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Calcium & Bone Metabolism
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
  • 6,428 View
  • 282 Download
  • 17 Web of Science
  • 20 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Ukrainian Consensus on Diagnosis and Management of Vitamin D Deficiency in Adults
    Nataliia Grygorieva, Mykola Tronko, Volodymir Kovalenko, Serhiy Komisarenko, Tetiana Tatarchuk, Ninel Dedukh, Mykola Veliky, Serhiy Strafun, Yulia Komisarenko, Andrii Kalashnikov, Valeria Orlenko, Volodymyr Pankiv, Oleg Shvets, Inna Gogunska, Svitlana Reg
    Nutrients.2024; 16(2): 270.     CrossRef
  • Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population
    Pawel Pludowski, William B. Grant, Spyridon N. Karras, Armin Zittermann, Stefan Pilz
    Nutrients.2024; 16(3): 391.     CrossRef
  • Clinical Characteristics and Outcomes of Limb Fractures in Saudi Children
    Lamia Aldhbiban, Fai Alhoshan, Raghad Alomari, Shahad A Almatrafi, Yousef Alanazi, Samir Alsayegh, Haifa Y Alfaraidi, Ayman H Jawadi, Fahad N Aljuraibah
    Cureus.2024;[Epub]     CrossRef
  • The interplay of rheumatoid arthritis and osteoporosis: exploring the pathogenesis and pharmacological approaches
    Nikhil Gupta, Navjot Kanwar, Anchal Arora, Kavin Khatri, Abhinav Kanwal
    Clinical Rheumatology.2024; 43(5): 1421.     CrossRef
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    A.E. Smit, O.C. Meijer, E.M. Winter
    Bone Reports.2024; 20: 101750.     CrossRef
  • Vitamin D Deficiency in Patients With Low-Energy Hip Fractures in Accordance With the Mediterranean Paradox
    Christos Konstantinidis, Ourania Psoma, Christos Kotsias, Vasileios Panagiotopoulos , Sotiris Plakoutsis, Dimitrios Tsiampas, Dimitrios Vardakas, Dimitrios Giotis
    Cureus.2024;[Epub]     CrossRef
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    Long Tan, Ruiqian He, Xiaoxue Zheng
    BMC Geriatrics.2024;[Epub]     CrossRef
  • Association of vitamin and/or nutritional supplements with fall among patients with diabetes: A prospective study based on ACCORD and UK Biobank
    Lingfang He, Tianqi Ma, Guogang Zhang, Xunjie Cheng, Yongping Bai
    Frontiers in Nutrition.2023;[Epub]     CrossRef
  • Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs
    Gavriela Voulgaridou, Sousana K. Papadopoulou, Paraskevi Detopoulou, Despoina Tsoumana, Constantinos Giaginis, Foivi S. Kondyli, Evgenia Lymperaki, Agathi Pritsa
    Diseases.2023; 11(1): 29.     CrossRef
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    Yaohui Yu, Yudan Wang, Xiaoli Hou, Faming Tian
    Frontiers in Public Health.2023;[Epub]     CrossRef
  • Can Nutrition Contribute to a Reduction in Sarcopenia, Frailty, and Comorbidities in a Super-Aged Society?
