1
|
Bhatnagar K, Raju S, Patki N, Motiani RK, Chaudhary S. Targeting mineral metabolism in cancer: Insights into signaling pathways and therapeutic strategies. Semin Cancer Biol 2025; 112:1-19. [PMID: 40024314 DOI: 10.1016/j.semcancer.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 01/29/2025] [Accepted: 02/21/2025] [Indexed: 03/04/2025]
Abstract
Cancer remains the second leading cause of death worldwide, emphasizing the critical need for effective treatment and control strategies. Essential minerals such as copper, iron, zinc, selenium, phosphorous, calcium, and magnesium are integral to various biological processes and significantly influence cancer progression through altered metabolic pathways. For example, dysregulated copper levels promote tumor growth, while cancer cells exhibit an increased dependency on iron for signaling and redox reactions. Zinc influences tumor development through pathways such as Akt-p21. Selenium, primarily through its role in selenoproteins, exhibits anticancer potential but may also contribute to tumor progression. Similarly, dietary phosphate exacerbates tumorigenesis, metastasis, and angiogenesis through signaling pathway activation. Calcium, the most abundant mineral in the body, is tightly regulated within cells, and its dysregulation is a hallmark of various cancers. Magnesium deficiency, on the other hand, promotes cancer progression by fostering inflammation and free radical-induced DNA mutations. Interestingly, magnesium also plays a dual role, with low levels enhancing epithelial-mesenchymal transition (EMT), a critical process in cancer metastasis. This complex interplay of essential minerals underscores their potential as therapeutic targets. Dysregulation of these minerals and their pathways could be exploited to selectively target cancer cells, offering novel therapeutic strategies. This review summarizes current research on the abnormal accumulation or depletion of these microelements in tumor biology, drawing evidence from animal models, cell lines, and clinical samples. We also highlight the potential of these minerals as biomarkers for cancer diagnosis and prognosis, as well as therapeutic approaches involving metal chelators, pharmacological agents, and nanotechnology. By highlighting the intricate roles of these minerals in cancer biology, we aim to inspire further research in this critical yet underexplored area of oncology.
Collapse
Affiliation(s)
- Kartik Bhatnagar
- Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India.
| | - Sharon Raju
- Laboratory of Calciomics and Systemic Pathophysiology, Regional Centre for Biotechnology (RCB), Faridabad-Gurugram Expressway, Faridabad, Haryana 121001, India.
| | - Ninad Patki
- Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India.
| | - Rajender K Motiani
- Laboratory of Calciomics and Systemic Pathophysiology, Regional Centre for Biotechnology (RCB), Faridabad-Gurugram Expressway, Faridabad, Haryana 121001, India.
| | - Sarika Chaudhary
- Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India.
| |
Collapse
|
2
|
Ndifor AR, Dominique N, Claude MD, Raoul K, Ebouel FLE, Dongmo YKM, Pantaléon A, Henoumont C, Stanislaus NN, Laurent S, Jean S, Bathelemy N, Ghislain FW. Constituents, Nutrient Content, and In Vitro Antioxidant and Anti-Inflammatory Activity of Tricholomopsis aurea (Agaricomycetes) from Cameroon. Int J Med Mushrooms 2025; 27:71-85. [PMID: 39912608 DOI: 10.1615/intjmedmushrooms.2024057418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2025]
Abstract
Tricholomopsis aurea is used as food in different parts of the world, but has not been investigated for its nutrients, metabolites, and biological potentials like other edible mushrooms. This work aimed to quantify the metabolic and nutrient content of T. aurea and evaluate the antioxidant and anti-inflammatory activities of the extract and isolated compounds. The method employed involves chromatographic, spectroscopic, bovine serum albumin microplate, analytical and standard assays. Oleic, elaidic, petroselinic acids, ergosterol, ergosterol peroxide, 22E724R)-24-ethylcholesta-5,7,22-trien-3β-ol, and adenosine were isolated and identified using 1D and 2D-NMR spectroscopy and spectrometric data. The metabolic content revealed high phenolics (799.62 μgGaE/g of dry matter (DM)), low flavonoids (24.54 μgQE/g DM), alkaloids (32.92 μgQiE/g DM), and saponins (88.00 μgQSE/g DM). The nutrients content was made up of proteins (4.79%), lipids (10.43%), fibers (16.01%), ashes (15.96%), carbohydrates (8.74%), dry matter (85.93%), and moisture (14.07%) with energy value of 362.89 kcal. In mg/100 g, the minerals were phosphorus (283.97%), calcium (817.25%), potassium (67.10%), magnesium (94.42%), iron (57.27%), and sodium (74.4%). The extract displayed the antioxidant activity against TAC and FRAP (100-1000 μg/mL), DPPH (SC50 of 248.95 μg/mL) and ABTS (SC50 of 180.7 μg/mL), while the test compounds were not active. The extract, adenosine, ergosterol peroxide, and ergosterol showed anti-inflammatory activity with IC50 of 49.19 μg/mL, 4.91 μg/mL, 6.85 μg/mL, and 29.51 μg/mL, respectively. Conclusively, this study will help to promote the application of T. aurea in traditional dishes and functional or nutraceutical foods.
Collapse
Affiliation(s)
| | - Ngnintedo Dominique
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
| | | | - Kemzeu Raoul
- Laboratory of Phytobiochemistry and Medicinal Plants Studies, Antimicrobial and Biocontrol Agent Unit (AmBcAU), Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon
| | | | - Yanick Kevin Melogmo Dongmo
- Laboratory of Phytobiochemistry and Medicinal Plants Studies, Antimicrobial and Biocontrol Agent Unit (AmBcAU), Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon
| | - Ambassa Pantaléon
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
| | - Céline Henoumont
- General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium
| | | | - Sophie Laurent
- General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium; Center for Microscopy and Molecular Imaging (CMMI), Gosseilies, Belgium
| | - Sonchieu Jean
- Higher Technical Teachers Training College, University of Bamenda, Cameroon
| | - Ngameni Bathelemy
- Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Fotso Wabo Ghislain
- Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
| |
Collapse
|
3
|
Lee SJ, Kim JA, Ihn HJ, Choi JY, Kwon TY, Shin HI, Cho ES, Bae YC, Jiang R, Kim JE, Park EK. The transcription factor BBX regulates phosphate homeostasis through the modulation of FGF23. Exp Mol Med 2024; 56:2436-2448. [PMID: 39482539 PMCID: PMC11612488 DOI: 10.1038/s12276-024-01341-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 07/19/2024] [Accepted: 08/11/2024] [Indexed: 11/03/2024] Open
Abstract
Fibroblast growth factor 23 (FGF23) plays an important role in phosphate homeostasis, and increased FGF23 levels result in hypophosphatemia; however, the molecular mechanism underlying increased FGF23 expression has not been fully elucidated. In this study, we found that mice lacking the bobby sox homolog (Bbx-/-) presented increased FGF23 expression and low phosphate levels in the serum and skeletal abnormalities such as a low bone mineral density (BMD) and bone volume (BV), as well as short and weak bones associated with low bone formation. Osteocyte-specific deletion of Bbx using Dmp-1-Cre resulted in similar skeletal abnormalities, elevated serum FGF23 levels, and reduced serum phosphate levels. In Bbx-/- mice, the expression of sodium phosphate cotransporter 2a (Npt2a) and Npt2c in the kidney and Npt2b in the small intestine, which are negatively regulated by FGF23, was downregulated, leading to phosphate excretion/wasting and malabsorption. An in vitro Fgf23 promoter analysis revealed that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced transactivation of the Fgf23 promoter was significantly inhibited by BBX overexpression, whereas it was increased following Bbx knockdown. Interestingly, 1,25(OH)2D3 induced an interaction of the 1,25(OH)2D3 receptor (VDR) with BBX and downregulated BBX protein levels. Cycloheximide (CHX) only partially downregulated BBX protein levels, indicating that 1,25(OH)2D3 regulates BBX protein stability. Furthermore, the ubiquitination of BBX followed by proteasomal degradation was required for the increase in Fgf23 expression induced by 1,25(OH)2D3. Collectively, our data demonstrate that BBX negatively regulates Fgf23 expression, and consequently, the ubiquitin-dependent proteasomal degradation of BBX is required for FGF23 expression, thereby regulating phosphate homeostasis and bone development in mice.
Collapse
Affiliation(s)
- Su Jeong Lee
- Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio‑tooth Regeneration (IHBR), Kyungpook National University, Daegu, Republic of Korea
| | - Ju Ang Kim
- Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio‑tooth Regeneration (IHBR), Kyungpook National University, Daegu, Republic of Korea
| | - Hye Jung Ihn
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea
| | - Je-Yong Choi
- Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Tae-Yub Kwon
- Department of Dental Biomaterials, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
| | - Hong-In Shin
- Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio‑tooth Regeneration (IHBR), Kyungpook National University, Daegu, Republic of Korea
| | - Eui-Sic Cho
- Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Jeonbuk National University, Jeonju, Republic of Korea
| | - Yong Chul Bae
- Department of Oral Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea
| | - Rulang Jiang
- Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Ohio, TX, USA
| | - Jung-Eun Kim
- Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea
- Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Eui Kyun Park
- Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Institute for Hard Tissue and Bio‑tooth Regeneration (IHBR), Kyungpook National University, Daegu, Republic of Korea.
| |
Collapse
|
4
|
Duan X, Zhang Y, Xu T. CYP4A22 loss-of-function causes a new type of vitamin D-dependent rickets (VDDR1C). J Bone Miner Res 2024; 39:967-979. [PMID: 38847469 DOI: 10.1093/jbmr/zjae084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 05/08/2024] [Accepted: 06/06/2024] [Indexed: 08/07/2024]
Abstract
Vitamin D-dependent rickets (VDDR) is a group of genetic disorders characterized by early-onset rickets due to deficiency of active vitamin D or a failure to respond to activated vitamin D. VDDR is divided into several subtypes according to the corresponding causative genes. Here we described a new type of autosomal dominant VDDR in a Chinese pedigree. The proband and his mother had severe bone malformations, dentin abnormalities, and lower serum 25 hydroxyvitamin D3 (25[OH]D3) and phosphate levels. The proband slightly responded to a high dose of vitamin D3 instead of a daily low dose of vitamin D3. Whole-exome sequencing, bioinformatic analysis, PCR, and Sanger sequencing identified a nonsense mutation in CYP4A22 (c.900delG). The overexpressed wild-type CYP4A22 mainly localized in endoplasmic reticulum and Golgi apparatus, and synthesized 25(OH)D3 in HepG2 cells. The overexpressed CYP4A22 mutant increased the expression of CYP2R1 and produced little 25(OH)D3 with vitamin D3 supplementation, which was reduced by CYP2R1 siRNA treatment. We concluded that CYP4A22 functions as a new kind of 25-hydroxylases for vitamin D3. Loss-of-function mutations in CYP4A22 lead to a new type of VDDR type 1 (VDDR1C). CYP2R1 and CYP4A22 may have some genetic compensation responding to nonsense-mediated mRNA decay effect of each other.
Collapse
Affiliation(s)
- Xiaohong Duan
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare Diseases and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an 710032, China
| | - Yanli Zhang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare Diseases and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an 710032, China
| | - Taoyun Xu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare Diseases and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an 710032, China
| |
Collapse
|
5
|
Eliason O, Malitsky S, Panizel I, Feldmesser E, Porat Z, Sperfeld M, Segev E. The photo-protective role of vitamin D in the microalga Emiliania huxleyi. iScience 2024; 27:109884. [PMID: 38799580 PMCID: PMC11126961 DOI: 10.1016/j.isci.2024.109884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/16/2024] [Accepted: 04/30/2024] [Indexed: 05/29/2024] Open
Abstract
An essential interaction between sunlight and eukaryotes involves vitamin D production through exposure to ultraviolet (UV) radiation. While extensively studied in vertebrates, the role of vitamin D in non-animal eukaryotes like microalgae remains unclear. Here, we investigate the potential involvement of vitamin D in the UV-triggered response of Emiliania huxleyi, a microalga inhabiting shallow ocean depths that are exposed to UV. Our results show that E. huxleyi produces vitamin D2 and D3 in response to UV. We further demonstrate that E. huxleyi responds to external administration of vitamin D at the transcriptional level, regulating protective mechanisms that are also responsive to UV. Our data reveal that vitamin D addition enhances algal photosynthetic performance while reducing harmful reactive oxygen species buildup. This study contributes to understanding the function of vitamin D in E. huxleyi and its role in non-animal eukaryotes, as well as its potential importance in marine ecosystems.
Collapse
Affiliation(s)
- Or Eliason
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Sergey Malitsky
- Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Irina Panizel
- Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Ester Feldmesser
- Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Ziv Porat
- Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Martin Sperfeld
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Einat Segev
- Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| |
Collapse
|
6
|
Carvalho Filho I, Arikawa LM, Mota LFM, Campos GS, Fonseca LFS, Fernandes Júnior GA, Schenkel FS, Lourenco D, Silva DA, Teixeira CS, Silva TL, Albuquerque LG, Carvalheiro R. Genome-wide association study considering genotype-by-environment interaction for productive and reproductive traits using whole-genome sequencing in Nellore cattle. BMC Genomics 2024; 25:623. [PMID: 38902640 PMCID: PMC11188527 DOI: 10.1186/s12864-024-10520-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 06/13/2024] [Indexed: 06/22/2024] Open
Abstract
BACKGROUND The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies (GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained ∼ 2.41 M SNPs for SC, PWG, and YW and ∼ 5.06 M SNPs for AFC. RESULTS Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. CONCLUSIONS GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.
