DHR) systems viz., Operating Grade Decay Heat Removal System (OGDHRS) and Safety Grade Decay Heat Removal System (SGDHRS). OGDHRS utilizes the secondary sodium loops and Steam–Water System with special decay heat removal condensers for DHR function. The unreliability of this system is of the order of 0.1–0.01. The safety requirements of the present generation of fast reactors are very high, and specifically for DHR function the failure frequency should be less than 1E-7/ry. Therefore, a passive SGDHR system using four completely independent thermo-siphon loops in natural convection mode is provided to ensure adequate core cooling for all Design Basis Events. The very high reliability requirement for DHR function is achieved mainly with the help of SGDHRS. This paper presents the reliability analysis of SGDHR system. Analysis is performed by Fault Tree method using "CRAFT" software developed at Indira Gandhi Centre for Atomic Research. This software has special features for compact representation and CCF analysis of high redundancy safety systems encountered in nuclear reactors. Common Cause Failures (CCF) are evaluated by beta-factor method. The reliability target for SGDHRS arrived from DHR reliability requirement and the ultimate number of demands per year (7/y) on SGDHRS is that the failure frequency should be <=1.4E-8/de. Since it is found from the analysis that the unreliability of SGDHRS with identical loops is 5.2E-6/de and dominated by leak rates of components like AHX, DHX and sodium dump and isolation valves, options with diversity measures in important components were studied. The failure probability of SGDHRS for a design consisting of 2 types of diverse loops (Diverse AHX, DHX and sodium dump and isolation valves) is 2.1E-8/de, which practically meets the reliability requirement.
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| 19. |
- Bauermeister, S, et al.
(author)
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The Dementias Platform UK (DPUK) Data Portal
- 2020
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In: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 35:6, s. 601-611
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Journal article (peer-reviewed)abstract
- The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
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| 20. |
- Bortz, Robert H., et al.
(author)
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Single-Dilution COVID-19 Antibody Test with Qualitative and Quantitative Readouts
- 2021
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In: mSphere. - : American Society for Microbiology. - 2379-5042. ; 6:2
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Journal article (peer-reviewed)abstract
- The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to place an immense burden on societies and health care systems. A key component of COVID-19 control efforts is serological testing to determine the community prevalence of SARS-CoV-2 exposure and quantify individual immune responses to prior SARS-CoV-2 infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood samples with high sensitivity and specificity. We further show that this sensitive test affords the estimation of viral spike-specific IgG titers from a single sample measurement, thereby providing a simple and scalable method to measure the strength of an individual's immune response. The accuracy, adaptability, and cost-effectiveness of this test make it an excellent option for clinical deployment in the ongoing COVID-19 pandemic.IMPORTANCE Serological surveillance has become an important public health tool during the COVID-19 pandemic. Detection of protective antibodies and seroconversion after SARS-CoV-2 infection or vaccination can help guide patient care plans and public health policies. Serology tests can detect antibodies against past infections; consequently, they can help overcome the shortcomings of molecular tests, which can detect only active infections. This is important, especially when considering that many COVID-19 patients are asymptomatic. In this study, we describe an enzyme-linked immunosorbent assay (ELISA)-based qualitative and quantitative serology test developed to measure IgG and IgA antibodies against the SARS-CoV-2 spike glycoprotein. The test can be deployed using commonly available laboratory reagents and equipment and displays high specificity and sensitivity. Furthermore, we demonstrate that IgG titers in patient samples can be estimated from a single measurement, enabling the assay's use in high-throughput clinical environments.
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| 22. |
- Dand, Nick, et al.
(author)
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Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
- 2017
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In: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
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Journal article (peer-reviewed)abstract
- Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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| 23. |
- Dhama, Kuldeep, et al.
(author)
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SARS-CoV-2 emerging Omicron subvariants with a special focus on BF.7 and XBB.1.5 recently posing fears of rising cases amid ongoing COVID-19 pandemic
- 2022
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In: Journal of Experimental Biology and Agricultural Sciences. - : JEBAS. - 2320-8694. ; 10:6, s. 1215-1221
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Journal article (peer-reviewed)abstract
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron versions have been the sole one circulating for quite some time. Subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 of the Omicron emerged over time and through mutation, with BA.1 responsible for the most severe global pandemic between December 2021 and January 2022. Other Omicron subvariants such as BQ.1, BQ.1.1, BA.4.6, BF.7, BA.2.75.2, XBB.1 appeared recently and could cause a new wave of increased cases amid the ongoing COVID-19 pandemic. There is evidence that certain Omicron subvariants have increased transmissibility, extra spike mutations, and ability to overcome protective effects of COVID-19 neutralizing antibodies through immunological evasion. In recent months, the Omicron BF.7 subvariant has been in the news due to its spread in China and a small number of other countries, raising concerns about a possible rebound in COVID-19 cases. More recently, the Omicron XBB.1.5 subvariant has captured international attention due to an increase in cases in the United States. As a highly transmissible sublineage of Omicron BA.5, as well as having a shorter incubation time and the potential to reinfect or infect immune population, BF.7 has stronger infection ability. It appears that the regional immunological landscape is affected by the amount and timing of previous Omicron waves, as well as the COVID-19 vaccination coverage, which in turn determines whether the increased immune escape of BF.7 and XBB.1.5 subvariants is sufficient to drive new infection waves. Expanding our understanding of the transmission and efficacy of vaccines, immunotherapeutics, and antiviral drugs against newly emerging Omicron subvariants and lineages, as well as bolstering genomic facilities for tracking their spread and maintaining a constant vigilance, and shedding more light on their evolution and mutational events, would help in the development of effective mitigation strategies. Importantly, reducing the occurrence of mutations and recombination in the virus can be aided by bolstering One health approach and emphasizing its significance in combating zoonosis and reversal zoonosis linked with COVID-19. This article provides a brief overview on Omicron variant, its recently emerging lineages and subvairants with a special focus on BF.7 and XBB.1.5 as much more infectious and highly transmissible variations that may once again threaten a sharp increase in COVID-19 cases globally amid the currently ongoing pandemic, along with presenting salient mitigation measures.
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| 25. |
- Ferrari, S. L., et al.
(author)
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Diagnosis and management of bone fragility in diabetes : an emerging challenge
- 2018
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:12, s. 2585-2596
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Journal article (peer-reviewed)abstract
- Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.
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