Endocrinology and Metabolism

Editorial

Mineral, bone & muscle
Romosozumab and Cardiovascular Safety: Bridging the Gap between Clinical Trials and Real-World Evidence: Beom-Jun Kim; Endocrinol Metab. 2026;41(3):390-392. Published online June 26, 2026; DOI: https://doi.org/10.3803/EnM.2026.3119

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Original Article

Elevated Serum CXCL9 Levels Are Associated with Greater Frailty Risk in Older Women: Da Hea Seo, Nancy E. Lane, Seongbin Hong, Beom-Jun Kim; Received November 11, 2025 Accepted March 17, 2026 Published online June 15, 2026; DOI: https://doi.org/10.3803/EnM.2025.2783 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Frailty is a clinical syndrome that increases the vulnerability to adverse outcomes in older adults. C-X-C motif ligand 9 (CXCL9), a marker of chronic inflammation, has been implicated in musculoskeletal decline and mortality. However, its relationship with frailty in older individuals has not been well studied.
Methods
This study included 237 community-dwelling women, aged 65 years or older, who underwent a comprehensive geriatric assessment. Serum CXCL9 levels were measured by enzyme-linked immunosorbent assay. Frailty was defined using the Fried phenotype and the Rockwood deficit accumulation index. Associations between serum CXCL9 levels and frailty outcomes were examined using a multivariate regression analysis.
Results
Serum CXCL9 increased progressively across the frailty categories (robust: 239.3±110.1 pg/mL; frail: 347.5±119.0 pg/mL; P<0.001). Higher levels of CXCL9 were independently associated with a greater frailty index (β=0.0001, P<0.001), lower skeletal muscle index (β=−0.001, P=0.004), weaker grip strength (β=−0.010, P<0.001), and slower gait speed (β=−0.0003, P=0.039). Women in the highest CXCL9 quartile had 3.20-fold greater odds of frailty (95% confidence interval [CI], 1.70 to 14.56), 3.41-fold greater odds of sarcopenia (95% CI, 1.25 to 9.30), and 6.71-fold greater odds of low muscle strength (95% CI, 1.75 to 25.78) compared with the lowest quartile.
Conclusion
Elevated CXCL9 levels were independently associated with greater frailty burden and adverse musculoskeletal phenotypes in older women. These findings support CXCL9 as a promising biomarker of chronic inflammation and frailty, and warrant further investigation through longitudinal studies.

Review Articles

Miscellaneous Big Data Articles (National Health Insurance Service Database)
Nationwide Big Data Studies of Endocrine Diseases Using the Korean National Health Information Database: Research Trends and Standardization of Operational Definitions: Sun Wook Cho, Jung Hee Kim, Kyoung Jin Kim, Beom-Jun Kim, Mee Kyoung Kim, Eun Jung Rhee; Endocrinol Metab. 2026;41(1):86-104. Published online February 26, 2026; DOI: https://doi.org/10.3803/EnM.2026.2953

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The Korean National Health Information Database (NHID) is a large-scale dataset created through linkage of National Health Insurance claims with nationwide health screening records. Because it is released in a cohort-based format, the NHID enables longitudinal follow-up and allows investigation of rare endocrine conditions with low population prevalence. Mortality data, including both dates and causes of death, are additionally obtained through linkage with Statistics Korea. Over recent years, use of the NHID has expanded rapidly, establishing it as a major resource for epidemiological research in endocrinology. Nevertheless, because the database was originally developed for administrative and screening purposes rather than for research, investigators face several methodological limitations, particularly the need to construct and validate robust operational definitions of diseases. In this review, we describe the key features of the Korean NHID, summarize operational definitions of endocrine disorders that have been applied in prior research, and provide an overview of recent endocrine studies conducted using this database.