Collapse
Affiliation(s)
- Ivan Carvalho Filho
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Leonardo M Arikawa
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Lucio F M Mota
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil.
| | - Gabriel S Campos
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Larissa F S Fonseca
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Gerardo A Fernandes Júnior
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Flavio S Schenkel
- Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph, Ontario, N1G2W1, Canada
| | - Daniela Lourenco
- Department of Animal and Dairy Science, University of Georgia, Athens, GA, 30602, USA
| | - Delvan A Silva
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Caio S Teixeira
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Thales L Silva
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| | - Lucia G Albuquerque
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
- National Council for Science and Technological Development, Brasilia, DF, 71605-001, Brazil
| | - Roberto Carvalheiro
- Department of Animal Science, School of Agricultural and Veterinarian Sciences, São Paulo State University (UNESP), Jaboticabal, SP, 14884-900, Brazil
| |
Collapse
|
7
|
Fisher M, Weiler HA, Kuiper JR, Borghese M, Buckley JP, Shutt R, Ashley-Martin J, Subramanian A, Arbuckle TE, Potter BK, Little J, Morisset AS, Jukic AM. Vitamin D and Toxic Metals in Pregnancy - a Biological Perspective. CURR EPIDEMIOL REP 2024; 11:153-163. [PMID: 39156920 PMCID: PMC11329583 DOI: 10.1007/s40471-024-00348-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2024] [Indexed: 08/20/2024]
Abstract
Purpose of Review To discuss the potential biological mechanisms between vitamin D and toxic metals and summarize epidemiological studies examining this association in pregnant women. Recent Findings We identified four plausible mechanisms whereby vitamin D and toxic metals may interact: nephrotoxicity, intestinal absorption of metals, endocrine disruption, and oxidative stress. Few studies have examined the association between vitamin D and toxic metals in pregnant women. North American studies suggest that higher vitamin D status early in pregnancy are associated with lower blood metals later in pregnancy. However, a trial of vitamin D supplementation in a pregnant population, with higher metal exposures and lower overall nutritional status, does not corroborate these findings. Summary Given ubiquitous exposure to many toxic metals, nutritional intervention could be a means for prevention of adverse outcomes. Future prospective studies are needed to establish a causal relationship and clarify the directionality of vitamin D and metals. Supplementary Information The online version contains supplementary material available at 10.1007/s40471-024-00348-0.
Collapse
Affiliation(s)
- Mandy Fisher
- Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON Canada
| | - Hope A. Weiler
- Nutrition Research Division, Health Products and Food Branch, Health Canada, Ottawa, ON Canada
| | - Jordan R. Kuiper
- Milken Institute School of Public Health, The George Washington University, Washington, DC USA
| | - Michael Borghese
- Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON Canada
| | - Jessie P. Buckley
- Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health Sciences, Chapel Hill, North Carolina USA
| | - Robin Shutt
- Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON Canada
| | | | - Anita Subramanian
- National Institute of Environmental Health Sciences (NIEHS), Duram, North Carolina USA
| | - Tye E. Arbuckle
- Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON Canada
| | - Beth K. Potter
- School of Epidemiology and Public Health (SEPH), University of Ottawa, Ottawa, ON Canada
| | - Julian Little
- School of Epidemiology and Public Health (SEPH), University of Ottawa, Ottawa, ON Canada
| | | | - Anne Marie Jukic
- National Institute of Environmental Health Sciences (NIEHS), Duram, North Carolina USA
| |
Collapse
|
8
|
Nouhravesh N, Garg J, Rockhold FW, De Pasquale CG, O’Meara E, Lewis GD, Butler J, Harrington J, Ezekowitz JA, Ponikowski P, Troughton RW, Wong YW, Blackman N, Numan S, Adamczyk R, Hernandez AF, Mentz RJ. Characterization of serum phosphate levels over time with intravenous ferric carboxymaltose versus placebo as treatment for heart failure with reduced ejection fraction and iron deficiency: An exploratory prospective substudy from HEART-FID. Eur J Heart Fail 2024:10.1002/ejhf.3348. [PMID: 38896006 PMCID: PMC11655705 DOI: 10.1002/ejhf.3348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 05/13/2024] [Accepted: 06/02/2024] [Indexed: 06/21/2024] Open
Abstract
AIMS Ferric carboxymaltose (FCM) is guideline-recommended for iron deficiency (ID) in heart failure with reduced ejection fraction (HFrEF). Despite a well-established safety profile, the magnitude and clinical significance of FCM-induced hypophosphataemia in HFrEF remains unclear. This pre-specified substudy of HEART-FID evaluated serum phosphate, 1,25-dihydroxyvitamin D, and plasma parathyroid hormone (PTH) subsequent to FCM. METHODS AND RESULTS HEART-FID was a randomized, double-blind, placebo-controlled trial of ambulatory patients with HFrEF and ID randomized to FCM versus placebo. This substudy assessed mean change from baseline across eight visits over 6 months for the following endpoints: serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH, in addition to the clinical severity of potential hypophosphataemia. Overall, 133 patients (n = 62 FCM, n = 71 placebo) were prospectively enrolled. Mean age was 68 ± 11 years, 55 (41.4%) were women, and 29 (21.8%) had chronic kidney disease. Phosphate levels decreased in 34 (57.6%) patients in the FCM group compared with 7 (10.3%) in the placebo group. Mean change in phosphate levels reached a nadir at day 21 (-0.36 ± 0.27 mmol/L) subsequent to FCM infusion with 28 (51%) having moderate-to-severe hypophosphataemia. Reductions in 1,25-dihydroxyvitamin D were also observed, whilst PTH increased. These biochemical changes returned to baseline levels by day 91. Serum levels of 25-hydroxyvitamin D remained stable throughout the study. No serious adverse events associated with hypophosphataemia were reported. CONCLUSIONS Transient moderate-to-severe hypophosphataemia was frequent subsequent to FCM infusion, accompanied by 1,25-dihydroxyvitamin D decrease and PTH increase. Serum levels of 25-hydroxyvitamin D remained stable. No evidence of symptomatic hypophosphataemia was reported, collectively indicating FCM-related hypophosphataemia to be clinically benign and transient in HFrEF.
Collapse
Affiliation(s)
| | - Jyotsna Garg
- Duke Clinical Research Institute, Durham, NC, USA
| | | | | | - Eileen O’Meara
- Montreal Heart Institute and Université de Montréal, Quebec, Canada
| | - Gregory D. Lewis
- Division of Cardiology, Massachusetts General Hospital, Boston, USA
| | - Javed Butler
- Department of Medicine, University of Mississippi, Jackson, USA
| | | | | | - Piotr Ponikowski
- The Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland
| | - Richard W. Troughton
- Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
| | - Yee Weng Wong
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | | | | | | | | | | |
Collapse
|
9
|
Fukumoto S. Tumor-induced osteomalacia. Panminerva Med 2024; 66:188-197. [PMID: 38127062 DOI: 10.23736/s0031-0808.23.05047-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
Tumor-induced osteomalacia is one of paraneoplastic syndromes characterized by hypophosphatemia caused by excessive actions of fibroblast growth factor 23 (FGF23). Since the cloning of FGF23 about 20 years ago, more widespread awareness of this disease has been achieved. However, there still remain several difficulties in the management of patients with this disease. In this review, these clinical problems are discussed together with the physiological and pathophysiological functions of FGF23. Personal proposals in the management of patients with suspected patients with tumor-induced osteomalacia are also presented.
Collapse
Affiliation(s)
- Seiji Fukumoto
- Department of Diabetes and Endocrinology, Tamaki-Aozora Hospital, Tokushima, Japan -
| |
Collapse
|
10
|
Dobson R. Semaglutide and Patients Receiving Hemodialysis: Case Reports of Unexpected Benefits for Hyperphosphatemia and Hyperkalemia. Can J Hosp Pharm 2024; 77:e3534. [PMID: 38720915 PMCID: PMC11060791 DOI: 10.4212/cjhp.3534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 01/16/2024] [Indexed: 05/12/2024]
Affiliation(s)
- Raea Dobson
- , BSc, BScPharm, ACPR, PharmD, is with Sunnybrook Health Sciences Centre, Toronto, Ontario
| |
Collapse
|
11
|
Walker V. The Intricacies of Renal Phosphate Reabsorption-An Overview. Int J Mol Sci 2024; 25:4684. [PMID: 38731904 PMCID: PMC11083860 DOI: 10.3390/ijms25094684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 04/17/2024] [Accepted: 04/19/2024] [Indexed: 05/13/2024] Open
Abstract
To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in phosphate and composition of the renal filtrate and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long-held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully, this will raise questions and stimulate new ideas for further research.
Collapse
Affiliation(s)
- Valerie Walker
- Department of Clinical Biochemistry, University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton S016 6YD, UK
| |
Collapse
|
12
|
Stevens CM, Jain SK. Vitamin D/Bone Mineral Density and Triglyceride Paradoxes Seen in African Americans: A Cross-Sectional Study and Review of the Literature. Int J Mol Sci 2024; 25:1305. [PMID: 38279305 PMCID: PMC10816015 DOI: 10.3390/ijms25021305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 01/11/2024] [Accepted: 01/16/2024] [Indexed: 01/28/2024] Open
Abstract
Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D levels in AA. Another intriguing relationship seen in AA is the triglyceride (TG) paradox, an unusual phenomenon in which a normal TG status is observed even when patients house conditions known to be characterized by high TG levels, such as Type II diabetes. To the best of our knowledge, no study has examined whether these two paradoxical relationships exist simultaneously in AA subjects with Type II diabetes. In this study, we compared levels of blood markers, including HbA1c, TG, and vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)VD] µM/mL, [25(OH)VD]/TG, calcium, and BMD in AA (n = 56) and white (n = 26) subjects with Type II diabetes to see whether these relationships exist concurrently. We found that AA subjects had significantly lower TG and [25(OH)VD] levels and a significantly higher BMD status compared to white subjects, even when the ages, BMI, duration of diabetes, HbA1c, and calcium levels were similar between the two groups. This demonstrates that these two paradoxical relationships exist simultaneously in Type II diabetic AA subjects. In addition to these findings, we discuss the current hypotheses in the literature that attempt to explain why these two intriguing relationships exist. This review also discusses four novel hypotheses, such as altered circulating levels and the potential role of estrogen and hydrogen sulfide on BMD and HMG-CoA reductase as a possible contributor to the TG paradox in AA subjects. This manuscript demonstrates that there are still many unanswered questions regarding these two paradoxical relationships and further research is needed to determine why they exist and how they can be implemented to improve healthcare.
Collapse
Affiliation(s)
| | - Sushil K. Jain
- Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA;
| |
Collapse
|
13
|
Sauvé B, Guay F, Létourneau Montminy MP. Impact of deoxynivalenol in a calcium depletion and repletion nutritional strategy in piglets. J Anim Sci 2024; 102:skae099. [PMID: 38613476 PMCID: PMC11056887 DOI: 10.1093/jas/skae099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 04/12/2024] [Indexed: 04/15/2024] Open
Abstract
This study evaluated the effect of dietary calcium (Ca) levels and deoxynivalenol (DON) contamination on Ca and phosphorus (P) utilization and bone mineralization in piglets. During an initial 13-d depletion phase, 64 piglets (15.7 ± 0.7 kg) received a control (DON-) or DON-contaminated treatment (DON+, 2.7 mg DON/kg) with either a low Ca (Ca-, 0.39%) or normal Ca level (Ca+, 0.65%) with a constant digestible P level (0.40%). A second group of 16 piglets received DON- or DON+ treatments for 9 d for gene expression analysis. During the subsequent 14-d repletion phase, all piglets were fed a Ca+ DON- diet containing 0.65% Ca and 0.35% digestible P without DON. After 5 d of the depletion phase, the absorption of P (DON × Ca; P < 0.05) and Ca was increased by the Ca- (P < 0.01) and DON+ (P < 0.01) diet. After 13 d, feed conversion ratio (P < 0.01) and average daily feed intake (P = 0.06) tended to decrease with the Ca- diet. The bone mineral content (BMC) gain was decreased by Ca, especially with Ca- DON + (DON × Ca, P < 0.05). The P absorption was increased by Ca- DON + (DON × Ca, P < 0.01), although the P retention efficiency was only increased by Ca+ DON + (DON × Ca, P < 0.001). The absorption of Ca was increased by DON+ (P < 0.001), and the Ca efficiency was increased by Ca- DON- (DON × Ca, P < 0.01). After 9 d, the gene expression of intestinal claudin 12 (P < 0.01) and CYP24A1 (P < 0.05), femur cortical RANKL (P < 0.05) and OPG (P = 0.06), and renal calbindin D9K (P < 0.05) and Klotho (P = 0.07) were decreased by DON+. The Ca (P = 0.06) and magnesium (P < 0.01) concentrations were decreased by DON+, and the Ca (P = 0.06) and P digestibility (P < 0.01) were increased. After the repletion phase, Ca- piglets recovered their BMC deficit, but not those receiving DON+ (DON × Ca; P = 0.06). The Ca (P < 0.05) and P (P = 0.06) retention efficiency tended to increase with Ca-. The absorption of Ca and P was increased by Ca- and DON+ (DON × Ca, P < 0.05). The results show that piglets increased their Ca and P utilization efficiency, allowing them to recover the BMC deficit caused by Ca-, but not when the piglets were exposed to DON. Pigs previously receiving Ca-deficient diet with DON still have lower body Ca and P, leading to elevated calcitriol concentrations and enhanced Ca and P intestinal absorption. The fact that DON decreased the expression of genes implicated in Ca intestinal and renal transport and P excretion after 9 d can potentially explain the reduced plasma Ca concentration.