    Sadao Yoshida, Ryo Shiraishi, Yuki Nakayama, Yasuko Taira
    Nutrients.2023; 15(13): 2991.     CrossRef
  • Safety Profile of Vitamin D in Italy: An Analysis of Spontaneous Reports of Adverse Reactions Related to Drugs and Food Supplements
    Valentina Maggini, Giada Crescioli, Ilaria Ippoliti, Eugenia Gallo, Francesca Menniti-Ippolito, Adelaide Chiaravalloti, Vittorio Mascherini, Roberto Da Cas, Simona Potenza, Giulia Gritti, Maria Galiulo, Laura Sottosanti, Alfredo Vannacci, Niccolò Lombardi
    Journal of Clinical Medicine.2023; 12(14): 4726.     CrossRef
  • Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly
    Sabrina Chiloiro, Stefano Frara, Irene Gagliardi, Antonio Bianchi, Antonella Giampietro, Margherita Medici, Agnese Allora, Luigi di Filippo, Maria Rosaria Ambrosio, Alfredo Pontecorvi, Maria Chiara Zatelli, Laura De Marinis, Andrea Giustina
    The Journal of Clinical Endocrinology & Metabolism.2023; 109(1): e58.     CrossRef
  • Proceedings of the 2023 Santa Fe Bone Symposium: Progress and Controversies in the Management of Patients with Skeletal Diseases
    E. Michael Lewiecki, Teresita Bellido, John P. Bilezikian, Jacques P. Brown, Azeez Farooki, Christopher S. Kovacs, Brendan Lee, William D. Leslie, Michael R. McClung, Mark L. Prasarn, Deborah E. Sellmeyer
    Journal of Clinical Densitometry.2023; 26(4): 101432.     CrossRef
  • Diagnosis, prevention and treatment of vitamin D deficiency in adults: Ukrainian experts consensus statement
    N.V. Grygorieva, M.D. Tronko, V.M. Kovalenko, S.V. Komisarenko, T.F. Tatarchuk, N.V. Dedukh, M.M. Veliky, S.S. Strafun, Y.I. Komisarenko, A.V. Kalashnikov, V.L. Orlenko, V.I. Pankiv, O.V. Shvets, I.V. Gogunska, S.I. Regeda
    PAIN, JOINTS, SPINE.2023; 13(2): 60.     CrossRef
  • Serum 25-Hydroxyvitamin D Level Is Negatively Associated with Fatigue in Elderly Maintenance Hemodialysis Patients
    Menglin Pang, Lin Chen, Na Jiang, Mengmeng Jiang, Baofeng Wang, Lili Wang, Xiao-yan Jia
    Kidney and Blood Pressure Research.2023; 48(1): 231.     CrossRef
  • Vitamin D for Clinical Diseases in Women: An Indispensable Factor in Medicine and Dentistry
    Dario Calafiore, Leonzio Fortunato, Mario Migliario
    Journal of Clinical Medicine.2022; 11(11): 3104.     CrossRef
  • Malnutrition in Older Adults—Effect on Falls and Fractures: A Narrative Review
    Malgorzata Kupisz-Urbanska, Ewa Marcinowska-Suchowierska
    Nutrients.2022; 14(15): 3123.     CrossRef
  • Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group
    Thierry Chevalley, Maria Luisa Brandi, Kevin D. Cashman, Etienne Cavalier, Nicholas C. Harvey, Stefania Maggi, Cyrus Cooper, Nasser Al-Daghri, Oliver Bock, Olivier Bruyère, Mario Miguel Rosa, Bernard Cortet, Alfonso J. Cruz-Jentoft, Antonio Cherubini, Bes
    Aging Clinical and Experimental Research.2022; 34(11): 2603.     CrossRef
  • The Relationship of Osteoporosis with Menopause: Review of Article
    Hadeel Anwar Alsarraje, *Liqaa Khalel Alhyali
    International Journal of Research in Medical Sciences and Technology.2022; 14(01): 127.     CrossRef
Close layer
Calcium & Bone Metabolism
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
  • 4,075 View
  • 214 Download
  • 13 Web of Science
  • 15 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Automated detection of vertebral fractures from X-ray images: A novel machine learning model and survey of the field
    Li-Wei Cheng, Hsin-Hung Chou, Yu-Xuan Cai, Kuo-Yuan Huang, Chin-Chiang Hsieh, Po-Lun Chu, I-Szu Cheng, Sun-Yuan Hsieh