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Age-specific loss of life expectancy after hip fracture in Asian adults: A nationwide population-based cohort study
Kyoung Jin Kim, Su Jin Kwon, Seunghyun Lee, Seong Hee Ahn, So Young Park, Ha-Young Kim, Kyoung Min Kim
Bone.2026; 208: 117896. CrossRef
Diabetes progression and its association with fracture risk in type 2 diabetes
Bongsung Kim, Kyu-Na Lee, Kyungdo Han, Mee Kyoung Kim
Osteoporosis International.2026;[Epub] CrossRef

Mineral, bone & muscle
Sarcopenia and Muscle Aging: Updated Insights into Molecular Mechanisms and Translational Therapeutics: Thanh T. Nguyen, Tam Dao, Ha Thu Nguyen, Jun-Hyeon Park, Seung-Jun Jeong, Sei Kim, Yunju Jo, Nhung T.H. Thieu, Jiangqi Zhao, Fuan Ding, Ying Yu, Vu Chi Dung, Karim Gariani, Beom-Jun Kim, Dongryeol Ryu; Endocrinol Metab. 2026;41(1):57-85. Published online February 12, 2026; DOI: https://doi.org/10.3803/EnM.2025.2656

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Sarcopenia is a progressive, age-related condition characterized by the loss of skeletal muscle mass, strength, and function, which increases the risk of falls, frailty, and loss of independence. Despite growing recognition and its incorporation into geriatric assessments, there is still no approved pharmacological treatment. This review provides an updated overview of sarcopenia, encompassing diagnostic criteria, biological mechanisms, and emerging therapeutic strategies. Key molecular features include mitochondrial dysfunction, nicotinamide adenine dinucleotide (NAD⁺) decline, fiber-type alterations, and dysregulation of myokines. Recent singlecell and multi-omics studies have revealed the heterogeneity of muscle tissue and distinct cell-type-specific aging patterns. Therapeutic efforts are evolving beyond lifestyle interventions toward targeted approaches, including myostatin inhibitors, NAD⁺ boosters, senolytics, and microbiome modulators. However, clinical translation remains constrained by heterogeneity in trial design and the absence of standardized outcome measures. Future sarcopenia care will likely involve precision medicine guided by biomarkers and supported by digital monitoring tools. Progressing from molecular discovery to clinical application will be essential for preserving muscle health and function in aging populations.

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Molecular Mechanisms and Nutritional Modulation in Sarcopenia: A Narrative Review
Hui San Chin, Ling Liu, Pei-Ju Liao, Alexandra L. R. M. Wee, Xiu-Yi Kwek, Bin Tean Teh, Frederick H. Koh
Nutrients.2026; 18(7): 1161. CrossRef
Elevated Circulating Ceramides 18:0 and 24:1 as a Risk Factor for Sarcopenia: In Vitro, Animal, and Clinical Evidence
So Jeong Park, Ji Yeon Baek, Shibo Wei, Jin Young Lee, Yuna Lee, Sang‐Hoon Lee, Il‐Young Jang, Hyuk Sakong, Hyun Ju Yoo, Hee‐Won Jung, Eunju Lee, Su Jung Kim, Yunju Jo, Kyunggon Kim, Dongryeol Ryu, Beom‐Jun Kim
Journal of Cachexia, Sarcopenia and Muscle.2026;[Epub] CrossRef
Dysregulation of the ubiquitin–proteasome system in aging skeletal muscle
Gunju Song, Boo-Yong Lee, Kwang-Hyun Baek
Biomedicine & Pharmacotherapy.2026; 199: 119504. CrossRef
Trends in Low Muscle Mass and Sarcopenia Prevalence in Korea Using Korea National Health and Nutrition Examination Survey (KNHANES) 2024 and 2008–2011: The KSBMR-KSOS KNHANES DXA Joint Task Force Report
Namki Hong, Jun-Il Yoo, Jeonghoon Ha, Seong Hee Ahn, Young-Kyun Lee, Hyun Sik Gong, Ki-Hyun Baek, Yumie Rhee, Yong-Chan Ha
Journal of Bone Metabolism.2026; 33(2): 197. CrossRef
Differential Effects of Stroke Stage and Age on Sarcopenia in Stroke Patients: A Cross-Sectional Study
Guan-Bo Chen, I-Hsiu Liou, Shu-Fen Sun, Chien-Hui Li, Sheng-Hui Tuan
Life.2026; 16(7): 1073. CrossRef
From organ age gaps to precision geromedicine: Multi-omic and imaging frameworks for heterogeneous biological aging
Qian-Man Li, Xiao-Xuan Ge, Tian-Jiao Wen, Li-Wen Zhang, Hao-Yu Liu, Xiu-Wen Shi, Lu Liu, Ting-Ting Gong, Qi-Jun Wu, Shan-Yan Gao
Ageing Research Reviews.2026; 121: 103238. CrossRef
Effect of moderate-intensity aerobic exercise on early oxidative stress and muscle atrophy in SAMP8 mice through modulation of the DAO/SRR and Nrf2/Keap1 pathways
Xiangli Tong, Jinkun Xue, Zixuan Chen, Rongsiqing Luo, Zihan Huang, Fengxuan Chen, Ying Liu, Jingran Xiao, Jia Jiang, Zhiyuan Wang, Wenfeng Liu
Cellular Signalling.2026; 147: 112760. CrossRef
A Stimulus-Resolved Framework for Investigating Putative Neurotrophic Secretome–Metabolome Coupling in Aging Skeletal Muscle: CNTF and CLCF1 as Non-Equivalent Nodes
Fei Tong, Yirui Chen, Hongxin Gui, Aowei Li, Hongyu Li, Yusen Pei, Zimu Wu, Mengyang Wang
Metabolites.2026; 16(8): 562. CrossRef
Beyond local injury: Sarcopenia as a systemic host-related determinant of esophageal stenosis after endoscopic submucosal dissection
Wen-Mao Li, Bo Liu, Qing Liu
World Journal of Gastroenterology.2026;[Epub] CrossRef

