Article
Biochemistry & Molecular Biology
Debora Varela, Tatiana Varela, Natercia Conceicao, M. Leonor Cancela
Summary: This study provides novel insights into the regulation of ZNF687 gene by demonstrating that NF kappa B, PU.1, DLX5, and SOX9 are regulators of ZNF687 promoters, and DNA methylation influences their activity. The contribution of the dysregulation of these mechanisms in Paget's disease of bone should be further elucidated.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wanki Yoo, Yi Wei Song, Jihyun Kim, Jihye Ahn, Jaehoon Kim, Yongdae Shin, Je-Kyung Ryu, Kyeong Kyu Kim
Summary: This study provides valuable mechanistic insights into the collaborative interplay of SOX2 and its coactivator p300 in transcriptional condensation and activation within SOX2-enriched SEs.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Developmental Biology
Ivelisse Cajigas, Abhijit Chakraborty, Madison Lynam, Kelsey R. Swyter, Monique Bastidas, Linden Collens, Hao Luo, Ferhat Ay, Jhumku D. Kohtz
Summary: The study reveals that Evf2 interacts with factors like Sox2 to regulate gene expression on chromosome 6 in mice. The interactions between Evf2 and Sox2 influence the activity of Dlx5/6UCE, ultimately affecting gene expression.
Article
Biochemistry & Molecular Biology
Tiebin Wang, Nathan Tague, Stephen A. Whelan, Mary J. Dunlop
Summary: Transcription factor decoys can effectively regulate gene expression, with tunability through changes in copy number or modifications to the DNA decoy site sequence. Introducing the decoy system can significantly increase arginine production in metabolic flux steering, without affecting growth compared to wild type strains.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Tiegh Taylor, Natalia Sikorska, Virlana M. Shchuka, Sanjay Chahar, Chenfan Ji, Neil N. Macpherson, Sakthi D. Moorthy, Marit A. C. de Kort, Shanelle Mullany, Nawrah Khader, Zoe E. Gillespie, Lida Langroudi, Ian C. Tobias, Tineke L. Lenstra, Jennifer A. Mitchell, Tom Sexton
Summary: The connection between transcriptional control and chromatin architecture is not clearly understood. This study using genome editing and chromatin interaction analysis in mouse embryonic stem cells found a disconnect where Sox2 transcriptional activation is traced back to a few key transcription factor binding sites that have no effect on promoter-enhancer interaction frequencies or topological domain organization. Maintenance of local chromatin architecture, including at the topologically associating domain boundary downstream from the Sox2 enhancer, is distributed across multiple transcription factor-bound regions and is independent of CTCF. Additionally, disruption of promoter-enhancer interactions has no effect on Sox2 transcription. These findings suggest that many transcription factors can modulate chromatin architecture independently of CTCF.
GENES & DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Michela Maresca, Teun van den Brand, Hangpeng Li, Hans Teunissen, James Davies, Elzo de Wit
Summary: This study demonstrates the importance of the pioneer transcription factor SOX2 in maintaining chromatin accessibility and reveals that open chromatin sites maintained by SOX2 are highly predictive of gene expression. Other SOX2 binding sites, however, are largely dispensable for gene regulation.
Article
Biochemistry & Molecular Biology
Ran Brosh, Camil Coedho, Andre M. Ribeiro-dos-Santos, Gwen Ellis, Megan S. Hogan, Hannah J. Ashe, Nicolette Somogyi, Raquel Ordonez, Raven D. Luther, Emily Huang, Jef D. Booke, Matthew T. Maurano
Summary: The expression of Sox2 gene in mouse embryonic stem cells (mESCs) relies on a cluster of distal DNase I hypersensitive sites (DHSs), but the individual contributions and the degree of interdependence between these DHSs are still unknown. Through the use of Big-IN technology, we found that two DHSs were sufficient to activate Sox2 gene expression over long distances, while three nearby DHSs were entirely context dependent and showed no activity alone, but significantly enhanced the activity of autonomous DHSs. Our study highlights the role of context in modulating genomic regulatory element function, and our synthetic regulatory genomics approach provides a roadmap for dissecting other genomic loci.
