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Shetty S, Ravindra S, Acharya H, Rao SK. A mysterious case of recurrent fracture: Tumour-induced osteomalacia. J Family Med Prim Care 2022; 11:1204-1207. [PMID: 35495830 PMCID: PMC9051695 DOI: 10.4103/jfmpc.jfmpc_947_21] [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: 05/22/2021] [Revised: 10/08/2021] [Accepted: 10/29/2021] [Indexed: 11/06/2022] Open
Abstract
We report a case of tumour-induced osteomalacia in a 59-year-old man who presented with a long-standing history of myalgia, bone pain and pathological fracture of the bilateral femur at different intervals in the past 4 years. A biochemical evaluation revealed hypophosphatemia secondary to phosphaturia. Localization study by Ga-68 DOTANOC PET-CT for adult-onset hypophosphatemic osteomalacia revealed a tumour in the right femoral head. Resection of the tumour resulted in clinical improvement as well as normalization of biochemical parameters.
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Affiliation(s)
- Sahana Shetty
- Department of Endocrinology, Kasturba Medical College, Manipal Academy of Higher Education, MAHE, Manipal, Karnataka, India
| | - Shruthi Ravindra
- Department of Endocrinology, Kasturba Medical College, Manipal Academy of Higher Education, MAHE, Manipal, Karnataka, India
| | - Himamshu Acharya
- Department of Endocrinology, Kasturba Medical College, Manipal Academy of Higher Education, MAHE, Manipal, Karnataka, India
| | - Sharath K Rao
- Department of Orthopaedics, Kasturba Medical College, Manipal Academy of Higher Education, MAHE, Manipal, Karnataka, India
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Aligail K, Dave JA, Ross IL. Tumor-induced osteomalacia: a case report. J Med Case Rep 2022; 16:22. [PMID: 35016725 PMCID: PMC8752187 DOI: 10.1186/s13256-021-03220-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 12/03/2021] [Indexed: 11/30/2022] Open
Abstract
Background Tumor-induced osteomalacia is a rare, acquired paraneoplastic syndrome, including hypophosphatemia, high serum alkaline phosphatase, reduced active vitamin D, suboptimal bone mineral density, bone pain, fragility fractures, and muscle weakness. Case presentation We report a case of 74–year–old male of mixed ancestry with hypophosphatemia resistant to treatment despite optimal compliance, associated with profound reduction of bone mineral density and multiple nontraumatic fractures, including bilateral rib fractures, lower-thoracic (T11, T12) vertebrae, and two fractures involving the surgical and anatomical neck of the right humerus. We discuss an approach to identifying the underlying cause of hypophosphatemia associated with fragility fractures, and options for management of this rare condition. Conclusion Although rare, tumor-induced osteomalacia can be diagnosed if a logical stepwise approach is implemented. Surgery could be curative if the tumor is properly located and is resectable.
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Affiliation(s)
- Khalid Aligail
- Division of Endocrinology, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital and University of Cape Town, J47-85 Old Main Building, Private Bag X3, Observatory, Cape Town, 7935, South Africa
| | - Joel A Dave
- Division of Endocrinology, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital and University of Cape Town, J47-85 Old Main Building, Private Bag X3, Observatory, Cape Town, 7935, South Africa
| | - Ian Louis Ross
- Division of Endocrinology, Department of Medicine, Faculty of Health Sciences, Groote Schuur Hospital and University of Cape Town, J47-85 Old Main Building, Private Bag X3, Observatory, Cape Town, 7935, South Africa.
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Yang M, Doshi KB, Roarke MC, Nguyen BD. Molecular Imaging in Diagnosis of Tumor-induced Osteomalacia. Curr Probl Diagn Radiol 2019; 48:379-386. [DOI: 10.1067/j.cpradiol.2018.06.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 05/31/2018] [Accepted: 06/20/2018] [Indexed: 11/22/2022]
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Jacquillet G, Unwin RJ. Physiological regulation of phosphate by vitamin D, parathyroid hormone (PTH) and phosphate (Pi). Pflugers Arch 2019; 471:83-98. [PMID: 30393837 PMCID: PMC6326012 DOI: 10.1007/s00424-018-2231-z] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 10/20/2018] [Accepted: 10/25/2018] [Indexed: 01/05/2023]
Abstract
Inorganic phosphate (Pi) is an abundant element in the body and is essential for a wide variety of key biological processes. It plays an essential role in cellular energy metabolism and cell signalling, e.g. adenosine and guanosine triphosphates (ATP, GTP), and in the composition of phospholipid membranes and bone, and is an integral part of DNA and RNA. It is an important buffer in blood and urine and contributes to normal acid-base balance. Given its widespread role in almost every molecular and cellular function, changes in serum Pi levels and balance can have important and untoward effects. Pi homoeostasis is maintained by a counterbalance between dietary Pi absorption by the gut, mobilisation from bone and renal excretion. Approximately 85% of total body Pi is present in bone and only 1% is present as free Pi in extracellular fluids. In humans, extracellular concentrations of inorganic Pi vary between 0.8 and 1.2 mM, and in plasma or serum Pi exists in both its monovalent and divalent forms (H2PO4- and HPO42-). In the intestine, approximately 30% of Pi absorption is vitamin D regulated and dependent. To help maintain Pi balance, reabsorption of filtered Pi along the renal proximal tubule (PT) is via the NaPi-IIa and NaPi-IIc Na+-coupled Pi cotransporters, with a smaller contribution from the PiT-2 transporters. Endocrine factors, including, vitamin D and parathyroid hormone (PTH), as well as newer factors such as fibroblast growth factor (FGF)-23 and its coreceptor α-klotho, are intimately involved in the control of Pi homeostasis. A tight regulation of Pi is critical, since hyperphosphataemia is associated with increased cardiovascular morbidity in chronic kidney disease (CKD) and hypophosphataemia with rickets and growth retardation. This short review considers the control of Pi balance by vitamin D, PTH and Pi itself, with an emphasis on the insights gained from human genetic disorders and genetically modified mouse models.
