Endocrinology and Metabolism

Review Article

Mineral, Bone & Muscle
Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use: Jeonghoon Ha, Youn-Ju Lee, Jinyoung Kim, Chaiho Jeong, Yejee Lim, Jeongmin Lee, Ki-Hyun Baek, on Behalf of the Catholic Medical Center Bone Research Group; Endocrinol Metab. 2025;40(1):47-56. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2125

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Abstract PDF PubReader ePub: Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab’s sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

Original Article

Thyroid
Deep Learning Technology for Classification of Thyroid Nodules Using Multi-View Ultrasound Images: Potential Benefits and Challenges in Clinical Application: Jinyoung Kim, Min-Hee Kim, Dong-Jun Lim, Hankyeol Lee, Jae Jun Lee, Hyuk-Sang Kwon, Mee Kyoung Kim, Ki-Ho Song, Tae-Jung Kim, So Lyung Jung, Yong Oh Lee, Ki-Hyun Baek; Endocrinol Metab. 2025;40(2):216-224. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2058

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Abstract PDF Supplementary Material PubReader ePub: Background
This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules.
Methods
This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images.
Results
Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity.
Conclusion
CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

Review Articles

Mineral, Bone & Muscle
Effects of Endocrine-Disrupting Chemicals on Bone Health: So Young Park, Sung Hye Kong, Kyoung Jin Kim, Seong Hee Ahn, Namki Hong, Jeonghoon Ha, Sihoon Lee, Han Seok Choi, Ki-Hyun Baek, Jung-Eun Kim, Sang Wan Kim, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society; Endocrinol Metab. 2024;39(4):539-551. Published online July 17, 2024; DOI: https://doi.org/10.3803/EnM.2024.1963

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This comprehensive review critically examines the detrimental impacts of endocrine-disrupting chemicals (EDCs) on bone health, with a specific focus on substances such as bisphenol A (BPA), per- and polyfluoroalkyl substances (PFASs), phthalates, and dioxins. These EDCs, by interfering with the endocrine system’s normal functioning, pose a significant risk to bone metabolism, potentially leading to a heightened susceptibility to bone-related disorders and diseases. Notably, BPA has been shown to inhibit the differentiation of osteoblasts and promote the apoptosis of osteoblasts, which results in altered bone turnover status. PFASs, known for their environmental persistence and ability to bioaccumulate in the human body, have been linked to an increased osteoporosis risk. Similarly, phthalates, which are widely used in the production of plastics, have been associated with adverse bone health outcomes, showing an inverse relationship between phthalate exposure and bone mineral density. Dioxins present a more complex picture, with research findings suggesting both potential benefits and adverse effects on bone structure and density, depending on factors such as the timing and level of exposure. This review underscores the urgent need for further research to better understand the specific pathways through which EDCs affect bone health and to develop targeted strategies for mitigating their potentially harmful impacts.

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Elucidating the mechanism of phthalates induced osteoporosis through network toxicology and molecular docking
Xiao Zhang, Xi Zhu, Wenbo Gu, Xusheng Li, Tenyao Niu, Pengcheng Mao, Haifeng Yuan
Ecotoxicology and Environmental Safety.2025; 291: 117820. CrossRef
Exposure to polycyclic aromatic hydrocarbons and bone mineral density in children and adolescents: results from the 2011–2016 National Health and Nutrition Examination Survey
Peng Zhang, Shuailei Li, Hao Zeng, Yongqiang Sun
Frontiers in Public Health.2025;[Epub] CrossRef

Mineral, Bone & Muscle
Bone Loss after Solid Organ Transplantation: A Review of Organ-Specific Considerations: Kyoung Jin Kim, Jeonghoon Ha, Sang Wan Kim, Jung-Eun Kim, Sihoon Lee, Han Seok Choi, Namki Hong, Sung Hye Kong, Seong Hee Ahn, So Young Park, Ki-Hyun Baek, on Behalf of Metabolic Bone Disease Study Group of Korean Endocrine Society; Endocrinol Metab. 2024;39(2):267-282. Published online April 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.1939

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This review article investigates solid organ transplantation-induced osteoporosis, a critical yet often overlooked issue, emphasizing its significance in post-transplant care. The initial sections provide a comprehensive understanding of the prevalence and multifactorial pathogenesis of transplantation osteoporosis, including factors such as deteriorating post-transplantation health, hormonal changes, and the impact of immunosuppressive medications. Furthermore, the review is dedicated to organ-specific considerations in transplantation osteoporosis, with separate analyses for kidney, liver, heart, and lung transplantations. Each section elucidates the unique challenges and management strategies pertinent to transplantation osteoporosis in relation to each organ type, highlighting the necessity of an organ-specific approach to fully understand the diverse manifestations and implications of transplantation osteoporosis. This review underscores the importance of this topic in transplant medicine, aiming to enhance awareness and knowledge among clinicians and researchers. By comprehensively examining transplantation osteoporosis, this study contributes to the development of improved management and care strategies, ultimately leading to improved patient outcomes in this vulnerable group. This detailed review serves as an essential resource for those involved in the complex multidisciplinary care of transplant recipients.

