Endocrinology and Metabolism

Original Articles

Effects of Sequential Anti-Resorptive Agents on Bone Mineral Density Following Denosumab Withdrawal: A Multicenter Real-World Study in Korea (MAXCARE Study): Jeonghoon Ha, Kyong Yeun Jung, Kyoung Jin Kim, Seong Hee Ahn, Hyo-Jeong Kim, Yoon-Sok Chung, on Behalf of MAXCARE Research Group; Received October 31, 2024 Accepted January 13, 2025 Published online February 11, 2025; DOI: https://doi.org/10.3803/EnM.2024.2227 [Epub ahead of print]

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Abstract PDF PubReader ePub: Background
Denosumab is a potent anti-resorptive agent widely used for osteoporosis. However, its discontinuation results in a ‘rebound phenomenon’ of rapid bone loss, necessitating transition to alternative anti-resorptive therapies. Despite this, there is limited evidence to guide the selection of the most effective agent, particularly among bisphosphonates. This study aimed to evaluate the efficacy of different anti-resorptive therapies following denosumab discontinuation in a real-world clinical setting.
Methods
This retrospective study included 360 patients (low-dose alendronate/calcitriol combination [MXM, n=118], alendronate [ALD, n=53], risedronate [RIS, n=20], ibandronate [IBN, n=30], zoledronic acid [ZOL, n=106], selective estrogen receptor modulator [SERM, n=33]) who received at least 12 months of post-denosumab anti-resorptive therapy. Bone mineral density (BMD) changes from baseline and fracture patterns were assessed over the treatment period.
Results
Baseline characteristics, including age and body mass index, were comparable across groups, with an average of 4.2 denosumab administrations per patient. The SERM group experienced the greatest BMD decline across all sites. Significant BMD reductions in the lumbar spine and femoral neck and in the femoral neck alone were observed in the IBN and RIS groups, respectively. While BMD decline was also observed in the MXM, ALD, and ZOL groups, these changes were not statistically significant.
Conclusion
MXM, ALD, and ZOL mitigated BMD loss following denosumab discontinuation. Conversely, RIS, IBN, and SERM did not adequately prevent BMD decline. These findings underscore the importance of selecting the most appropriate sequential antiresorptive therapy in clinical practice to minimize BMD loss and reduce the risk of adverse outcomes.

Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study: Eu Jeong Ku, Won Sang Yoo, Yu Been Hwang, Subin Jang, Jooyoung Lee, Shinje Moon, Eun Kyung Lee, Hwa Young Ahn; Received July 13, 2024 Accepted November 11, 2024 Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2101 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group.
Methods
This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006–2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated.
Results
Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures.
Conclusion
In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

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 Articles

Mineral, Bone & Muscle
Association of Delayed Denosumab Dosing with Increased Risk of Fractures: A Population-Based Retrospective Study: Kyoung Min Kim, Seol A Jang, Nam Ki Hong, Chul Sik Kim, Yumie Rhee, Seok Won Park, Steven R. Cummings, Gi Hyeon Seo; Endocrinol Metab. 2024;39(6):946-955. Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2047

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Background
Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data.
Methods
The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures.
Results
A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures.
Conclusion
Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.

Citations

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Medication related osteonecrosis (MRONJ) in the management of CTIBL in breast and prostate cancer patients. Joint report by SIPMO AND SIOMMMS
Francesco Bertoldo, Cristina Eller-Vainicher, Vittorio Fusco, Rodolfo Mauceri, Jessica Pepe, Alberto Bedogni, Andrea Palermo, Umberto Romeo, Giuseppe Guglielmi, Giuseppina Campisi
Journal of Bone Oncology.2025; 50: 100656. CrossRef

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study: Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim; Endocrinol Metab. 2025;40(1):82-92. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.1990

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Abstract PDF Supplementary Material PubReader ePub: Background
In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods
From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results
Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion
These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

Review Article

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.