Special Article

Mineral, bone & muscle
Medication-Related Osteonecrosis of the Jaw: An Evidence-Based 2025 Position Statement from a Korean Multidisciplinary Task Force: Jin-Woo Kim, Sung-Hye Kong, Jae-Young Kim, Mi Kyung Kwak, Jun-Young Kim, Ji-Hyeon Oh, Hyung-Youl Park, BeomTaek Kim, Young-Kyun Lee, Jeong Joon Han, Moon-Young Kim, Yong Jun Choi, Yong-Dae Kwon, Kwang-Sup Song, Beom-Jun Kim, Sun-Jong Kim, Seung-Hoon Baek, Dong Ock Lee, Han Seok Choi, Ha Young Kim, Tae-Geon Kwon; Endocrinol Metab. 2025;40(6):787-810. Published online December 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2712

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With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Society of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Osteoporosis Society, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3 to 4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management. This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

Citations

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Asia-Pacific consensus statement on medication-related osteonecrosis of the jaw in patients with osteoporosis
Akira Taguchi, Daisuke Inoue, Jin-Woo Kim, Keskanya Subbalekha, Wai Sin Chan, Hee Dong Chae, Chung-Hwan Chen, Ching-Lung Cheung, Eddie Siu Lun Chow, Yoon-Sok Chung, Linsey Gani, Muhammad Kamil bin Hassan, Unnop Jaisamrarn, Chakorn Vorakulpipat, Nutchada S
Osteoporosis and Sarcopenia.2026; 12(1): 1. CrossRef
Targeted drug repurposing in medication-related osteonecrosis of the jaw: a review of teriparatide and pentoxifylline/α-tocopherol protocols
Weijia Huang, Jishizhan Chen, Quan Zhou, Azadeh Rezaei
Frontiers in Medicine.2026;[Epub] CrossRef
The Korean medication-related osteonecrosis of the jaw position paper—a milestone toward practical, evidence-based guidance
Won Lee
Journal of the Korean Association of Oral and Maxillofacial Surgeons.2026; 52(1): 1. CrossRef
Timing, Geography, and Pragmatic Risk Reduction in Prevention of Medication-Related Osteonecrosis of the Jaw During Low-Dose BMA Therapy
Giuseppina Campisi, Martina Coppini, Vittorio Fusco, Alberto Bedogni, Francesco Bertoldo, Rodolfo Mauceri
Oral.2026; 6(3): 62. CrossRef
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West Kazakhstan Medical Journal.2026; 68(2): 132. CrossRef

Original Articles

Mineral, bone & muscle
Higher Circulating Kynurenine Levels Linked to Higher Risk of Sarcopenia in Older Adults: A Cohort Study and UK Biobank Analysis: June Yeon Kim, Yunju Jo, So Jeong Park, Ji Yeon Baek, Geonyoung Jang, Eunju Lee, Hyuk Sakong, Su Jung Kim, Sung-Jin Kim, Dongryeol Ryu, Hyun Ju Yoo, Beom-Jun Kim; Endocrinol Metab. 2026;41(3):428-441. Published online December 12, 2025; DOI: https://doi.org/10.3803/EnM.2025.2586