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Romosozumab as Treatment for Severe Osteoporosis in Heart and Lung Transplant Recipients
Lisa M. Raven, Jacqueline R. Center, Christopher A. Muir
Endocrines.2025; 6(1): 2. CrossRef
Side Effects of Immunosuppressant Drugs After Liver Transplant
Filippo Gabrielli, Elisa Bernasconi, Arianna Toscano, Alessandra Avossa, Alessia Cavicchioli, Pietro Andreone, Stefano Gitto
Pharmaceuticals.2025; 18(3): 342. CrossRef
Exploiting regulatory T cells (Tregs): Cutting-edge therapy for autoimmune diseases
Marwa Hassan, Mohamed Elzallat, Dina Mostafa Mohammed, Mahmoud Balata, Walaa H. El-Maadawy
International Immunopharmacology.2025; 155: 114624. CrossRef

Original Article

Mineral, Bone & Muscle
Persistence with Denosumab in Male Osteoporosis Patients: A Real-World, Non-Interventional Multicenter Study: Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek; Endocrinol Metab. 2023;38(2):260-268. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1663

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Background
Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.
Methods
We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.
Results
Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.
Conclusion
Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.

Citations

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Denosumab

Reactions Weekly.2023; 1963(1): 206. CrossRef

Editorial

Miscellaneous
Forty Years Together, New Leap Forward! The 40th Anniversary of the Korean Endocrine Society: Jong Chul Won, Ki-Hyun Baek; Endocrinol Metab. 2022;37(6):851-857. Published online December 26, 2022; DOI: https://doi.org/10.3803/EnM.2022.604

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Original Articles

Thyroid Big Data Articles (National Health Insurance Service Database)
Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea: Jinyoung Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2022;37(2):303-311. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1332

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Background
High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer.
Methods
The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models.
Results
A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126).
Conclusion
Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.

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Ocular motor cranial neuropathy and risk of thyroid cancer: A Korean population-based study
Jaeryung Kim, Kyung-Ah Park, Kyungdo Han, Jin-Hyung Jung, Sei Yeul Oh, Soolienah Rhiu, Xing Xiong,
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Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
Scientific Reports.2024;[Epub] CrossRef
Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013–2014 National Health and Nutrition Examination Survey
Fu-Jen Cheng, Kai-Fan Tsai, Kuo-Chen Huang, Chia-Te Kung, Wan-Ting Huang, Huey-Ling You, Shau-Hsuan Li, Chin-Chou Wang, Wen-Chin Lee, Hsiu-Yung Pan
Frontiers in Public Health.2024;[Epub] CrossRef
Low serum total cholesterol levels predict inferior prognosis of patients with POEMS syndrome
Jue Zhang, Ting Zhang, Ye Yao, Xuxing Shen, Yuanyuan Jin, Run Zhang, Lijuan Chen
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Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field
Michal Olejarz, Ewelina Szczepanek-Parulska, Marek Ruchala
Frontiers in Endocrinology.2024;[Epub] CrossRef
Associations Between Metabolic Obesity Phenotypes and Pathological Characteristics of Papillary Thyroid Carcinoma
Xiuyun Li, Xiujuan Zhang, Li Sun, Lulu Yang, Qihang Li, Zhixiang Wang, Yafei Wu, Ling Gao, Jiajun Zhao, Qingling Guo, Meng Zhou
Endocrine Practice.2024; 30(7): 624. CrossRef
Analysis of risk factors for papillary thyroid carcinoma and the association with thyroid function indicators
Jianning Liu, Zhuoying Feng, Ru Gao, Peng Liu, Fangang Meng, Lijun Fan, Lixiang Liu, Yang Du
Frontiers in Endocrinology.2024;[Epub] CrossRef
Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort
Xue Xiao, Yi Huang, Fetemeh Sadeghi, Maria Feychting, Niklas Hammar, Fang Fang, Zhe Zhang, Qianwei Liu
Cancers.2023; 15(2): 520. CrossRef
Altered serum lipid levels are associated with prognosis of diffuse large B cell lymphoma and influenced by utility of rituximab
Fei Wang, Luo Lu, HuiJuan Chen, Yanhua Yue, Yanting Sun, Feng Yan, Bai He, Rongrong Lin, Weiying Gu
Annals of Hematology.2023; 102(2): 393. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
High-density lipoprotein cholesterol and carcinogenesis
Meijuan Tan, Shijie Yang, Xiequn Xu
Trends in Endocrinology & Metabolism.2023; 34(5): 303. CrossRef
Low Serum Cholesterol Level Is a Significant Prognostic Factor That Improves CLL-IPI in Chronic Lymphocytic Leukaemia
Rui Gao, Kaixin Du, Jinhua Liang, Yi Xia, Jiazhu Wu, Yue Li, Bihui Pan, Li Wang, Jianyong Li, Wei Xu
International Journal of Molecular Sciences.2023; 24(8): 7396. CrossRef
Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study
Weiwei Liang, FangFang Sun
Frontiers in Endocrinology.2023;[Epub] CrossRef
Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: a Mendelian randomization study
Qiang Ma, Yu Li, Lijuan An, Liang Guo, Xiaokang Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Risk factors and diagnostic prediction models for papillary thyroid carcinoma
Xiaowen Zhang, Yuyang Ze, Jianfeng Sang, Xianbiao Shi, Yan Bi, Shanmei Shen, Xinlin Zhang, Dalong Zhu
Frontiers in Endocrinology.2022;[Epub] CrossRef
Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: A case-control study
Jia-liu He, Hua-bing Wu, Wen-lei Hu, Jian-jun Liu, Qian Zhang, Wei Xiao, Ming-jun Hu, Ming Wu, Fen Huang
International Journal of Hygiene and Environmental Health.2022; 246: 114049. CrossRef