Article
Multidisciplinary Sciences
Xianchun Lan, Song Ding, Tianzhe Zhang, Ying Yi, Conghui Li, Wenwen Jin, Jian Chen, Kaiwei Liang, Hengbin Wang, Wei Jiang
Summary: This study reveals that PCGF6 plays a crucial role in determining the lineage specification of human pluripotent stem cells by promoting neuroectoderm differentiation and repressing mesendoderm differentiation. The activation of the SOX2 gene and the repression of the WNT/beta-catenin signaling pathway are key mechanisms involved in this process.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Cristiana Barone, Mariachiara Buccarelli, Francesco Alessandrini, Miriam Pagin, Laura Rigoldi, Irene Sambruni, Rebecca Favaro, Sergio Ottolenghi, Roberto Pallini, Lucia Ricci-Vitiani, Paolo Malatesta, Silvia K. Nicolis
Summary: The transcription factor Sox2 plays a crucial role in the maintenance of cancer stem cells (CSC) in brain gliomas. Deletion of Sox2 leads to cell proliferation arrest and derepression of multiple genes, which are involved in glioma CSC maintenance. Overexpression of certain derepressed genes such as Ebf1, Hey2, Zfp423, and Cdkn2b significantly reduces cell proliferation in vitro and tumorigenesis in vivo, pointing to them as potential therapeutic targets.
Article
Cell Biology
Alvaro Quintanal-Villalonga, Vidushi Durani, Amin Sabet, Esther Redin, Kenta Kawasaki, Moniquetta Shafer, Wouter R. Karthaus, Samir Zaidi, Yingqian A. Zhan, Parvathy Manoj, Harsha Sridhar, Nisargbhai S. Shah, Andrew Chow, Umesh K. Bhanot, Irina Linkov, Marina Asher, Helena A. Yu, Juan Qiu, Elisa de Stanchina, Radhika A. Patel, Colm Morrissey, Michael C. Haffner, Richard P. Koche, Charles L. Sawyers, Charles M. Rudin
Summary: In lung and prostate adenocarcinomas, up-regulation of exportin 1 is observed, especially after inactivation of TP53 and RB1 genes, and its inhibition can prevent NE transformation and improve response to targeted therapies. Ectopic SOX2 expression can restore NE phenotype despite exportin 1 inhibition. Furthermore, selinexor sensitizes NE-transformed small cell carcinomas to standard cytotoxic treatments. These findings suggest that exportin 1 inhibition could be a potential therapeutic target for preventing or treating NE transformation in lung and prostate adenocarcinoma.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Nikhil Baban Ghate, Sungmin Kim, Roasa Mehmood, Yonghwan Shin, Kyunghwan Kim, Woojin An
Summary: VprBP is an overexpressed kinase in cancer cells that plays a major role in epigenetic gene silencing and tumorigenesis. It has been found to phosphorylate p53 at serine 367 (S367p), leading to attenuation of p53's transcriptional and growth suppressive activities.
Article
Cell Biology
Miriam Pagin, Mattias Pernebrink, Mattia Pitasi, Federica Malighetti, Chew-Yee Ngan, Sergio Ottolenghi, Giulio Pavesi, Claudio Cantu, Silvia K. Nicolis
Summary: The transcription factor SOX2 is crucial for brain development and neural stem cell maintenance. Study shows that FOS, a SOX2 transcriptional target, can rescue defects in neuronal production caused by Sox2 deletion.
Article
Biochemistry & Molecular Biology
Sara Mercurio, Chiara Alberti, Linda Serra, Simone Meneghini, Pietro Berico, Jessica Bertolini, Andrea Becchetti, Silvia K. Nicolis
Summary: The study shows that deleting Sox2 at different developmental stages in mice impacts hippocampal development, leading to intellectual disability and seizures. Early deletion of Sox2 significantly affects the DG region, and downregulation of related functional genes may be one of the molecular mechanisms contributing to the defect.