Collapse
Affiliation(s)
- Béatrice Sauvé
- Department of Animal Sciences, Université Laval, Québec (QC), CanadaG1V 0A6
| | - Frédéric Guay
- Department of Animal Sciences, Université Laval, Québec (QC), CanadaG1V 0A6
| | | |
Collapse
|
14
|
Perumal NL, Padidela R. Phosphate Homeostasis and Disorders of Phosphate Metabolism. Curr Pediatr Rev 2024; 20:412-425. [PMID: 36545737 DOI: 10.2174/1573396319666221221121350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/24/2022]
Abstract
Phosphate is indispensable for human life and evolutionary changes over several millions of years have established tightly regulated mechanisms to ensure phosphate homeostasis. In this process, calcium and phosphate metabolism have come to be intricately linked together. Three hormones (PTH, FGF23 and Calcitriol) maintain the fine balance of calcium and phosphate metabolism through their actions at three sites (the gut, the kidneys and the skeleton). Disorders that disrupt this balance can have serious clinical consequences. Acute changes in serum phosphate levels can result in life threatening complications like respiratory failure and cardiac arrythmias. Chronic hypophosphataemia predominantly affects the musculoskeletal system and presents as impaired linear growth, rickets, osteomalacia and dental problems. Hyperphosphataemia is very common in the setting of chronic kidney disease and can be difficult to manage. A thorough understanding of calcium and phosphate homeostasis is essential to diagnose and treat conditions associated with hypo and hyperphosphataemia. In this review, we will discuss the calcium and phosphate metabolism, aetiologies and management of hypo and hyperphosphataemia.
Collapse
Affiliation(s)
| | - Raja Padidela
- Department of Endocrinology, Royal Manchester Children's Hospital, Manchester, United Kingdom
| |
Collapse
|
15
|
Evanchuk JL, Kozyrskyj A, Vaghef-Mehrabani E, Lamers Y, Giesbrecht GF, Letourneau N, Aghajafari F, Dewey D, Leung B, Bell RC, Field CJ. Maternal Iron and Vitamin D Status during the Second Trimester Is Associated with Third Trimester Depression Symptoms among Pregnant Participants in the APrON Cohort. J Nutr 2024; 154:174-184. [PMID: 37984742 DOI: 10.1016/j.tjnut.2023.10.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/21/2023] [Accepted: 10/16/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed. OBJECTIVES This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals. METHODS The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained. RESULTS Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (β: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (β: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (β: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 μg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (β: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 μg/L) and vitamin D (25(OH)D <75 nmol/L) (β: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients. CONCLUSIONS A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy.
Collapse
Affiliation(s)
- Jenna L Evanchuk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Anita Kozyrskyj
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | | | - Yvonne Lamers
- Food, Nutrition and Health Program, University of British Columbia, Vancouver, BC, Canada; British Columbia's Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Gerald F Giesbrecht
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Nicole Letourneau
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Department of Psychiatry, University of Calgary, Calgary, AB, Canada
| | - Fariba Aghajafari
- Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Department of Family Medicine, University of Calgary, Calgary, AB, Canada
| | - Deborah Dewey
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Brenda Leung
- Faculty of Health Sciences, University of Lethbridge, Lethbridge, AB, Canada
| | - Rhonda C Bell
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
| |
Collapse
|
16
|
Cashion C, Bonnitcha P, Stevenson W. Acute onset severe hypophosphataemia in transformed acute myeloid leukaemia: an unusual biochemical presentation. J Clin Pathol 2023:jcp-2023-208907. [PMID: 37985139 DOI: 10.1136/jcp-2023-208907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 09/15/2023] [Indexed: 11/22/2023]
Affiliation(s)
- Catelyn Cashion
- Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Paul Bonnitcha
- Chemical Pathology Department, NSW Health Pathology, Royal Prince Albert Hospital, Camperdown, New South Wales, Australia
- Chemical Pathology Department, SydPath, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia
| | - William Stevenson
- Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
- Northern Blood Research Centre, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
| |
Collapse
|
17
|
Kells MR, Roske C, Watters A, Puckett L, Wildes JE, Crow SJ, Mehler PS. Vitamin D and hypophosphatemia in patients with anorexia nervosa and avoidant/restrictive food intake disorder: a case control study. J Eat Disord 2023; 11:195. [PMID: 37919813 PMCID: PMC10623827 DOI: 10.1186/s40337-023-00913-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 10/16/2023] [Indexed: 11/04/2023] Open
Abstract
BACKGROUND Refeeding hypophosphatemia (RH) is a common complication of nutritional restoration in malnourished individuals, yet clear risk stratification remains elusive. Individuals with anorexia nervosa (AN) and avoidant/restrictive food intake disorder (ARFID) may be deficient in vitamin D, an important component of dietary phosphorus absorption in the gut. The relationship between vitamin D and RH in AN and ARFID is unknown. Therefore, the aims of this study were to (1) report rates of low serum 25-hydroxy vitamin D and RH in AN and ARFID; (2) describe associations between phosphorus and variables associated with RH identified in extant literature; (3) examine the relationship between 25-hydroxy vitamin D and RH and (4) investigate moderation by vitamin D between variables of interest and phosphorus level. METHOD Analyses included retrospective chart review of 307 individuals admitted to the ACUTE Center for Eating Disorders and Severe Malnutrition with a diagnosis of AN or ARFID. Variables of interest included admission laboratory values (vitamin D level, comprehensive metabolic panel, hemoglobin, point-of-care blood glucose), anthropometric measures (weight, body mass index [BMI], % ideal body weight [IBW]), age, duration of illness, length of stay, feeding method, and serum phosphorus nadir. Pearson and Spearman rank correlation, one-way ANOVA, and regression analyses were used to determine the relationship between variables and serum phosphorus. RESULTS Over 1/3 of the sample (35.3%) had serum phosphorus levels ≤ 2.9 mg/dL. There were no significant differences between groups in phosphorus nadir (p = .17, η2 = 0.12) or hypophosphatemia (p = .16, ϕc = 0.11). Thirty-five (35%) of individuals with ARFID were either deficient or insufficient in vitamin D, compared to 29% of individuals with AN. Individuals with AN had significantly higher mean vitamin D levels compared to those with ARFID (p = .03; η2 = 0.015). Nadir phosphorus showed a positive association with weight, BMI, %IBW, potassium, and calcium on admission, and a negative association with length of stay, hemoglobin, and total number of tube-fed days. Higher levels of 25-hydroxy vitamin D moderated the relationship between serum phosphorus nadir and weight on admission (p = .0004). CONCLUSION Individuals diagnosed with ARFID are as nutritionally fragile as those with AN regarding vitamin D and RH. The negative feedback loop involving vitamin D that maintains phosphorus homeostasis may play a role in the development of RH in AN and ARFID.
Collapse
Affiliation(s)
- Meredith R Kells
- Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
- School of Nursing, University of Rochester, Rochester, NY, USA.
| | - Chloe Roske
- Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
- Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ashlie Watters
- ACUTE Center for Eating Disorders and Severe Malnutrition, Denver, CO, USA
- University of Colorado School of Medicine, Aurora, CO, USA
| | - Leah Puckett
- ACUTE Center for Eating Disorders and Severe Malnutrition, Denver, CO, USA
- University of Colorado School of Medicine, Aurora, CO, USA
| | - Jennifer E Wildes
- Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA
| | - Scott J Crow
- University of Minnesota, Minneapolis, MN, USA
- The Emily Program, St. Paul, MN, USA
| | - Philip S Mehler
- ACUTE Center for Eating Disorders and Severe Malnutrition, Denver, CO, USA
- University of Colorado School of Medicine, Aurora, CO, USA
| |
Collapse
|
18
|
Altahan MF, AbdelAzzem M. A new approach for determination of orthophosphate based on mixed valent molybdenum oxide/poly 1,2-diaminoanthraquinone in seawater. Sci Rep 2023; 13:13634. [PMID: 37604877 PMCID: PMC10442350 DOI: 10.1038/s41598-023-40479-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 08/10/2023] [Indexed: 08/23/2023] Open
Abstract
Orthophosphate is an essential macronutrient in natural water that controls primary production and strongly influences the global ocean carbon cycle. Electrochemical determination of orthophosphate is highly recommended because electrochemistry provides the simplest means of determination. Here the determination of orthophosphate based on the formation of a phosphomolybdate complex is reported. Mixed-valent molybdenum oxide (MoxOy) was prepared by cyclic voltammetry on poly-1,2-diaminoanthraquinone (1,2-DAAQ), which was performed by cyclic voltammetry on the surface of a glassy carbon electrode under pre-optimized conditions for the thickness of the modified electrode layers. The proposed modified electrode was used for square-wave voltammetry of orthophosphate ions under pre-optimized square-wave parameters (i.e., frequency and amplitude) in strongly acidic medium (pH < 1). The linear range was 0.05-4 µM with a limit of quantification (LOD) of 0.0093 µM with no effect on two peaks due to cross interference from silicate. Furthermore, MoxOy/PDAAQ shows good reproducibility with a relative standard deviation (RSD) of 2.17% for the peak at 0.035 V and 3.56% for the peak at 0.2 V. Real seawater samples were also analyzed for PO43- analysis by UV spectrophotometry and the results were compared with the measurement results of our proposed electrode, with good recoveries obtained.
Collapse
Affiliation(s)
- Mahmoud Fatehy Altahan
- Central Laboratory for Environmental Quality Monitoring, National Water Research Center, El-Qanater El-Khairia, 13621, Egypt.
| | - Magdi AbdelAzzem
- Electrochemistry Laboratory, Chemistry Department, Faculty of Science, Menoufia University, Shibin El-Kom, 32511, Egypt
| |
Collapse
|
19
|
Kim KJ, Song JE, Kim JH, Hong N, Kim SG, Lee J, Rhee Y. Elevated morbidity and mortality in patients with chronic idiopathic hypophosphatemia: a nationwide cohort study. Front Endocrinol (Lausanne) 2023; 14:1229750. [PMID: 37635983 PMCID: PMC10448510 DOI: 10.3389/fendo.2023.1229750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Accepted: 07/26/2023] [Indexed: 08/29/2023] Open
Abstract
Background Chronic idiopathic hypophosphatemia (CIH) induced by X-linked hypophosphatemic rickets or tumor-induced osteomalacia is a rare inherited or acquired disorder. However, due to its rarity, little is known about the epidemiology and natural course of CIH. Therefore, we aimed to identify the prevalence and long-term health outcomes of CIH patients. Methods Using the Korean Health Insurance Review and Assessment claims database, we evaluated the incidence of hypophosphatemia initially diagnosed from 2003 to 2018. After excluding secondary conditions that could change serum phosphorus levels, we identified 154 patients (76 men and 78 women) with non-secondary and non-renal hypophosphatemia. These hypophosphatemic patients were compared at a ratio of 1:10 with age-, sex-, and index-year-matched controls (n = 1,540). Results In the distribution of age at diagnosis, a large peak was observed in patients aged 1-4 years and small peaks were observed in ages from 40-70 years. The age-standardized incidence rate showed non-statistically significant trend from 0.24 per 1,000,000 persons in 2003 to 0.30 in 2018. Hypophosphatemic patients had a higher risk of any complication (adjusted hazard ratio [aHR], 2.17; 95% confidence interval [CI], 1.67-2.69) including cardiovascular outcomes, chronic kidney disease, hyperparathyroidism, osteoporotic fractures, periodontitis, and depression. Hypophosphatemic patients also had higher risks of mortality and hospitalization than the controls (aHR, 3.26; 95% CI, 1.83-5.81; and aHR, 2.49; 95% CI, 1.97-3.16, respectively). Conclusion This first nationwide study of CIH in South Korea found a bimodal age distribution and no sex differences among patients. Hypophosphatemic patients had higher risks of complications, mortality, and hospitalization compared to age- and sex-matched controls.
Collapse
Affiliation(s)
- Kyoung Jin Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Ji Eun Song
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Ji Hyun Kim
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Namki Hong
- Department of Internal Medicine, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Juneyoung Lee
- Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yumie Rhee
- Department of Internal Medicine, Endocrine Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
20
|
Błaszczyk JW. Metabolites of Life: Phosphate. Metabolites 2023; 13:860. [PMID: 37512567 PMCID: PMC10385453 DOI: 10.3390/metabo13070860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Revised: 07/14/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
The process of aging and escalating the failure of all body organs has become the center of interest in contemporary science and medicine. The leading role of phosphate-calcium tandem deficiency as a pacemaker of metabolic senescence has emerged recently. Most of the phosphates in the human body are stored in the bones, which seem to play a pivotal role in all metabolic and energetic processes. Bone metabolism combines physical activity with adaptive changes in the internal environment of the body, which is necessary for its survival. Phosphate-calcium signaling is the primary mechanism for controlling homeostasis and its recovery after exercise-induced disorders. Phosphates play an important role in the regulation of energy metabolism both by regulating postprandial glucose storage in the muscles and in the liver, as well as the distribution and adaptation of energy metabolites to the needs of the brain and skeletal muscles. The bone-driven energy metabolism is of decisive importance for maintaining all vital functions of the body organs, including their proper functioning and integrated interplay. The phosphate-calcium tandem contributes to the development and proper functioning of the organism, whereas energy dysmetabolism is the main cause of aging and the final termination of life.