Mineral, Bone & Muscle
Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment: Eunhee Jang, Jeonghoon Ha, Ki-Hyun Baek, Moo Il Kang; Endocrinol Metab. 2021;36(6):1211-1218. Published online December 8, 2021; DOI: https://doi.org/10.3803/EnM.2021.1248

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Background
Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/β-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT.
Methods
We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment.
Results
After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (–11.3%±1.6% relative to the baseline at 48 weeks, P<0.05).
Conclusion
Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

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Pharmacological modes of plant-derived compounds for targeting inflammation in rheumatoid arthritis: A comprehensive review on immunomodulatory perspective
Laiba Nazakat, Shaukat Ali, Muhammad Summer, Fakiha Nazakat, Shehzeen Noor, Anfah Riaz
Inflammopharmacology.2025;[Epub] CrossRef
Fracture risk and assessment in adults with cancer
Carrie Ye, William D. Leslie
Osteoporosis International.2023; 34(3): 449. CrossRef
Short-Term Impact of Hematopoietic Stem Cell Transplantation in Leukemia Patients on Bone Bio Markers, Electrolytes and Blood Profile
Rhythm Joshi, Zehva Khan, Aakriti Garg, Dinesh Bhurani, Nidhi B Agarwal, Ubada Aqeel, Mohd Ashif Khan
OBM Transplantation.2023; 07(02): 1. CrossRef

Bone Metabolism
Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek; Endocrinol Metab. 2021;36(4):895-903. Published online August 9, 2021; DOI: https://doi.org/10.3803/EnM.2021.1026

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Background
Prospective comparative studies on the effects of various antidiabetic agents on bone metabolism are limited. This study aimed to assess changes in bone mass and biochemical bone markers in postmenopausal patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective, multicenter, open-label, comparative trial included 264 patients with T2DM. Patients who had received a metformin, or sulfonylurea/metformin combination (Group 1); a thiazolidinedione combination (Group 2); a dipeptidyl peptidase-4 inhibitor (gemigliptin) combination (Group 3); or an sodium-glucose cotransporter 2 inhibitor (empagliflozin) combination (Group 4) were prospectively treated for 12 months; bone mineral density (BMD) and bone turnover marker (BTM) changes were evaluated.
Results
The femoral neck BMD percentage changes were −0.79%±2.86% (Group 1), −2.50%±3.08% (Group 2), −1.05%±2.74% (Group 3), and −1.24%±2.91% (Group 4) (P<0.05). The total hip BMD percentage changes were −0.57%±1.79% (Group 1), −1.74%±1.48% (Group 2), −0.75%±1.87% (Group 3), and −1.27%±1.72% (Group 4) (P<0.05). Mean serum BTM (C-terminal type 1 collagen telopeptide and procollagen type 1 amino-terminal propeptide) levels measured during the study period did not change over time or differ between groups.
Conclusion
Significant bone loss in the femoral neck and total hip was associated with thiazolidinedione combination regimens. However, bone loss was not significantly associated with combination regimens including gemigliptin or empagliflozin. Caution should be exercised during treatment with antidiabetic medications that adversely affect the bone in patients with diabetes at a high risk of bone loss.

