Endocrinology and Metabolism

Review Articles

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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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
Osteoporosis International.2024; 35(4): 575. CrossRef
Bone Marrow Adipose Tissue Is Not Required for Reconstitution of the Immune System Following Irradiation in Male Mice
Jessica A. Keune, Carmen P. Wong, Adam J. Branscum, Scott A. Menn, Urszula T. Iwaniec, Russell T. Turner
International Journal of Molecular Sciences.2024; 25(4): 1980. CrossRef
Dietary restriction plus exercise change gene expression of Cxcl12 abundant reticular cells in female mice
Aoi Ikedo, Yuuki Imai
Journal of Bone and Mineral Metabolism.2024;[Epub] CrossRef

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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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,
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
Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea
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

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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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
Vitamin D in Melanoma: Potential Role of Cytochrome P450 Enzymes
Mohamed Ben-Eltriki, Erysa J. Gayle, Jhoanne M. Paras, Louisa Nyame-Addo, Manik Chhabra, Subrata Deb
Life.2024; 14(4): 510. CrossRef
Heat stress as a potential risk factor for vitamin D deficiency
Martina Balducci, Letizia Pruccoli, Andrea Tarozzi
Medical Hypotheses.2023; 176: 111085. CrossRef
Association and Haplotype Analysis of the PON1, ITGB3 and CYP3A4 Genes, Strong Candidates for Familial Coronary Artery Disease Susceptibility
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
Chemosphere.2023; 338: 139488. CrossRef
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
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Original Articles

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

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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.

Citations

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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
The multi-faceted nature of age-associated osteoporosis
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
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
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Recent advances in the identification of related factors and preventive strategies of hip fracture
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
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The Relationship of Osteoporosis with Menopause: Review of Article
Hadeel Anwar Alsarraje, *Liqaa Khalel Alhyali
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Calcium & Bone Metabolism
Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study: Ye An Kim, Ji Won Yoon, Young Lee, Hyuk Jin Choi, Jae Won Yun, Eunsin Bae, Seung-Hyun Kwon, So Eun Ahn, Ah-Ra Do, Heejin Jin, Sungho Won, Do Joon Park, Chan Soo Shin, Je Hyun Seo; Endocrinol Metab. 2021;36(6):1189-1200. Published online December 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.1241

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Background
Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).
Methods
We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.
Results
rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.
Conclusion
The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

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Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization
Caroline De Souza Silverio , Carolina Bonilla
Biomédica.2024; 44(1): 45. CrossRef
Implications of vitamin D deficiency in systemic inflammation and cardiovascular health
Sanjay Kumar Dey, Shashank Kumar, Diksha Rani, Shashank Kumar Maurya, Pratibha Banerjee, Madhur Verma, Sabyasachi Senapati
Critical Reviews in Food Science and Nutrition.2023; : 1. CrossRef
Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study
Ji Hyun Lee, Ye An Kim, Young Sik Kim, Young Lee, Je Hyun Seo
Nutrients.2023; 15(13): 3043. CrossRef
Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait
Abdur Rahman, Mohamed Abu-Farha, Arshad Channanath, Maha M. Hammad, Emil Anoop, Betty Chandy, Motasem Melhem, Fahd Al-Mulla, Thangavel Alphonse Thanaraj, Jehad Abubaker
Frontiers in Endocrinology.2023;[Epub] CrossRef
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The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies
Massimiliano Berretta, Vincenzo Quagliariello, Alessia Bignucolo, Sergio Facchini, Nicola Maurea, Raffaele Di Francia, Francesco Fiorica, Saman Sharifi, Silvia Bressan, Sara N. Richter, Valentina Camozzi, Luca Rinaldi, Carla Scaroni, Monica Montopoli
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A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts
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Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health
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On the Centennial of Vitamin D—Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications
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The genetic and epigenetic contributions to the development of nutritional rickets
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Clinical Study
Association of Vitamin D Deficiency with Diabetic Nephropathy: So-hyeon Hong, Young Bin Kim, Hoon Sung Choi, Tae-Dong Jeong, Jin Taek Kim, Yeon Ah Sung; Endocrinol Metab. 2021;36(1):106-113. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.826

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Background
Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM.
Methods
This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay.
Results
The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables.
Conclusion
Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy.