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Background
While experimental studies show kynurenine, a tryptophan metabolite, drives muscle catabolism through pro-oxidative and inflammatory mechanisms, clinical evidence linking circulating kynurenine to sarcopenia in humans remains scarce.
Methods
In a cross-sectional study of 165 community-dwelling older adults, sarcopenia was diagnosed using Asian-specific criteria and serum kynurenine levels were measured by liquid chromatography-tandem mass spectrometry. Using UK Biobank datasets, plasma indoleamine 2,3-dioxygenase 1 (IDO1)—the enzyme converting tryptophan to kynurenine—was quantified via Olink proteomics, and Mendelian randomization was used to assess the causal effect of plasma IDO1 on sarcopenia risk based on genomewide association study data.
Results
In multivariable adjusted analyses, older adults with sarcopenia, low muscle mass, or weak muscle strength had 21.3%–29.2% higher serum kynurenine concentrations than controls (P<0.001 to 0.010). Circulating kynurenine levels were inversely correlated with skeletal muscle index and grip strength (P=0.001 and 0.022, respectively). Each standard deviation increase in serum kynurenine was associated with a 1.80–2.97-fold increased risk for sarcopenia-related outcomes (P<0.001 to 0.010). In the UK Biobank, higher IDO1 activity was associated with reduced muscle mass and strength (P=0.007 and P=0.004, respectively), and Mendelian randomization indicated a significant causal relationship between plasma IDO1 levels and increased sarcopenia risk (P= 0.010, β=0.105).
Conclusion
These findings extend previous experimental evidence to the clinical setting, suggesting that elevated kynurenine—driven by IDO1 activity—contributes to sarcopenia in older adults. Circulating kynurenine may serve as an exploratory biomarker candidate for identifying individuals at heightened risk for muscle deterioration, warranting further validation in future studies.

Citations

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Biomarkers and Early Mechanisms of Sarcopenia: Central Roles of Mitochondrial Dysfunction, Inflammaging, Cellular Senescence, and Neuromuscular Degeneration
Hechmi Toumi, Ahmad Almhdie-Imjabbar, Nada Ibrahim, Eric Lespessailles
International Journal of Molecular Sciences.2026; 27(14): 6332. CrossRef

Mineral, bone & muscle Big Data Articles (National Health Insurance Service Database)
Low Serum 25-Hydroxyvitamin D as a Risk Factor for Frailty in Community-Dwelling Older Men: A Korean Nationwide Study: Jeongmin Lee, Min-gu Kang, Jeonghoon Ha, Yunju Jo, Dongryeol Ryu, Hee-Won Jung, Ki-Hyun Baek, Beom-Jun Kim; Endocrinol Metab. 2025;40(6):961-973. Published online November 7, 2025; DOI: https://doi.org/10.3803/EnM.2025.2462

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Background
Despite the critical role of vitamin D in various biological processes, its impact on frailty—a condition closely linked to biological age—remains inconclusive. This study aimed to explore the association between serum 25-hydroxyvitamin D (25[OH] D) levels and frailty status in older Korean adults, utilizing a comprehensive frailty index (FI) and a nationally representative dataset.
Methods
This cross-sectional study included 6,589 participants aged ≥65 years from the Korea National Health and Nutrition Examination Survey (2008–2012). Frailty was assessed using a deficit accumulation FI based on 38 physical, cognitive, psychological, and social items.
Results
After adjusting for potential confounders, frail men showed 6.8% lower serum 25(OH)D concentrations compared to nonfrail controls (P=0.007). Men in the lowest serum 25(OH)D quartile (≤39.3 nmol/L) exhibited a 5.3% higher FI (P=0.047) and 1.71-fold increased odds of frailty (P=0.005), compared to those in the highest quartile (>63.3 nmol/L). Similarly, men with vitamin D deficiency (<30 nmol/L) exhibited a 9.6% higher FI compared to those with sufficient vitamin D levels (≥50 nmol/L; P=0.004). However, no significant association between serum 25(OH)D concentration and frailty was observed in women across any analysis.
Conclusion
These findings suggest that low serum 25(OH)D concentrations are a potential risk factor for frailty, particularly in men. Further research is warranted to determine whether vitamin D supplementation in such high-risk older adults could help mitigate frailty.