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Dapagliflozin Improves High‐Fat Diet‐Induced Cognitive Impairment in Female Mice
Xiaolin Chen, Mingxia Fan, Zhuoni Xiao, Xiaoxing Xiong
Brain and Behavior.2025;[Epub] CrossRef
Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis
Lili Huang, Wei Zhong, Xinghuan Liang, Huijuan Wang, Shi-en Fu, Zuojie Luo
Journal of Clinical Densitometry.2024; 27(1): 101455. CrossRef
A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin
Soo Lim, Seung‐Hwan Lee, Kyung‐Wan Min, Chang Beom Lee, Sang Yong Kim, Hye Jin Yoo, Nan Hee Kim, Jae Hyeon Kim, Seungjoon Oh, Jong Chul Won, Hyuk Sang Kwon, Mi Kyung Kim, Jung Hwan Park, In‐Kyung Jeong, Sungrae Kim
Diabetes, Obesity and Metabolism.2024; 26(6): 2188. CrossRef
Bone Loss in Diabetes Mellitus: Diaporosis
Krisztina Kupai, Hsu Lin Kang, Anikó Pósa, Ákos Csonka, Tamás Várkonyi, Zsuzsanna Valkusz
International Journal of Molecular Sciences.2024; 25(13): 7269. CrossRef
The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review
L. M. Pechmann, F. I. Pinheiro, V. F. C. Andrade, C. A. Moreira
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
The effect of antidiabetic drugs on bone metabolism: a concise review
Stavroula Psachna, Maria Eleni Chondrogianni, Konstantinos Stathopoulos, Antonis Polymeris, Antonios Chatzigeorgiou, Efstathios Chronopoulos, Symeon Tournis, Eva Kassi
Endocrine.2024; 87(3): 907. CrossRef
Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study
Yilin Hou, Xiaoyu Hou, Qian Nie, Qiuyang Xia, Rui Hu, Xiaoyue Yang, Guangyao Song, Luping Ren
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1177. CrossRef
Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model
Yun Kyung Lee, Tae Jung Oh, Ji In Lee, Bo Yoon Choi, Hyen Chung Cho, Hak Chul Jang, Sung Hee Choi
European Journal of Pharmacology.2023; 957: 175946. CrossRef

Hypothalamus and Pituitary Gland
Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma: Jeonghoon Ha, Hansang Baek, Chaiho Jeong, Minsoo Yeo, Seung-Hwan Lee, Jae Hyoung Cho, Ki-Hyun Baek, Moo Il Kang, Dong-Jun Lim; Endocrinol Metab. 2021;36(3):678-687. Published online June 10, 2021; DOI: https://doi.org/10.3803/EnM.2021.978

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Background
Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction.
Methods
A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies.
Results
In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007).
Conclusion
HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.

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Maria Bernadette Cilona, Filippo D’Amico, Chiara Asperti, Giuseppe Alvise Ramirez, Stefano Turi, Giovanni Benanti, Shai Marc Bohane, Serena Nannipieri, Rosa Labanca, Matteo Gervasini, Federica Russetti, Naomi Viapiana, Martina Lezzi, Giovanni Landoni, Lor
Vaccines.2023; 11(3): 567. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef
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Journal of Clinical Medicine.2022; 11(12): 3421. CrossRef

Clinical Study
Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study: Ki-Hyun Baek, Yoon-Sok Chung, Jung-Min Koh, In Joo Kim, Kyoung Min Kim, Yong-Ki Min, Ki Deok Park, Rajani Dinavahi, Judy Maddox, Wenjing Yang, Sooa Kim, Sang Jin Lee, Hyungjin Cho, Sung-Kil Lim; Endocrinol Metab. 2021;36(1):60-69. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.848

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Background
This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis.
Methods
Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months.
Results
At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively.
Conclusion
Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