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International Journal of General Medicine.2021; Volume 14: 5233. CrossRef
Association Between 25(OH)Vitamin D, HbA1c and Albuminuria in Diabetes Mellitus: Data From a Population-Based Study (VIDAMAZON)
João Soares Felício, Hana Andrade de Rider Britto, Pedro Celeira Cortez, Fabrício de Souza Resende, Manuela Nascimento de Lemos, Lorena Vilhena de Moraes, Vitória Teixeira de Aquino, Fernanda de Souza Parente, Natércia Neves Marques de Queiroz, João Felíc
Frontiers in Endocrinology.2021;[Epub] CrossRef
Vitamin D Analogs Can Retard the Onset or Progression of Diabetic Kidney Disease: A Systematic Review
Samuel N. Uwaezuoke
Frontiers in Clinical Diabetes and Healthcare.2021;[Epub] CrossRef

Clinical Study
Vitamin D Deficiency at Mid-Pregnancy Is Associated with a Higher Risk of Postpartum Glucose Intolerance in Women with Gestational Diabetes Mellitus: Kyung-Soo Kim, Seok Won Park, Yong-Wook Cho, Soo-Kyung Kim; Endocrinol Metab. 2020;35(1):97-105. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.97

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Background

To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) at mid-pregnancy and postpartum glucose intolerance in women with gestational diabetes mellitus (GDM).

Methods

We enrolled 348 pregnant women diagnosed with GDM from August 2012 to October 2016. We measured serum 25(OH)D levels at mid-pregnancy and carried out a 75-g oral glucose tolerance test at 6 to 12 weeks after delivery. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/mL.

Results

The prevalence of vitamin D deficiency was 76.7% (n=267). Women with vitamin D deficiency had a higher prevalence of postpartum glucose intolerance than did those without vitamin D deficiency (48.7% vs. 32.1%, P=0.011). Serum 25(OH)D level was negatively correlated with hemoglobin A1c at antepartum and postpartum period (antepartum: r=−0.186, P=0.001; postpartum: r=−0.129, P=0.047). Homeostasis model assessment of β-cell function was positively correlated with serum 25(OH)D level only postpartum (r=0.138, P=0.035). The risk of postpartum glucose intolerance was 2.00 times (95% confidence interval, 1.13 to 3.55) higher in women with vitamin D deficiency than in those without vitamin D deficiency (P=0.018).

Conclusion

In women with GDM, vitamin D deficiency at mid-pregnancy is associated with an elevated risk of postpartum glucose intolerance.

Citations

Citations to this article as recorded by

Vitamin D Supplementation for the Outcomes of Patients with Gestational Diabetes Mellitus and Neonates: A Meta-Analysis and Systematic Review
Chunfeng Wu, Yang Song, Xueying Wang, Pier P. Sainaghi
International Journal of Clinical Practice.2023; 2023: 1. CrossRef
Influence of hypovitaminosis D during pregnancy on glycemic and lipid profile, inflammatory indicators and anthropometry of pregnant and newborn
Sara de Figueiredo dos Santos, Paula Normando dos Reis Costa, Thaise Gasser Gouvêa, Nathalia Ferreira Antunes de Almeida, Felipe de Souza Cardoso
Clinical Nutrition ESPEN.2023; 54: 81. CrossRef
Risk factors associated with early postpartum glucose intolerance in women with a history of gestational diabetes mellitus: a systematic review and meta-analysis
Zhe Liu, Qianghuizi Zhang, Leyang Liu, Weiwei Liu
Endocrine.2023; 82(3): 498. CrossRef
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
Effect of Evidence-Based Diet Nursing on Intestinal Flora and Maternal and Infant Prognosis in Patients with Gestational Diabetes
Ying Jiang, Chunbo Qiu, Yuanping Wang, Bin He, Peng-Yue Zhang
Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1. CrossRef
Vitamin D in gestational diabetes: A broadened frontier
Yu Zhu, Ling Li, Ping Li
Clinica Chimica Acta.2022; 537: 51. CrossRef
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Endocrinology and Metabolism.2021; 36(3): 628. CrossRef
Fetal Abdominal Obesity Detected At 24 to 28 Weeks of Gestation Persists Until Delivery Despite Management of Gestational Diabetes Mellitus (Diabetes Metab J 2021;45:547-57)
Kyung-Soo Kim
Diabetes & Metabolism Journal.2021; 45(6): 966. CrossRef