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Affiliation(s)
- Grégory Jacquillet
- Centre for Nephrology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK
| | - Robert J Unwin
- Centre for Nephrology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
- AstraZeneca IMED ECD CVRM R&D, Gothenburg, Sweden.
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Yin Z, Du J, Yu F, Xia W. Tumor-induced osteomalacia. Osteoporos Sarcopenia 2018; 4:119-127. [PMID: 30775554 PMCID: PMC6372818 DOI: 10.1016/j.afos.2018.12.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 12/02/2018] [Accepted: 12/04/2018] [Indexed: 12/30/2022] Open
Abstract
Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.
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Affiliation(s)
| | | | | | - Weibo Xia
- Department of Endocrinology, Key Laboratory of Endocrinology, The National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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Aniteli TM, de Siqueira FR, Dos Reis LM, Dominguez WV, de Oliveira EMC, Castelucci P, Moysés RMA, Jorgetti V. Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi-IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE). Pflugers Arch 2018; 470:623-632. [PMID: 29372301 DOI: 10.1007/s00424-018-2111-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 01/10/2018] [Accepted: 01/11/2018] [Indexed: 11/29/2022]
Abstract
Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (Pi) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent Pi absorption is modulated by dietary Pi. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary Pi concentration over 2 days would alter hormones involved in Pi metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LPi), normal (Nx/NPi), and high (Nx/HPi). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HPi group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LPi group compared with the Nx/HPi group. Modification of Pi concentration in the diet affected the apoptosis of enterocytes, particularly with Pi overload. MEPE expression was higher in the Nx/HPi group than in the Nx/NPi. These data reveal the importance of early control of Pi in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.
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Affiliation(s)
| | | | | | | | | | - Patrícia Castelucci
- Department of Anatomy, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil
| | - Rosa Maria Affonso Moysés
- Medical School, Division of Nephrology, Universidade de São Paulo, São Paulo, Brazil.,Universidade Nove de Julho - UNINOVE, São Paulo, Brazil
| | - Vanda Jorgetti
- Medical School, Division of Nephrology, Universidade de São Paulo, São Paulo, Brazil. .,Faculdade de Medicina, Serviço de Nefrologia, Universidade de São Paulo, Av. Dr. Arnaldo, 455, 3° andar, sala 3342, São Paulo, SP, 01246-903, Brazil.
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7
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Bishay RH, Ganda K, Seibel MJ. Long-term iron polymaltose infusions associated with hypophosphataemic osteomalacia: a report of two cases and review of the literature. Ther Adv Endocrinol Metab 2017; 8:14-19. [PMID: 28203361 PMCID: PMC5298444 DOI: 10.1177/2042018816678363] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Iron-induced hypophosphataemic osteomalacia remains under-recognized as a potential complication of parenteral iron therapy. We here report two cases of symptomatic hypophosphataemic osteomalacia with multiple insufficiency fractures in the context of chronic gastrointestinal blood loss, necessitating monthly iron polymaltose infusions over prolonged periods of time. Respective blood tests revealed severe hypophosphataemia [0.29 and 0.43; normal range (NR) 0.8-1.5 mmol/l] in the presence of normal serum calcium and 25-hydroxy vitamin D levels. Urinary fractional phosphate excretion was elevated (16% and 24%; NR < 5%) and the tubular maximum phosphate reabsorption was reduced, consistent with renal phosphate wasting. Serum fibroblast growth factor 23 (FGF23) obtained in one patient was significantly elevated at 285 pg/ml (NR < 54 pg/ml). Bone mineral density was significantly reduced and whole-body bone scans revealed metabolic bone disease and multiple insufficiency fractures consistent with osteomalacia. Cessation of iron infusions resulted in clinical and biochemical improvement within 2 months in one patient whereas the second patient required phosphate and calcitriol supplementation to improve symptomatically. Iron-induced hypophosphataemic osteomalacia is thought to be due to reduced degradation of FGF23, resulting in phosphaturia and reduced synthesis of 1,25-dihydroxy vitamin D. Monitoring of patients on long-term parenteral iron is recommended to avoid clinically serious adverse effects.
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Affiliation(s)
| | - Kirtan Ganda
- Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, NSW, Australia
- Concord Clinical School, Sydney Medical School, University of Sydney, NSW, Australia
| | - Markus J. Seibel
- Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, NSW, Australia
- Concord Clinical School, Sydney Medical School, University of Sydney, NSW, Australia
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Kasiske BL, Kumar R, Kimmel PL, Pesavento TE, Kalil RS, Kraus ES, Rabb H, Posselt AM, Anderson-Haag TL, Steffes MW, Israni AK, Snyder JJ, Singh RJ, Weir MR. Abnormalities in biomarkers of mineral and bone metabolism in kidney donors. Kidney Int 2016; 90:861-8. [PMID: 27370408 PMCID: PMC5026566 DOI: 10.1016/j.kint.2016.05.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 04/26/2016] [Accepted: 05/05/2016] [Indexed: 12/22/2022]
Abstract
Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors.