    Neurocomputing.2024; 566: 126946.     CrossRef
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    Baisen Chen, Jiaming Cui, Chaochen Li, Pengjun Xu, Guanhua Xu, Jiawei Jiang, Pengfei Xue, Yuyu Sun, Zhiming Cui
    Journal of Orthopaedic Research.2024; 42(6): 1356.     CrossRef
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    Satoshi Maki, Takeo Furuya, Masahiro Inoue, Yasuhiro Shiga, Kazuhide Inage, Yawara Eguchi, Sumihisa Orita, Seiji Ohtori
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  • A CT-based Deep Learning Model for Predicting Subsequent Fracture Risk in Patients with Hip Fracture
    Yisak Kim, Young-Gon Kim, Jung-Wee Park, Byung Woo Kim, Youmin Shin, Sung Hye Kong, Jung Hee Kim, Young-Kyun Lee, Sang Wan Kim, Chan Soo Shin
    Radiology.2024;[Epub]     CrossRef
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    Pengwei Xiao, Tinghe Zhang, Yufei Huang, Xiaodu Wang
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    Yu He, Jiaxi Lin, Shiqi Zhu, Jinzhou Zhu, Zhonghua Xu
    Journal of International Medical Research.2024;[Epub]     CrossRef
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    Min Wook Joo, Taehoon Ko, Min Seob Kim, Yong-Suk Lee, Seung Han Shin, Yang-Guk Chung, Hong Kwon Lee
    Clinical Orthopaedics & Related Research.2023; 481(11): 2247.     CrossRef
  • Automated Opportunistic Trabecular Volumetric Bone Mineral Density Extraction Outperforms Manual Measurements for the Prediction of Vertebral Fractures in Routine CT
    Sophia S. Goller, Jon F. Rischewski, Thomas Liebig, Jens Ricke, Sebastian Siller, Vanessa F. Schmidt, Robert Stahl, Julian Kulozik, Thomas Baum, Jan S. Kirschke, Sarah C. Foreman, Alexandra S. Gersing
    Diagnostics.2023; 13(12): 2119.     CrossRef
  • Machine learning‐based prediction of osteoporosis in postmenopausal women with clinical examined features: A quantitative clinical study
    Kainat A. Ullah, Faisal Rehman, Muhammad Anwar, Muhammad Faheem, Naveed Riaz
    Health Science Reports.2023;[Epub]     CrossRef
  • Skeletal Fracture Detection with Deep Learning: A Comprehensive Review
    Zhihao Su, Afzan Adam, Mohammad Faidzul Nasrudin, Masri Ayob, Gauthamen Punganan
    Diagnostics.2023; 13(20): 3245.     CrossRef
  • Deep learning system for automated detection of posterior ligamentous complex injury in patients with thoracolumbar fracture on MRI
    Sang Won Jo, Eun Kyung Khil, Kyoung Yeon Lee, Il Choi, Yu Sung Yoon, Jang Gyu Cha, Jae Hyeok Lee, Hyunggi Kim, Sun Yeop Lee
    Scientific Reports.2023;[Epub]     CrossRef
  • Vertebra Segmentation Based Vertebral Compression Fracture Determination from Reconstructed Spine X-Ray Images
    Srinivasa Rao Gadu, Chandra Sekhar Potala
    International Journal of Electrical and Electronics Research.2023; 11(4): 1225.     CrossRef
  • Computer Vision in Osteoporotic Vertebral Fracture Risk Prediction: A Systematic Review
    Anthony K. Allam, Adrish Anand, Alex R. Flores, Alexander E. Ropper
    Neurospine.2023; 20(4): 1112.     CrossRef
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    Jeonghoon Ha
    Endocrinology and Metabolism.2022; 37(4): 617.     CrossRef
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    Hans Peter Dimai
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Close layer
Calcium & Bone Metabolism
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
  • 3,254 View
  • 144 Download
  • 11 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   ePub   
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.