Citations

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Oxidative stress in frailty among older adults: are malondialdehyde and superoxide dismutase the key biomarkers?
Yuyang Zhang, Jiali Zheng, Xiaoxiao Zhang, Yanwen Zhang, Kexin Zhang, Yujiao Hao, Yang Li, Tingting Ma, Xinyu Bai, Yulu Wang, Yaogang Wang, Qi Lu, Yue Zhao
Biogerontology.2026;[Epub] CrossRef

Editorial

Mineral, bone & muscle
Establishing Blood-Based Biomarkers for Sarcopenia: Current Challenges and Future Directions: Beom-Jun Kim; Endocrinol Metab. 2025;40(5):693-695. Published online September 3, 2025; DOI: https://doi.org/10.3803/EnM.2025.2600

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Citations

Citations to this article as recorded by

Higher Circulating Kynurenine Levels Linked to Higher Risk of Sarcopenia in Older Adults: A Cohort Study and UK Biobank Analysis
June Yeon Kim, Yunju Jo, So Jeong Park, Ji Yeon Baek, Geonyoung Jang, Eunju Lee, Hyuk Sakong, Su Jung Kim, Sung-Jin Kim, Dongryeol Ryu, Hyun Ju Yoo, Beom-Jun Kim
Endocrinology and Metabolism.2026; 41(3): 428. CrossRef
Elevated Circulating Ceramides 18:0 and 24:1 as a Risk Factor for Sarcopenia: In Vitro, Animal, and Clinical Evidence
So Jeong Park, Ji Yeon Baek, Shibo Wei, Jin Young Lee, Yuna Lee, Sang‐Hoon Lee, Il‐Young Jang, Hyuk Sakong, Hyun Ju Yoo, Hee‐Won Jung, Eunju Lee, Su Jung Kim, Yunju Jo, Kyunggon Kim, Dongryeol Ryu, Beom‐Jun Kim
Journal of Cachexia, Sarcopenia and Muscle.2026;[Epub] CrossRef

Original Articles

Mineral, bone & muscle Big Data Articles (National Health Insurance Service Database)
Comprehensive Evaluation of Treatment Patterns in Postmenopausal Patients with Osteoporosis without Fractures: Insights from Tertiary Care Institutions and Nationwide OMOP-CDM Data: Kyoung Jin Kim, Dachung Boo, Jimi Choi, Hyemin Yoon, Chai Young Jung, Seong Hee Ahn, Namki Hong, Beom-Jun Kim, Ji Seon Oh, Seng Chan You; Endocrinol Metab. 2025;40(5):737-747. Published online May 28, 2025; DOI: https://doi.org/10.3803/EnM.2024.2252

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Background
Osteoporosis is a global health concern. Despite emerging treatment options for this condition, limited data are available on hospital practices in South Korea. This study addresses the need for a hospital network database that reflects changes in routine clinical practice for osteoporosis in a timely manner.
Methods
We analyzed prescription patterns for anti-osteoporosis medications (AOMs) in postmenopausal women aged ≥50 years diagnosed with osteoporosis between 2012 and 2021 using data from Osteoporosis Analysis and Surveillance Initiative using Standardized data (OASIS) (four tertiary hospitals in South Korea) and a nationwide database from the Health Insurance Review and Assessment (HIRA) Service. AOMs were categorized into antiresorptive and anabolic agents, with a focus on secular changes in the use of oral bisphosphonates, denosumab, selective estrogen receptor modulators (SERMs), and anabolic agents.
Results
In the OASIS cohort, oral bisphosphonates were the most prescribed first-line AOM (49.0%), followed by denosumab (15.7%) and SERMs (18.0%). Denosumab use increased from 2% in 2016 to 40% in 2020, while oral bisphosphonate use declined from 69% in 2012 to 22% in 2021. The use of anabolic agents, including romosozumab and teriparatide, doubled to 6% after 2019. In the HIRA cohort, parenteral bisphosphonates were most common (54.3%), with significant denosumab use (17.3%).
Conclusion
Pronounced shifts in AOM prescription patterns were observed in South Korea, marked by a notable increase in denosumab prescriptions and a decline in bisphosphonate use. These trends highlight the impact of policy changes and clinical guidelines on osteoporosis treatment and may inform future management strategies.