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Effect of precise health management combined with physical rehabilitation on bone biomarkers in senile osteoporosis patients
Litao Chen, Xiaojing Yan, Yongjian Liu, Yongbin Pei, Jin Zhou, Lei Zhang, Zhixing Du
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Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials
Takaomi Kobayashi, Megumi Hara, Chisato Shimanoe, Tadatsugu Morimoto, Mawatari Masaaki, Koji Ito, Takafumi Shimazaki
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Treatment effects, adverse outcomes and cardiovascular safety of romosozumab – Existing worldwide data: A systematic review and meta-analysis
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Romosozumab for the treatment of osteoporosis – a systematic review
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Mechanisms Underlying Medication‐Related Osteonecrosis of the Jaw
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Seo-Yong Choi, Jeong-Min Kim, Sang-Hyeon Oh, Seunghyun Cheon, Jee-Eun Chung
Korean Journal of Clinical Pharmacy.2023; 33(2): 128. CrossRef
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E. Carlos Rodriguez-Merchan, Alonso Moreno-Garcia, Hortensia De la Corte-Rodriguez
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Frideriki Poutoglidou, Efthimios Samoladas, Nikolaos Raikos, Dimitrios Kouvelas
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Yun Sun Lee, So Jeong Park, Jin Young Lee, Eunah Choi, Beom-Jun Kim
The Korean Journal of Internal Medicine.2022; 37(4): 821. CrossRef
What is the risk of cardiovascular events in osteoporotic patients treated with romosozumab?
I. R. Reid
Expert Opinion on Drug Safety.2022; 21(12): 1441. CrossRef
Proxied Therapeutic Inhibition on Wnt Signaling Antagonists and Risk of Cardiovascular Diseases: Multi-Omics Analyses
Yu Qian, Cheng-Da Yuan, Saber Khederzadeh, Ming-Yu Han, Hai-Xia Liu, Mo-Chang Qiu, Jian-Hua Gao, Wei-Lin Wang, Yun-Piao Hou, Guo-Bo Chen, Ke-Qi Liu, Lin Xu, David Karasik, Shu-Yang Xie, Hou-Feng Zheng
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Clinical Study
Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study: Chaiho Jeong, Hye In Kwon, Hansang Baek, Hun-Sung Kim, Dong-Jun Lim, Ki-Hyun Baek, Jeonghoon Ha, Moo Il Kang; Endocrinol Metab. 2020;35(4):925-932. Published online December 10, 2020; DOI: https://doi.org/10.3803/EnM.2020.725

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Background
Concomitant papillary thyroid cancer (PTC) and hyperparathyroidism (HPT) have been reported in several studies. Our study aimed to investigate the incidence of concomitant PTC in HPT patients upon preoperative diagnosis and present a clinical opinion on detecting thyroid malignancy in case of parathyroidectomy.
Methods
Patients who underwent parathyroidectomy between January 2009 and December 2019 in two medical centers were included. Of the 279 participants 154 were diagnosed as primary hyperparathyroidism (pHPT) and 125 as secondary hyperparathyroidism (sHPT). The incidence of concomitant PTC and its clinical characteristics were compared with 98 patients who underwent thyroidectomy and were diagnosed with classical PTC during the same period.
Results
Concurrent PTC was detected in 14 patients (9.1%) with pHPT and in nine patients (7.2%) with sHPT. Ten (71.4%) and seven (77.8%) PTCs were microcarcinomas in the pHPT and sHPT cases respectively. In the pHPT patients, vitamin D was lower in the pHPT+PTC group (13.0±3.7 ng/mL) than in the pHPT-only group (18.5±10.4 ng/mL; P=0.01). Vitamin D levels were also lower in the sHPT+PTC group (12.3±5.6 ng/mL) than in the sHPT-only group (18.0±10.2 ng/mL; P=0.12). In the concomitant PTC group, lymph node ratio was higher than in the classical PTC group (P=0.00).
Conclusion
A high prevalence of concomitant PTC was seen in patients with pHPT and sHPT. Those concomitant PTCs were mostly microcarcinomas and had more aggressive features, suggesting that efforts should be made to detect concomitant malignancies in the preoperative parathyroidectomy evaluation.

