Article
Cell Biology
Wen Pan, Jianyu Gu, Shihan Xu, Chunmei Zhang, Jinsong Wang, Songlin Wang, Junji Xu
Summary: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication in patients with osteoporosis or metastatic bone cancer. The study found that dietary nitrate, abundant in green vegetables, can protect against BRONJ-like lesions in mice. Nitrate intake increased plasma nitric oxide levels, reducing monocyte necrosis and inflammatory cytokine production. The findings suggest that dietary nitrate can inhibit monocyte necroptosis in BRONJ and promote bone remodeling after injury.
CELL PROLIFERATION
(2023)
Review
Immunology
Weidong Zhang, Ling Gao, Wenhao Ren, Shaoming Li, Jingjing Zheng, Shasha Li, Chunmiao Jiang, Shuying Yang, Keqian Zhi
Summary: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect, with hypotheses involving reduced bone remodeling, infection, inflammation, and bisphosphonates-induced immune dysfunction. Treatment with bisphosphonates disrupts mucosal and osteo immune homeostasis, impairing the body's ability to resist infection and repair from injury, contributing to the development of MRONJ.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Gabor Kammerhofer, Daniel Vegh, Dorottya Banyai, Adam Vegh, Arpad Joob-Fancsaly, Peter Hermann, Zoltan Geczi, Tamas Hegedus, Kata Sara Somogyi, Bulcsu Bencze, Zita Biczo, Donat Huba Juhasz, Peter Zaborszky, Marta Ujpal, Mihaly Tamas Vaszilko, Zsolt Nemeth
Summary: This study aimed to evaluate the association between hyperglycemia and medication-related osteonecrosis of the jaw (MRONJ). The results showed a significant association between hyperglycemia and MRONJ, suggesting that hyperglycemia may lead to vascular anomaly and immune dysfunction, resulting in necrosis after tooth extraction.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Hironobu Hata, Kenji Imamachi, Michihiro Ueda, Masashi Matsuzaka, Hiroaki Hiraga, Toshihisa Osanai, Toru Harabayashi, Katsuya Fujimoto, Satoshi Oizumi, Masato Takahashi, Kazuhito Yoshikawa, Jun Sato, Yutaka Yamazaki, Yoshimasa Kitagawa
Summary: The study aimed to clarify the incidence of MRONJ and the corresponding survival rate of patients treated with zoledronic acid for different types of cancer. The results showed that patients with shorter survival times did not develop MRONJ, and dentists need to be aware of prognosis-related factors to predict MRONJ risk for effective dental management planning.
SUPPORTIVE CARE IN CANCER
(2022)
Review
Chemistry, Multidisciplinary
Krzysztof Wrobel, Maciej Sikora, Maciej Checinski, Maria Jas, Dariusz Chlubek
Summary: MRONJ is a condition that is becoming more common in dental and maxillofacial practice, requiring comprehensive, accessible, and up-to-date data. Besides bisphosphonates, angiogenesis inhibitors and anti-RANKL monoclonal antibodies can also increase the risk of the disease. Thorough physical examination, periodic correction of dental prostheses, and adequate preparation for oral procedures can prevent or minimize the risk of MRONJ.
APPLIED SCIENCES-BASEL
(2021)
Review
Toxicology
Bhumrapee Srivichit, Chanisa Thonusin, Nipon Chattipakorn, Siriporn C. Chattipakorn
Summary: Bisphosphonates are commonly used in the treatment of bone and joint diseases, but long-term use can lead to osteonecrosis. Osteonecrosis is characterized by cell death and impaired cell functions, with medication-related osteonecrosis of the jaw being the most concerning condition. In addition to surgical treatment, non-surgical interventions have been explored to mitigate bisphosphonate-induced osteonecrosis.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Jie Liu, Nikos Mattheos, Chuanxi Deng, Cheng Su, Zekun Wang, Nanyu Luo, Hua Tang
Summary: Icariin benefits MRONJ by improving soft tissue wound area and empty bone lacuna ratio, while teriparatide activates RANKL expression and reduces bone necrosis area and empty lacuna ratio. These findings suggest potential therapeutic benefits for patients with MRONJ.
