Endocrinology and Metabolism

Review Article

Calcium & bone metabolism
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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Abstract PDF: 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.

Original Article

Calcium & bone metabolism
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.

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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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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
Discover Oncology.2024;[Epub] CrossRef
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
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

Calcium & Bone Metabolism
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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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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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;[Epub] 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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Heart Rate Variability in Subjects with Severe Allergic Background Undergoing COVID-19 Vaccination
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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Keyla Vargas-Román, Emilia I. De la Fuente-Solana, Jonathan Cortés-Martín, Juan Carlos Sánchez-García, Christian J. González-Vargas, Lourdes Díaz-Rodríguez
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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Zepeng Chen, Ming Li, Shuzhen Li, Yuxi Li, Junyan Wu, Kaifeng Qiu, Xiaoxia Yu, Lin Huang, Guanghui Chen
Expert Opinion on Drug Safety.2023; 22(4): 339. CrossRef
Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta‐analysis of randomized controlled trials (CDM‐J)
Wenbo Huang, Masashi Nagao, Naohiro Yonemoto, Sen Guo, Takeshi Tanigawa, Yuji Nishizaki
Pharmacoepidemiology and Drug Safety.2023; 32(6): 671. CrossRef
Efficacy and Cardiovascular Safety of Romosozumab: A Meta-analysis and Systematic Review
Seo-Yong Choi, Jeong-Min Kim, Sang-Hyeon Oh, Seunghyun Cheon, Jee-Eun Chung
Korean Journal of Clinical Pharmacy.2023; 33(2): 128. CrossRef
Clinical Studies On Romosozumab: An Alternative For Individuals With A High Risk Of Osteoporotic Fractures: A Current Concepts Review (Part I)
E. Carlos Rodriguez-Merchan, Alonso Moreno-Garcia, Hortensia De la Corte-Rodriguez
SurgiColl.2023;[Epub] CrossRef
Romosozumab in osteoporosis: yesterday, today and tomorrow
Dong Wu, Lei Li, Zhun Wen, Guangbin Wang
Journal of Translational Medicine.2023;[Epub] CrossRef
Efficacy and safety of anti-sclerostin antibodies in the treatment of osteoporosis: A meta-analysis and systematic review
Frideriki Poutoglidou, Efthimios Samoladas, Nikolaos Raikos, Dimitrios Kouvelas
Journal of Clinical Densitometry.2022; 25(3): 401. CrossRef
Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates
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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Yu Qian, Peng-Lin Guan, Saber Khederzadeh, Ke-Qi Liu, Cheng-Da Yuan, Ming-Yu Han, Hai-Xia Liu, Mo-Chang Qiu, Jian-Hua Gao, Wei-Lin Wang, Yun-Piao Hou, Guo-Bo Chen, Lin Xu, David Karasik, Shu-Yang Xie, sheng zhifeng, 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.

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Ahmet Tarik Harmantepe, Belma Kocer, Zulfu Bayhan, Emre Gonullu, Ugur Can Dulger
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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.

Citations

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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
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MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors
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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
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Nanoscale.2021; 13(15): 7334. CrossRef

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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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
Journal of Diabetes Investigation.2023; 14(4): 582. CrossRef
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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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Leif Schiffmann, Karel Kostev, Matthias Kalder
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Combination of peroxisome proliferator–activated receptor gamma and retinoid X receptor agonists induces sodium/iodide symporter expression and inhibits cell growth of human thyroid cancer cells
Jui-Yu Chen, Jane-Jen Wang, Hsin-Chen Lee, Chin-Wen Chi, Chen-Hsen Lee, Yi-Chiung Hsu
Journal of the Chinese Medical Association.2020; 83(10): 923. CrossRef
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