Collapse
|
21
|
Kells MR, Roske C, Watters A, Puckett L, Wildes JE, Crow SJ, Mehler P. Vitamin D and Hypophosphatemia in Patients with Anorexia Nervosa and Avoidant/Restrictive Food Intake Disorder: A Case Control Study. RESEARCH SQUARE 2023:rs.3.rs-3101384. [PMID: 37503154 PMCID: PMC10371151 DOI: 10.21203/rs.3.rs-3101384/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
Background Refeeding hypophosphatemia (RH) is a common complication of nutritional restoration in malnourished individuals, yet clear risk stratification remains elusive. Individuals with anorexia nervosa (AN) and avoidant/restrictive food intake disorder (ARFID) may be deficient in vitamin D, an important component of dietary phosphorus absorption in the gut. The relationship between vitamin D and RH in AN and ARFID is unknown. Therefore, the aims of this of this study were to 1) describe the prevalence of low serum 25-hydroxy vitamin D levels and RH in AN and ARFID 2) report associations between nadir phosphorus level and variables associated with RH in extant literature and 3) examine the relationship between 25-hydroxy vitamin D levels and serum phosphorus nadir in AN and ARFID. Method Analyses included retrospective chart review of 307 individuals admitted to the ACUTE Center for Eating Disorders and Severe Malnutrition with a diagnosis of AN or ARFID. Variables of interest included admission laboratory values (vitamin D level, comprehensive metabolic panel, hemoglobin, point-of-care blood glucose), anthropometric measures (weight, body mass index [BMI], % ideal body weight [IBW]), age, duration of illness, length of stay, feeding method, and serum phosphorus nadir. Pearson and Spearman rank correlation, one-way ANOVA, and regression analyses were used to determine the relationship between variables and serum phosphorus. Results Over 1/3 of the sample (35.3%) had serum phosphorus levels ≤ 2.9 mg/dL. There were no significant differences between groups in phosphorus nadir (p = .17, η2 = 0.12) or hypophosphatemia (p = .16, ϕc = 0.11); 44% of individuals with ARFID and 33% of individuals with AN had hypophosphatemia. Nadir phosphorus showed a positive association with weight, BMI, %IBW, potassium, and calcium on admission, and a negative association with length of stay, hemoglobin, and total number of tube-fed days. Higher levels of 25-hydroxy vitamin D moderated the relationship between serum phosphorus nadir and weight on admission (p = .0004). Conclusion Individuals diagnosed with ARFID are as nutritionally fragile as those with AN regarding vitamin D and RH. The negative feedback loop involving vitamin D that maintains phosphorus homeostasis may play a role in the development of RH in AN and ARFID.
Collapse
|
22
|
Sauvé B, Chorfi Y, Montminy MPL, Guay F. Vitamin D Supplementation Impacts Calcium and Phosphorus Metabolism in Piglets Fed a Diet Contaminated with Deoxynivalenol and Challenged with Lipopolysaccharides. Toxins (Basel) 2023; 15:394. [PMID: 37368695 DOI: 10.3390/toxins15060394] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/17/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Using alternative feed ingredients in pig diets can lead to deoxynivalenol (DON) contamination. DON has been shown to induce anorexia, inflammation, and-more recently-alterations in the vitamin D, calcium, and phosphorus metabolisms. Adding vitamin D supplementation in the form of vitamin D3 and 25-OH-D3 to the feed could modify the effects of DON in piglets. In this study, vitamin D3 or 25-OH-D3 supplementation was used in a control or DON-contaminated treatment. A repetitive exposure over 21 days to DON in the piglets led to disruptions in the vitamin D, calcium, and phosphorus metabolisms, resulting in a decreased growth performance, increased bone mineralization, and the downregulation of genes related to calcium and to phosphorus intestinal and renal absorption. The DON challenge also decreased blood concentrations of 25-OH-D3, 1,25-(OH)2-D3, and phosphate. The DON contamination likely decreased the piglets' vitamin D status indirectly by modifying the calcium metabolism response. Vitamin D supplementations did not restore vitamin D status or bone mineralization. After a lipopolysaccharide-induced inflammatory stimulation, feeding a 25-OH-D3 supplementation increased 25-OH-D3 concentration and 1,25-(OH)2-D3 regulations during the DON challenge. DON contamination likely induced a Ca afflux by altering the intestinal barrier, which resulted in hypercalcemia and hypovitaminosis D. The vitamin D supplementation could increase the calcitriol production to face the combined LPS and DON challenge.
Collapse
Affiliation(s)
- Béatrice Sauvé
- Department of Animal Sciences, Laval University, Quebec, QC G1V 0A6, Canada
| | - Younes Chorfi
- Department of Veterinary Biomedicine, Montreal University, Saint-Hyacinthe, QC J2S 2M2, Canada
| | | | - Frédéric Guay
- Department of Animal Sciences, Laval University, Quebec, QC G1V 0A6, Canada
| |
Collapse
|
23
|
Busa P, Huang N, Kuthati Y, Wong CS. Vitamin D reduces pain and cartilage destruction in knee osteoarthritis animals through inhibiting the matrix metalloprotease (MMPs) expression. Heliyon 2023; 9:e15268. [PMID: 37123896 PMCID: PMC10130884 DOI: 10.1016/j.heliyon.2023.e15268] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 03/11/2023] [Accepted: 03/31/2023] [Indexed: 05/02/2023] Open
Abstract
Aim of the study In this study, we investigated the therapeutic potential of vitamin D (VITD) in OA Wistar rats induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT + MMx). In ACLT + MMx-induced OA rats, pain severity, cartilage destruction, inflammatory cytokines, and MMPs were all measured. Materials and methods ACLT + MMx methods were used to induce OA, and pain behavioral studies such as the weight bearing test and paw withdrawal test were performed while the knee width and body weights were also measured. Furthermore, Hematoxylin and Eosin (H&E) staining was used to determine knee histopathological studies, as well as OARSI scoring, cartilage thickness, cartilage width, and cartilage degradation scores. The enzyme-linked immunosorbent assay (ELISA) studies were used to check the serum levels of VITD, C-telopeptide of Type II collagen (CTX-II), and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-10 (IL-10), and MMPs (MMP-3, MMP-9, and MMP-13). Finally, the reverse transcription polymerase chain reaction (RT-PCR) test was used to determine the levels of MMPs, nuclear factor-kappa B (NF-κB), TNF-α, IL-6, and IL-10 in IL-1β stimulated chondrocytes. Results The oral VITD supplement significantly reduced OA pain, inflammation, cartilage destruction, and MMPs levels. Furthermore, serum VITD levels increased while CTX-II levels decreased, indicating that VITD reduced cartilage degradation effectively. Moreover, VITD supplementation reduced the expression of pro-inflammatory TNF-α, IL-1β, and IL-6 cytokines while increasing the expression of anti-inflammatory IL-10. The elevation of MMPs after ACLT + MMx surgery contributed to articular cartilage destruction, which was reduced by VITD supplementation. Finally, VITD supplementation significantly reduces serum levels of MMPs, IL-1β, TNF-α, and IL-6 while increasing IL-10 levels. Then, using the in-vitro cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT assay, examine the cytotoxicity profile of VITD in rat chondrocytes after stimulated with IL-1β, which shows no toxicity in the dose range of VITD 0-500 IU. Finally, RT-PCR studies in IL-1β stimulated rat chondrocytes revealed that VITD (50, 100, and 500 IU) significantly reduced the mRNA levels of MMPs, NF-κB, TNF-α, and IL-6, while increasing IL-10 levels, indicating that VITD reduced chondrocyte destruction and overcame harsh conditions in a dose-dependent manner. Conclusion Overall, the in vivo and in vitro findings show that VITD effectively reduces OA pain, inflammation, and chondrocyte destruction by lowering MMPs levels specifically.
Collapse
Affiliation(s)
- Prabhakar Busa
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
| | - Niancih Huang
- Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
| | - Yaswanth Kuthati
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
| | - Chih-Shung Wong
- Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan
- Department of Anesthesiology, Tri-Service General Hospital, Taipei, Taiwan
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
- Corresponding author. Department of Anesthesiology, Cathay General Hospital, #280, Renai Road, Section 4, Taipei, Taiwan.
| |
Collapse
|
24
|
Liu CC, Huang JP. Potential benefits of vitamin D supplementation on pregnancy. J Formos Med Assoc 2023:S0929-6646(23)00058-X. [PMID: 36925361 DOI: 10.1016/j.jfma.2023.02.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 02/01/2023] [Accepted: 02/14/2023] [Indexed: 03/17/2023] Open
Abstract
BACKGROUND The level of vitamin D in pregnant women and the effect of vitamin D supplementation are lack in Taiwan. OBJECTIVE To investigate the vitamin D serum level and the effect of its supplementation on pregnancy. METHODS We included 1048 pregnant women who underwent prenatal exam with known serum 25-hydroxyvitamin D3 [25(OH)D3] levels and delivery at the Mackay Memorial Hospital, Taipei, Taiwan during 2015-2018. A daily dose 2000 IU of vitamin D was given, starting at 12-16 weeks of pregnancy, to reach the level of 20 ng/mL, and then a maintenance dose of 800 IU/day was given. The other 3654 women without vitamin D supplementation delivered in 2018 served as control group. Pregnancy outcomes were recorded for analysis. RESULTS Over 80% of the 1048 pregnant women were vitamin D deficiency. There was an inverse correlation between serum vitamin D levels and maternal body mass index (p = 0.0366). We compared 375 women with serum vitamin D levels increased above 30 ng/mL after supplementation with control group. The rates of preterm birth, low birth weight, and postpartum hemorrhage between these 2 groups were 6.67% vs. 11.19% (p = 0.007), 6.40% vs. 10.0% (p = 0.025), and 1.33% vs. 3.20% (p = 0.04), respectively. CONCLUSIONS Vitamin D deficiency is very prevalent in pregnant women, especially those with high BMI, in Taiwan. It can be corrected by adequate vitamin D supplementation, which may decrease the risk of pregnancy complications and bring benefits to the fetus.
Collapse
Affiliation(s)
- Cheng-Chiang Liu
- Division of General Obstetrics and Gynecology, Department of Obstetrics & Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Jian-Pei Huang
- Division of General Obstetrics and Gynecology, Department of Obstetrics & Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; MacKay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
| |
Collapse
|
25
|
Effects of Low-Phosphorus Diets Supplemented with Phytase on the Production Performance, Phosphorus-Calcium Metabolism, and Bone Metabolism of Aged Hy-Line Brown Laying Hens. Animals (Basel) 2023; 13:ani13061042. [PMID: 36978583 PMCID: PMC10044119 DOI: 10.3390/ani13061042] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/15/2023] Open
Abstract
This study was conducted to evaluate the effects of phytase supplementation in low-phosphorus diets on the production performance, phosphorus–calcium metabolism, and bone metabolism in laying hens from 69 to 78 weeks of age. Hy-Line Brown laying hens (n = 1350) were assigned randomly to six treatments with five replicates of 45 birds. A corn–soybean meal-based diet with no inorganic phosphates was formulated to contain 0.12% non-phytate phosphorus (NPP) and 1470 FTU/kg phytase (Released phytate phosphorus content ≥ 0.1%). Inorganic phosphorus (dicalcium phosphate) was supplemented into the basal diet to construct five test diets (level of NPP supplementation = 0.10%, 0.15%, 0.20%, 0.25%, and 0.30%). The level of calcium carbonate was adjusted to ensure that all six experimental diets contained the same calcium percentage (3.81%). The feeding trial lasted 10 weeks (hens from 69 to 78 weeks of age). Upon supplementation with phytase (1470 FTU/kg), supplemental inorganic phosphates (dicalcium phosphate) had no significant effects (p > 0.05) on the production performance or egg quality. Significant differences in serum levels of calcium, phosphorus, copper, iron, zinc, or manganese were not detected across treatments (p > 0.05). Hens fed NPP (0.15%, 0.20%, 0.25%, and 0.30%) had higher levels (p < 0.0001) of tibial ash, calcium, and phosphorus than those not fed inorganic phosphates. The tibial breaking strength of the group without inorganic phosphates was significantly lower than that of the other groups (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of calcitonin (CT) and 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3). Hens that did not receive supplementation with inorganic phosphates had higher serum levels of parathyroid hormone (PTH), osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) compared with those in the other groups (p < 0.01). Serum levels of CTX-I and TRACP-5b were significantly lower in the NPP-supplementation groups of 0.25% and 0.30% than in the 0.10% NPP-supplementation group (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of bone-alkaline phosphatase (BAP), osteocalcin (OCN), or osteopontin (OPN). Hens not fed inorganic phosphate had the highest renal expression of phosphorus transporter type IIa Na/Pi cotransporter (NaPi-Ⅱa). Renal expression of NaPi-Ⅱa was increased significantly in NPP-supplementation groups of 0.10–0.20% compared with that in NPP-supplementation groups of 0.25% and 0.30% (p < 0.0001). The results indicated that a reduction in NPP supplementation to 0.15% (dietary NPP level = 0.27%) with phytase inclusion did not have an adverse effect on the production performance or bone health of laying hens from 69 to 78 weeks of age, which might be attributed to renal phosphorus reabsorption and bone resorption. These findings could support the application of low-phosphorus diets in the poultry industry.
Collapse
|
26
|
Jodar E, Campusano C, de Jongh RT, Holick MF. Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency. Eur J Nutr 2023; 62:1579-1597. [PMID: 36862209 PMCID: PMC9979899 DOI: 10.1007/s00394-023-03103-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Accepted: 01/31/2023] [Indexed: 03/03/2023]
Abstract
BACKGROUND In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D3) has recently become available more widely. METHODS By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D3, and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions. RESULTS For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3-10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D3, calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D3, it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D3 and thus is less prone to sequestration in adipose tissue. CONCLUSION Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.