JOURNAL OF PERIODONTOLOGY
(2021)
Article
Endocrinology & Metabolism
Judith Everts-Graber, Daniel Lehmann, John-Patrik Burkard, Benoit Schaller, Brigitta Gahl, HansJoerg Haeuselmann, Ueli Studer, Hans-Rudolf Ziswiler, Stephan Reichenbach, Thomas Lehmann
Summary: This study aimed to determine the risk of ONJ in a real-world population, showing a higher incidence rate in patients receiving denosumab therapy compared to those receiving BPs, with previous BP therapy potentially being an additional risk factor for ONJ development.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Dentistry, Oral Surgery & Medicine
Vy Ngoc Thuy Tran, Risa Chaisuparat
Summary: The study investigated the morphology and quantity of osteoclasts in MRONJ, showing enhanced activity and increased number. Presence of osteoblasts, inflammation, and bacteria correlated with changes in osteoclasts. TRAP-positive numbers and intensity did not significantly differ between MRONJ and other groups.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Ilaria Roato, Rodolfo Mauceri, Vincenzo Notaro, Tullio Genova, Vittorio Fusco, Federico Mussano
Summary: The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) involves various factors, and antiresorptive drugs (ARDs), such as bisphosphonates (BPs) and denosumab (Dmab), play a significant role in its development. The time exposure, cumulative dose, and administration intensity of these drugs are crucial in the treatment of patients, particularly cancer patients who have the highest incidence of MRONJ. BPs and Dmab have different mechanisms of action on bone and immune subsets, which ultimately contribute to the onset of MRONJ. However, there is a lack of data on the effects of Dmab, highlighting the need for further studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Athanasios D. Anastasilakis, Jessica Pepe, Nicola Napoli, Andrea Palermo, Christos Magopoulos, Aliya A. Khan, M. Carola Zillikens, Jean-Jacques Body
Summary: This study evaluates the differences of MRONJ among different patient categories and provides recommendations on how to mitigate the risk and optimally manage MRONJ. The results indicate that patients with advanced malignancies are at a higher risk for MRONJ compared to those with benign bone diseases, but the overall risk is considerably lower than the benefits of treatment.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Environmental Sciences
Guillermo Pardo-Zamora, Yanet Martinez, Jose Antonio Moreno, Antonio J. Ortiz-Ruiz
Summary: MRONJ is a rare and severe disease with unclear exact cause and potential multifactorial origins. A case series of three stage 2 MRONJ patients showed complete healing within 12 months of therapeutic protocol application, with radiography demonstrating slow but progressive healing with normal bone structure. Conservative treatment and minimally invasive surgical intervention are effective for stage 2 MRONJ, while application of PRF-L in refractory cases can improve outcomes in soft tissue healing and bone regeneration, though further research is needed to confirm effectiveness.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Medicine, General & Internal
Xiao-Hong Wu, Shi-Wei Chen
Summary: This report presents a case of multiple myeloma (MM) identified in a surgical specimen previously diagnosed as medication-related osteonecrosis of the jaw (MRONJ) in a patient with MM. The patient exhibited symptoms of both MRONJ and MM, suggesting that MM and MRONJ can occur simultaneously at the same site.
Review
Physiology
Siti Salmiah Mohd Yunus, Hui Yuh Soh, Mariati Abdul Rahman, Xin Peng, Chuanbin Guo, Roszalina Ramli
Summary: Medication related osteonecrosis of the jaw (MRONJ) is a condition caused by inhibition of osteoclast activity by certain drugs. It is characterized by exposed necrotic bone or non-healing fistula, accompanied by inflammation and possible infection. There is currently no reliable biomarker for diagnosis.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Se Hwa Kim, Young-Kyun Lee, Tae-Young Kim, Yong-Chan Ha, Sunmee Jang, Ha Young Kim
Summary: The study aimed to estimate the incidence of osteonecrosis of the jaw (ONJ) in Korean osteoporosis patients treated with bisphosphonates (BPs) and identified clinical risk factors such as advanced age, diabetes, and rheumatoid arthritis that increase the risk for ONJ.
Article
Dentistry, Oral Surgery & Medicine
Luciano Pitzurra, Ineke D. C. Jansen, Teun J. de Vries, Michel A. Hoogenkamp, Bruno G. Loos
JOURNAL OF PERIODONTAL RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Cindy Kelder, Jolanda M. A. Hogervorst, Daniel Wismeijer, Cornelis J. Kleverlaan, Teun J. de Vries, Astrid D. Bakker
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Giuliana Ascone, Yixuan Cao, Ineke D. C. Jansen, Irene Di Ceglie, Martijn H. J. van den Bosch, Arjen B. Blom, Peter L. E. M. van Lent, Vincent Everts, Teun J. de Vries
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Jenny A. F. Vermeer, Jonathan Ient, Bostjan Markelc, Jakob Kaeppler, Lydie M. O. Barbeau, Arjan J. Groot, Ruth J. Muschel, Marc A. Vooijs
DISEASE MODELS & MECHANISMS
(2020)
Article
Biochemistry & Molecular Biology
Cindy Kelder, Cornelis J. Kleverlaan, Marjolijn Gilijamse, Astrid D. Bakker, Teun J. de Vries
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Pharmacology & Pharmacy
Shuting Sun, Jianguo Tao, Parish P. Sedghizadeh, Philip Cherian, Adam F. Junka, Esmat Sodagar, Lianping Xing, Robert K. Boeckman, Venkatesan Srinivasan, Zhenqiang Yao, Brendan F. Boyce, Brea Lipe, Jeffrey D. Neighbors, R. Graham G. Russell, Charles E. McKenna, Frank H. Ebetino
Summary: Advancements in designing bone-selective drugs have opened up new possibilities for treating various bone-related diseases. These drugs show promising potential in improving efficacy and safety, especially in addressing bone-related cancers, infections, and osteomyelitis.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ineke D. C. Jansen, Wikky Tigchelaar-Gutter, Jolanda M. A. Hogervorst, Teun J. de Vries, Paul Saftig, Vincent Everts
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Ineke D. C. Jansen, Socrates E. Papapoulos, Nathalie Bravenboer, Teun J. de Vries, Natasha M. Appelman-Dijkstra
Summary: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia caused by a deficiency of cathepsin K. The increase in NTX and CTX levels in lactating women is associated with increased bone resorption, but the consequences of cathepsin K deficiency in lactating women are not yet known.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ton Schoenmaker, Michal Mokry, Dimitra Micha, Coen Netelenbos, Nathalie Bravenboer, Marjolijn Gilijamse, E. Marelise W. Eekhoff, Teun J. de Vries
Summary: The study revealed that Activin-A exclusively induces differential gene expression in FOP cells compared to control cells, with upregulated genes associated with bone metabolism pathways. This early transcriptomic analysis highlights potential mechanisms underlying ACVR1 R206H-mediated ossifications in FOP patients.