Citations

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The unexpected effect of parathyroid adenoma on inflammation
Ahmet Tarik Harmantepe, Belma Kocer, Zulfu Bayhan, Emre Gonullu, Ugur Can Dulger
Updates in Surgery.2024; 76(2): 589. CrossRef
Risk of Malignant Neoplasm in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-analysis
Nipith Charoenngam, Thanitsara Rittiphairoj, Chalothorn Wannaphut, Watsachon Pangkanon, Sakditat Saowapa
Calcified Tissue International.2024; 115(1): 1. CrossRef
Complimentary Role of [18F]FDG and [18F]NaF-PET/CT in Evaluating Synchronous Thyroid Carcinoma and Parathyroid Adenoma with Brown Tumors
Yeshwanth Edamadaka, Rahul V. Parghane, Sandip Basu
World Journal of Nuclear Medicine.2024; 23(03): 220. CrossRef
Primary hyperparathyroidism in patients with thyroid cancer: prevalence and prognosis in a retrospective monocentric study
I. Patelli, M. Comina, L. Musso, A. De’Luca Di Pietralata, L. Vera, M. Minuto, M. Albertelli, M. Giusti, M. Bagnasco, D. Ferone, S. Gay
Endocrine.2024; 88(1): 304. CrossRef
Evaluation of Nodular Goiter and Papillary Thyroid Cancer Coincidence in Patients with Primary Hyperparathyroidism
Mustafa ÇALIŞKAN, Hasret CENGİZ, Taner DEMİRCİ
Düzce Tıp Fakültesi Dergisi.2023; 25(2): 200. CrossRef
Papillary thyroid carcinoma coexisting with benign thyroid and parathyroid pathology: clinical and pathomorphological features
A. Dinets, M. Gorobeiko, V. Hoperia, A. Lovin, S. Tarasenko
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2023; 19(4): 274. CrossRef
The Nexus of Hyperparathyroidism and Thyroid Carcinoma: Insights into Pathogenesis and Diagnostic Challenges—A Narrative Review
Gregorio Scerrino, Nunzia Cinzia Paladino, Giuseppina Orlando, Giuseppe Salamone, Pierina Richiusa, Stefano Radellini, Giuseppina Melfa, Giuseppa Graceffa
Journal of Clinical Medicine.2023; 13(1): 147. CrossRef
Is preoperative parathyroid localization necessary for tertiary hyperparathyroidism?
Rongzhi Wang, Peter Abraham, Brenessa Lindeman, Herbert Chen, Jessica Fazendin
The American Journal of Surgery.2022; 224(3): 918. CrossRef
Papillary thyroid carcinoma prevalence and its predictors in patients with primary hyperparathyroidism
Elif Tutku DURMUŞ, Ayşegül ATMACA, Mehmet KEFELİ, Ramis ÇOLAK, Buğra DURMUŞ, Cafer POLAT
Journal of Health Sciences and Medicine.2022; 5(5): 1499. CrossRef
Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study (Endocrinol Metab 2020;35:925-32, Chaiho Jeong et al.)
Chaiho Jeong, Jeonghoon Ha, Moo Il Kang
Endocrinology and Metabolism.2021; 36(1): 205. CrossRef
Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study (Endocrinol Metab 2020;35:925-32, Chaiho Jeong et al.)
Burcu Candemir, Coşkun Meriç
Endocrinology and Metabolism.2021; 36(1): 203. CrossRef

Clinical Study
Gemigliptin Inhibits Interleukin-1β–Induced Endothelial-Mesenchymal Transition via Canonical-Bone Morphogenetic Protein Pathway: Oak-Kee Hong, Seong-Su Lee, Soon Jib Yoo, Min-Kyung Lee, Mee-Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon; Endocrinol Metab. 2020;35(2):384-395. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.384

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Background
Endothelial-to-mesenchymal transition (EndMT) contributes to inflammatory conditions inducing conversion of endothelial cells (ECs) into activated fibroblasts, promoting fibrotic diseases. Pro-inflammatory cytokine is the most potent inducer of EndMT. We investigated inhibition of interleukin-1β (IL-1β)-induced EndMT by gemigliptin, a dipeptidyl peptidase-IV inhibitor.
Methods
We exposed human umbilical vein endothelial cells (HUVECs) to 10 ng/mL IL-1β/20 μM gemigliptin and analyzed the expression of endothelial, smooth muscle, mesenchymal, and osteoblastic markers, bone morphogenetic protein (BMP), Smad, and non-Smad signaling pathway proteins.
Results
Morphological changes showed gemigliptin blocked IL-1β-induced EndMT, upregulated EC markers, and downregulated smooth muscle and mesenchymal markers. IL-1β activation of HUVECs is initiated by the BMP/Smad and non-smad BMP signaling pathways. Gemigliptin inhibited IL-1β induction of BMP2 and 7, activin receptor type IA, BMP receptor type IA, and BMP receptor type II. Reversal of IL-1β-mediated inhibition of BMP-induced Smad1/5/8, Smad2, and Smad3 phosphorylation by gemigliptin suggests involvement of the Smad pathway in gemigliptin action. In the non-Smad BMP pathway, gemigliptin treatment significantly increased the deactivation of extracellular regulated protein kinase (ERK), p38, and JNK by IL-1β. Gemigliptin treatment suppressed BMP-2-induced expression of key osteoblastic markers including osterix, runt-related transcription factor 2, and hepcidin during IL-1β-induced EndMT.
Conclusion
We demonstrated a novel protective mechanism of gemigliptin against fibrosis by suppressing IL-1β-induced EndMT.