Collapse
Affiliation(s)
- Esteban Jodar
- grid.119375.80000000121738416Department of Endocrinology and Nutrition, Quirón Salud Madrid and Ruber Juan Bravo University Hospitals, Universidad Europea de Madrid, Madrid, Spain
| | - Claudia Campusano
- grid.440627.30000 0004 0487 6659Department of Internal Medicine, Endocrine Section, Clínica Universidad de los Andes and School of Medicine, Universidad de los Andes, Santiago, Chile
| | - Renate T. de Jongh
- grid.12380.380000 0004 1754 9227Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands
| | - Michael F. Holick
- grid.189504.10000 0004 1936 7558Vitamin D, Skin, and Bone Research Laboratory, Section Endocrinology, Diabetes, Nutrition and Weight Management, Department of Medicine, Boston University School of Medicine, 85 E Newton St, M-1013, Boston, MA 02118 USA
| |
Collapse
|
27
|
de Oliveira NM, Lopes L, Chéu MH, Soares E, Meireles D, Machado J. Updated Mineral Composition and Potential Therapeutic Properties of Different Varieties of Olive Leaves from Olea europaea. PLANTS (BASEL, SWITZERLAND) 2023; 12:916. [PMID: 36840264 PMCID: PMC9959211 DOI: 10.3390/plants12040916] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/15/2023] [Indexed: 06/18/2023]
Abstract
Olea europaea L. folium has been studied for its potential nutraceutical properties. Quantitative and qualitative analyses were conducted on samples of Madural, Verdeal, and Cobrançosa elementary leaves and leave sprouts (mamões) collected in the region of Valpaços, Portugal. Mineral analysis determined the measurements of the levels of several macro- and micro-elements based on ICP-MS techniques. The inorganic analysis in this work allowed us to propose olive leaf extract (OLE) from different cultivars as a viable and affordable source of mineral substrates to address disorders related to essential elements such as Na, K, Mg, Ca, Mn, Fe, and Cu deficiencies. Given the importance of the research on novel therapies, finding a suitable substrate for extracting quality amounts of mineral is a priority. The physiological influence of enzymes dependent on minerals with regard to neuroinflammatory and neurobehavioral, metabolic, cardiovascular, osteodegenerative, anti-aging, pulmonary, and immunological defense disorders might dictate the importance of further research for designing supplementation based on the nutraceutical potential of OLE of these cultivars predominant in the northern region of Portugal.
Collapse
Affiliation(s)
- Natália M. de Oliveira
- ICBAS-UP Laboratory of Applied Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
- CBSin, Centre of Biosciences in Integrative Health, 4250-105 Porto, Portugal
| | - Lara Lopes
- ICBAS-UP Laboratory of Applied Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
- CBSin, Centre of Biosciences in Integrative Health, 4250-105 Porto, Portugal
| | - Maria Helena Chéu
- RECI—Research Unit in Education and Community Intervention, Instituto Piaget—ISEIT/Viseu, 3515-776 Viseu, Portugal
| | - Eugénio Soares
- Laboratório Central de Análises, Universidade de Aveiro-UA, 3810-193 Aveiro, Portugal
| | - Diana Meireles
- ICBAS-UP Laboratory of Applied Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
| | - Jorge Machado
- ICBAS-UP Laboratory of Applied Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
- CBSin, Centre of Biosciences in Integrative Health, 4250-105 Porto, Portugal
| |
Collapse
|
28
|
Prevalence and Risk Factors for Vitamin D Deficiency in Children and Adolescents in the Kingdom of Bahrain. Nutrients 2023; 15:nu15030494. [PMID: 36771201 PMCID: PMC9919096 DOI: 10.3390/nu15030494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/11/2023] [Accepted: 01/12/2023] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Vitamin D deficiency has reached pandemic levels in the Middle East and North Africa (MENA) region, even though sunshine is abundant all year round for the cutaneous synthesis of vitamin D through the skin. This study aimed to determine the prevalence of vitamin D deficiency and risk factors associated with serum 25-hydroxy vitamin D (25(OH)D) in children and adolescents aged from 10 to 19 years, as well as the possible associations of vitamin D with calcium, magnesium and phosphate levels. METHODS A multi-center, cross-sectional study was conducted between May and August 2019 at the Ministry of Health in the Kingdom of Bahrain. A total of 383 boys and girls were selected from five health centers from five different regions in the Kingdom of Bahrain. Information about sex, age, education level, weight, height, degree of sunlight exposure, and physical activity levels was recorded. A blood sample was taken from each participant to test serum levels of 25(OH)D, calcium, magnesium and phosphate. RESULTS The results revealed that 92.1% of the participants were deficient in vitamin D. A significantly higher percentage of boys (96.2%) were vitamin D deficient (<20 ng/mL) than girls (88.3%) (p value = 0.004). Vitamin D deficiency were more prevalent among overweight (96.8%) and obese (96.2%) participants than normal body weight and wasted participants (p value < 0.001). Being male, overweight, or obese was significantly positively associated with a risk of vitamin D deficiency. Vitamin D deficiency was significantly associated with low serum levels of magnesium. No significant associations were detected between vitamin D deficiency and calcium and phosphate serum levels. However, vitamin D deficiency was significantly associated with low serum level of magnesium (p value = 0.017). CONCLUSIONS Our study revealed that vitamin D deficiency was more prevalent among overweight and obese adolescents and mostly boys rather than girls. Magnesium and phosphate were lower in adolescents and children with lower serum 25(OH)D, showing a clear association between these biomarkers and the 25(OH)D.
Collapse
|
29
|
Guedes M, Bieber B, Dasgupta I, Vega A, Nitta K, Brunelli S, Hartman J, Raimann JG, Robinson BM, Pisoni RL. Serum Phosphorus Level Rises in US Hemodialysis Patients Over the Past Decade: A DOPPS Special Report. Kidney Med 2022; 5:100584. [PMID: 36704450 PMCID: PMC9871331 DOI: 10.1016/j.xkme.2022.100584] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Mineral bone disorder (MBD) is a frequent consequence of chronic kidney disease, more so in patients with kidney failure treated by kidney replacement therapy. Despite the wide availability of interventions to control serum phosphate and parathyroid hormone levels, unmet gaps remain on optimal targets and best practices, leading to international practice pattern variations over time. In this Special Report, we describe international trends from the Dialysis Outcomes and Practice Patterns Study (DOPPS) for MBD biomarkers and treatments from 2002-2021, including data from a group of 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom), Japan, and the United States. From 2002-2012, mean phosphate levels declined in Japan (5.6 to 5.2 mg/dL), Europe (5.5 to 4.9 mg/dL), and the United States (5.7 to 5.0 mg/dL). Since then, levels rose in the United States (to mean 5.6 mg/dL, 2021), were stable in Japan (5.3 mg/dL), and declined in Europe (4.8 mg/dL). In 2021, 52% (United States), 27% (Europe), and 39% (Japan) had phosphate >5.5 mg/dL. In the United States, overall phosphate binder use was stable (80%-84% over 2015-2021), and parathyroid hormone levels rose only modestly. Although these results potentially stem from pervasive knowledge gaps in clinical practice, the noteworthy steady increase in serum phosphate in the United States over the past decades may be consequential to patient outcomes, an uncertainty that hopefully will soon be addressed by ongoing clinical trials. The DOPPS will continue to monitor international trends as new interventions and strategies ensue for MBD management in chronic kidney disease.
Collapse
Affiliation(s)
- Murilo Guedes
- Pontificia Universidade Católica do Paraná, Curitiba, Paraná, Brazil,Arbor Research Collaborative for Health, Ann Arbor, Michigan,Address for Correspondence: Murilo Guedes, R. Imaculada Conceicao, Curitiba, PR, Brazil 80215-901.
| | - Brian Bieber
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
| | - Indranil Dasgupta
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK,Warwick Medical School, University of Warwick, Coventry, UK
| | - Almudena Vega
- La Fundacion para la Investigacion Biomedica del Hospital Gregorio Maranon, Madrid, Comunidad de Madrid, Spain
| | - Kosaku Nitta
- Department of Nephrology, Tokyo Women’s Medical University, Tokyo, Japan
| | | | | | | | | | | |
Collapse
|
30
|
Dai T, Jiao L, Tao X, Lu J, Jin M, Sun P, Zhou Q. Effects of dietary vitamin D 3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. Br J Nutr 2022; 128:793-801. [PMID: 34879881 DOI: 10.1017/s0007114521004931] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
An 8-week feeding trial was conducted to investigate the effects of dietary vitamin D3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. A total of 720 shrimp (initial weight 0·50 ± 0·01 g) were randomly distributed into six treatments, each of which had three duplicates of forty shrimp per duplicate. Six isonitrogenous and isolipidic diets were formulated to contain graded vitamin D3 (0·18, 0·23, 0·27, 0·48, 0·57 and 0·98 mg/kg of vitamin D3, measured) supplementation levels. The results revealed that L. vannamei fed diet containing 0·48 mg/kg of vitamin D3 achieved the best growth performance. Compared with the control group, supplementing 0·48 mg/kg of vitamin D3 significantly increased (P < 0·05) the activities of catalase, total antioxidative capacity, alkaline phosphatase and acid phosphatase in serum and hepatopancreas. Expression levels of antioxidant and immune-related genes were synchronously increased (P < 0·05). Carapace P and Ca concentrations were increased (P < 0·05) with the increased vitamin D3 supplementation levels. Further analysis of lipid metabolism-related genes expression showed that shrimp fed 0·48 mg of vitamin D3 per kg diet showed the highest value in the expression of lipid synthesis-related genes, while shrimp fed 0·98 mg of vitamin D3 per kg diet showed the highest value in the expression of lipolysis-related genes. In conclusion, the results of present study indicated that dietary supplementation of 0·48 mg/kg of vitamin D3 could increase Ca and P concentrations, improve antioxidant capacity and immune response, and influence lipid metabolism in L. vannamei.
Collapse
Affiliation(s)
- Tianmeng Dai
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Lefei Jiao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Xinyue Tao
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Jingjing Lu
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Min Jin
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Peng Sun
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| | - Qicun Zhou
- Laboratory of Fish and Shellfish Nutrition, School of Marine Sciences, Ningbo University, Ningbo315211, People's Republic of China
| |
Collapse
|
31
|
Turcotte A, Achi S, Mamlouk O, Mandayam S. Electrolytes disturbances in cancer patients. Curr Opin Nephrol Hypertens 2022; 31:425-434. [PMID: 35894276 DOI: 10.1097/mnh.0000000000000819] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Hypernatremia, hyperphosphatemia, hypocalcaemia, hyperkalaemia and hypermagnesemia are electrolytes disturbances that can arise in cancer patients in relation to unique causes that are related to the cancer itself or its treatment and can lead to delay or interruption of cancer therapy. This article summarizes these main causes, the proposed pathophysiology and the recommended management for these disturbances. RECENT FINDINGS There have been many cancer drugs approved in the field of oncology over the past several years and a subset of these drugs have been associated with electrolytes disturbances. This includes, for example, immune checkpoint inhibitor related hyperkalemia, fibroblast growth factor 23 inhibitor associated hyperphosphatemia and epidermal growth factor receptor inhibitor associated hypomagnesemia and hypocalcaemia. SUMMARY This article provides an updated review of certain electrolytes disturbance in cancer patients and allows clinicians to have a greater awareness and knowledge of these electrolyte abnormalities in efforts to early recognition and timely management.
Collapse
Affiliation(s)
- Anna Turcotte
- Section of Nephrology, The University of Texas MD Anderson Cancer Center
| | - Sai Achi
- Department of Nephrology, The University of Texas McGovern Medical School, Houston, Texas, USA
| | - Omar Mamlouk
- Section of Nephrology, The University of Texas MD Anderson Cancer Center
| | - Sreedhar Mandayam
- Section of Nephrology, The University of Texas MD Anderson Cancer Center
| |
Collapse
|
32
|
Chan KS, Mohan S, Shelat VG. Outcomes of patients with post-hepatectomy hypophosphatemia: A narrative review. World J Hepatol 2022; 14:1550-1561. [PMID: 36157866 PMCID: PMC9453469 DOI: 10.4254/wjh.v14.i8.1550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 05/31/2022] [Accepted: 08/01/2022] [Indexed: 02/06/2023] Open
Abstract
Phosphate is an essential electrolyte for proper mineralisation of bone, buffering of urine, and diverse cellular actions. Hypophosphatemia (HP) is a clinical spectrum which range from asymptomatic to severe complications such as neuromuscular and pulmonary complications, or even death. Post-hepatectomy HP (PHH) has been reported to be 55.5%-100%. Post-hepatectomy, there is rapid uptake of phosphate and increased mitotic counts to aid in regeneration of residual liver. Concurrently, PHH may be due to increased urinary phosphorous from activation of matrix extracellular phosphoglycoprotein in the injured liver, which decreases phosphate influx into hepatocytes to sustain adenosine triphosphate synthesis. A literature review was performed on PubMed till January 2022. We included 8 studies which reported on impact of PHH on post-operative outcomes. In patients with diseased liver, PHH was reported to have either beneficial or deleterious effects on post-hepatectomy liver failure (PHLF), morbidity and/or mortality in various cohorts. In living donor hepatectomy, PHLF was higher in PHH. Benefits of correction of PHH with reduced post-operative complications have been shown. Correction of PHH should be done based on extent of PHH. Existing studies were however heterogenous; further studies should be conducted to assess PHH on post-operative outcomes with standardized phosphate replacement regimes.