Citations

Citations to this article as recorded by  
  • Mechanism and physical activities in bone-skeletal muscle crosstalk
    Zhonghan Zhao, Kai Yan, Qiao Guan, Qiang Guo, Can Zhao
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Musculoskeletal disorders and coronary artery disease —promising molecular markers: literature review
    Viktoria N. Karetnikova, Anastasiya G. Neeshpapa, Evgenia I. Carpova, Olga L. Barbarash
    CardioSomatics.2024; 15(1): 55.     CrossRef
  • Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue
    Carina O. Walowski, Catrin Herpich, Janna Enderle, Wiebke Braun, Marcus Both, Mario Hasler, Manfred J. Müller, Kristina Norman, Anja Bosy-Westphal
    Scientific Reports.2023;[Epub]     CrossRef
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    Anika Shimonty, Lynda F. Bonewald, Fabrizio Pin
    Current Osteoporosis Reports.2023; 21(3): 303.     CrossRef
  • The role of sclerostin in lipid and glucose metabolism disorders
    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
    Biochemical Pharmacology.2023; 215: 115694.     CrossRef
  • Cytokines and exosomal miRNAs in skeletal muscle–adipose crosstalk
    Liu Guo, Menchus Quan, Weijun Pang, Yulong Yin, Fengna Li
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    Antimo Moretti, Giovanni Iolascon
    Journal of International Medical Research.2023;[Epub]     CrossRef
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    Giovanni Iolascon, Sara Liguori, Marco Paoletta, Giuseppe Toro, Antimo Moretti
    Therapeutic Advances in Musculoskeletal Disease.2023;[Epub]     CrossRef
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    Hyon-Seung Yi
    Endocrinology and Metabolism.2022; 37(3): 430.     CrossRef
  • Organokines, Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise
    Giulia Minniti, Letícia Maria Pescinini-Salzedas, Guilherme Almeida dos Santos Minniti, Lucas Fornari Laurindo, Sandra Maria Barbalho, Renata Vargas Sinatora, Lance Alan Sloan, Rafael Santos de Argollo Haber, Adriano Cressoni Araújo, Karina Quesada, Jesse
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Close layer
Calcium & Bone Metabolism
Real-World Safety and Effectiveness of Denosumab in Patients with Osteoporosis: A Prospective, Observational Study in South Korea
Yumie Rhee, Dong-Gune Chang, Jeonghoon Ha, Sooa Kim, Yusun Lee, Euna Jo, Jung-Min Koh
Endocrinol Metab. 2022;37(3):497-505.   Published online June 3, 2022
DOI: https://doi.org/10.3803/EnM.2022.1427
  • 5,561 View
  • 269 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
The efficacy and safety of denosumab have been established in a phase 3, randomized, placebo-controlled trial in Korean postmenopausal women with osteoporosis. This postmarketing surveillance study was aimed to investigate the safety and effectiveness of denosumab in Korean real-world clinical practice.
Methods
Patients with osteoporosis who had received denosumab per the Korean approved indications in the postmarketing setting between September 2014 and September 2019 were enrolled. The primary endpoint was the incidence of adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was the percent change from baseline in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck.
Results
Of the 3,221 patients enrolled, 3,185 were included in the safety analysis set; 2,973 (93.3%) were female, and the mean± standard deviation (SD) age was 68.9±9.9 years. The mean±SD study period was 350.0±71.4 days. AEs, fatal AEs, and ADRs occurred in 19.3%, 0.8%, and 1.6%, respectively. The most frequent AEs, occurring in >0.5% of patients, were dizziness (0.7%), arthralgia (0.7%), back pain (0.6%), and myalgia (0.6%). Hypocalcemia occurred in 0.3% of patients. There were no cases of osteonecrosis of the jaw and atypical femoral fracture. Mean±SD percent change from baseline in BMD of the lumbar spine, total hip, and femoral neck was 7.3%±23.6%, 3.6%±31.4%, and 3.2%±10.7%, respectively.
Conclusion
The safety and effectiveness of denosumab in Korean patients with osteoporosis in this study were comparable with those in the Korean randomized controlled trial, with no new safety findings.