Citations

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Comparison of the Efficacy of Denosumab and Alendronate in Improving Bone Mineral Density in Osteoporosis Patients and High-Risk Populations: A Systematic Review and Meta-Analysis
Kejia Zhu, Hang Li, Hui Zhang, Zongke Zhou, Bin Shen, Yong Nie
Clinical Drug Investigation.2026; 46(3): 243. CrossRef
Trends and prescribing patterns of antiosteoporosis medicines in Chinese patients: a real-world retrospective study
Shuo Zhang, Yuqing Fan, Mengyao Xue, Linfeng Jiang, Chen Mu, Nan Peng, Dongning Yao
Aging Clinical and Experimental Research.2026;[Epub] CrossRef
Trends in Osteoporosis Prevalence in Korea Using Korea National Health and Nutrition Examination Survey (KNHANES) 2024 and 2008–2011: The KSBMR KNHANES DXA Task Force Report
Namki Hong, Jeonghoon Ha, Jun-Il Yoo, Seong Hee Ahn, Young-Kyun Lee, Hyun Sik Gong, Yong-Chan Ha, Ki-Hyun Baek, Yumie Rhee
Journal of Bone Metabolism.2026; 33(2): 141. CrossRef
Romosozumab and Cardiovascular Safety: Bridging the Gap between Clinical Trials and Real-World Evidence
Beom-Jun Kim
Endocrinology and Metabolism.2026; 41(3): 390. CrossRef
Risk of Cardiovascular Events in Patients with Osteoporosis on Romosozumab Treatment Compared with Denosumab: A Multicenter Observational Cohort Study
Seong Hee Ahn, Dachung Boo, Kyoung Jin Kim, Jimi Choi, Hyemin Yoon, Chai Young Jung, Seng Chan You, Ji Seon Oh, Namki Hong
Endocrinology and Metabolism.2026; 41(3): 442. CrossRef
Smartphone-based patient-reported outcome of acute phase reaction after zoledronic acid infusion and prediction algorithm: a multicenter, prospective cohort study
Sung Joon Cho, Sang Wouk Cho, Min Heui Yu, Seng Chan You, Seong Hee Ahn, Yumie Rhee, Namki Hong
Osteoporosis International.2026;[Epub] CrossRef

Mineral, Bone & Muscle
Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health: Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim; Endocrinol Metab. 2025;40(1):73-81. Published online October 24, 2024; DOI: https://doi.org/10.3803/EnM.2024.2100

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Background
Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated.
Methods
We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.
Results
After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).
Conclusion
These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

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Irisin, Sclerostin, and Inflammatory Axis: Implication in Bone‐Muscle Wasting Diseases
Mohamad Maged, Sameh Heikal, Salma Ibrahim, Sameh E. Hassanein
Cell Biochemistry and Function.2026;[Epub] CrossRef
The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration
Jiekang Wang, Xu Cao, Mei Wan
Journal of Clinical Investigation.2026;[Epub] CrossRef

Letter

Mineral, Bone & Muscle
Beyond Bone: Embracing Osteosarcopenia for Comprehensive Fracture Prevention: Beom-Jun Kim; Endocrinol Metab. 2024;39(3):531-533. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.2002

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Citations

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Sarcopenia and Muscle Aging: Updated Insights into Molecular Mechanisms and Translational Therapeutics
Thanh T. Nguyen, Tam Dao, Ha Thu Nguyen, Jun-Hyeon Park, Seung-Jun Jeong, Sei Kim, Yunju Jo, Nhung T.H. Thieu, Jiangqi Zhao, Fuan Ding, Ying Yu, Vu Chi Dung, Karim Gariani, Beom-Jun Kim, Dongryeol Ryu
Endocrinology and Metabolism.2026; 41(1): 57. CrossRef
Elevated Circulating Ceramides 18:0 and 24:1 as a Risk Factor for Sarcopenia: In Vitro, Animal, and Clinical Evidence
So Jeong Park, Ji Yeon Baek, Shibo Wei, Jin Young Lee, Yuna Lee, Sang‐Hoon Lee, Il‐Young Jang, Hyuk Sakong, Hyun Ju Yoo, Hee‐Won Jung, Eunju Lee, Su Jung Kim, Yunju Jo, Kyunggon Kim, Dongryeol Ryu, Beom‐Jun Kim
Journal of Cachexia, Sarcopenia and Muscle.2026;[Epub] CrossRef
Cloud-Enabled Automated CT Assessment of Pelvic Muscle Quality in Women With and Without Low-Energy Femoral Neck Fracture
Emre Emekli, Burak Can Demirel, Serhat Demir, Zeynep Ece Yağcı, Merve Oğuz, Murat Tepe
Calcified Tissue International.2026;[Epub] CrossRef
Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health
Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim
Endocrinology and Metabolism.2025; 40(1): 73. CrossRef
Establishing Blood-Based Biomarkers for Sarcopenia: Current Challenges and Future Directions
Beom-Jun Kim
Endocrinology and Metabolism.2025; 40(5): 693. CrossRef