Seasonal Variation in Serum 25-Hydroxyvitamin D in The Elderly in Korean.: Eun Jig Lee, Kyung Rae Kim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Choon Hee Chung, Sung Kil Lim, Yoon Sok Chung; J Korean Endocr Soc. 1994;9(2):121-127. Published online November 6, 2019

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Abstract PDF: The seasonal variations in the parameters of calcium metabolism including 25-hydroxyvitamin D were analyzed in 19 free-living elderly subjects (mean age:68.7±6.7 yr) in Seoul. Mean serum total calcium concentration was 9.0±0.3 mg/dl in March and had risen to 9.3±0.3mg/dl in the following September(p<0.001). Despite their comparable calcium intake. Serum phosphorus and alkaline phosphatase concentrations did not show any seasonal variations, whereas serum PTH concentrations were significantly lower in September than in March(20.1±8.6 vs. 32.5±8.4 pg/ml, p<0.001). Seasonal changes in serum 25-hydroxyvitamin D concentrations were also found between the value(17.3±6.9 ng/ml) in March and that (28.5±7.4 ng/ml) in September(p<0.001). There was a significant correlation between seasonal increase in 25-hydroxyvitamin D and seasonal reduction in serum PTH/Cr(r=-0.5394, p<0.05). This study suggests that the winter minimum of serum 25-hydroxyvitamin D concentration and the elevated PTH may be a contributing risk factor for the development of osteopenia especially in the elderly individuals. When exposure to sunlight is reduced, as in the case of nursing home population, an additional exogenous form of the vitamin D may be advisable.

Miscellaneous
Influence of Vitamin D Deficiency on Progression of Experimental Otitis Media in Rats: Hee-Bok Kim, So Hyun Lim, Chang Gun Cho, Han Seok Choi; Endocrinol Metab. 2018;33(2):296-304. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.296

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Background

Vitamin D plays an important role in the immune response against infection. The purpose of the present study was to investigate the influence of vitamin D deficiency on the progression of otitis media (OM) using an experimental rat model.

Methods

Four-week-old male Sprague-Dawley rats (n=72) were divided into two groups based on their diet: a control diet group (n=36) and a vitamin D-deficient diet group (n=36). After 8 weeks of diet, experimental OM was induced by inoculation of non-typeable Haemophilus influenzae in the middle ear cavity. The rats were evaluated with otomicroscopy to determine the inflammation in the middle ear mucosa on days 1, 2, 4, 7, and 14 post-inoculation. Bullae from sacrificed rats were collected and analyzed histologically.

Results

The middle ear mucosa from rats with vitamin D deficiency showed a significantly higher thickness than that of controls during the course of OM. The maximum mucosal thickness was 56.0±9.1 µm in the vitamin D deficiency group, and 43.9±9.8 µm in the control group, although there was no significant difference in the tympanic membrane score between the two groups evaluated with otomicroscopy. An immunohistochemical study showed increased expression of interleukin 6 (IL-6) and tumor necrosis factor α in rats manifesting vitamin D deficiency and decreased expression of IL-10 compared with controls.

Conclusion

Our results showed that vitamin D deficiency may exacerbate the pathophysiological changes of OM via altered cytokine production. Therefore, maintaining vitamin D status in the optimal range may be beneficial for proper management of OM.

Citations

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The role of vitamin D in subjective tinnitus—A case-control study
Magdalena Nowaczewska, Stanisław Osiński, Maria Marzec, Michał Wiciński, Katarzyna Bilicka, Wojciech Kaźmierczak, Rafael da Costa Monsanto
PLOS ONE.2021; 16(8): e0255482. CrossRef
Vitamin D and Otitis Media
Rebecca E. Walker, Jim Bartley, Carlos A. Camargo, Edwin A. Mitchell
Current Allergy and Asthma Reports.2019;[Epub] CrossRef

Clinical Study
Effects of Single Vitamin D₃ Injection (200,000 Units) on Serum Fibroblast Growth Factor 23 and Sclerostin Levels in Subjects with Vitamin D Deficiency: Dongdong Zhang, Da Hea Seo, Han Seok Choi, Hye-Sun Park, Yoon-Sok Chung, Sung-Kil Lim; Endocrinol Metab. 2017;32(4):451-459. Published online December 14, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.451