Citations

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  • Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection
    Anna Spångeus, Johan Rydetun, Mischa Woisetschläger
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    Huei-Kai Huang, Albert Tzu-Ming Chuang, Tzu-Chi Liao, Shih-Chieh Shao, Peter Pin-Sung Liu, Yu-Kang Tu, Edward Chia-Cheng Lai
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    Chaiho Jeong, Jinyoung Kim, Jeongmin Lee, Yejee Lim, Dong-Jun Lim, Ki-Hyun Baek, Jeonghoon Ha
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    Sung Hye Kong
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Close layer
Calcium & Bone Metabolism
Association between Elevated Plasma Homocysteine and Low Skeletal Muscle Mass in Asymptomatic Adults
Jae-Hyeong Choi, Jin-Woo Seo, Mi-Yeon Lee, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park
Endocrinol Metab. 2022;37(2):333-343.   Published online February 8, 2022
DOI: https://doi.org/10.3803/EnM.2021.1202
  • 8,115 View
  • 190 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Homocysteine has been drawing attention with a closed linkage with skeletal muscle. However, the association of hyperhomocysteinemia with decreased skeletal muscle mass remains unclear. We aimed to investigate the association of hyperhomocysteinemia with low skeletal muscle mass (LMM) in asymptomatic adults.
Methods
This was a cross-sectional study of 114,583 community-dwelling adults without cancer, stroke, or cardiovascular diseases who underwent measurements of plasma homocysteine and body composition analysis from 2012 to 2018. Hyperhomocysteinemia was defined as >15 μmol/L. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: “normal,” “mildly low,” and “severely low.”
Results
The prevalence of hyperhomocysteinemia was the highest in subjects with severely LMM (12.9%), followed by those with mildly LMM (9.8%), and those with normal muscle mass (8.5%) (P for trend <0.001). In a multivariable logistic regression model, hyperhomocysteinemia was significantly associated with having a mildly LMM (odds ratio [OR], 1.305; 95% confidence interval [CI], 1.224 to 1.392) and severely LMM (OR, 1.958; 95% CI, 1.667 to 2.286), respectively. One unit increment of log-transformed homocysteine was associated with 1.360 and 2.169 times higher risk of having mildly LMM and severely LMM, respectively.
Conclusion
We demonstrated that elevated homocysteine has an independent association with LMM in asymptomatic adults, supporting that hyperhomocysteinemia itself can be a risk for decline in skeletal musculature.

Citations

Citations to this article as recorded by  
  • The role of the mitochondrial trans-sulfuration in cerebro-cardio renal dysfunction during trisomy down syndrome
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    Juan Xiong, Yanxia Wu, Lingling Huang, Xujuan Zheng
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  • Causal effects of homocysteine levels on the components of sarcopenia: A two-sample mendelian randomization study
    Hongwei Yu, Gan Luo, Tianwei Sun, Qiong Tang
    Frontiers in Genetics.2022;[Epub]     CrossRef
  • Association between serum homocysteine and sarcopenia among hospitalized older Chinese adults: a cross-sectional study
    Bing Lu, Lingyu Shen, Haiqiong Zhu, Ling Xi, Wei Wang, Xiaojun Ouyang
    BMC Geriatrics.2022;[Epub]     CrossRef
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Review Articles
Calcium & Bone Metabolism
Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer
Siva Swapna Kasarla, Vannuruswamy Garikapati, Yashwant Kumar, Sujatha Dodoala
Endocrinol Metab. 2022;37(3):392-407.   Published online June 3, 2022
DOI: https://doi.org/10.3803/EnM.2021.1349
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AbstractAbstract PDFPubReader   ePub   
Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.