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Affiliation(s)
- Bertram L Kasiske
- Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
| | - Rajiv Kumar
- Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
| | - Paul L Kimmel
- Division of Kidney Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Todd E Pesavento
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
| | - Roberto S Kalil
- Department of Medicine, University of Iowa, Iowa City, Iowa, USA
| | - Edward S Kraus
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Hamid Rabb
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
| | - Andrew M Posselt
- Department of Surgery, University of California, San Francisco, San Francisco, California, USA
| | | | - Michael W Steffes
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Ajay K Israni
- Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA; Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA
| | - Jon J Snyder
- Minneapolis Medical Research Foundation, Minneapolis, Minnesota, USA
| | - Ravinder J Singh
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Matthew R Weir
- Department of Medicine, University of Maryland, Baltimore, Maryland, USA
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Kouloulias V, Tolia M, Tsoukalas N, Papaloucas C, Pistevou-Gombaki K, Zygogianni A, Mystakidou K, Kouvaris J, Papaloucas M, Psyrri A, Kyrgias G, Gennimata V, Leventakos K, Panayiotides I, Liakouli Z, Kelekis N, Papaloucas A. Is there any Potential Clinical Impact of Serum Phosphorus and Magnesium in Patients with Lung Cancer at First Diagnosis? A Multi-institutional Study. Asian Pac J Cancer Prev 2015; 16:77-81. [DOI: 10.7314/apjcp.2015.16.1.77] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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10
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Nakahashi O, Yamamoto H, Tanaka S, Kozai M, Takei Y, Masuda M, Kaneko I, Taketani Y, Iwano M, Miyamoto KI, Takeda E. Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice. J Clin Biochem Nutr 2014; 54:102-8. [PMID: 24688219 PMCID: PMC3947966 DOI: 10.3164/jcbn.13-109] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Accepted: 12/25/2013] [Indexed: 12/15/2022] Open
Abstract
Members of the fibroblast growth factor (FGF) 19 subfamily, including FGF23, FGF15/19, and FGF21, have a role as endocrine factors which influence the metabolism of inorganic phosphate (Pi) and vitamin D, bile acid, and energy. It has been reported that dietary Pi regulates circulating FGF23. In this study, the short-term effects of dietary Pi restriction on the expression of FGF19 subfamily members in mice were analyzed. An initial analysis confirmed plasma FGF23 levels positively correlated with the amount of dietary Pi. On the other hand, ileal Fgf15 gene expression, but not hepatic Fgf21 gene expression, was up-regulated by dietary Pi restriction. In addition, we observed the increase of plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels by dietary Pi restriction, and the up-regulation of ileal Fgf15 mRNA expression by 1,25(OH)2D3 and vitamin D receptor (VDR). Importantly, dietary Pi restriction-induced Fgf15 gene expression was prevented in VDR-knockout mice. Furthermore, diurnal variations of plasma triglyceride concentrations and hepatic mRNA expression of the bile acid synthesis enzyme Cyp7a1 as one of Fgf15 negative target genes was influenced by dietary Pi restriction. These results suggest that dietary Pi restriction up-regulates ileal Fgf15 gene expression through 1,25(OH)2D3 and VDR, and may affect hepatic bile acid homeostasis.
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Affiliation(s)
- Otoki Nakahashi
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Hironori Yamamoto
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan ; Department of Health and Nutrition, Faculty of Human Life, Jin-ai University, 3-1-1 Ohde-cho, Echizen-shi, Fukui 915-8586, Japan ; Division of Nephrology, Department of General Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan
| | - Sarasa Tanaka
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Mina Kozai
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Yuichiro Takei
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Masashi Masuda
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Ichiro Kaneko
- Department of Molecular Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Yutaka Taketani
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Masayuki Iwano
- Division of Nephrology, Department of General Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan
| | - Ken-Ichi Miyamoto
- Department of Molecular Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
| | - Eiji Takeda
- Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
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11
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Rosner MH, Dalkin AC. Electrolyte disorders associated with cancer. Adv Chronic Kidney Dis 2014; 21:7-17. [PMID: 24359982 DOI: 10.1053/j.ackd.2013.05.005] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Revised: 05/22/2013] [Accepted: 05/30/2013] [Indexed: 12/17/2022]
Abstract
Patients with malignancies commonly experience abnormalities in serum electrolytes, including hyponatremia, hypokalemia, hyperkalemia, hypophosphatemia, and hypercalcemia. In many cases, the causes of these electolyte disturbances are due to common etiologies not unique to the underlying cancer. However, at other times, these electrolyte disorders signal the presence of paraneoplastic processes and portend a poor prognosis. Furthermore, the development of these electrolyte abnormalities may be associated with symptoms that can negatively affect quality of life and may prevent certain chemotherapeutic regimens. Thus, prompt recognition of these disorders and corrective therapy is critical in the care of the patient with cancer.
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Papaloucas CD, Papaloucas MD, Kouloulias V, Neanidis K, Pistevou-Gompaki K, Kouvaris J, Zygogianni A, Mystakidou K, Papaloucas AC. Measurement of blood phosphorus: a quick and inexpensive method for detection of the existence of cancer in the body. Too good to be true, or forgotten knowledge of the past? Med Hypotheses 2013; 82:24-5. [PMID: 24252275 DOI: 10.1016/j.mehy.2013.10.028] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Revised: 10/15/2013] [Accepted: 10/28/2013] [Indexed: 11/16/2022]
Abstract
The possible elevation of phosphorous (P) in cancer patients blood serum has been reported in the past. This however seems to have passed unnoticed. One hundred individuals, divided into two groups of fifty each, i.e. cancer patients (group A) and healthy individuals (group B), were included in this retrospective study. The incidence of cancer by site in group A was 24% head and neck, 50% non-small cell lung cancer (SCLC) and 26% cervical cancer. In all cancer patients in group A the serum P was over the normal values, in contrast with the normal values of P measured in group B. The mean value of serum P in group A and B were 7.80 (± 2.24) and 3.38 (± 0.58), respectively (P<0.001, Mann Whitney test). Increased amount of phosphorus in the blood, when other causes justifying the increase were excluded, should be considered as indicative for the existence of unidentified cancerous lesions.