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Broadening horizons: molecular mechanisms and disease implications of endothelial-to-mesenchymal transition
Cheng Qian, Guanglu Dong, Chunmei Yang, Weiwei Zheng, Chongjin Zhong, Qiuhong Shen, Yin Lu, Yang Zhao
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The mechanism of curcumin protecting against IL-1β-induced oxidative stress and inflammation in chondrocytes via the Bmp2/Smad5/Runx2 pathway
Jinlei Li, Weitong Liu, Tao Wang, Yanbo Wang, Guang Yang, Jiankun Chen, Yongsheng Xu, Jingfan Yang
Cytotechnology.2025;[Epub] CrossRef
MFGE8 regulates the EndoMT of HLMECs through the BMP signaling pathway and fibrosis in acute lung injury
Qingqiang Shi, Huang Liu, Hanghang Wang, Ling Tang, Qi Di, Daoxin Wang
Respiratory Research.2025;[Epub] CrossRef
Molecular mechanisms of endothelial–mesenchymal transition and its pathophysiological feature in cerebrovascular disease
Huimin Jiang, Yifan Zhou, Weiyue Zhang, Hui Li, Wei Ma, Xunming Ji, Chen Zhou
Cell & Bioscience.2025;[Epub] CrossRef
Injured Endothelial Cell: A Risk Factor for Pulmonary Fibrosis
Weiming Zhao, Lan Wang, Yaxuan Wang, Hongmei Yuan, Mengxia Zhao, Hui Lian, Shuaichen Ma, Kai Xu, Zhongzheng Li, Guoying Yu
International Journal of Molecular Sciences.2023; 24(10): 8749. CrossRef
Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances
Zuxiang Yu, Chaoyu Xu, Bin Song, Shihao Zhang, Chong Chen, Changlong Li, Shuyu Zhang
Journal of Translational Medicine.2023;[Epub] CrossRef
MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors
Mor Zaaroor Levy, Noa Rabinowicz, Maia Yamila Kohon, Avshalom Shalom, Ariel Berl, Tzipi Hornik-Lurie, Liat Drucker, Shelly Tartakover Matalon, Yair Levy
Biomedicines.2022; 10(3): 629. CrossRef
Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies
Li Li, Sainan Liu, Jianying Tan, Lai Wei, Dimeng Wu, Shuai Gao, Yajun Weng, Junying Chen
Journal of Tissue Engineering.2022;[Epub] CrossRef
Vascular Calcification: New Insights Into BMP Type I Receptor A
Zhixing Niu, Guanyue Su, Tiantian Li, Hongchi Yu, Yang Shen, Demao Zhang, Xiaoheng Liu
Frontiers in Pharmacology.2022;[Epub] CrossRef
Yi-Shen-Hua-Shi Granule Alleviates Adriamycin-Induced Glomerular Fibrosis by Suppressing the BMP2/Smad Signaling Pathway
Zhuojing Tan, Yachen Si, Yan Yu, Jiarong Ding, Linxi Huang, Ying Xu, Hongxia Zhang, Yihan Lu, Chao Wang, Bing Yu, Li Yuan
Frontiers in Pharmacology.2022;[Epub] CrossRef
Panax notoginseng Suppresses Bone Morphogenetic Protein-2 Expression in EA.hy926 Endothelial Cells by Inhibiting the Noncanonical NF-κB and Wnt/β-Catenin Signaling Pathways
Tsu-Ni Ping, Shu-Ling Hsieh, Jyh-Jye Wang, Jin-Bor Chen, Chih-Chung Wu
Plants.2022; 11(23): 3265. CrossRef
Vascular calcification: New insights into endothelial cells
Cheng Yuan, Lihua Ni, Changjiang Zhang, Xiaorong Hu, Xiaoyan Wu
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Concentrated small extracellular vesicles from menstrual blood-derived stromal cells improve intrauterine adhesion, a pre-clinical study in a rat model
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Clinical Study
Consistency of the Glycation Gap with the Hemoglobin Glycation Index Derived from a Continuous Glucose Monitoring System: Han Na Joung, Hyuk-Sang Kwon, Ki-Hyun Baek, Ki-Ho Song, Mee Kyoung Kim; Endocrinol Metab. 2020;35(2):377-383. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.377