Original Articles

Mineral, Bone & Muscle
Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults: Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim; Endocrinol Metab. 2023;38(6):701-708. Published online October 18, 2023; DOI: https://doi.org/10.3803/EnM.2023.1783

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Background
Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults.
Methods
This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay.
Results
After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012).
Conclusion
These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

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Integration of multiple omics reveals key targets and cellular mechanisms for intervention in sarcopenia
Zhu Zhu, Wenji Wang, Qi Zhang, Xiao Bi, Shaojun Ma, Yue Shen, Feng Ding
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Qiaowei Li, Tingting Liu, Wei Lin, Zhiqiang Ye, Cai Jiang, Feng Huang, Zhonghua Lin, Pengli Zhu
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Circulating BMP-7 Level is Independent of Sarcopenia in Older Asian Adults
Ahin Choi, Ji Yeon Baek, Eunhye Ji, Il-Young Jang, Hee-Won Jung, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Beom-Jun Kim
Annals of Geriatric Medicine and Research.2025; 29(1): 75. CrossRef
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Chang Won Won, Miji Kim, Hyung Eun Shin, Gustavo Duque
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Unlocking diagnosis of sarcopenia: The role of circulating biomarkers – A clinical systematic review
F. Veronesi, F. Salamanna, V. Borsari, A. Ruffilli, C. Faldini, G. Giavaresi
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Mineral, Bone & Muscle
Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia: Seong Hee Ahn, Hee-Won Jung, Eunju Lee, Ji Yeon Baek, Il-Young Jang, So Jeong Park, Jin Young Lee, Eunah Choi, Yun Sun Lee, Seongbin Hong, Beom-Jun Kim; Endocrinol Metab. 2022;37(3):487-496. Published online May 27, 2022; DOI: https://doi.org/10.3803/EnM.2022.1428

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Background
Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia.
Methods
Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay.
Results
The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025).
Conclusion
Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.

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Haoqi Chen, Junhong Peng, Shanshan Guo, Ting Chen, Si Chen, Xinyuan Jin, Wenge Huang, Chao Xu, Mengchu Li, Mengxing Xie, Mengtao Yang, Jinzhu Pang, Huilian Zhu
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Ben Kirk, Giovanni Lombardi, Gustavo Duque
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Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health
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Endocrinology and Metabolism.2024; 39(3): 521. CrossRef
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Carina O. Walowski, Catrin Herpich, Janna Enderle, Wiebke Braun, Marcus Both, Mario Hasler, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal
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Hewen Jiang, Dijie Li, Ying Han, Nanxi Li, Xiaohui Tao, Jin Liu, Zongkang Zhang, Yuanyuan Yu, Luyao Wang, Sifan Yu, Ning Zhang, Huan Xiao, Xin Yang, Yihao Zhang, Ge Zhang, Bao-Ting Zhang
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Adrenal Gland
Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor: Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim; Endocrinol Metab. 2021;36(4):865-874. Published online July 30, 2021; DOI: https://doi.org/10.3803/EnM.2021.1108

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Background
Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research.
Results
Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone.
Conclusion
These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

