Endocrinology and Metabolism

Original Articles

Mineral, bone & muscle
Synthetic Data-Enhanced Classification of Prevalent Osteoporotic Fractures Using Dual-Energy X-Ray Absorptiometry-Based Geometric and Material Parameters: Luca Quagliato, Jiin Seo, Jiheun Hong, Taeyong Lee, Yoon-Sok Chung; Endocrinol Metab. 2025;40(3):484-497. Published online May 14, 2025; DOI: https://doi.org/10.3803/EnM.2024.2211

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Abstract PDF PubReader ePub: Background
Bone fracture risk assessment for osteoporotic patients is essential for implementing early countermeasures and preventing discomfort and hospitalization. Current methodologies, such as Fracture Risk Assessment Tool (FRAX), provide a risk assessment over a 5- to 10-year period rather than evaluating the bone’s current health status.
Methods
The database was collected by Ajou University Medical Center from 2017 to 2021. It included 9,260 patients, aged 55 to 99, comprising 242 femur fracture (FX) cases and 9,018 non-fracture (NFX) cases. To model the association of the bone’s current health status with prevalent FXs, three prediction algorithms—extreme gradient boosting (XGB), support vector machine, and multilayer perceptron—were trained using two-dimensional dual-energy X-ray absorptiometry (2D-DXA) analysis results and subsequently benchmarked. The XGB classifier, which proved most effective, was then further refined using synthetic data generated by the adaptive synthetic oversampler to balance the FX and NFX classes and enhance boundary sharpness for better classification accuracy.
Results
The XGB model trained on raw data demonstrated good prediction capabilities, with an area under the curve (AUC) of 0.78 and an F1 score of 0.71 on test cases. The inclusion of synthetic data improved classification accuracy in terms of both specificity and sensitivity, resulting in an AUC of 0.99 and an F1 score of 0.98.
Conclusion
The proposed methodology demonstrates that current bone health can be assessed through post-processed results from 2D-DXA analysis. Moreover, it was also shown that synthetic data can help stabilize uneven databases by balancing majority and minority classes, thereby significantly improving classification performance.

Thyroid Big Data Articles (National Health Insurance Service Database)
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; Endocrinol Metab. 2025;40(2):225-235. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2101

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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.

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

Review Articles

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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Lisa M. Raven, Jacqueline R. Center, Christopher A. Muir
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A. Monegal, J. L. Carrasco, P. Peris, B. Frade-Sosa, A. Azuaga, H. Florez, A. Dura, N. Guañabens, J. Colmenero
Osteoporosis International.2025; 36(7): 1213. CrossRef
Treatment of osteoporosis in the solid organ transplant recipient: an organ-based approach
Soumya Kurnool, Nandi Shah, Preethika Ekanayake
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Global and regional prevalence of osteoporosis in kidney transplant recipients: a systematic review and meta-analysis
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Clinical and Experimental Medicine.2025;[Epub] CrossRef

Mineral, Bone & Muscle
Acromegaly and Bone: An Update: Andrea Giustina; Endocrinol Metab. 2023;38(6):655-666. Published online December 22, 2023; DOI: https://doi.org/10.3803/EnM.2023.601

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Since our discovery in 2006 that acromegaly is associated with an increased risk of vertebral fractures, many authors have confirmed this finding in both cross-sectional and prospective studies. Due to the high epidemiological and clinical impact of this newly discovered comorbidity of acromegaly, this topic has progressively become more important and prominent over the years, and the pertinent literature has been enriched by new findings on the pathophysiology and treatment. The aim of this narrative review was to discuss these novel findings, integrating them with the seminal observations, in order to give the reader an updated view of how the field of acromegaly and bone is developing, from strong clinical observations to a mechanistic understanding and possible prevention and treatment.