Collapse
Affiliation(s)
- Kai Siang Chan
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore.
| | - Swetha Mohan
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| |
Collapse
|
33
|
Avidime O, Avidime S, Randawa AJ, Kawu MU, Mohammed A, Yama OE, Oweh OT. Physiological Changes in Serum Calcium, Phosphate, Vitamin D, Parathyroid Hormone and Calcitonin During Pregnancy and Lactation in Randomised Population of Zaria Women. Niger J Physiol Sci 2022; 37:77-82. [PMID: 35947844 DOI: 10.54548/njps.v37i1.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 06/18/2022] [Indexed: 06/15/2023]
Abstract
Pregnancy and lactation are usual but stressful physiological conditions accompanied by changes in calcium and phosphate metabolism and their regulatory hormones which may lead to calcium-related disorders in pregnant women. This study aimed to evaluate the changes in serum levels of calcium, phosphate, vitamin D and their regulatory hormones in pregnant and lactating women in Zaria, Nigeria. A cross‑sectional descriptive study was conducted at Ahmadu Bello University Teaching Hospital, Zaria for three (3) months. Blood samples were collected, anthropometric measurements (weight, height and body mass index) of 179 women were taken. Serum calcium, phosphate, vitamin D, parathyroid hormone and calcitonin were determined using standard methods. Data were presented as mean ± SD, analysis was performed using one-way ANOVA and Pearson's correlation analysis. Values were considered significant at p ≤ 0.05. There was a significant decrease in serum calcium concentration (p < 0.01) during the third trimester of pregnancy and lactation. An increase in serum concentration of vitamin D, parathyroid hormone, and calcitonin in the 2nd trimester and a decrease during the third trimester and lactation although not statistically significant when compared with the control. There was a negative correlation between serum calcium concentration and gestational age (r = 0.255) while no correlation between gestational age and serum phosphate concentration. Changes in serum calcium, vitamin D, parathyroid hormone and calcitonin during pregnancy and lactation has been demonstrated suggesting a relationship between calcium metabolism and these hormones at some stages of pregnancy.
Collapse
Affiliation(s)
- Ohunene Avidime
- Dept of Human Physiology, Faculty of Basic Medical Sciences, College of Medicine, Kaduna State University, Kaduna.
| | | | | | | | | | | | | |
Collapse
|
34
|
Cianferotti L, Delli Poggi C, Bertoldo F, Caffarelli C, Crotti C, Gatti D, Giannini S, Gonnelli S, Mazzantini M, Ombretta V, Sella S, Setti A, Varenna M, Zucchi F, Brandi ML. Persistence and recurrence in tumor-induced osteomalacia: A systematic review of the literature and results from a national survey/case series. Endocrine 2022; 76:709-721. [PMID: 35381903 PMCID: PMC9156492 DOI: 10.1007/s12020-022-03039-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 03/08/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE Tumor induced osteomalacia (TIO) is a rare disease of mineral metabolism, whose clinical picture is dominated by hypophosphatemia usually due to an excess of circulating FGF23 produced by small mesenchymal tumors. Data on the real prevalence of the disease are lacking, with the knowledge of the disease mainly relying on case reports and small case series. No estimate is available on the prevalence of uncured TIO. METHODS National multi-center, cross-sectional and retrospective study on persistent or recurrent cases of TIO followed in referral centers for bone diseases; systematic review of the published persistent and recurrent cases of TIO. Data from patients consecutively evaluated in referral Italian centers for bone diseases were collected; a PubMed search on persistent, recurrent and unoperable cases of TIO was carried out. RESULTS Sixteen patients (mean age at diagnosis 52.5 ± 10.6 years) with persistent (n = 6, 37,5%), recurrent (n = 7, 43.7%) or not operable (n = 3, 18.8%) TIO were described. Delay in diagnosis (2.5 ± 1.3 years) was demonstrated. All patients experienced fragility fractures or pseudofractures and disabling bone and muscle pain. BMD was significantly reduced (mean T-score -2.7 ± 1.7 and -2.7 ± 0.9 at lumbar spine and femoral neck, respectively). Fourteen patients were maintained under therapy with phosphate salts and calcitriol, while in 2 patients therapy with burosumab, an anti-FGF23 antibody, was commenced. CONCLUSION A significant number of patients with TIO remain either undiagnosed for tumor localization or tumor recur or persist after surgery. These patients with active disease represent possible candidates for burosumab treatment.
Collapse
Affiliation(s)
- Luisella Cianferotti
- Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Bone Metabolic Diseases Unit, University Hospital of Florence, largo Palagi 1, 50139, Florence, Italy
| | - Chiara Delli Poggi
- Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Bone Metabolic Diseases Unit, University Hospital of Florence, largo Palagi 1, 50139, Florence, Italy
| | - Francesco Bertoldo
- Department of Medicine, University of Verona, Piazzale LA Scuro 10, Policlinico GB Rossi, Piazzale LA Scuro 10, 37134, Verona, Italy
| | - Carla Caffarelli
- Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy
| | - Chiara Crotti
- Bone Diseases Unit, Department of Rheumatology, Gaetano Pini Institute, Via Pini, 9, Milan, 20122, Italy
| | - Davide Gatti
- Rheumatology Section, Department of Medicine, University of Verona Hospital Trust, Policlinico G.B. Rossi, Piazzale LA Scuro 10, 37134, Verona, Italy
| | - Sandro Giannini
- Department of Medicine (DIMED), Clinica Medica Uno, University of Padua, via Nicolò Giustiniani, 2, 35128, Padua, Italy
| | - Stefano Gonnelli
- Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy
| | - Maurizio Mazzantini
- Rheumatology Unit, and Fracture Liaison Service, University Hospital of Pisa, via Roma 67, 56126, Pisa, Italy
| | - Viapiana Ombretta
- Rheumatology Section, Department of Medicine, University of Verona Hospital Trust, Policlinico G.B. Rossi, Piazzale LA Scuro 10, 37134, Verona, Italy
| | - Stefania Sella
- Department of Medicine (DIMED), Clinica Medica Uno, University of Padua, via Nicolò Giustiniani, 2, 35128, Padua, Italy
| | - Angela Setti
- Department of Medicine, University of Verona, Piazzale LA Scuro 10, Policlinico GB Rossi, Piazzale LA Scuro 10, 37134, Verona, Italy
| | - Massimo Varenna
- Bone Diseases Unit, Department of Rheumatology, Gaetano Pini Institute, Via Pini, 9, Milan, 20122, Italy
| | - Francesca Zucchi
- Bone Diseases Unit, Department of Rheumatology, Gaetano Pini Institute, Via Pini, 9, Milan, 20122, Italy
| | | |
Collapse
|
35
|
The human pathogenic 91del7 mutation in SLC34A1 has no effect in mineral homeostasis in mice. Sci Rep 2022; 12:6102. [PMID: 35414099 PMCID: PMC9005600 DOI: 10.1038/s41598-022-10046-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 04/01/2022] [Indexed: 11/29/2022] Open
Abstract
Kidneys are key regulators of phosphate homeostasis. Biallelic mutations of the renal Na+/phosphate cotransporter SLC34A1/NaPi-IIa cause idiopathic infantile hypercalcemia, whereas monoallelic mutations were frequently noted in adults with kidney stones. Genome-wide-association studies identified SLC34A1 as a risk locus for chronic kidney disease. Pathogenic mutations in SLC34A1 are present in 4% of the general population. Here, we characterize a mouse model carrying the 91del7 in-frame deletion, a frequent mutation whose significance remains unclear. Under normal dietary conditions, 12 weeks old heterozygous and homozygous males have similar plasma and urinary levels of phosphate as their wild type (WT) littermates, and comparable concentrations of parathyroid hormone, fibroblast growth factor 23 (FGF-23) and 1,25(OH)2 vitamin D3. Renal phosphate transport, and expression of NaPi-IIa and NaPi-IIc cotransporters, was indistinguishable in the three genotypes. Challenging mice with low dietary phosphate did not result in differences between genotypes with regard to urinary and plasma phosphate. Urinary and plasma phosphate, plasma FGF-23 and expression of cotransporters were similar in all genotypes after weaning. Urinary phosphate and bone mineral density were also comparable in 300 days old WT and mutant mice. In conclusion, mice carrying the 91del7 truncation do not show signs of impaired phosphate homeostasis.
Collapse
|
36
|
Carpenter KA, Davison R, Shakthivel S, Anderson KD, Ko FC, Ross RD. Sclerostin antibody improves phosphate metabolism hormones, bone formation rates, and bone mass in adult Hyp mice. Bone 2022; 154:116201. [PMID: 34537437 PMCID: PMC8671249 DOI: 10.1016/j.bone.2021.116201] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/12/2021] [Accepted: 09/13/2021] [Indexed: 01/03/2023]
Abstract
X-linked hypophosphatemia (XLH) is caused by a loss-of-function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX). Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23), impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily by osteocytes, suppresses bone formation by antagonizing canonical Wnt-signaling and is reported to be elevated in XLH patients. Our previous study reported that a monoclonal antibody to sclerostin (Scl-Ab) decreases FGF23 and increases phosphate and bone mass in growing Hyp mice (XLH murine model). In the current study, we investigated the efficacy of Scl-Ab in treating XLH pathophysiology in adult Hyp mice that are past the period of rapid skeletal growth (12 and 20-weeks old). We hypothesized that Scl-Ab would not only increase bone formation, bone strength and bone mass, but would also normalize phosphate regulating hormones, FGF23, parathyroid hormone (PTH), and vitamin 1,25(OH)2D. Scl-Ab treatment increased cortical area, trabecular bone volume fraction, trabecular bone formation rate, and the bending moment in both sexes of both age groups. Scl-Ab treatment suppressed circulating levels of intact FGF23 and c-term FGF23 in treated male and female wild-type and Hyp mice of both age groups and improved both vitamin 1,25(OH)2D and PTH. Scl-Ab treated Hyp mice also showed evidence of increased renal expression of the sodium-phosphate co-transporter, NPT2a, specifically in the female Hyp mice. Our study suggests that Scl-Ab treatment can improve several skeletal and metabolic pathologies associated with XLH, further establishes the role of sclerostin in the regulation of FGF23 and provides evidence that Scl-Ab can improve phosphate regulation by targeting the bone-renal axis.
Collapse
Affiliation(s)
- Kelsey A Carpenter
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America
| | - Reid Davison
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America
| | - Shruti Shakthivel
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America
| | - Kyle D Anderson
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America
| | - Frank C Ko
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America
| | - Ryan D Ross
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America.
| |
Collapse
|
37
|
Bendarska-Czerwińska A, Zmarzły N, Morawiec E, Panfil A, Bryś K, Czarniecka J, Ostenda A, Dziobek K, Sagan D, Boroń D, Michalski P, Pallazo-Michalska V, Grabarek BO. Endocrine disorders and fertility and pregnancy: An update. Front Endocrinol (Lausanne) 2022; 13:970439. [PMID: 36733805 PMCID: PMC9887196 DOI: 10.3389/fendo.2022.970439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 12/28/2022] [Indexed: 01/18/2023] Open
Abstract
It is estimated that more and more couples suffer from fertility and pregnancy maintenance disorders. It is associated with impaired androgen secretion, which is influenced by many factors, ranging from genetic to environmental. It is also important to remember that fertility disorders can also result from abnormal anatomy of the reproductive male and female organ (congenital uterine anomalies - septate, unicornuate, bicornuate uterus; acquired defects of the uterus structure - fibroids, polyps, hypertrophy), disturbed hormonal cycle and obstruction of the fallopian tubes resulting from the presence of adhesions due to inflammation, endometriosis, and surgery, abnormal rhythm of menstrual bleeding, the abnormal concentration of hormones. There are many relationships between the endocrine organs, leading to a chain reaction when one of them fails to function properly. Conditions in which the immune system is involved, including infections and autoimmune diseases, also affect fertility. The form of treatment depends on infertility duration and the patient's age. It includes ovulation stimulation with clomiphene citrate or gonadotropins, metformin use, and weight loss interventions. Since so many different factors affect fertility, it is important to correctly diagnose what is causing the problem and to modify the treatment regimen if necessary. This review describes disturbances in the hormone secretion of individual endocrine organs in the context of fertility and the maintenance of pregnancy.