Article
Cell Biology
Jonathan Lerner, Andrew Katznelson, Jingchao Zhang, Kenneth S. Zaret
Summary: Pioneer transcription factors interact with nucleosomes to scan silent, compact chromatin, enabling cooperative events that modulate gene activity. While at a subset of sites pioneer factors access chromatin by assisted loading with other transcription factors, the nucleosome-binding properties of pioneer factors enable them to initiate zygotic genome activation, embryonic development, and cellular reprogramming. Thus, pioneer factors target compact chromatin through distinct processes.
Article
Medicine, General & Internal
Ana-Maria Gheorghe, Laura-Semonia Stanescu, Eugenia Petrova, Mara Carsote, Claudiu Nistor, Adina Ghemigian
Summary: This study reports a rare case of a patient diagnosed with both Paget's disease of the bone and Lynch syndrome. Pathogenic variants in the SQSTM1 and MSH2 genes were found through whole exome sequencing. The patient's daughter carries these pathogenic variants but is currently clinically asymptomatic.
Article
Endocrinology & Metabolism
Delphine Farlay, Sebastien Rizzo, Louis-Georges Ste-Marie, Laetitia Michou, Suzanne N. Morin, Shijing Qiu, Pascale Chavassieux, Roland D. Chapurlat, Sudhaker D. Rao, Jacques P. Brown, Georges Boivin
Summary: Bisphosphonates are commonly used drugs for treating osteoporosis, but long-term use may increase the risk of atypical femur fracture. Research found that patients with AFF had higher bone mineralization levels compared to non-AFF patients, potentially due to the accumulation of bisphosphonates in bone mineral affecting the osteocyte cytoskeleton.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Clinical Neurology
Andreia Adriao, Isabel Santana, Carolina Ribeiro, M. Leonor Cancela, Natercia Conceicao, Manuela Grazina
Summary: This study identified a heterozygous deletion of 13 nucleotides in the 5' UTR region of the MEF2C gene in a FTLD patient, indicating its potential contribution to the disease phenotype. The mutation may affect mRNA secondary structure and stability, thus potentially influencing MEF2C protein levels.
NEUROLOGICAL SCIENCES
(2022)
Article
Endocrinology & Metabolism
Emil Schemitsch, Jonathan D. Adachi, Jacques P. Brown, Jean-Eric Tarride, Natasha Burke, Thiago Oliveira, Lubomira Slatkovska
Summary: In this large retrospective cohort study, one in four patients experienced a subsequent hip fracture after any initial fracture, with the most common being hip fractures, occurring on average within 1.5 years. These findings emphasize the importance of early post-fracture interventions to reduce the risk of imminent hip fractures and the associated high costs.
OSTEOPOROSIS INTERNATIONAL
(2022)
Article
Endocrinology & Metabolism
Julie-Catherine Coll, Elodie Garceau, William D. Leslie, Mathieu Genest, Laetitia Michou, S. John Weisnagel, Fabrice Mac-Way, Caroline Albert, Suzanne N. Morin, Remi Rabasa-Lhoret, Claudia Gagnon
Summary: The prevalence of vertebral fractures is comparable between individuals with well-controlled T1D and nondiabetic controls, but T1D patients have lower bone density and trabecular bone score.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Rheumatology
Laetitia Michou, Anne-Sophie Julien, Holly O. Witteman, Jean Legare, Lucie Ratelle, Alexandra Godbout, Johanne Tardif, Suzanne Cote, Genevieve Boily, Rebecca Lui, Alena Ikic, Judith Trudeau, Jean-Luc Tremblay, Isabelle Fortin, Louis Bessette, Anne-Laure Chetaille, Paul R. Fortin
Summary: This study suggests that for patients with active rheumatoid arthritis receiving biological or targeted synthetic disease-modifying antirheumatic drugs, an educational DVD followed by a teleconference intervention can improve their self-care safety skills in practical situations.