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Affiliation(s)
| | | | - V Kouloulias
- National University of Athens, Medical School, 2nd Dpt. Radiology, ATTIKO Hospital, Rimini 1, Xaidari, Greece.
| | - K Neanidis
- Medical Oncologist, 424 Military Hospital, Thessaloniki, Greece
| | | | - J Kouvaris
- National University of Athens, Medical School, Greece
| | - A Zygogianni
- National University of Athens, Medical School, Greece
| | - K Mystakidou
- National University of Athens, Medical School, Greece
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de Brito Galvao JF, Nagode LA, Schenck PA, Chew DJ. Calcitriol, calcidiol, parathyroid hormone, and fibroblast growth factor-23 interactions in chronic kidney disease. J Vet Emerg Crit Care (San Antonio) 2013; 23:134-62. [PMID: 23566108 PMCID: PMC3677418 DOI: 10.1111/vec.12036] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Accepted: 02/05/2013] [Indexed: 12/13/2022]
Abstract
Objective To review the inter-relationships between calcium, phosphorus, parathyroid hormone (PTH), parent and activated vitamin D metabolites (vitamin D, 25(OH)-vitamin D, 1,25(OH)2-vitamin D, 24,25(OH)2-vitamin D), and fibroblast growth factor-23 (FGF-23) during chronic kidney disease (CKD) in dogs and cats. Data Sources Human and veterinary literature. Human Data Synthesis Beneficial effects of calcitriol treatment during CKD have traditionally been attributed to regulation of PTH but new perspectives emphasize direct renoprotective actions independent of PTH and calcium. It is now apparent that calcitriol exerts an important effect on renal tubular reclamation of filtered 25(OH)-vitamin D, which may be important in maintaining adequate circulating 25(OH)-vitamin D. This in turn may be vital for important pleiotropic actions in peripheral tissues through autocrine/paracrine mechanisms that impact the health of those local tissues. Veterinary Data Synthesis Limited information is available reporting the benefit of calcitriol treatment in dogs and cats with CKD. Conclusions A survival benefit has been shown for dogs with CKD treated with calcitriol compared to placebo. The concentrations of circulating 25(OH)-vitamin D have recently been shown to be low in people and dogs with CKD and are related to survival in people with CKD. Combination therapy for people with CKD using both parental and activated vitamin D compounds is common in human nephrology and there is a developing emphasis using combination treatment with activated vitamin D and renin-angiotensin-aldosterone-system (RAAS) inhibitors.
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Proszkowiec-Weglarz M, Angel R. Calcium and phosphorus metabolism in broilers: Effect of homeostatic mechanism on calcium and phosphorus digestibility. J APPL POULTRY RES 2013. [DOI: 10.3382/japr.2012-00743] [Citation(s) in RCA: 103] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Ye Z, Palazzo JP, Lin L, Lai Y, Guiles F, Myers RE, Han J, Xing J, Yang H. Postoperative hyperphosphatemia significantly associates with adverse survival in colorectal cancer patients. J Gastroenterol Hepatol 2013; 28:1469-75. [PMID: 23611210 PMCID: PMC3775915 DOI: 10.1111/jgh.12237] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/11/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Hyperphosphatemia has been implicated in the development and treatment of various cancers. However, whether it can be used as a direct prognostic marker of colorectal cancer (CRC) has remained unexplored. Given new insights into the importance of hyperphosphatemia in CRC, we sought to evaluate the association of hyperphosphatemia with the clinical outcomes of this disease. METHODS In a retrospective analysis of a well-characterized clinic-based cohort with 1241 CRC patients, we assessed the association of postoperative hyperphosphatemia with patient overall survival. RESULTS Postoperative hyperphosphatemia measured within the first month after surgery was significantly associated with CRC survival. Compared to patients with a normal phosphate level, those with hyperphosphatemia exhibited a significant unfavorable overall survival with a hazard ratio (HR) of 1.84 (95% confidence interval [CI] 1.49-2.29, P = 2.6 × 10(-8) (log-rank P = 1.2 × 10(-7) ). Stratified analyses indicated the association was more pronounced in patients with colon (HR = 2.00, 95% CI 1.57-2.56, P = 3.17 × 10(-8) ) but not rectal cancer (HR = 0.96, 95% CI 0.58-1.59, P = 0.889) (P interaction = 0.023), as well as in those not receiving chemotherapy (HR = 2.15, 95% CI 1.59-2.90, P = 6.2 × 10(-7) ) but not in those receiving chemotherapy (HR = 1.30, 95% CI 0.92-1.82, P = 0.136) (P interaction = 0.012). Flexible parametric survival model demonstrated that the increased risk for death conferred by postoperative hyperphosphatemia persisted over 150 months after surgery. CONCLUSION Our data indicated that postoperative hyperphosphatemia might be used as a prognostic marker of CRC patients after surgery. Since phosphate level is routinely tested in clinics, it may be incorporated into clinical models to predict CRC survival.
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Affiliation(s)
- Zhong Ye
- Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Juan P. Palazzo
- Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Liz Lin
- Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Yinzhi Lai
- Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Fran Guiles
- Oncology Data Service, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Ronald E. Myers
- Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Jin Han
- Department of Pharmacy, Rush University Medical Center, Chicago, IL 60612
| | - Jinliang Xing
- Experimental Teaching Center, Fourth Military Medical University, Xi’an, 710032, China
| | - Hushan Yang
- Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA,Correspondence to: Hushan Yang, PhD, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Tel: 215-503-6521; Fax: 267-336-0247;
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Starke S, Cox C, Südekum KH, Huber K. Adaptation of electrolyte handling to low crude protein intake in growing goats and consequences for in vivo electrolyte excretion. Small Rumin Res 2013. [DOI: 10.1016/j.smallrumres.2013.06.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Thoracic phosphaturic mesenchymal tumors causing oncogenic osteomalacia. J Clin Neurosci 2013; 20:1057-61. [DOI: 10.1016/j.jocn.2012.09.035] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2012] [Accepted: 09/15/2012] [Indexed: 11/22/2022]
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Moreira Guimarães Penido MG, de Sousa Tavares M. Bone disease in pediatric idiopathic hypercalciuria. World J Nephrol 2012; 1:54-62. [PMID: 24175242 PMCID: PMC3782196 DOI: 10.5527/wjn.v1.i2.54] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2011] [Revised: 11/11/2011] [Accepted: 02/10/2012] [Indexed: 02/06/2023] Open
Abstract
Idiopathic hypercalciuria (IH) is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density (BMD), as described previously in pediatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs (gut, bone and kidney), which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins (i.e., fibroblast growth-factor-23). Usually, a primary defect in one organ induces compensatory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary to a primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular transport of this ion in intestines, kidneys and bones. Reduced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.