Article
Biochemistry & Molecular Biology
Jakob R. Kaeppler, Jianzhou Chen, Mario Buono, Jenny Vermeer, Pavitra Kannan, Wei-Chen Cheng, Dimitrios Voukantsis, James M. Thompson, Mark A. Hill, Danny Allen, Ana Gomes, Veerle Kersemans, Paul Kinchesh, Sean Smart, Francesca Buffa, Claus Nerlov, Ruth J. Muschel, Bostjan Markelc
Summary: This study used multiphoton microscopy to investigate the effect of radiation therapy on tumor vasculature. The results showed that there was minimal structural change in the perfused vasculature after radiation therapy, but non-perfused vessels and blind ends were significantly impaired, accompanied by apoptosis and reduced proliferation of endothelial cells.
Article
Dentistry, Oral Surgery & Medicine
Sune Demant, Ton Schoenmaker, Sophie M. G. van Erck, Sally Dabelsteen, Teun J. de Vries, Lars Bjorndal
Summary: The formation of dense connective tissue within the dental pulp and its association with pulpal inflammation in teeth with advanced carious lesions were investigated in this study. In addition, the study investigated whether inflammation affects the expression of markers related to chondrogenesis/osteogenesis in pulp cells in vitro.
INTERNATIONAL ENDODONTIC JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Bernard J. Smilde, Esmee Botman, Teun J. de Vries, Ralph de Vries, Dimitra Micha, Ton Schoenmaker, Jeroen J. W. M. Janssen, Elisabeth M. W. Eekhoff
Summary: Fibroblasts play a crucial role in maintaining the extracellular matrix of connective tissues. Recent studies have found donor-derived fibroblasts in bone marrow transplant recipients, though some findings were not replicated. This systematic review provides an overview of hematopoietic stem cells differentiating into fibroblasts in various tissues, revealing evidence of fibroblasts derived from hematopoietic stem cells in almost all organs.
Article
Biochemistry & Molecular Biology
Ton Schoenmaker, Joy Zwaak, Bruno G. Loos, Richard Volckmann, Jan Koster, E. Marelise W. Eekhoff, Teun J. de Vries
Summary: Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease characterized by progressive heterotopic ossification that leads to immobility and premature death. It is caused by a mutation in the ACVR1 gene, resulting in altered response to Activin-A. Activin-A induces changes in osteoclastogenesis at the gene expression level, regardless of the presence of the mutated ACVR1 receptor. RNA sequencing analysis revealed differentially expressed genes and enriched pathways associated with osteoclast differentiation, cell fusion, and inflammation. These findings suggest that Activin-A plays a significant role in gene expression during osteoclast formation in FOP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Karina E. Pigeaud, Melanie L. Rietveld, Aster F. Witvliet, Jolanda M. A. Hogervorst, Chen Zhang, Tim Forouzanfar, Nathalie Bravenboer, Ton Schoenmaker, Teun J. de Vries
Summary: Sclerostin is an inhibitor of bone formation produced by osteocytes, and it has been reported to be expressed in periodontal ligament fibroblasts as well. This study aimed to explore the role of sclerostin and its inhibitor romosozumab in osteogenesis and osteoclastogenesis. The results showed that sclerostin did not affect the osteogenic capacity of periodontal ligament fibroblasts, while romosozumab slightly reduced osteoclast formation in co-cultures with peripheral blood mononuclear cells at high concentrations. Further analysis revealed significant differences in the expression of SOST and its receptors between osteocytes and periodontal ligament cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Teun J. de Vries, Antonella S. Kleemann, Jianfeng Jin, Ton Schoenmaker
Summary: Metformin has differential effects on bone cells, promoting bone formation while inhibiting bone resorption. It lowers the expression of negative regulators of bone formation in osteocytes and shifts the osteoblasts' regulation of bone resorption towards decrease RANKL expression and increase OPG expression. Metformin also activates bone formation parameters in osteoblast lineage cells and inhibits osteoclast formation and activity. These effects are likely mediated by the activation of phosphorylated AMP kinase (AMPK). Overall, metformin shows promising potential as a drug in the field of bone research.
CURRENT OSTEOPOROSIS REPORTS
(2023)
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.