ARCHIVES OF RHEUMATOLOGY
(2022)
Article
Endocrinology & Metabolism
Delphine Farlay, Sebastien Rizzo, David W. Dempster, Shuang Huang, Arkadi Chines, Jacques P. Brown, Georges Boivin
Summary: In postmenopausal women with osteoporosis, denosumab therapy for 10 years significantly increased bone mineralization, with more pronounced changes within the first 5 years. The study showed that denosumab treatment for 5 years led to a transition of mineral to more mature crystals and lower microhardness, indicating a persistence of low bone remodeling state at 5 and 10 years.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Ron Goeree, Natasha Burke, Manon Jobin, Jacques P. Brown, Donna Lawrence, Bjorn Stollenwerk, Damon Willems, Ben Johnson
Summary: This study shows that romosozumab followed by alendronate is a cost-effective treatment option for postmenopausal women with osteoporosis at high risk for fracture in Canada. It is associated with reduced costs and greater benefit compared to alendronate and risedronate alone.
ARCHIVES OF OSTEOPOROSIS
(2022)
Article
Multidisciplinary Sciences
Tatiana Varela, Debora Varela, Gil Martins, Natercia Conceicao, M. Leonor Cancela
Summary: CDKL5 deficiency disorder is a rare neurodevelopmental condition characterized by genetic mutations, and zebrafish models provide insights into the pathophysiology of this disorder.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
T. Oliveira, D. L. Kendler, P. Schneider, A. G. Juby, R. J. Wani, M. Packalen, S. Avcil, S. Li, C. Waters-Banker, E. Graves, S. McMullen, J. Brown
Summary: The study found that the rate of low-energy fractures slightly decreased in the first few months of the COVID-19 pandemic, while the rates of surgeries and surgical outcomes remained stable.
ARCHIVES OF OSTEOPOROSIS
(2022)
Article
Endocrinology & Metabolism
T. Oliveira, J. Brown, A. G. Juby, P. Schneider, R. J. Wani, M. Packalen, S. Avcil, S. Li, M. Farris, E. Graves, S. McMullen, D. L. Kendler
Summary: This study aimed to describe the care patterns for osteoporosis during the COVID-19 pandemic in Alberta, Canada, compared to the preceding three years. The study found a decline in healthcare resource utilization, physician visits, diagnostic and laboratory tests, and treatment initiations for osteoporosis during the pandemic. Despite an increase in telehealth visits, oral bisphosphonate treatment initiations remained lower than pre-pandemic levels.
ARCHIVES OF OSTEOPOROSIS
(2022)
Article
Medical Laboratory Technology
Jacques P. Brown, Andrew Don-Wauchope, Pierre Douville, Caroline Albert, Samuel D. Vasikaran
Summary: Bone turnover markers provide a dynamic assessment of bone remodeling, but are not useful in diagnosing osteoporosis or predicting bone loss and fractures. However, they have proven to be valuable in elucidating the pharmacodynamics and effectiveness of osteoporosis medications in clinical trials.
CLINICAL BIOCHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Iris A. L. Silva, Debora Varela, M. Leonor Cancela, Natercia Conceicao
Summary: This study characterized the zebrafish optn gene and protein structure and investigated its transcriptional regulation. Comparative analysis revealed similarities between zebrafish and human OPTN in genomic features, neighboring genes, and structure. Conservation of functional domains and three-dimensional structure of OPTN protein was observed across different species. In vitro experiments identified a functional promoter and a region important for transcriptional regulation in the zebrafish optn gene.
Article
Biochemistry & Molecular Biology
Debora Varela, Tatiana Varela, Natercia Conceicao, M. Leonor Cancela
Summary: This study provides novel insights into the regulation of ZNF687 gene by demonstrating that NF kappa B, PU.1, DLX5, and SOX9 are regulators of ZNF687 promoters, and DNA methylation influences their activity. The contribution of the dysregulation of these mechanisms in Paget's disease of bone should be further elucidated.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Joao M. A. Santos, Vincent Laize, Paulo J. Gavaia, Natercia Conceicao, M. Leonor Cancela
Summary: Ectopic calcification refers to the accumulation of calcium ions in soft tissues due to proteins dysfunction. The traditional model organism for studying abnormal calcium deposition, mice, often have limited understanding of the disease. The zebrafish model has gained popularity recently as it shares similarities with human pathological mineralization disorders and offers insights into potential therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andreia Adriao, Sara Mariano, Jose Mariano, Paulo J. J. Gavaia, M. Leonor Cancela, Marta Vitorino, Natercia Conceicao
Summary: The zebrafish mef2ca;mef2cb double mutants display multiple abnormal phenotypes, including severe craniofacial deformities, developmental arrest due to cardiac edema, and clear alterations in behavior. These mutant lines are valuable for studying MRD20 disease, identifying new therapeutic targets, and screening for potential rescue strategies.