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Affiliation(s)
- Maria Goretti Moreira Guimarães Penido
- Maria Goretti Moreira Guimarães Penido, Marcelo de Sousa Tavares, Department of Pediatrics, Pediatric Nephrology Unit, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Belo Horizonte, CEP 30130100, Minas Gerais, Brazil
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Abstract
Tumor-induced osteomalacia (TIO) is a rare and fascinating paraneoplastic syndrome in which patients present with bone pain, fractures, and muscle weakness. The cause is high blood levels of the recently identified phosphate and vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23). In TIO, FGF23 is secreted by mesenchymal tumors that are usually benign, but are typically very small and difficult to locate. FGF23 acts primarily at the renal tubule and impairs phosphate reabsorption and 1α-hydroxylation of 25-hydroxyvitamin D, leading to hypophosphatemia and low levels of 1,25-dihydroxy vitamin D. A step-wise approach utilizing functional imaging (F-18 fluorodeoxyglucose positron emission tomography and octreotide scintigraphy) followed by anatomical imaging (computed tomography and/or magnetic resonance imaging), and, if needed, selective venous sampling with measurement of FGF23 is usually successful in locating the tumors. For tumors that cannot be located, medical treatment with phosphate supplements and active vitamin D (calcitriol or alphacalcidiol) is usually successful; however, the medical regimen can be cumbersome and associated with complications. This review summarizes the current understanding of the pathophysiology of the disease and provides guidance in evaluating and treating these patients. Novel imaging modalities and medical treatments, which hold promise for the future, are also reviewed.
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Affiliation(s)
- William H Chong
- Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892, USA
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20
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Akhter M, Sugrue PA, Bains R, Khavkin YA. Oncogenic osteomalacia of the cervical spine: a rare case of curative resection and reconstruction. J Neurosurg Spine 2011; 14:453-6. [DOI: 10.3171/2010.11.spine09750] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome, with only 100 reported cases in the literature. The majority of OO-associated mesenchymal tumors are due to a lesion called phosphaturic mesenchymal tumor, mixed connective tissue (PMTMCT) variant. There have been only 6 reported cases of OO of the spine. With this paper the authors present a case of OO of the cervical spine in a patient who initially presented with multiple pathological fractures of unknown cause, and who eventually underwent staged C-5 spondylectomy followed by circumferential stabilization. Resection of the cervical lesion led to resolution of his hypophosphatemia and prevention of any further pathological fractures. The authors describe a rare cervical neoplasm, its treatment, and review the literature on this rare bony pathological entity.
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Affiliation(s)
- Murtaza Akhter
- 1Northwestern University Feinberg School of Medicine, Chicago
| | - Patrick A. Sugrue
- 1Northwestern University Feinberg School of Medicine, Chicago
- 2Department of Neurological Surgery,
| | - Rick Bains
- 3Department of Pathology, NorthShore University Health System, Evanston, Illinois; and
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Blaine J, Weinman EJ, Cunningham R. The regulation of renal phosphate transport. Adv Chronic Kidney Dis 2011; 18:77-84. [PMID: 21406291 DOI: 10.1053/j.ackd.2011.01.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2010] [Revised: 12/09/2010] [Accepted: 01/18/2011] [Indexed: 12/17/2022]
Abstract
Renal phosphate transport is mediated by the abundance and activity of the sodium-dependent phosphate transporters, Npt2a, Npt2c, and PiT-2, present within the apical brush border membrane of the proximal tubule. Recent studies have demonstrated differential expression and activity of these sodium-dependent phosphate transporters within the proximal tubule. In general, phosphate transport is regulated by a variety of physiological stimuli, including parathyroid hormone, glucocorticoids, vitamin D3, estrogen, and thyroid hormone. Phosphatonins are now recognized as major regulators of phosphate transport activity. Other factors that affect phosphate transport include dopamine, dietary phosphate, acid-base status, lipid composition, potassium deficiency, circadian rhythm, and hypertension. Studies have shown that the PDZ-containing sodium/hydrogen exchanger regulatory factor (NHERF) proteins, specifically NHERF-1 and NHERF-3, play a critical role in the physiological regulation of phosphate transport, particularly in response to dietary phosphate. In addition, recent studies have found that NHERF-1 is also important in both the parathyroid hormone- and dopamine-mediated inhibition of phosphate transport. This review will detail the various hormones and agents involved in the regulation of phosphate transport as well as provide a brief summary of the signaling pathways and cytoskeletal proteins active in the transport of phosphate in the renal proximal tubule.
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22
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The osteocyte--a novel endocrine regulator of body phosphate homeostasis. Maturitas 2010; 67:327-38. [PMID: 20884141 DOI: 10.1016/j.maturitas.2010.08.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2010] [Revised: 08/27/2010] [Accepted: 08/30/2010] [Indexed: 11/22/2022]
Abstract
Although osteocytes are the most abundant cell type in bone, much of their biology remains enigmatic. They are known to transduce mechanical stress into signals that initiate local bone remodeling, and are targets for systemic and local endocrine signals that affect bone architecture and mineral homeostasis. However, recent data reveal that osteocytes themselves act as endocrine cells that synthesize fibroblast growth factor 23 (FGF23) and several other phosphatonins, shown to underpin the systemic regulation of phosphate homeostasis. This review will synthesize the emerging discoveries concerning the osteocytic endocrine role in phosphate homeostasis through the biology and pathophysiology of these phosphatonins. We also suggest future research paths that might resolve existing uncertainties, and look ahead at how greater understanding might improve the management of clinical disorders of phosphate homeostasis.