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Vitamin D and hip protectors in osteosarcopenia: a combined hip fracture preventing approach
Alessandro Giustina, Andrea Giustina
Reviews in Endocrine and Metabolic Disorders.2025; 26(1): 1. CrossRef
Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data
Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2025; 40(1): 1. CrossRef
Frailty and pituitary surgery: a systematic review
Mendel Castle-Kirszbaum, Ann McCormack, Christopher Ovenden, Jeremy Kam, James King, Yi Yuen Wang, Tony Goldschlager
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Luciana Martel-Duguech, Helena Bascuñana, Jordi Cuartero, Susan M. Webb, Elena Valassi
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Evaluation of bone density and microstructure by DXA, TBS and HR-pQCT: an assessment of cortical porosity and its association with vertebral fractures in patients with acromegaly
PG Ornellas, EMF Gama, LMC Mendonça, C Villela-Nogueira, FP Paranhos-Neto, L Kasuki, MR Gadelha, MLF Farias, M Madeira
Journal of Endocrinological Investigation.2025;[Epub] CrossRef
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Luigi di Filippo, John P. Bilezikian, Ernesto Canalis, Umberto Terenzi, Andrea Giustina
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Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot single center experience
Sabrina Chiloiro, Antonella Giampietro, Amato Infante, Pier Paolo Mattogno, Liverana Lauretti, Alessandro Olivi, Laura De Marinis, Alfredo Pontecorvi, Francesco Doglietto, Antonio Bianchi
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Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE)
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Nicholas A. Tritos
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Tongxin Xiao, Xinxin Mao, Ou Wang, Yong Yao, Kan Deng, Huijuan Zhu, Lian Duan
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Iris C. M. Pelsma, Herman M. Kroon, Cornelie D. Andela, Enrike M. J. van der Linden, Margreet Kloppenburg, Nienke R. Biermasz, Kim M. J. A. Claessen
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Original Articles

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Association between Smoking Status and the Risk of Hip Fracture in Patients with Type 2 Diabetes: A Nationwide Population-Based Study: Se-Won Lee, Jun-Young Heu, Ju-Yeong Kim, Jinyoung Kim, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2023;38(6):679-689. Published online December 6, 2023; DOI: https://doi.org/10.3803/EnM.2023.1760

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Background
Limited longitudinal evidence exists regarding the potential association between smoking status and hip fracture among individuals with type 2 diabetes. We investigated this association using large-scale, nationwide cohort data for the Korean population.
Methods
This nationwide cohort study included 1,414,635 adults aged 40 and older who received Korean National Health Insurance Service health examinations between 2009 and 2012. Subjects with type 2 diabetes were categorized according to their smoking status, amount smoked (pack-years), number of cigarettes smoked per day, and duration of smoking. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between smoking status parameters and risk of hip fracture in multivariable Cox proportional hazard regression analysis.
Results
Compared with never-smokers, an increased adjusted HR (aHR) for hip fracture was observed in current smokers (1.681; 95% CI, 1.578 to 1.791), and a comparable aHR for hip fracture was found in former smokers (1.065; 95% CI, 0.999 to 1.136). For former smokers who had smoked 20 pack-years or more, the risk was slightly higher than that for never-smokers (aHR, 1.107; 95% CI, 1.024 to 1.196). The hip fracture risk of female former smokers was similar to that of female current smokers, but the hip fracture risk in male former smokers was similar to that of male never-smokers.
Conclusion
Smoking is associated with an increased risk of hip fracture in patients with type 2 diabetes. Current smokers with diabetes should be encouraged to quit smoking because the risk of hip fracture is greatly reduced in former smokers.

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Hip fractures and type 2 diabetes in the elderly: Risk factors analysis of the Nedices cohort
Federico Hawkins Carranza, Cristina Martín-Arriscado Arroba, Arturo Corbatón-Anchuelo, Guillermo Martínez Díaz-Guerra, Félix Bermejo Pareja
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Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2024; 18(5): 103044. CrossRef

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea: Jiwon Kim, Namki Hong, Jimi Choi, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Sin Gon Kim, Cheol Ryong Ku; Endocrinol Metab. 2023;38(6):690-700. Published online October 30, 2023; DOI: https://doi.org/10.3803/EnM.2023.1782

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Background
Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly.
Methods
We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database.
Results
The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05).
Conclusion
Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Citations

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Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data
Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2025; 40(1): 1. CrossRef
Musculoskeletal disease in acromegaly—a population-based registry study
Christian Rosendal, Mai Christiansen Arlien-Søborg, Eigil Husted Nielsen, Claus Larsen Feltoft, Åse Krogh Rasmussen, Marianne Skovsager Andersen, Jens Otto Lunde Jørgensen, Jakob Dal
European Journal of Endocrinology.2025; 192(3): 308. CrossRef
Novel approach to bone comorbidity in resistant acromegaly
Stefano Frara, Matteo Acanfora, Vincenzo Franzese, Maria Luisa Brandi, Marco Losa, Andrea Giustina
Pituitary.2024; 27(6): 813. CrossRef

Mineral, Bone & Muscle
Age-Dependent Association of Height Loss with Incident Fracture Risk in Postmenopausal Korean Women: Chaewon Lee, Hye-Sun Park, Yumie Rhee, Namki Hong; Endocrinol Metab. 2023;38(6):669-678. Published online September 1, 2023; DOI: https://doi.org/10.3803/EnM.2023.1734