Citations

Citations to this article as recorded by

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

Original Article

Mineral, Bone & Muscle
End-to-End Semi-Supervised Opportunistic Osteoporosis Screening Using Computed Tomography: Jieun Oh, Boah Kim, Gyutaek Oh, Yul Hwangbo, Jong Chul Ye; Endocrinol Metab. 2024;39(3):500-510. Published online May 9, 2024; DOI: https://doi.org/10.3803/EnM.2023.1860

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Background
Osteoporosis is the most common metabolic bone disease and can cause fragility fractures. Despite this, screening utilization rates for osteoporosis remain low among populations at risk. Automated bone mineral density (BMD) estimation using computed tomography (CT) can help bridge this gap and serve as an alternative screening method to dual-energy X-ray absorptiometry (DXA).
Methods
The feasibility of an opportunistic and population agnostic screening method for osteoporosis using abdominal CT scans without bone densitometry phantom-based calibration was investigated in this retrospective study. A total of 268 abdominal CT-DXA pairs and 99 abdominal CT studies without DXA scores were obtained from an oncology specialty clinic in the Republic of Korea. The center axial CT slices from the L1, L2, L3, and L4 lumbar vertebrae were annotated with the CT slice level and spine segmentation labels for each subject. Deep learning models were trained to localize the center axial slice from the CT scan of the torso, segment the vertebral bone, and estimate BMD for the top four lumbar vertebrae.
Results
Automated vertebra-level DXA measurements showed a mean absolute error (MAE) of 0.079, Pearson’s r of 0.852 (P<0.001), and R² of 0.714. Subject-level predictions on the held-out test set had a MAE of 0.066, Pearson’s r of 0.907 (P<0.001), and R² of 0.781.
Conclusion
CT scans collected during routine examinations without bone densitometry calibration can be used to generate DXA BMD predictions.

Citations

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Phantomless estimation of bone mineral density on computed tomography: a scoping review
Aleena Waqar, Alberto Bazzocchi, Maria Pilar Aparisi Gómez
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Unaccounted Variations Can Surreptitiously Spoil the Validity of “Good” Biostatistical Models
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Review Article

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
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Filippo Gabrielli, Elisa Bernasconi, Arianna Toscano, Alessandra Avossa, Alessia Cavicchioli, Pietro Andreone, Stefano Gitto
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Original Article

Mineral, Bone & Muscle
Characteristics Associated with Bone Loss after Spinal Cord Injury: Implications for Hip Region Vulnerability: Sora Han, Sungjae Shin, Onyoo Kim, Namki Hong; Endocrinol Metab. 2023;38(5):578-587. Published online October 10, 2023; DOI: https://doi.org/10.3803/EnM.2023.1795

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Background
In individuals with spinal cord injury (SCI), bone loss progresses rapidly to the area below the level of injury, leading to an increased risk of fracture. However, there are limited data regarding SCI-relevant characteristics for bone loss and the degree of bone loss in individuals with SCI compared with that in non-SCI community-dwelling adults.
Methods
Data from men with SCI who underwent dual-energy X-ray absorptiometry at the National Rehabilitation Center (2008 to 2020) between 12 and 36 months after injury were collected and analyzed. Community-dwelling men were matched 1:1 for age, height, and weight as the control group, using data from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008 to 2011).
Results
A comparison of the SCI and the matched control group revealed significantly lower hip region T-scores in the SCI group, whereas the lumbar spine T-score did not differ between groups. Among the 113 men with SCI, the paraplegia group exhibited significantly higher Z-scores of the hip region than the tetraplegia group. Participants with motor-incomplete SCI showed relatively preserved Z-scores of the hip region compared to those of the lumbar region. Moreover, in participants with SCI, the percentage of skeletal muscle displayed a moderate positive correlation with femoral neck Z-scores.
Conclusion
Men with SCI exhibited significantly lower bone mineral density of the hip region than community-dwelling men. Paraplegia rather than tetraplegia, and motor incompleteness rather than motor completeness were protective factors in the hip region. Caution for loss of skeletal muscle mass or increased adiposity is also required.

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Multifaceted Pathophysiology and Secondary Complications of Chronic Spinal Cord Injury: Focus on Pressure Injury
Mario Martínez-Torija, Pedro F. Esteban, Angela Santos-De-La-Mata, Matilde Castillo-Hermoso, Eduardo Molina-Holgado, Rafael Moreno-Luna
Journal of Clinical Medicine.2025; 14(5): 1556. CrossRef

Review Articles

Mineral, Bone & Muscle
Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis: Brendan F. Boyce, Jinbo Li, Zhenqiang Yao, Lianping Xing; Endocrinol Metab. 2023;38(5):504-521. Published online September 26, 2023; DOI: https://doi.org/10.3803/EnM.2023.501

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Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor β (TGFβ)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFβ and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFβ causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3β/β-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFβ+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.