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Background
Discordances between glycated hemoglobin (HbA1c) levels and glycemic control are common in clinical practice. We aimed to investigate the consistency of the glycation gap with the hemoglobin glycation index (HGI).
Methods
From 2016 to 2019, 36 patients with type 2 diabetes were enrolled. HbA1c, glycated albumin (GA), and fasting blood glucose levels were simultaneously measured and 72-hour continuous glucose monitoring (CGM) was performed on the same day. Repeated tests were performed at baseline and 1 month later, without changing patients’ diabetes management. The HGI was calculated as the difference between the measured HbA1c and the predicted HbA1c that was derived from CGM. The glycation gap was calculated as the difference between the measured and GA-based predicted HbA1c levels.
Results
Strong correlations were found between the mean blood glucose (MBG)-based HGI and the prebreakfast glucose-based HGI (r=0.867, P<0.001) and between the glycation gap and the MBG-based HGI (r=0.810, P<0.001). A close correlation was found between the MBG-based HGI at baseline and that after 1 month (r=0.729, P<0.001), with a y-intercept of 0 and a positive slope.
Conclusion
The HGI and glycation gap were highly reproducible, and the magnitudes of repeated determinations were closely correlated. Patients with similar mean glucose levels may have significantly different HbA1c levels.

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Lin Zheng, Weifeng Zheng, Mingming Zhang, Bo Li
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Naoki Sakane, Yushi Hirota, Akane Yamamoto, Junnosuke Miura, Hiroko Takaike, Sari Hoshina, Masao Toyoda, Nobumichi Saito, Kiminori Hosoda, Masaki Matsubara, Atsuhito Tone, Satoshi Kawashima, Hideaki Sawaki, Tomokazu Matsuda, Masayuki Domichi, Akiko Suganu
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Hemoglobin glycation index, calculated from a single fasting glucose value, as a prediction tool for severe hypoglycemia and major adverse cardiovascular events in DEVOTE
Klara R Klein, Edward Franek, Steven Marso, Thomas R Pieber, Richard E Pratley, Amoolya Gowda, Kajsa Kvist, John B Buse
BMJ Open Diabetes Research & Care.2021; 9(2): e002339. CrossRef

Clinical Study
Comparison of Natural Course between Thyroid Cancer Nodules and Thyroid Benign Nodules: Kyun-Jin Yun, Jeonghoon Ha, Min-Hee Kim, Ye Young Seo, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek; Endocrinol Metab. 2019;34(2):195-202. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.195

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Background

The natural course of thyroid cancer nodules and benign nodules is different. This study was to compare the changes in size between thyroid cancer nodules and thyroid benign nodules. The risk factors associated with the changes of thyroid cancer nodules were assessed.

Methods

This study contains retrospective observational and prospective analysis. A total of 113 patients with 120 nodules were recruited in the cancer group, and 116 patients with 119 nodules were enrolled in the benign group. Thyroid ultrasonography was performed at least two times at more than 1-year interval.

Results

The mean follow-up durations were 29.5±18.8 months (cancer group) and 31.9±15.8 months (benign group) (P=0.32). The maximum diameter change in length was 0.36±0.97 mm/year in the cancer group and –0.04±0.77 mm/year in the benign group (P<0.01). The volume was significantly increased in the cancer group compared with the benign group (0.06±0.18 mL/year vs. 0.004±0.05 mL/year, respectively, P<0.01; 26.9%±57.9%/year vs. 1.7%±26.0%/year, P<0.01). Initial maximum diameter (β=0.02, P<0.01) and initial volume (β=0.13, P<0.01) were significantly associated with volume change (mL)/year. Initial maximum standardized uptake value did not predict the nodule growth.

Conclusion

It is suggested that thyroid cancer nodules progress rapidly compared with benign nodules. Initial size and volume of nodule were independent risk factors for cancer nodule growth.

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José R. González, Charbel Damião, Maira Moran, Cristina A. Pantaleão, Rubens A. Cruz, Giovanna A. Balarini, Aura Conci
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Leif Schiffmann, Karel Kostev, Matthias Kalder
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