Review
Endocrinology & Metabolism
Jemima E. Schadow, David Maxey, Toby O. Smith, Mikko A. J. Finnila, Sarah L. Manske, Neil A. Segal, Andy Kin On Wong, Rachel A. Davey, Tom Turmezei, Kathryn S. Stok
Summary: This study systematically reviewed the published parameters for assessing subchondral bone in human osteoarthritis using computed tomography. The study identified clinically meaningful parameter categories and emphasized the importance of quantification and standardized measurement methods for improving the evaluation of disease progression.
Article
Endocrinology & Metabolism
Lindsay L. Loundagin, Kim D. Harrison, Xuan Wei, David M. L. Cooper
Summary: This study developed new techniques to define zones of BMU activity based on the 3D morphology of remodeling spaces in rabbit cortical bone and integrated morphological data with the BMU longitudinal erosion rate (LER) to elucidate the spatial-temporal coordination of BMUs and estimate mineral apposition rate (MAR). The results showed that the manual and semi-automated methods accurately defined the zones of remodeling spaces, and these techniques have the potential to assess dynamic parameters of bone resorption and formation.
Article
Endocrinology & Metabolism
Soroush Masrouri, Farzad Esmaeili, Maryam Tohidi, Fereidoun Azizi, Farzad Hadaegh
Summary: This study examined the association between estimated glomerular filtration rate (eGFR) decline and fracture incidence. The results showed that rapid kidney function decline (RKFD) can increase the incidence of fractures among the general population.
Article
Endocrinology & Metabolism
Steven J. Meas, Gabriella M. Daire, Michael A. Friedman, Rachel Denapoli, Preetam Ghosh, Joshua N. Farr, Henry J. Donahue
Summary: Age- and disuse-related bone loss both lead to decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. It is important to experimentally compare these two mechanisms at a structural and transcriptomic level to better understand their similarities and differences. This study compares the effects of hindlimb unloading and aging on bone microarchitecture and gene expression in mice, finding that while both induce similar changes, aging has a greater impact on the transcriptome and tissue level.
Correction
Endocrinology & Metabolism
Masaru Matsuoka, Sho Tsukamoto, Yuta Orihara, Rieko Kawamura, Mai Kuratani, Nobuhiko Haga, Kenji Ikebuchi, Takenobu Katagiri
Article
Endocrinology & Metabolism
Rachel Kohler, Amy Creecy, David R. Williams, Matthew R. Allen, Joseph M. Wallace
Summary: Osteogenesis imperfecta is a hereditary bone disease that weakens bones and increase fracture risk. Current interventions mainly focus on increasing bone mass, but the compromised tissue-level material properties are not addressed. A study found that a RAL analog could reduce fracture risk, but further development is needed for optimal results in patients with osteogenesis imperfecta.
Article
Endocrinology & Metabolism
So Jeong Park, Eunhye Ji, Hyun Ju Yoo, Kyunggon Kim, Sunghwan Ji, Ji Yeon Baek, Jin Young Lee, Hee-Won Jung, Il-Young Jang, Eunju Lee, Namki Hong, Beom-Jun Kim
Summary: The study analyzed the relationship between serum lumican levels and osteosarcopenia in older adults, showing that older adults with osteosarcopenia had lower serum lumican levels. Lower serum lumican levels were associated with reduced bone mass and grip strength, indicating that lumican levels could be used as a biomarker for assessing the risk of osteosarcopenia, osteoporosis, or sarcopenia in older adults.
Article
Endocrinology & Metabolism
Michael B. Chavez, Michelle H. Tan, Tamara N. Kolli, Natalie L. Andras, Brian L. Foster
Summary: This study revealed the complex mechanisms by which disabling BSP functional domains led to profound and distinct changes in cementoblast cell functions, including dysregulated gene expression and reduced mineralization.