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Background

Vitamin D deficiency remains common in all age groups and affects skeletal and non-skeletal health. Fibroblast growth factor 23 is a bone-derived hormone that regulates phosphate and 1,25-dihydroxyvitamin D homeostasis as a counter regulatory factor. 1,25-Dihydroxyvitamin D stimulates fibroblast growth factor 23 synthesis in bone, while fibroblast growth factor 23 suppresses 1,25-dihydroxyvitamin D production in the kidney. The aim of this study was to evaluate the effects of vitamin D₃ intramuscular injection therapy on serum fibroblast growth factor 23 concentrations, and several other parameters associated with bone metabolism such as sclerostin, dickkopf-1, and parathyroid hormone.

Methods

A total of 34 subjects with vitamin D deficiency (defined by serum 25-hydroxyvitamin D levels below 20 ng/mL) were randomly assigned to either the vitamin D injection group (200,000 units) or placebo treatment group. Serum calcium, phosphate, urine calcium/creatinine, serum 25-hydroxyvitamin D, fibroblast growth factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were serially measured after treatment.

Results

Comparing the vitamin D injection group with the placebo group, no significant changes were observed in serum fibroblast growth factor 23, parathyroid hormone, or dickkopf-1 levels. Serum sclerostin concentrations transiently increased at week 4 in the vitamin D group. However, these elevated levels declined later and there were no statistically significant differences as compared with baseline levels.

Conclusion

Serum fibroblast factor 23, sclerostin, parathyroid hormone, and dickkopf-1 levels were not affected significantly by single intramuscular injection of vitamin D₃.

Citations

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Lisa Ceglia, Anastassios G. Pittas, Bess Dawson-Hughes
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Cureus.2023;[Epub] CrossRef
The effect of vitamin D supplementation on serum levels of fibroblast growth factor- 23: A systematic review and meta-analysis of randomized controlled trials
Fatemeh Meshkini, Sepideh Soltani, Cain C.T. Clark, Vivian Tam, David Meyre, Omid Toupchian, Sahar Saraf-Bank, Shima Abdollahi
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International Journal of Endocrinology.2021; 2021: 1. CrossRef
The effect of vitamin D supplementation on fibroblast growth factor‐23 in patients with chronic kidney disease: A systematic review and meta‐analysis
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Vitamin D Deficiency at Mid-Pregnancy Is Associated with a Higher Risk of Postpartum Glucose Intolerance in Women with Gestational Diabetes Mellitus
Kyung-Soo Kim, Seok Won Park, Yong-Wook Cho, Soo-Kyung Kim
Endocrinology and Metabolism.2020; 35(1): 97. CrossRef
Effects of vitamin D supplementation on bone turnover markers and other bone-related substances in subjects with vitamin D deficiency
Rolf Jorde, Astrid Kamilla Stunes, Julia Kubiak, Ragnar Joakimsen, Guri Grimnes, Per Medbøe Thorsby, Unni Syversen
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Review Articles

Thyroid
Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease: Wilmar M. Wiersinga; Endocrinol Metab. 2016;31(2):213-222. Published online May 13, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.213

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Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD). Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO)-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy.

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Adrenal gland
Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone: Lars Rejnmark, Line Underbjerg, Tanja Sikjaer; Endocrinol Metab. 2015;30(4):436-442. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.436

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Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL) and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

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Original Articles

Obesity and Metabolism
Comparison of Serum Ferritin and Vitamin D in Association with the Severity of Nonalcoholic Fatty Liver Disease in Korean Adults: Dong Wook Jeong, Hye Won Lee, Young Hye Cho, Dong Won Yi, Sang Yeoup Lee, Seok Man Son, Yang Ho Kang; Endocrinol Metab. 2014;29(4):479-488. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.479

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Background

Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D₃ levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults.

Methods

A cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OH)D₃, from men (n=295) and women (n=263) who underwent a routine health check-up in 2012.