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  • Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis
    Mohamed I. Elsalahaty, Samar Sami Alkafaas, Aya O. Bashir, Khaled A. El-Tarabily, Mohamed T. El-Saadony, Eman H. Yousef
    Frontiers in Genetics.2024;[Epub]     CrossRef
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    Mohamed Ben-Eltriki, Erysa J. Gayle, Jhoanne M. Paras, Louisa Nyame-Addo, Manik Chhabra, Subrata Deb
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    Martina Balducci, Letizia Pruccoli, Andrea Tarozzi
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    Faruk SAYDAM, İrfan DEĞİRMENCİ, Alparslan BİRDANE, Cansu ÖZBAYER, Taner ULUS, Mahmut ÖZDEMİR, Necmi ATA, Hasan Veysi GÜNEŞ
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  • Association of flame retardants, polybrominated diethyl ethers (PBDEs), with vitamin D in female subjects
    Alexandra E. Butler, Edwina Brennan, Daniel S. Drage, Thozhukat Sathyapalan, Stephen L. Atkin
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  • Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro
    Sai-li Xie, Xiayan Zhu, Nanyong Gao, Qianmeng Lin, Chaojie Chen, Yun-jun Yang, Jian-ping Cai, Guo-xin Hu, Ren-ai Xu
    Food and Chemical Toxicology.2023; 181: 114101.     CrossRef
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Calcium & Bone Metabolism
Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism
Hye-Sun Park, Namki Hong, Jong Ju Jeong, Mijin Yun, Yumie Rhee
Endocrinol Metab. 2022;37(5):744-755.   Published online October 25, 2022
DOI: https://doi.org/10.3803/EnM.2022.1589
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AbstractAbstract PDFPubReader   ePub   
Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi–single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient’s clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

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  • Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue
    Anne L. Worth, Mesrop Ayrapetyan, Susan J. Maygarden, Zibo Li, Zhanhong Wu, Chris B. Agala, Lawrence T. Kim
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    Helena Martínez Sánchez, Francisca Moreno Macián, Sara León Cariñena, Carmen de Mingo Alemany, Lidia Blasco González, Raquel Sánchez Vañó
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  • Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue
    Mara Carsote, Mihaela Stanciu, Florina Ligia Popa, Oana-Claudia Sima, Eugenia Petrova, Anca-Pati Cucu, Claudiu Nistor
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    Max H. M. C. Scheepers, Zaid Al-Difaie, Lloyd Brandts, Andrea Peeters, Bjorn Winkens, Mahdi Al-Taher, Sanne M. E. Engelen, Tim Lubbers, Bas Havekes, Nicole D. Bouvy, Alida A. Postma
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Close layer
Calcium & bone metabolism
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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AbstractAbstract PDFPubReader   ePub   
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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  • The Role of Rosavin in the Pathophysiology of Bone Metabolism
    Piotr Wojdasiewicz, Paweł Turczyn, Anna Lach-Gruba, Łukasz A. Poniatowski, Daryush Purrahman, Mohammad-Reza Mahmoudian-Sani, Dariusz Szukiewicz
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Original Article
Calcium & Bone Metabolism
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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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
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 (PUGFR), proteinuric DKD with normal eGFR (PU+GFR), non-proteinuric DKD with reduced eGFR (PUGFR+), 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 PUGFR+ 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 PUGFR+ 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; PUGFR+ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PUGFR 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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  • Proteinuria screening and risk of bone fracture: a retrospective cohort study using a nationwide population-based database
    Akira Okada, Akira Honda, Hideaki Watanabe, Yusuke Sasabuchi, Shotaro Aso, Kayo Ikeda Kurakawa, Masaomi Nangaku, Toshimasa Yamauchi, Hideo Yasunaga, Hirotaka Chikuda, Takashi Kadowaki, Satoko Yamaguchi
    Clinical Kidney Journal.2024;[Epub]     CrossRef
  • Fracture risks associated with sodium-glucose cotransporter-2 inhibitors in type 2 diabetes patients across eGFR and albuminuria categories: A population-based study in Hong Kong
    David Tak Wai Lui, Tingting Wu, Eric Ho Man Tang, Ivan Chi Ho Au, Chi Ho Lee, Yu Cho Woo, Kathryn Choon Beng Tan, Carlos King Ho Wong