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Background
Height loss is a simple clinical measure associated with increased fracture risk. However, limited data exists on the association between height loss and fracture risk in postmenopausal Korean women. It is unknown whether this association varies with age.
Methods
Data on height loss over a 6-year period were collected from a community-based longitudinal follow-up cohort (Ansung cohort of the Korean Genome and Epidemiology Study). Incident fractures were defined based on self-reported fractures after excluding those due to severe trauma or toes/fingers. The association between incident fractures and height loss was investigated using a Cox proportional hazards model.
Results
During a median follow-up of 10 years after the second visit, 259/1,806 participants (median age, 64 years) experienced incident fractures. Overall, a 1 standard deviation (SD) decrease in height (1.6 cm/median 5.8 years) was associated with 9% increased risk of fracture (hazard ratio [HR], 1.09; P=0.037), which lost statistical significance after adjustment for covariates. When stratified into age groups (50–59, 60–69, 70 years or older), a 1 SD decrease in height remained a robust predictor of fracture in the 50 to 59 years age group after adjusting for covariates (adjusted hazard ratio [aHR], 1.52; P=0.003), whereas height loss was not an independent predictor of fracture in the 60 to 69 (aHR, 1.06; P=0.333) or the 70 years or older age groups (aHR, 1.05; P=0.700; P for interaction <0.05, for all).
Conclusion
Height loss during the previous 6 years was associated with an increased 10-year fracture risk in postmenopausal women in their 50s.

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Daihun Kang
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Joon-Kiong Lee, Juzaily Fekry Leong, Fu-Yuen Thong, Mohd Ariff Sharifudin, Azlina Amir Abbas, Nur Azree Ferdaus Kamudin, Sanjiv Rampal, Nor Faissal Yasin, Kwong-Weng Loh, Chee-Ken Chan, Paul James Mitchell
Archives of Osteoporosis.2024;[Epub] CrossRef

Review Article

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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Calcium Supplementation: To Do or Not to Do
Emanuella Graciela Borges Fonseca, Carlos Marques dos Santos, Felipe Freire da Silva, Ana Tereza Amoedo Martinez, Jozélio Freire de Carvalho
Journal of Bone Metabolism.2025; 32(1): 67. CrossRef
Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study
Mariangela Rondanelli, Salvatore Minisola, Marco Barale, Daniele Barbaro, Francesca Mansueto, Santina Battaglia, Gloria Bonaccorsi, Santina Caliri, Alessandro Cavioni, Luciano Colangelo, Sabrina Corbetta, Federica Coretti, Giorgia Dito, Valentina Gavioli,
Aging Clinical and Experimental Research.2024;[Epub] CrossRef
Association between Daily Dietary Calcium Intake and the Risk of Cardiovascular Disease (CVD) in Postmenopausal Korean Women
Jae Kyung Lee, Thi Minh Chau Tran, Euna Choi, Jinkyung Baek, Hae-Rim Kim, Heeyon Kim, Bo Hyon Yun, Seok Kyo Seo
Nutrients.2024; 16(7): 1043. CrossRef
Calcium deficiency and its implications for cardiovascular disease and cancer: Strategies for resolution via agronomic fortification
Liping Cheng, Jiapan Lian, Yongfeng Ding, Xin Wang, Mehr Ahmed Mujtaba Munir, Shafqat Ullah, Erjiang Wang, Zhenli He, Xiaoe Yang
Food Science & Nutrition.2024; 12(11): 8594. CrossRef
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Journal of Clinical Medicine.2023; 12(21): 6904. CrossRef

Original Articles

Mineral, Bone & Muscle
Development of a Spine X-Ray-Based Fracture Prediction Model Using a Deep Learning Algorithm: Sung Hye Kong, Jae-Won Lee, Byeong Uk Bae, Jin Kyeong Sung, Kyu Hwan Jung, Jung Hee Kim, Chan Soo Shin; Endocrinol Metab. 2022;37(4):674-683. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1461

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Background
Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-based fracture prediction model using deep learning with longitudinal data.
Methods
This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baseline fractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whether vertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age, sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models.
Results
Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of 40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with images and clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method without clinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women.
Conclusion
DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAX and CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.

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Mineral, Bone & Muscle
Effect of Vitamin D Supplementation on Risk of Fractures and Falls According to Dosage and Interval: A Meta-Analysis: Sung Hye Kong, Han Na Jang, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin; Endocrinol Metab. 2022;37(2):344-358. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1374