Results

In men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and FLI ≥60 (P=0.010) were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012). Regarding 25(OH)D₃, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001); however, no significant differences in 25(OH)D₃ level were observed in men. No significant differences in either serum ferritin or 25(OH)D₃ level were observed among women with different levels of severity of US-NAFLD.

Conclusion

Increased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.

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Qi Sheng, Huanchen Shi, Shousheng Liu, Likun Zhuang, Zhenzhen Zhao, Yongning Xin
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Do Vitamin D Levels Affect Bone Mineral Density in Reproductive Women with Low Ferritin Levels?
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Junfeng Zhang, Jiajia Cao, Hui Xu, Guanping Dong, Ke Huang, Wei Wu, Jingjing Ye, Junfen Fu
Journal of Clinical Laboratory Analysis.2021;[Epub] CrossRef
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AhmedA Hassan, MohieeE.-D.A El-Aziz Awad, HananH Soliman, RedaA.F Usef, DinaS Ata
Alexandria Journal of Pediatrics.2021; 34(3): 253. CrossRef
Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: a community-based study
Li-Wei Chen, Cheng-Hung Chien, Sheng-Fong Kuo, Chia-Ying Yu, Chih-Lang Lin, Rong-Nan Chien
BMC Gastroenterology.2019;[Epub] CrossRef
Association between Vitamin D Levels and Nonalcoholic Fatty Liver Disease: Potential Confounding Variables
Lucia Pacifico, John F. Osborn, Enea Bonci, Pasquale Pierimarchi, Claudio Chiesa
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The association between serum ferritin and 25-hydroxyvitamin D and metabolic syndrome in Korean women: the Korea National Health and Nutrition Examination Survey 2010–2012
Hyun Yoon, Nan Young Bae, Mi Young Gi, Bu Yeon Park, Jeong Min Seong
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Gender difference in relationship between serum ferritin and 25-hydroxyvitamin D in Korean adults
Jeong Min Seong, Yo Sang Yoon, Kyu Su Lee, Nan Young Bae, Mi Young Gi, Hyun Yoon, Andrzej T Slominski
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The Association of Serum Ferritin and Metabolic Syndrome and Metabolic Syndrome Score in Korean Adults
Hyun Yoon, Jae Seong Go, Kang Uk Kim, Keon Woo Lee
The Korean Journal of Clinical Laboratory Science.2016; 48(4): 287. CrossRef
AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells
Jinmi Lee, Seok-Woo Hong, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
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Bone Metabolism
Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis: In-Jin Cho, Ho-Yeon Chung, Sung-Woon Kim, Jae-Won Lee, Tae-Won Lee, Hye-Soon Kim, Sin-Gon Kim, Han Seok Choi, Sung-Hee Choi, Chan Soo Shin, Ki-Won Oh, Yong-Ki Min, Jung-Min Koh, Yumie Rhee, Dong-Won Byun, Yoon-Sok Chung, Jeong Hyun Park, Dong Jin Chung, Minho Shong, Eun-Gyoung Hong, Chang Beom Lee, Ki Hyun Baek, Moo-Il Kang; Endocrinol Metab. 2015;30(3):272-279. Published online December 9, 2014; DOI: https://doi.org/10.3803/EnM.2015.30.3.272

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Background

The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis.

Methods

This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period.

Results

After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment.

Conclusion

The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Citations

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Review Article

Bone Metabolism
Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia: Seiji Fukumoto; Endocrinol Metab. 2014;29(2):136-143. Published online June 26, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.2.136

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Fibroblast growth factor 23 (FGF23) is a hormone that is produced by osteocytes and regulates phosphate and vitamin D metabolism through binding to the Klotho-FGF receptor complex. Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. Tumor-induced rickets/osteomalacia (TIO) is a paraneoplastic syndrome caused by overproduction of FGF23 from the responsible tumors. Because TIO is cured by complete resection of the causative tumors, it is of great clinical importance to locate these tumors. Several imaging methods including skeletal survey by magnetic resonance imaging and octreotide scintigraphy have been used to identify the tumors that cause TIO. However, none of these imaging studies indicate that the detected tumors are actually producing FGF23. Recently, systemic venous sampling was conducted for locating FGF23-producing tumor in suspected patients with TIO and demonstrated that this test might be beneficial to a subset of patient. Further studies with more patients are necessary to establish the clinical utility of venous sampling in patients with TIO.

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