    Diabetes Research and Clinical Practice.2023; 197: 110576.     CrossRef
  • Diagnose und Management der Osteoporose bei Diabetes mellitus (Update 2023)
    Christian Muschitz, Alexandra Kautzky-Willer, Yvonne Winhofer, Martina Rauner, Judith Haschka, Daniel Cejka, Robert Wakolbinger-Habel, Peter Pietschmann
    Wiener klinische Wochenschrift.2023; 135(S1): 207.     CrossRef
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    Seung Eun Lee, Juhwan Yoo, Bong-Seong Kim, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi
    Archives of Osteoporosis.2023;[Epub]     CrossRef
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    Seung Eun Lee, Juhwan Yoo, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim
    Diabetes & Metabolism Journal.2023; 47(4): 523.     CrossRef
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Review Articles
Calcium & Bone Metabolism
A Key Metabolic Regulator of Bone and Cartilage Health
Elizabeth Pérez-Hernández, Jesús Javier Pastrana-Carballo, Fernando Gómez-Chávez, Ramesh C. Gupta, Nury Pérez-Hernández
Endocrinol Metab. 2022;37(4):559-574.   Published online August 8, 2022
DOI: https://doi.org/10.3803/EnM.2022.1443
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AbstractAbstract PDFPubReader   ePub   
Taurine, a cysteine-derived zwitterionic sulfonic acid, is a common ingredient in energy drinks and is naturally found in fish and other seafood. In humans, taurine is produced mainly in the liver, and it can also be obtained from food. In target tissues, such as the retina, heart, and skeletal muscle, it functions as an essential antioxidant, osmolyte, and antiapoptotic agent. Taurine is also involved in energy metabolism and calcium homeostasis. Taurine plays a considerable role in bone growth and development, and high-profile reports have demonstrated the importance of its metabolism for bone health. However, these reports have not been collated for more than 10 years. Therefore, this review focuses on taurine–bone interactions and covers recently discovered aspects of taurine’s effects on osteoblastogenesis, osteoclastogenesis, bone structure, and bone pathologies (e.g., osteoporosis and fracture healing), with due attention to the taurine–cartilage relationship.

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  • Anti-osteoporotic effects of enzymatic hydrolysates of mackerel Scomber japonicus byproduct in MC3T3-E1 cells and ovariectomized rat model
    Seung Tae Im, Minji Kim, Wook Chul Kim, Yun-Su Lee, Seung-Hong Lee
    Fisheries Science.2024;[Epub]     CrossRef
  • Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
    Mengxing Yin, Dezhi Zhou, Fu Jia, Xiaosan Su, Xiufang Li, Ruifen Sun, Junmin Li
    Journal of Orthopaedic Surgery and Research.2023;[Epub]     CrossRef
  • An in-silico approach to the potential modulatory effect of taurine on sclerostin (SOST) and its probable role during osteoporosis
    Mazumder Adhish, I. Manjubala
    Journal of Biomolecular Structure and Dynamics.2023; : 1.     CrossRef
  • Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that’ s the question
    Kwok M. Ho, Anna Lee, William Wu, Matthew T.V. Chan, Lowell Ling, Jeffrey Lipman, Jason Roberts, Edward Litton, Gavin M. Joynt, Martin Wong
    Journal of Geriatric Cardiology.2023; 20(11): 813.     CrossRef
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Calcium & bone metabolism
New Insights into Calorie Restriction Induced Bone Loss
Linyi Liu, Clifford J. Rosen
Endocrinol Metab. 2023;38(2):203-213.   Published online April 27, 2023
DOI: https://doi.org/10.3803/EnM.2023.1673
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AbstractAbstract PDFPubReader   ePub   
Caloric restriction (CR) is now a popular lifestyle choice due to its ability in experimental animals to improve lifespan, reduce body weight, and lessen oxidative stress. However, more and more emerging evidence suggests this treatment requires careful consideration because of its detrimental effects on the skeletal system. Experimental and clinical studies show that CR can suppress bone growth and raise the risk of fracture, but the specific mechanisms are poorly understood. Reduced mechanical loading has long been thought to be the primary cause of weight loss-induced bone loss from calorie restriction. Despite fat loss in peripheral depots with calorie restriction, bone marrow adipose tissue (BMAT) increases, and this may play a significant role in this pathological process. Here, we update recent advances in our understanding of the effects of CR on the skeleton, the possible pathogenic role of BMAT in CR-induced bone loss, and some strategies to mitigate any potential side effects on the skeletal system.