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Serum phosphate in white-coat hypertensive patients: focus on dipping status and metabolic syndrome. Hypertens Res 2010; 33:825-30. [PMID: 20505672 DOI: 10.1038/hr.2010.86] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Recent studies indicate an association between serum phosphate levels and blood pressure in hypertensive patients. A growing body of evidence suggests that white-coat hypertension (WCH) is associated with target organ damage. Furthermore, metabolic syndrome (MS) and a non-dipping pattern are associated with increased cardiovascular risk. The purpose of this study was to explore the nocturnal blood pressure fall in patients with WCH according to their serum phosphate levels and number of MS components fulfilled. The study included 2600 patients with WCH who attended our outpatient clinics. All patients underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring and full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria. Dipping pattern was defined as follows: 'dippers' had a nocturnal systolic blood pressure (NSBP) fall > or =10% but <20%; 'non-dippers' had an NSBP fall <10%; 'extreme dippers' had an NSBP fall > or =20% and 'reverse dippers' had an NSBP increase. There were 314 extreme dippers, 1337 dippers, 734 non-dippers and 116 reverse dippers. Reverse dippers presented with significantly lower levels of serum phosphate, whereas extreme dippers had significantly higher levels (3.39+/-3.29 vs. 3.58+/-3.52 mg per 100 ml, P<0.0001). The patients were classified according to the number of MS components and the main observation was the inverse relationship of serum phosphate with MS components (3.53+/-0.36, 3.50+/-0.38, 3.49+/-0.38, 3.44+/-0.36 and 3.35+/-0.31 mg per 100 ml, respectively, P=0.003). Patients with WCH and low serum phosphate levels appear to have a higher incidence of a non-dipping NSBP profile and an impaired metabolic profile. This observation may be important for the stratification of the cardiovascular risk in WCH patients.
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Abstract
In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal phosphate excretion by reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Most insights gained into the regulation of phosphate homeostasis by these factors are derived from human genetic disorders and genetically engineered mice, which are reviewed in this paper.
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Affiliation(s)
- Clemens Bergwitz
- Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
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25
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Loghmani S, Maracy MR, Kheirmand R. Serum phosphate level in burn patients. Burns 2010; 36:1112-5. [PMID: 20409642 DOI: 10.1016/j.burns.2009.12.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2009] [Revised: 12/19/2009] [Accepted: 12/27/2009] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Despite plasma phosphate imbalance being rare, it is a relatively common finding in certain subsets of burn patients. It may occur due to the burn itself or as a result of the treatment. Severe hypophosphataemia (<1.0 mg dl(-1)) is associated with a significant morbidity and a fourfold increase in mortality. In this study, the relation between serum phosphate level and the total body surface area (TBSA) of the burn was compared. METHODS According to the percentage of TBSA of the burn, the patients (n=155) were divided into three groups: group A with 20-29% TBSA burns, group B with 30-39% and group C with more than 40% TBSA burns (62, 48 and 45 patients, respectively). Analysis of variance (ANOVA)-repeated measure was used to detect any statistically significant difference in the three post-burn time-points of 3rd, 6th and 9th days and the mean score of the serum phosphate level between the three groups. RESULTS The incidence of hypophosphataemia at 9th post-burn day in the three groups was 6.1%, 32.4% and 73.5%, respectively. There were significant differences (p<0.05) between mean serum phosphate levels of groups A and C, B and C and A and B as well. We found significant differences between the three post-burn follow-up time stages. DISCUSSION We have shown that hypophosphataemia, defined as mean serum phosphate levels below 3.0 mg dl(-1), was very common following burn, based on 75.6% of patients with more than 40% burn at the 3rd post-burn day. As the percentage of TBSA of burn increases, the incidence of hypophosphataemia significantly increases. We suggest that phosphate level be routinely measured after a major burn, especially in patients with a complicated course, so that appropriate replacement therapy may be started in a timely manner.
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Affiliation(s)
- Shahriar Loghmani
- Department of Plastic Surgery, Imam Musa-Kazem Burn Hospital, Isfahan University of Medical Sciences, Kaveh Street, Isfahan, Iran.
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26
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Furlanetto TW. Etiology of Hyperparathyroidism in McCune-Albright Syndrome. J Oral Maxillofac Surg 2009; 67:2037. [DOI: 10.1016/j.joms.2009.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2009] [Accepted: 04/04/2009] [Indexed: 10/20/2022]
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Abstract
PURPOSE OF REVIEW To discuss findings suggesting the presence of a phosphate-sensing mechanism in the various organs and the presence of a novel intestinal effector that alters renal phosphate excretion after the ingestion of a phosphate-containing meal. RECENT FINDINGS Although phosphate homeostasis is controlled by a variety of hormones (such as parathyroid hormone and 1,25-dihydroxyvitamin D), peptides (the phosphatonins - fibroblast growth factor 23, secreted frizzled-related protein-4, matrix extracellular phosphoglycoprotein) and small molecules (dopamine) that regulate the efficiency of phosphate absorption in the intestine and phosphate excretion in the renal tubule, recent data suggest that postcibal changes in renal phosphate excretion following a meal containing phosphate are mediated by signals generated within the intestine that alter the efficiency of phosphate excretion in the kidney. The intestine detects luminal phosphate and signals to the kidney via the release of the mediator that increases renal phosphate excretion. SUMMARY Such information would imply the existence of a phosphate-sensing mechanism within the intestine and the presence of intestinal factors that influence renal phosphate handling.