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Background
Although recent studies comparing various dosages and intervals of vitamin D supplementation have been published, it is yet to be elucidated whether there is an appropriate dose or interval to provide benefit regarding fracture risk. We aimed to assess the published evidence available to date regarding the putative beneficial effects of vitamin D supplements on fractures and falls according to various dosages and intervals.
Methods
We performed a meta-analysis of randomized controlled studies reporting associations between vitamin D supplementation and the risks of fractures and falls in PubMed, EMBASE, and Cochrane library. Studies with supplements of ergocalciferol or calcitriol, those with a number of event ≤10, or those with a follow-up duration of less than 6 months were also excluded.
Results
Thirty-two studies were included in the final analysis. Vitamin D supplementation with daily dose of 800 to 1,000 mg was associated with lower risks of osteoporotic fracture and fall (pooled relative risk [RR], 0.87; 95% confidence interval [CI], 0.78 to 0.97 and RR, 0.91; 95% CI, 0.85 to 0.98), while studies with <800 or >1,000 mg/day did not. Also, among intervals, daily administration of vitamin D was associated with the reduced risk of falls, while intermittent dose was not. Also, patients with vitamin D deficiency showed a significant risk reduction of falls after vitamin D supplementation.
Conclusion
Daily vitamin D dose of 800 to 1,000 IU was the most probable way to reduce the fracture and fall risk. Further studies designed with various regimens and targeted vitamin D levels are required to elucidate the benefits of vitamin D supplements.

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Review Article

Mineral, Bone & Muscle
Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature: Wei Lin Tay, Donovan Tay; Endocrinol Metab. 2022;37(2):183-194. Published online April 14, 2022; DOI: https://doi.org/10.3803/EnM.2021.1369

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1,208 Download
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Abstract PDF PubReader ePub

Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

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Original Articles

Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
Hip Fracture Risk According to Diabetic Kidney Disease Phenotype in a Korean Population: Seung Eun Lee, Juhwan Yoo, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi; Endocrinol Metab. 2022;37(1):148-158. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1315

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131 Download
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Background
Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype.
Methods
In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU⁻GFR⁻), proteinuric DKD with normal eGFR (PU⁺GFR⁻), non-proteinuric DKD with reduced eGFR (PU⁻GFR⁺), and proteinuric DKD with reduced eGFR (PU⁺GFR⁺)
Results
The cumulative incidence of hip fractures was highest in the PU⁺GFR⁺ group, followed by the PU⁻GFR⁺ group and the PU⁺GFR⁻ group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU⁺GFR⁺ group. However, the PU⁺GFR⁻ group had a higher HR for hip fracture than the PU⁻GFR⁺ group (PU⁺GFR⁺ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU⁺GFR⁻ : HR, 1.37; 95% CI, 1.30 to 1.46; PU⁻GFR⁺ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU⁻GFR⁻ group as the reference category).
Conclusion
The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

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Wiener klinische Wochenschrift.2023; 135(S1): 207. CrossRef
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Mineral, Bone & Muscle Big Data Articles (National Health Insurance Service Database)
10-Year Fracture Risk in Postmenopausal Women with Osteopenia and Osteoporosis in South Korea: Yeon-Hee Baek, Sun Wook Cho, Han Eol Jeong, Ju Hwan Kim, Yunji Hwang, Jeffrey L. Lange, Ju-Young Shin; Endocrinol Metab. 2021;36(6):1178-1188. Published online December 16, 2021; DOI: https://doi.org/10.3803/EnM.2021.1215

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Background
In South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.
Methods
BMD was classified as normal (T-score ≥–1.0 standard deviation [SD]), osteopenia (T-score <–1.0 SD and >–2.5 SD), and osteoporosis (T score ≤–2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.
Results
Among the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.
Conclusion
Women with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.

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Review Article

Bone Metabolism
Operationalizing Treat-to-Target for Osteoporosis: E. Michael Lewiecki; Endocrinol Metab. 2021;36(2):270-278. Published online March 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.970

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374 Download
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Treat-to-target (TTT) for osteoporosis is a concept for individualizing patient treatment decisions that focuses on achieving an acceptable level of fracture risk rather than response to treatment alone. While a response to treatment is essential in order to achieve an acceptable level of risk, it is not necessarily sufficient. Some patients have a good response to treatment yet remain at high level of fracture risk. Since there is no way to directly measure bone strength in patients treated for osteoporosis, a surrogate measurement must be used. Bone mineral density (BMD) is commonly used to select patients for treatment and has emerged as the most useful surrogate for assessing reduction of fracture risk after treatment is started. Recent large meta-regression studies have shown a robust correlation between larger increases in BMD with treatment and greater reductions in fracture risk. Application of TTT for osteoporosis involves assessing fracture risk before starting treatment and initiating treatment with an agent that is most likely to reduce fracture risk to an acceptable level, represented by a target BMD T-score, over a reasonable period of time. This review offers suggestions for implementing TTT for osteoporosis in clinical practice and managing patients who fail or succeed in reaching the target. More study is needed to fully validate the use of TTT for osteoporosis for initiating and modifying treatments to reduce fracture risk.

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