Collapse
Affiliation(s)
- Anna Bendarska-Czerwińska
- Department of Molecular, Biology Gyncentrum Fertility Clinic, Katowice, Poland
- Faculty of Medicine, Academy of Silesia, Zabrze, Poland
- American Medical Clinic, Katowice, Poland
- *Correspondence: Anna Bendarska-Czerwińska, ; Nikola Zmarzły, ; Beniamin Oskar Grabarek,
| | - Nikola Zmarzły
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
- *Correspondence: Anna Bendarska-Czerwińska, ; Nikola Zmarzły, ; Beniamin Oskar Grabarek,
| | - Emilia Morawiec
- Department of Molecular, Biology Gyncentrum Fertility Clinic, Katowice, Poland
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
- Department of Microbiology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
| | - Agata Panfil
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
| | - Kamil Bryś
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
| | - Justyna Czarniecka
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
| | | | | | - Dorota Sagan
- Medical Center Dormed Medical SPA, Busko-Zdroj, Poland
| | - Dariusz Boroń
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
- Department of Gynaecology and Obstetrics, Faculty of Medicine, Academy of Silesia, Zabrze, Poland
- Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Kraków, Poland
- Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, Katowice, Poland
| | | | | | - Beniamin Oskar Grabarek
- Department of Molecular, Biology Gyncentrum Fertility Clinic, Katowice, Poland
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, Zabrze, Poland
- Department of Gynaecology and Obstetrics, Faculty of Medicine, Academy of Silesia, Zabrze, Poland
- Department of Gynecology and Obstetrics with Gynecologic Oncology, Ludwik Rydygier Memorial Specialized Hospital, Kraków, Poland
- Department of Gynecology and Obstetrics, TOMMED Specjalisci od Zdrowia, Katowice, Poland
- *Correspondence: Anna Bendarska-Czerwińska, ; Nikola Zmarzły, ; Beniamin Oskar Grabarek,
| |
Collapse
|
38
|
Verlinden L, Carmeliet G. Integrated View on the Role of Vitamin D Actions on Bone and Growth Plate Homeostasis. JBMR Plus 2021; 5:e10577. [PMID: 34950832 PMCID: PMC8674772 DOI: 10.1002/jbm4.10577] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 10/22/2021] [Accepted: 10/31/2021] [Indexed: 12/12/2022] Open
Abstract
1,25(OH)2D3, the biologically active form of vitamin D3, is a major regulator of mineral and bone homeostasis and exerts its actions through binding to the vitamin D receptor (VDR), a ligand‐activated transcription factor that can directly modulate gene expression in vitamin D‐target tissues such as the intestine, kidney, and bone. Inactivating VDR mutations or vitamin D deficiency during development results in rickets, hypocalcemia, secondary hyperparathyroidism, and hypophosphatemia, pointing to the critical role of 1,25(OH)2D3‐induced signaling in the maintenance of mineral homeostasis and skeletal health. 1,25(OH)2D3 is a potent stimulator of VDR‐mediated intestinal calcium absorption, thus increasing the availability of calcium required for proper bone mineralization. However, when intestinal calcium absorption is impaired, renal calcium reabsorption is increased and calcium is mobilized from the bone to preserve normocalcemia. Multiple cell types within bone express the VDR, thereby allowing 1,25(OH)2D3 to directly affect bone homeostasis. In this review, we will discuss different transgenic mouse models with either Vdr deletion or overexpression in chondrocytes, osteoblasts, osteocytes, or osteoclasts to delineate the direct effects of 1,25(OH)2D3 on bone homeostasis. We will address the bone cell type–specific effects of 1,25(OH)2D3 in conditions of a positive calcium balance, where the amount of (re)absorbed calcium equals or exceeds fecal and renal calcium losses, as well as during a negative calcium balance, due to selective Vdr knockdown in the intestine or triggered by a low calcium diet. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Lieve Verlinden
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism KU Leuven Leuven Belgium
| | - Geert Carmeliet
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism KU Leuven Leuven Belgium
| |
Collapse
|
39
|
Meyer-Binzegger M, Ollagnier C, Eggerschwiler L, Bühler K, Meylan M, Schlegel P. Potential of a rumen bolus containing 1,25-dihydroxyvitamin D 3 glycosides for the prevention of hypocalcaemia in primiparous and multiparous dairy cows. Animal 2021; 16:100414. [PMID: 34890956 DOI: 10.1016/j.animal.2021.100414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 11/02/2021] [Accepted: 11/04/2021] [Indexed: 11/30/2022] Open
Abstract
Periparturient hypocalcaemia is a widespread metabolic disorder in dairy cows. Clinical and subclinical cases occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive strategy was investigated by administering the physiologically active vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) as a rumen bolus. The bolus contained tablets of 1,25(OH)2D3 glycoside extract from Solanum glaucophyllum (SGE), releasing SGE over several days. The aim was to study the effect of a bolus containing 0 (C) or 500 µg (SGE) of 1,25(OH)2D3 on 1,25(OH)2D3 and mineral status in periparturient cows up to three weeks into lactation and on colostrum, milk and calves' blood mineral contents. The bolus was administered three to four days prior to expected calving to Primi and Multi cows fed a herbage-based diet (dietary cation-anion difference of +522 mEq/kg DM). One C or SGE bolus was applied to 12 Primi and 12 Multi cows. Blood was regularly sampled (and selected a posteriori for antepartum samples) in regard to the actual calving day (d0), immediately prior to bolus application and at day -2, 0.5, 1, 1.5, 2, 4, 8, 11, 15, 18 and 22. Additional samples included urine (at bolus application, d0.5 and d2), colostrum, milk samples (weekly) and calves' blood (d2). Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE was increased on d2, indicating regulation of Ca excess. Three Multi-C cows with confirmed clinical hypocalcaemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased while Ca dropped by 40% between d0.5 and d2 in Multi-C, whereas 1,25(OH)2D3, Ca and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Mineral contents in colostrum, milk and blood serum of calves were not influenced to a relevant degree. In conclusion, Primi-C did not, in contrast to Multi-C, develop subclinical hypocalcaemia (<2.0 mmol Ca/l). Prevention of hypocalcaemia with one SGE bolus applied three to four days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over the critical first two days and up to the first three weeks of lactation, without any observed detrimental effects on cows or calves.
Collapse
Affiliation(s)
- M Meyer-Binzegger
- Agroscope, Ruminant Research Unit, Tioleyre 4, 1725 Posieux, Switzerland; Clinic for Ruminants, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109, 3012 Bern, Switzerland
| | - C Ollagnier
- Agroscope, Ruminant Research Unit, Tioleyre 4, 1725 Posieux, Switzerland
| | - L Eggerschwiler
- Agroscope, Ruminant Research Unit, Tioleyre 4, 1725 Posieux, Switzerland
| | - K Bühler
- Herbonis Animal Health GmbH, Rheinstrasse 30, 4302 Augst, Switzerland
| | - M Meylan
- Clinic for Ruminants, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109, 3012 Bern, Switzerland
| | - P Schlegel
- Agroscope, Ruminant Research Unit, Tioleyre 4, 1725 Posieux, Switzerland.
| |
Collapse
|
40
|
Cwiek A, Suzuki M, deRonde K, Conaway M, Bennett KM, El Dahr S, Reidy KJ, Charlton JR. Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth. Sci Rep 2021; 11:21667. [PMID: 34737344 PMCID: PMC8569166 DOI: 10.1038/s41598-021-00489-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 10/05/2021] [Indexed: 12/31/2022] Open
Abstract
Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.
Collapse
Affiliation(s)
- Aleksandra Cwiek
- Division of Nephrology, Department of Pediatrics, University of Virginia, Box 800386, Charlottesville, VA, 22903, USA
- Cell & Developmental Biology Graduate Program, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA
| | - Masako Suzuki
- Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA
| | - Kimberly deRonde
- Division of Nephrology, Department of Pediatrics, University of Virginia, Box 800386, Charlottesville, VA, 22903, USA
| | - Mark Conaway
- University of Virginia Health System, Charlottesville, VA, USA
- Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Kevin M Bennett
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Samir El Dahr
- Department of Pediatrics, Tulane University School of Medicine and Children's Hospital of New Orleans, New Orleans, LA, USA
| | - Kimberly J Reidy
- Division of Nephrology, Department of Pediatrics, Children's Hospital at Montefiore, New York, NY, USA
| | - Jennifer R Charlton
- Division of Nephrology, Department of Pediatrics, University of Virginia, Box 800386, Charlottesville, VA, 22903, USA.
| |
Collapse
|
41
|
Stoss therapy is safe for treatment of vitamin D deficiency in pediatric patients undergoing HSCT. Bone Marrow Transplant 2021; 56:2137-2143. [PMID: 33875811 DOI: 10.1038/s41409-021-01294-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 03/10/2021] [Accepted: 03/30/2021] [Indexed: 02/05/2023]
Abstract
Vitamin D deficiency remains common among pediatric patients undergoing hematopoietic stem cell transplant (HSCT) despite both aggressive and standard of care strategies. This study examined the safety and efficacy of single high-dose oral vitamin D therapy (Stoss therapy) for treatment of vitamin D deficiency in HSCT recipients. Patients ages 1-21 years presenting for HSCT were randomized to receive either Stoss regimen plus weekly/daily supplementation or standard of care, per US Endocrine Society guidelines. Among the total 48 subjects, 22 (46%) were randomized to Stoss and 26 (54%) to control arms. Baseline 25-hydroxyvitamin D (25-OHD) levels were insufficient/deficient in total of 34 (71%) patients, without difference between treatment groups. The Stoss regimen was well tolerated and no toxicity was observed. At Day +30, mean 25-OHD levels were significantly higher (P = 0.04) with Stoss (42.3 ± 12 μg/l) compared to controls (35.6 ± 14.3 μg/l), and a higher proportion of Stoss patients had adequate vitamin D levels than controls (85% vs 65%). Stoss therapy is a safe and efficacious treatment option for vitamin D deficiency in children undergoing HSCT and may achieve sufficient levels more rapidly than standard of care. This trial was registered at www.clinicaltrials.gov as NCT03176849.
Collapse
|
42
|
Dahir K, Zanchetta MB, Stanciu I, Robinson C, Lee JY, Dhaliwal R, Charles J, Civitelli R, Roberts MS, Krolczyk S, Weber T. Diagnosis and Management of Tumor-induced Osteomalacia: Perspectives From Clinical Experience. J Endocr Soc 2021; 5:bvab099. [PMID: 34286168 PMCID: PMC8282217 DOI: 10.1210/jendso/bvab099] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Indexed: 01/12/2023] Open
Abstract
Purpose Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of abnormal phosphate and vitamin D metabolism caused by typically small endocrine tumors that secrete fibroblast growth factor 23 (FGF23). TIO is characterized clinically by progressive musculoskeletal pain, fatigue, proximal muscle weakness, and multiple fractures, leading to long-term disability. Misdiagnosis and delayed diagnosis are common because of the nonspecific symptoms, and several years may elapse before patients receive an accurate diagnosis and appropriate treatment. Thus, it is vital that awareness of the appropriate recognition and management of TIO is increased among healthcare professionals who may encounter patients with suspected TIO. Methods A roundtable meeting was held on 10 January 2020 in Dallas, TX, USA, to gather perspectives on the diagnosis and treatment of TIO. The following topics were considered: clinical presentation, patient history, differential diagnosis, laboratory assessment, imaging, venous sampling, and treatment. Results This report provides a summary of our collective experiences in the management of TIO. Main conclusions Laboratory tests are mandatory to expedite TIO diagnosis and should include measurement of fasting serum phosphorus, renal phosphate reabsorption, serum 1,25-dihydroxyvitamin D, and serum FGF23 levels. Functional and anatomical imaging are essential to locate the FGF23-secreting tumor(s) causing TIO. Surgical resection is often a curative treatment when the tumor can be localized; however, better management of patients who cannot be operated on with targeted therapies is needed. Further efforts to increase awareness of TIO within the medical community, and education on recommended diagnostic and treatment pathways are required to improve the management of this debilitating disease.
Collapse
Affiliation(s)
- Kathryn Dahir
- Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | | | - Irinel Stanciu
- Panorama Orthopedics and Spine Center, Golden, CO 80401, USA
| | - Cemre Robinson
- Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Janet Y Lee
- University of California, San Francisco, CA 94143, USA
| | - Ruban Dhaliwal
- State University of New York Upstate Medical University, Syracuse, NY 13210, USA
| | - Julia Charles
- Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | | | | | - Stan Krolczyk
- Ultragenyx Pharmaceutical Inc., Novato, CA 94949, USA
| | - Thomas Weber
- Duke University School of Medicine, Durham, NC 27710, USA
| |
Collapse
|
43
|
Dodhia SA, West NX, Thomas SJ, Timpson NJ, Johansson I, Lif Holgerson P, Dudding T, Haworth S. Examining the causal association between 25-hydroxyvitamin D and caries in children and adults: a two-sample Mendelian randomization approach. Wellcome Open Res 2021; 5:281. [PMID: 34386609 PMCID: PMC8327219 DOI: 10.12688/wellcomeopenres.16369.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2021] [Indexed: 11/20/2022] Open
Abstract
Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome. Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years). Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68) Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries.
Collapse
Affiliation(s)
- Serena A. Dodhia
- Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK
| | - Nicola X. West
- Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK
| | - Steven J. Thomas
- Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK
| | - Nicholas J. Timpson
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 2BN, UK
- Avon Longitudinal Study of Parents and Children, University of Bristol, Bristol, UK
| | - Ingegerd Johansson
- Department of Odontology, Section of Cariology, Umea University, Umeå, Sweden
| | | | - Tom Dudding
- Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 2BN, UK
| | - Simon Haworth
- Bristol Dental School, University of Bristol, Bristol, BS1 2LY, UK
- Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, BS8 2BN, UK
| |
Collapse
|
44
|
Glaspy JA, Wolf M, Strauss WE. Intravenous Iron-Induced Hypophosphatemia: An Emerging Syndrome. Adv Ther 2021; 38:3531-3549. [PMID: 34053011 PMCID: PMC8279965 DOI: 10.1007/s12325-021-01770-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 04/30/2021] [Indexed: 12/14/2022]
Abstract
Some, but not all, intravenous iron formulations have been recognized to induce renal phosphate wasting syndrome. Most commonly this has been reported following treatment of iron deficiency anemia (IDA) with ferric carboxymaltose (FCM). A search of PubMed identified relevant randomized controlled trials (RCTs), and case studies evaluating hypophosphatemia (HPP) resulting from intravenous iron treatment. While more recent larger comparative RCTs have confirmed that the majority of patients receiving FCM, especially those with normal renal function, may experience severe HPP, complete documentation is hampered by inconsistent reporting of serum phosphate in such trials. Similarly, while case series and RCTs have documented the persistence of HPP for several weeks or even months, the lack of studies lasting beyond 5–6 weeks has constrained full understanding of the duration of effect. Clinical trials have established that the mechanism involves the bone/metabolic axis with the elevation of intact fibroblast growth factor 23 playing the central role. Reports continue to accumulate of the clinical consequences of severe HPP which are, most commonly, bone abnormalities following repetitive dosing. Case reports and studies, however, have also shown that symptomatic hypophosphatemia can occur after a single FCM dose. The frequency of such events remains unknown, in part due to lack of awareness of hypophosphatemia coupled with the fact that the most common acute symptoms of HPP (fatigue and weakness) are the same for IDA and for many of the chronic diseases that cause IDA. Changes to US and European prescribing information for FCM should raise awareness of the potential for HPP and need to monitor patients at risk for it.