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Affiliation(s)
- Rajiv Kumar
- Departments of Medicine, Biochemistry and Molecular Biology, Division of Nephrology and Hypertension, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
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Abstract
OBJECTIVE To determine precisely the role of parathyroid hormone (PTH) and of phosphatonins in the genesis of posthepatectomy hypophosphatemia. BACKGROUND Posthepatectomy hypophosphatemia has recently been related to increased renal fractional excretion of phosphate (FE P). To address the cause of hypophosphatemia, we measured serum concentrations of PTH, various phosphatonins, and the number of removed hepatic segment in patients with this disorder. METHODS Serum phosphate (PO4), ionized calcium (Ca++), HCO3-, pH and FE P, intact PTH (I-PTH), carboxyl-terminal fibroblast growth factor 23 (C-FGF-23) and intact fibroblast growth factor 23 (I-FGF-23), FGF-7, and secreted frizzled related-protein-4 (sFRP-4) were measured before and on postoperative (po) days 1, 2, 3, 5, and 7, in 18 patients undergoing liver resection. The number of removed hepatic segments was also assessed. RESULTS Serum PO4 concentrations decreased within 24 hours, were lowest (0.66 +/- 0.03 mmol/L; P < 0.001) at 48 hours, and returned to normal within 5 days of the procedure. FE P peaked at 25.07% +/- 2.26% on po day 1 (P < 0.05). Decreased ionized calcium concentrations (1.10 +/- 0.01 mmol/L; P < 0.01) were observed on po day 1 and were negatively correlated with increased I-PTH concentrations (8.8 +/- 0.9 pmol/L; P < 0.01; correlation: r = -0.062, P = 0.016). FE P was positively related to I-PTH levels on po day 1 (r = 0.52, P = 0.047) and negatively related to PO4 concentrations (r = -0.56, P = 0.024). Severe hypophosphatemia and increased urinary phosphate excretion persisted for 72 hours even when I-PTH concentrations had returned to normal. I-FGF-23 decreased to its nadir of 7.8 +/- 6.9 pg/mL (P < 0.001) on po day 3 and was correlated with PO4 levels on po days 0, 3, 5, and 7 (P < 0.001). C-FGF-23, FGF-7 and sFRP-4 levels could not be related to either PO4 concentrations or FE P. CONCLUSION Posthepatectomy hypophosphatemia is associated with increased FE P unrelated to I-FGF-23 or C-FGF-23, FGF-7, or sFRP-4. I-PTH contributes to excessive FE P partially on po day 1 but not thereafter. Other yet defined factors should explain post hepatectomy hypophosphatemia.
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Habra MA, Jimenez C, Huang SCE, Cote GJ, Murphy WA, Gagel RF, Hoff AO. Expression analysis of fibroblast growth factor-23, matrix extracellular phosphoglycoprotein, secreted frizzled-related protein-4, and fibroblast growth factor-7: identification of fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein as major factors involved in tumor-induced osteomalacia. Endocr Pract 2009; 14:1108-14. [PMID: 19158050 DOI: 10.4158/ep.14.9.1108] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE To evaluate the expression of various phosphaturic factors in the tumor of a patient with tumor-induced osteomalacia (TIO) and to analyze serum levels of fibroblast growth factor (FGF)-23 in TIO and healthy subjects. METHODS We measured serum FGF-23 levels in 2 patients with TIO and 6 healthy volunteers. Expression of FGF-23, matrix extracellular phosphoglycoprotein (MEPE), FGF-7, and secreted frizzled-related protein-4 (sFRP-4) was analyzed in a hemangiopericytoma from a patient with TIO, in a hemangiopericytoma from a patient without TIO, and in various control cell lines. RESULTS Serum FGF-23 levels were substantially higher in patients with TIO in comparison with those in healthy control subjects and normalized with successful resection of the tumor. Tissue expression analysis showed preferential expression of FGF-23 and MEPE in TIO-related hemangiopericytoma, whereas FGF-7 and sFRP-4 were widely expressed in all studied cell lines and tissues. CONCLUSION These results support the use of FGF-23 measurements for the diagnosis and follow-up of patients with TIO. In addition, the specific expression of FGF-23 and MEPE in the TIO-associated tumor suggests an important role of these two phosphatonins in the pathogenesis of TIO. Because of the limited number of patients in our report, further studies are needed to clarify the role of different phosphatonins in the development of the clinical features of TIO.
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Affiliation(s)
- Mouhammed Amir Habra
- Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
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Affiliation(s)
- Brendan M Reilly
- Department of Medicine, Weill Cornell Medical Center, New York, NY 10065, USA.
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Berndt T, Kumar R. Novel mechanisms in the regulation of phosphorus homeostasis. Physiology (Bethesda) 2009; 24:17-25. [PMID: 19196648 DOI: 10.1152/physiol.00034.2008] [Citation(s) in RCA: 153] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Phosphorus plays a critical role in diverse biological processes, and, therefore, the regulation of phosphorus balance and homeostasis are critical to the well being of the organism. Changes in environmental, dietary, and serum concentrations of inorganic phosphorus are detected by sensors that elicit changes in cellular function and alter the efficiency by which phosphorus is conserved. Short-term, post-cibal responses that occur independently of hormones previously thought to be important in phosphorus homeostasis may play a larger role than previously appreciated in the regulation of phosphorus homeostasis. Several hormones and regulatory factors such as the vitamin D endocrine system, parathyroid hormone, and the phosphatonins (FGF-23, sFRP-4, MEPE) among others, may play a role only in the long-term regulation of phosphorus homeostasis. In this review, we discuss how organisms sense changes in phosphate concentrations and how changes in hormonal factors result in the conservation or excretion of phosphorus.