Article
Endocrinology & Metabolism
Julien Seiller, Blandine Merle, Romain Fort, Emilie Virot, Solene Poutrel, Giovanna Cannas, Arnaud Hot, Roland Chapurlat
Summary: The purpose of this study was to assess the prevalence of bone fragility in sickle cell patients and to evaluate the potential risk factors and associated complications.
Article
Endocrinology & Metabolism
Chirantap Oza, Anuradha Khadilkar, Pranay Goel, Madhura Karguppikar, Nikhil Shah, Nikhil Lohiya, Shruti Mondkar, Prashant Patil, Hemchand Prasad, Ankita Maheshwari, Dipali Ladkat, Neha Kajale, Chidvilas More, Devarati Khurjekar, Vaman Khadilkar
Summary: This study revealed that BoneXpert (BX) can be used for accurate assessment of bone age and screening of bone health in Indian children and youth with type-1 diabetes (T1D). 51.5% of T1D subjects showed significantly decreased metacarpal index (MCI). Height, Tanner stage, and vitamin D concentrations were positively correlated with MCI, while HbA1c and disease duration were negatively correlated with MCI.
Article
Endocrinology & Metabolism
Mariam R. Farman, Catherine Rehder, Theodora Malli, Cheryl Rockman-Greenberg, Kathryn Dahir, Gabriel Angel Martos-Moreno, Agnes Linglart, Keiichi Ozono, Lothar Seefried, Guillermo del Angel, Gerald Webersinke, Francesca Barbazza, Lisa K. John, Sewmi M. A. Delana Mudiyanselage, Florian Hoegler, Erica Burner Nading, Erin Huggins, Eric T. Rush, Ahmed El-Gazzar, Priya S. Kishnani, Wolfgang Hoegler
Summary: The ALPL gene variant database serves as an archive for interpreting the clinical significance of ALPL gene variants, facilitating the reclassification of VUS and continuous updates. The project establishes an international expert consortium, providing a multidisciplinary collaboration framework to improve genetic counseling and medical decision-making for HPP patients.
Article
Endocrinology & Metabolism
Giovanni Adami, Davide Gatti, Maurizio Rossini, Alessandro Giollo, Matteo Gatti, Francesco Bertoldo, Eugenia Bertoldo, Amy S. Mudano, Kenneth G. Saag, Ombretta Viapiana, Angelo Fassio
Summary: Certain diseases requiring glucocorticoids are independently associated with an increased risk of fractures. Chronic obstructive pulmonary disease (COPD) and neurological diseases are associated with both vertebral and non-vertebral fracture risk, while rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) are only associated with non-vertebral fractures.
Article
Endocrinology & Metabolism
Frank C. Ko, Rong Xie, Brandon Willis, Zoe G. Herdman, Bryan A. Dulion, Hoomin Lee, Chun-do Oh, Di Chen, D. Rick Sumner
Summary: Intramembranous bone regeneration is important in joint and tooth replacement, but its underlying mechanisms are not well understood. This study found that increased periostin gene expression preceded increases in osteogenic genes during bone regeneration. Using a genetic mouse model, the researchers discovered that cells transiently expressing periostin played a critical role in intramedullary intramembranous bone regeneration.
Article
Endocrinology & Metabolism
T. Savikangas, T. H. Suominen, M. Alen, T. Rantalainen, S. Sipila
Summary: Regular exercise, especially high-intensity physical activity, can help slow down age-related bone loss and prevent a decline in femoral neck bone mineral density.
Article
Endocrinology & Metabolism
Mishaela R. Rubin, Ruban Dhaliwal
Summary: The increased risk of fractures observed in adults with type 1 diabetes (T1D) cannot be solely explained by modest decreases in areal bone mineral density (BMD). Accumulation of advanced glycation endproducts (AGEs) in bone has been suggested as a possible cause for the increased bone fragility in diabetes. Although the evidence linking AGEs and fractures in individuals with T1D is limited, recent data show that AGEs, as measured by skin intrinsic fluorescence, are a risk factor for lower BMD in T1D. Further research is needed to determine if there is a causal relationship between fractures and AGEs in T1D. If confirmed, this could lead to interventions that can reduce AGE accumulation and ultimately reduce fractures in T1D patients.