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Biphasic regulation of myogenesis by ALDH2, aldosterone, and oxidative stress
José Emmanuel Martínez-Cortés, Maikel Valle-Clara, Damaso Fernández-Hernández, Guillermo Ávila
Pflügers Archiv - European Journal of Physiology.2026;[Epub] CrossRef
Therapeutic Potential of Mineralocorticoid Receptors in Skeletal Muscle Aging
Ricardo Aparecido Baptista Nucci, Otávio de Toledo Nóbrega, Wilson Jacob-Filho
Receptors.2025; 4(3): 13. CrossRef
A Narrative Review on Nitrate-Rich Diets as Adjuncts to Antihypertensive Therapy: Enhancing Treatment Efficacy via Oxidative Stress Modulation
Mila Silva-Cunha, Carla Speroni Ceron, Heitor Moreno, José Eduardo Tanus-Santos
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Molecular mechanisms underlying sarcopenia in heart failure
Cody A. Rutledge
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Role of glucocorticoid and mineralocorticoid receptors in rainbow trout (Oncorhynchus mykiss) skeletal muscle: A transcriptomic perspective of cortisol action
Jorge E. Aedo, Rodrigo Zuloaga, Daniela Aravena-Canales, Alfredo Molina, Juan Antonio Valdés
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Rodrigo Zuloaga, Daniela Aravena-Canales, Jorge Eduardo Aedo, Cesar Osorio-Fuentealba, Alfredo Molina, Juan Antonio Valdés
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Yasuhiro Izumiya
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2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung
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Sunghwan Ji, Kyunggon Kim, So Jeong Park, Jin Young Lee, Hee-Won Jung, Hyun Ju Yoo, Il-Young Jang, Eunju Lee, Ji Yeon Baek, Beom-Jun Kim
Endocrinology and Metabolism.2023; 38(6): 701. CrossRef
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Endocrine Research
Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults: Da Ae Kim, So Jeong Park, Jin Young Lee, Jeoung Hee Kim, Seungjoo Lee, Eunju Lee, Il-Young Jang, Hee-Won Jung, Jin Hoon Park, Beom-Jun Kim; Endocrinol Metab. 2021;36(2):455-465. Published online April 14, 2021; DOI: https://doi.org/10.3803/EnM.2020.942

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Background
The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline.
Results
Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index.
Conclusion
Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

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Na Qiang, Junjie Ao, Masato Nakamura, Keichi Katayama, Jiaqi Zhang, Tadayoshi Kogure, Keita Ogawa, Hiroaki Kanzaki, Ryuta Kojima, Keisuke Koroki, Kazufumi Kobayashi, Masanori Inoue, Naoya Kanogawa, Soichiro Kiyono, Ryo Nakagawa, Takayuki Kondo, Sadahisa O
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Bagus Sarmito, Younjeong Oh, Nurkyz Alymkulova, Jeong Kyo Yoon
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Mingchong Liu, Xiao Fu, Daqian Yu, Meng Li, Yutao Pan, Chensong Yang, Guixin Sun
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Review Article

Mineral, Bone & Muscle
Potential Biomarkers to Improve the Prediction of Osteoporotic Fractures: Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh; Endocrinol Metab. 2020;35(1):55-63. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.55

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Osteoporotic fracture (OF) is associated with high disability and morbidity rates. The burden of OF may be reduced by early identification of subjects who are vulnerable to fracture. Although the current fracture risk assessment model includes clinical risk factors (CRFs) and bone mineral density (BMD), its overall ability to identify individuals at high risk for fracture remains suboptimal. Efforts have therefore been made to identify potential biomarkers that can predict the risk of OF, independent of or combined with CRFs and BMD. This review highlights the emerging biomarkers of bone metabolism, including sphongosine-1-phosphate, leucine-rich repeat-containing 17, macrophage migration inhibitory factor, sclerostin, receptor activator of nuclear factor-κB ligand, and periostin, and the importance of biomarker risk score, generated by combining these markers, in enhancing the accuracy of fracture prediction.

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Namgok Lecture 2017

Adrenal gland
Bone Health in Adrenal Disorders: Beom-Jun Kim, Seung Hun Lee, Jung-Min Koh; Endocrinol Metab. 2018;33(1):1-8. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.1

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Abstract PDF PubReader ePub

Secondary osteoporosis resulting from specific clinical disorders may be potentially reversible, and thus continuous efforts to find and adequately treat the secondary causes of skeletal fragility are critical to ameliorate fracture risk and to avoid unnecessary treatment with anti-osteoporotic drugs. Among the hyperfunctional adrenal masses, Cushing's syndrome, pheochromocytoma, and primary aldosteronism are receiving particularly great attention due to their high morbidity and mortality mainly by increasing cardiovascular risk. Interestingly, there is accumulating experimental and clinical evidence that adrenal hormones may have direct detrimental effects on bone metabolism as well. Thus, the present review discusses the possibility of adrenal disorders, especially focusing on pheochromocytoma and primary aldosteronism, as secondary causes of osteoporosis.

Citations

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Original Article

Clinical Study
The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women: Hyeonmok Kim, Seong Hee Ahn, Chaeho Shin, Seung Hun Lee, Beom-Jun Kim, Jung-Min Koh; Endocrinol Metab. 2016;31(3):454-461. Published online July 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.454

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Abstract PDF Supplementary Material PubReader

Background

Despite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women.

Methods

A total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria.

Results

Before and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73).

Conclusion

This study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.

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