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  • Obesity, diabetes and risk of bone fragility: How BMAT behavior is affected by metabolic disturbances and its influence on bone health
    Gregório Corrêa Guimarães, João Bosco Costa Coelho, João Gabriel Oliveira Silva, Ana Carolina Chalfun de Sant’Ana, Cássia Alves Carrilho de Sá, Júlia Marques Moreno, Lívia Marçal Reis, Camila Souza de Oliveira Guimarães
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    Jessica A. Keune, Carmen P. Wong, Adam J. Branscum, Scott A. Menn, Urszula T. Iwaniec, Russell T. Turner
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    Aoi Ikedo, Yuuki Imai
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    Morten S. Hansen, Eva M. Wölfel, Shakespeare Jeromdesella, Jens-Jakob K. Møller, Charlotte Ejersted, Niklas R. Jørgensen, Richard Eastell, Stinus G. Hansen, Morten Frost
    eClinicalMedicine.2024; 72: 102624.     CrossRef
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Calcium & bone metabolism
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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AbstractAbstract PDFPubReader   ePub   
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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  • 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,
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    Chaiho Jeong, Jinyoung Kim, Jeongmin Lee, Yejee Lim, Dong-Jun Lim, Ki-Hyun Baek, Jeonghoon Ha
    Journal of Clinical Medicine.2023; 12(21): 6904.     CrossRef
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Calcium & Bone Metabolism
Updates on Paget’s Disease of Bone
Yong Jun Choi, Young Bae Sohn, Yoon-Sok Chung
Endocrinol Metab. 2022;37(5):732-743.   Published online October 25, 2022
DOI: https://doi.org/10.3803/EnM.2022.1575
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AbstractAbstract PDFPubReader   ePub   
Paget’s disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget’s disease of bone with a clinical case.

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  • Effects of Erythropoietin-Promoted Fracture Healing on Bone Turnover Markers in Cats
    Radina Vasileva, Tsvetan Chaprazov, Aneliya Milanova
    Journal of Functional Biomaterials.2024; 15(4): 106.     CrossRef
  • Newly Diagnosed Monostotic Paget’s Disease of Bone during Living Kidney Donor Candidate Evaluation
    Diana Jędrzejuk, Paweł Poznański, Paweł Szewczyk, Oktawia Mazanowska, Marek Bolanowski, Magdalena Krajewska, Dorota Kamińska
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    Mehrzad Hajialiloo, Sepideh Tahsini Tekantapeh
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Calcium & bone metabolism
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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AbstractAbstract PDFPubReader   ePub   
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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  • Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration
    Shizhen Lei, Mang Hu, Zhongtao Wei
    Frontiers in Cellular Neuroscience.2024;[Epub]     CrossRef
  • The synergistic effect of diabetes mellitus and osteoporosis on the all-cause mortality: a cohort study of an American population
    Weihua Li, Siyu Xie, Shengdong Zhong, Liting Lan
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Identification of systemic biomarkers and potential drug targets for age-related macular degeneration
    Shizhen Lei, Mang Hu, Zhongtao Wei
    Frontiers in Aging Neuroscience.2024;[Epub]     CrossRef
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Calcium & Bone Metabolism
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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AbstractAbstract PDFPubReader   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.

Citations

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  • Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury
    Christopher M. Cirnigliaro, Michael F. La Fountaine, J. Scott Parrott, Steven C. Kirshblum, Susan J. Sauer, Sue A. Shapses, Isa A. McClure, William A. Bauman
    Osteoporosis International.2023; 34(4): 741.     CrossRef
  • 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
    Endocrinology and Metabolism.2023; 38(2): 260.     CrossRef
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