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Regenerative Biomaterials.2025;[Epub] CrossRef
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Piotr Wojdasiewicz, Paweł Turczyn, Anna Lach-Gruba, Łukasz A. Poniatowski, Daryush Purrahman, Mohammad-Reza Mahmoudian-Sani, Dariusz Szukiewicz
International Journal of Molecular Sciences.2024; 25(4): 2117. CrossRef
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Chun-Yi Huang, Huynh Hoai Thuong Le, Hsiao-Chi Tsai, Chih-Hsin Tang, Jian-Hong Yu
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Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells
Yerin Yu, Somin Lee, Minsung Bock, Seong Bae An, Hae Eun Shin, Jong Seop Rim, Jun-oh Kwon, Kwang-Sook Park, Inbo Han
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Mineral, Bone & Muscle
Skeletal Senescence with Aging and Type 2 Diabetes: Joshua Nicholas Farr; Endocrinol Metab. 2023;38(3):295-301. Published online June 14, 2023; DOI: https://doi.org/10.3803/EnM.2023.1727

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Osteoporosis and type 2 diabetes (T2D) are common diseases that often coexist. While both of these diseases are associated with poor bone quality and increased fracture risk, their pathogenesis of increased fracture risk differs and is multifactorial. Mounting evidence now indicates that key fundamental mechanisms that are central to both aging and energy metabolism exist. Importantly, these mechanisms represent potentially modifiable therapeutic targets for interventions that could prevent or alleviate multiple complications of osteoporosis and T2D, including poor bone quality. One such mechanism that has gained increasing momentum is senescence, which is a cell fate that contributes to multiple chronic diseases. Accumulating evidence has established that numerous boneresident cell types become susceptible to cellular senescence with old age. Recent work also demonstrates that T2D causes the premature accumulation of senescent osteocytes during young adulthood, at least in mice, although it remains to be seen which other bone-resident cell types become senescent with T2D. Given that therapeutically removing senescent cells can alleviate age-related bone loss and T2D-induced metabolic dysfunction, it will be important in future studies to rigorously test whether interventions that eliminate senescent cells can also alleviate skeletal dysfunction in context of T2D, as it does with aging.

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The synergistic effect of diabetes mellitus and osteoporosis on the all-cause mortality: a cohort study of an American population
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Thyroid
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association: A Ram Hong, Ho-Cheol Kang; Endocrinol Metab. 2023;38(2):175-189. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1701

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Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association’s position statement on the evaluation and management of bone health associated with thyroid diseases.

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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.

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Denosumab

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Review Articles

Mineral, Bone & Muscle
Cardiovascular Impact of Calcium and Vitamin D Supplements: A Narrative Review: Fatima Zarzour, Ahmad Didi, Mohammed Almohaya, David Kendler; Endocrinol Metab. 2023;38(1):56-68. Published online February 16, 2023; DOI: https://doi.org/10.3803/EnM.2022.1644

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Calcium and vitamin D play an important role in mineral homeostasis and the maintenance of skeletal health. Calcium and vitamin D supplements have been widely used for fracture prevention in elderly populations. Many trials have studied the effectiveness and cardiovascular safety of calcium and vitamin D supplementation, with disparate results. In this review, we summarize the most important trials and systematic reviews. There is significant heterogeneity in clinical trial design, differences in the nature of trial outcomes (self-reported vs. verified), prior calcium intake, and trial size. Inconsistent results have been reported concerning the effects of calcium and vitamin D supplementation on cardiovascular outcomes. Most current guidelines recommend calcium intake of up to 1,200 mg daily, preferably from the diet, without concern for cardiovascular risk. Recommendations regarding vitamin D supplementation vary widely. There is compelling evidence from well-conducted randomized trials that modest vitamin D supplementation is safe but does not confer cardiovascular benefit or cardiovascular harm.

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Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea
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Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2023;38(1):10-24. Published online February 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.102

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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

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