Collapse
Affiliation(s)
- John A Glaspy
- Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine, Los Angeles, CA, 90095, USA.
| | - Myles Wolf
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | | |
Collapse
|
45
|
Blumenstein I, Shanbhag S, Langguth P, Kalra PA, Zoller H, Lim W. Newer formulations of intravenous iron: a review of their chemistry and key safety aspects - hypersensitivity, hypophosphatemia, and cardiovascular safety. Expert Opin Drug Saf 2021; 20:757-769. [PMID: 33993818 DOI: 10.1080/14740338.2021.1912010] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: The newest intravenous (IV) iron products show an improved safety profile over predecessors, allowing for the rapid administration of relatively high doses. Ferric derisomaltose (FDI; also known as iron isomaltoside), ferric carboxymaltose (FCM), and ferumoxytol (FER), are successful treatments for iron deficiency (Europe; FDI and FCM) and iron deficiency anemia (US; FDI, FCM, and FER).Areas covered: This review focusses on the chemistry and structure of FDI, FCM, and FER, and on three key aspects of IV iron safety: (1) hypersensitivity; (2) hypophosphatemia and sequelae; (3) cardiovascular safety.Expert opinion: Although the safety of modern IV iron has improved, immediate infusion reactions and the development of hypophosphatemia must be appreciated and recognized by those who prescribe and administer IV iron. Immediate infusion reactions can occur with any IV iron and are usually mild; severe reactions - particularly anaphylaxis - are extremely rare. The recognition and appropriate management of infusion reactions is an important consideration to the successful administration of IV iron. Severe, persistent, hypophosphatemia is a specific side effect of FCM. No cardiovascular safety signal has been identified for IV iron. Ongoing trials in heart failure will provide additional long-term efficacy and safety data.
Collapse
Affiliation(s)
- Irina Blumenstein
- Medical Department 1, Department of Gastroenterology, Hepatology, and Clinical Nutrition, University Clinic Frankfurt, Frankfurt, Germany
| | - Satish Shanbhag
- Department of Hematology/Medical Oncology, Cancer Specialists of North Florida, Fleming Island, FL, USA.,Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MA, USA
| | - Peter Langguth
- Institute of Pharmacy and Biochemistry, Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University, Mainz, Germany
| | - Philip A Kalra
- Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Heinz Zoller
- Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Wendy Lim
- Department of Medicine, Division of Hematology and Thromboembolism, St. Joseph's Healthcare Hamilton, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
46
|
Detlie TE, Lindstrøm JC, Jahnsen ME, Finnes E, Zoller H, Moum B, Jahnsen J. Hypophosphatemia after high-dose intravenous iron treatment in patients with inflammatory bowel disease: Mechanisms and possible clinical impact. World J Gastroenterol 2021; 27:2039-2053. [PMID: 34007138 PMCID: PMC8108035 DOI: 10.3748/wjg.v27.i17.2039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/19/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND High-dose intravenous iron is an effective treatment option for iron deficiency (ID) or ID anaemia (IDA) in inflammatory bowel disease (IBD). However, treatment with ferric carboxymaltose (FCM) has been associated with the development of hypophosphatemia.
AIM To investigate mechanisms behind the development of hypophosphatemia after intravenous iron treatment, and disclose symptoms and clinical manifestations related to hypophosphatemia short-term.
METHODS A prospective observational study of adult IBD patients with ID or IDA was conducted between February 1, 2017 and July 1, 2018 at two separate university hospitals in the southeast region of Norway. Patients received one dose of 1000 mg of either FCM or ferric derisomaltose (FDI) and were followed for an observation period of at least 7 wk. Blood and urine samples were collected for relevant analyses at baseline, week 2 and at week 6. Clinical symptoms were assessed at the same timepoints using a respiratory function test, a visual analogue scale, and a health-related quality of life questionnaire.
RESULTS A total of 106 patients was available for analysis in this study. The FCM treatment group consisted of 52 patients and hypophosphatemia was present in 72.5% of the patients at week 2, and in 21.6% at week 6. In comparison, the FDI treatment group consisted of 54 patients and 11.3% of the patients had hypophosphatemia at week 2, and 3.7% at week 6. The difference in incidence was highly significant at both week 2 and 6 (P < 0.001 and P < 0.013, respectively). We observed a significantly higher mean concentration of intact fibroblast growth factor 23 (P < 0.001), a significant rise in mean urine fractional excretion of phosphate (P = 0.004), a significant decrease of 1,25-dihydroxyvitamin D (P < 0.001) and of ionised calcium levels (P < 0.012) in the FCM-treated patients compared with patients who received FDI. No clinical symptoms could with certainty be related to hypophosphatemia, since neither the respiratory function test, SF-36 (36-item short form health survey) or the visual analogue scale scores resulted in significant differences between patients who developed hypophosphatemia or not.
CONCLUSION Fibroblast growth factor 23 has a key role in FCM induced hypophosphatemia, probably by inducing loss of phosphate in the urine. Short-term clinical impact of hypophosphatemia was not demonstrated.
Collapse
Affiliation(s)
- Trond Espen Detlie
- Department of Gastroenterology, Akershus University Hospital, Lørenskog 1478, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo 0316, Norway
| | - Jonas Christoffer Lindstrøm
- Institute of Clinical Medicine, University of Oslo, Oslo 0316, Norway
- Health Services Research Unit, Akershus University Hospital, Lørenskog 1478, Norway
| | - Marte Eide Jahnsen
- Department of Gastroenterology, Akershus University Hospital, Lørenskog 1478, Norway
| | - Elisabeth Finnes
- Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo 0424, Norway
| | - Heinz Zoller
- Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck A-6020, Austria
| | - Bjørn Moum
- Institute of Clinical Medicine, University of Oslo, Oslo 0316, Norway
- Division of Medicine, Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo 0424, Norway
| | - Jørgen Jahnsen
- Department of Gastroenterology, Akershus University Hospital, Lørenskog 1478, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo 0316, Norway
| |
Collapse
|
47
|
Kulesza T, Piwkowska A. The impact of type III sodium-dependent phosphate transporters (Pit 1 and Pit 2) on podocyte and kidney function. J Cell Physiol 2021; 236:7176-7185. [PMID: 33738792 DOI: 10.1002/jcp.30368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 02/26/2021] [Accepted: 03/04/2021] [Indexed: 01/07/2023]
Abstract
The sodium-dependent phosphate transporters Pit 1 and Pit 2 belong to the solute carrier 20 (SLC20) family of membrane proteins. They are ubiquitously distributed in the human body. Their crucial function is the intracellular transport of inorganic phosphate (Pi) in the form of H2 PO4 - . They are one of the main elements in maintaining physiological phosphate homeostasis. Recent data have emerged that indicate novel roles of Pit 1 and Pit 2 proteins besides the well-known function of Pi transporters. These membrane proteins are believed to be precise phosphate sensors that mediate Pi-dependent intracellular signaling. They are also involved in insulin signaling and influence cellular insulin sensitivity. In diseases that are associated with hyperphosphatemia, such as diabetes and chronic kidney disease (CKD), disturbances in the function of Pit 1 and Pit 2 are observed. Phosphate transporters from the SLC20 family participate in the calcification of soft tissues, mainly blood vessels, during the course of CKD. The glomerulus and podocytes therein can also be a target of pathological calcification that damages these structures. A few studies have demonstrated the development of Pi-dependent podocyte injury that is mediated by Pit 1 and Pit 2. This paper discusses the role of Pit 1 and Pit 2 proteins in podocyte function, mainly in the context of the development of pathological calcification that disrupts permeability of the renal filtration barrier. We also describe the mechanisms that may contribute to podocyte damage by Pit 1 and Pit 2.
Collapse
Affiliation(s)
- Tomasz Kulesza
- Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
| | - Agnieszka Piwkowska
- Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
| |
Collapse
|
48
|
Stenhouse C, Halloran KM, Newton MG, Gaddy D, Suva LJ, Bazer FW. Novel mineral regulatory pathways in ovine pregnancy: I. phosphate, klotho signaling, and sodium-dependent phosphate transporters. Biol Reprod 2021; 104:1084-1096. [PMID: 33624764 DOI: 10.1093/biolre/ioab028] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/25/2021] [Accepted: 02/12/2021] [Indexed: 12/30/2022] Open
Abstract
Appropriate mineralization of the fetal skeleton requires an excess of phosphate in the fetus compared to the mother. However, mechanisms for placental phosphate transport are poorly understood. This study aimed to identify phosphate regulatory pathways in ovine endometria and placentae throughout gestation. Suffolk ewes were bred with fertile rams upon visual detection of estrus (Day 0). On Days 9, 12, 17, 30, 70, 90, 110, and 125 of pregnancy (n = 3-14/Day), ewes were euthanized and hysterectomized. Phosphate abundance varied across gestational days in uterine flushings, allantoic fluid, and homogenized endometria and placentae (P < 0.05). The expression of mRNAs for sodium-dependent phosphate transporters (SLC20A1 and SLC20A2) and klotho signaling mediators (FGF7, FGF21, FGF23, FGFR1-4, KL, KLB, ADAM10, and ADAM17) were quantified by qPCR. Day 17 conceptus tissue expressed SLC20A1, SLC20A2, KLB, FGF7, FGF21, FGF23, FGFR1, and FGFR2 mRNAs. Both sodium-dependent phosphate transporters and klotho signaling mediators were expressed in endometria and placentae throughout gestation. Gestational day influenced the expression of SLC20A1, ADAM10, ADAM17, FGF21, FGFR1, and FGFR3 mRNAs in both endometria and placentae (P < 0.05). Gestational day influenced endometrial expression of FGF7 (P < 0.001), and placental expression of FGF23 (P < 0.05). Immunohistochemistry confirmed that both FGF23 and KL proteins were expressed in endometria and placentae throughout gestation. The observed spatiotemporal profile of KL-FGF signaling suggests a potential role in the establishment of pregnancy and regulation of fetal growth. This study provides a platform for further mechanistic investigation into the role for KL-FGF signaling in the regulation of phosphate transport at the ovine maternal-conceptus interface.
Collapse
Affiliation(s)
- Claire Stenhouse
- Departments of Animal Science, Texas A&M University, College Station, Texas, USA
| | - Katherine M Halloran
- Departments of Animal Science, Texas A&M University, College Station, Texas, USA
| | - Makenzie G Newton
- Departments of Animal Science, Texas A&M University, College Station, Texas, USA
| | - Dana Gaddy
- Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas, USA
| | - Larry J Suva
- Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas, USA
| | - Fuller W Bazer
- Departments of Animal Science, Texas A&M University, College Station, Texas, USA
| |
Collapse
|
49
|
Forget the phosphorus: A case of hypervitaminosis D-induced symptomatic hypercalcemia. Clin Nephrol Case Stud 2021; 9:1-3. [PMID: 33614397 PMCID: PMC7890937 DOI: 10.5414/cncs110414] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 11/24/2020] [Indexed: 12/25/2022] Open
Abstract
Hypercalcemia is a frequently encountered electrolyte abnormality with a well-described differential diagnosis and classic algorithm for evaluation. The treatment for hypercalcemia is dependent on the underlying etiology. Hypervitaminosis D is an uncommon cause of hypercalcemia, but the use of vitamin D supplementation has expanded and case reports of supplemental vitamin D induced hypercalcemia have become more frequent. We present a case of hypervitaminosis D-induced altered mental status where diagnosis was delayed and additional invasive testing was performed due to an assumption regarding phosphatemia.
Collapse
|
50
|
Chacar FC, Kogika MM, Zafalon RVA, Brunetto MA. Vitamin D Metabolism and Its Role in Mineral and Bone Disorders in Chronic Kidney Disease in Humans, Dogs and Cats. Metabolites 2020; 10:E499. [PMID: 33291777 PMCID: PMC7761928 DOI: 10.3390/metabo10120499] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/21/2020] [Accepted: 11/24/2020] [Indexed: 11/17/2022] Open
Abstract
Some differences regarding Vitamin D metabolism are described in dogs and cats in comparison with humans, which may be explained by an evolutionary drive among these species. Similarly, vitamin D is one of the most important regulators of mineral metabolism in dogs and cats, as well as in humans. Mineral metabolism is intrinsically related to bone metabolism, thus disturbances in vitamin D have been implicated in the development of chronic kidney disease mineral and bone disorders (CKD-MBD) in people, in addition to dogs and cats. Vitamin D deficiency may be associated with Renal Secondary Hyperparathyroidism (RSHPT), which is the most common mineral disorder in later stages of CKD in dogs and cats. Herein, we review the peculiarities of vitamin D metabolism in these species in comparison with humans, and the role of vitamin D disturbances in the development of CKD-MBD among dogs, cats, and people. Comparative studies may offer some evidence to help further research about vitamin D metabolism and bone disorders in CKD.
Collapse
Affiliation(s)
- Fernanda C. Chacar
- Department of Internal Medicine, Federal Institute of Education, Science and Technology of South of Minas Gerais (IFSULDEMINAS), Muzambinho 37890-000, Brazil;
| | - Márcia M. Kogika
- Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of Sao Paulo, Sao Paulo 05508-270, Brazil;
| | - Rafael V. A. Zafalon
- Pet Nutrology Research Center, Nutrition and Production Department, School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga 13635-900, Brazil;
| | - Marcio A. Brunetto
- Pet Nutrology Research Center, Nutrition and Production Department, School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga 13635-900, Brazil;
| |
Collapse
|