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Affiliation(s)
- Theresa Berndt
- Department of Medicine, Nephrology Research, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
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van Etten E, Stoffels K, Gysemans C, Mathieu C, Overbergh L. Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 2009; 66:S125-34. [PMID: 18844839 DOI: 10.1111/j.1753-4887.2008.00096.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Vitamin D homeostasis in the immune system is the focus of this review. The production of both the activating (25- and 1alpha-hydroxylase) and the metabolizing (24-hydroxylase) enzymes by cells of the immune system itself, indicates that 1,25(OH)(2)D(3) can be produced locally in immune reaction sites. Moreover, the strict regulation of these enzymes by immune signals is highly suggestive for an autocrine/paracrine role in the immune system, and opens new treatment possibilities.
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Affiliation(s)
- Evelyne van Etten
- The Laboratory for Experimental Medicine and Endocrinology (LEGENDO), Katholieke Universiteit Leuven , Leuven, Belgium
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Biagini GLK, Coutinho PR, Jonasson TH, Ueda CE, Gama RR. Osteomalácia oncogênica: cintilografia com sestamibi-99mTc na localização do tumor. ACTA ACUST UNITED AC 2008; 52:1505-9. [DOI: 10.1590/s0004-27302008000900016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2008] [Accepted: 09/11/2008] [Indexed: 02/03/2023]
Abstract
A osteomalácia oncogênica hipofosfatêmica (OOH) é uma síndrome paraneoplásica induzida por tumor, de tecidos mole ou ósseo. Apresenta-se com dor e fraturas, acompanhada de hipofosfatemia, hiperfosfatúria e concentrações plasmáticas de 1,25(OH)2D3 inapropriadamente normais/diminuídas. Após a remoção do tumor, a completa resolução das anormalidades clínicas e bioquímicas é sua maior característica. Uma mulher de 44 anos de idade é descrita no caso com dificuldade para caminhar por causa de dores nos membros inferiores, fraqueza muscular generalizada e hipofosfatemia com relativa hiperfosfatúria. A cintilografia de corpo total com sestamibi-99mTc mostrou acúmulo do radiofármaco no terço superior de coxa esquerda onde pequeno tumor foi detectado no exame pelo ultra-som. Com a retirada do tumor, um lipoma, os sintomas melhoraram após um mês, com recuperação completa ao redor do quarto mês. Neste caso, a cintilografia de corpo inteiro com sestamibi-99mTc foi decisiva na localização do tumor causador da osteomalácia oncogênica.
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Marks J, Churchill LJ, Debnam ES, Unwin RJ. Matrix extracellular phosphoglycoprotein inhibits phosphate transport. J Am Soc Nephrol 2008; 19:2313-20. [PMID: 19005008 DOI: 10.1681/asn.2008030315] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits phosphate absorption in the jejunum but not the duodenum. Simultaneous measurement of urinary phosphate excretion suggests that the phosphaturic action of MEPE correlates with a significant reduction in the protein levels of the renal sodium-phosphate co-transporter NaPi-IIa in the proximal convoluted tubules of the outer renal cortex, assessed by Western blotting and immunohistochemistry. This short-term inhibitory effect of MEPE on renal and intestinal phosphate handling occurred without any changes in circulating levels of parathyroid hormone, 1,25-dihydroxyvitamin D(3), or fibroblast growth factor 23. Taken together, these findings suggest that MEPE is a candidate phosphatonin involved in phosphate homeostasis, acting in both the kidney and the gastrointestinal tract.
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Affiliation(s)
- Joanne Marks
- Department of Physiology, University College London Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF.
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Biber J, Hernando N, Forster I, Murer H. Regulation of phosphate transport in proximal tubules. Pflugers Arch 2008; 458:39-52. [PMID: 18758808 DOI: 10.1007/s00424-008-0580-8] [Citation(s) in RCA: 129] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2008] [Accepted: 08/13/2008] [Indexed: 12/13/2022]
Abstract
Homeostasis of inorganic phosphate (P(i)) is primarily an affair of the kidneys. Reabsorption of the bulk of filtered P(i) occurs along the renal proximal tubule and is initiated by apically localized Na(+)-dependent P(i) cotransporters. Tubular P(i) reabsorption and therefore renal excretion of P(i) is controlled by a number of hormones, including phosphatonins, and metabolic factors. In most cases, regulation of P(i) reabsorption is achieved by changing the apical abundance of Na(+)/Pi cotransporters. The regulatory mechanisms involve various signaling pathways and a number of proteins that interact with Na(+)/P(i) cotransporters.
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Affiliation(s)
- J Biber
- Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
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Hoffman WH, Jain A, Chen H, Fedarko NS. Matrix extracellular phosphoglycoprotein (MEPE) correlates with serum phosphorus prior to and during octreotide treatment and following excisional surgery in hypophosphatemic linear sebaceous nevus syndrome. Am J Med Genet A 2008; 146A:2164-8. [PMID: 18627046 PMCID: PMC2562707 DOI: 10.1002/ajmg.a.32395] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- William H. Hoffman
- Department of Pediatrics, Pediatric Endocrinology, Medical College of Georgia, Augusta, GA
| | - Alka Jain
- Department of Medicine, Johns Hopkins University, Baltimore, MD
| | - Harold Chen
- Department of Pediatrics, Louisiana State University Medical School, Shreveport, LA
| | - Neal S. Fedarko
- Department of Medicine, Johns Hopkins University, Baltimore, MD
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Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schüler C, Erben RG, Lanske B. Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet 2008; 4:e1000154. [PMID: 18688277 PMCID: PMC2483943 DOI: 10.1371/journal.pgen.1000154] [Citation(s) in RCA: 141] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2007] [Accepted: 07/08/2008] [Indexed: 12/21/2022] Open
Abstract
Maintenance of physiologic phosphate balance is of crucial biological importance, as it is fundamental to cellular function, energy metabolism, and skeletal mineralization. Fibroblast growth factor-23 (FGF-23) is a master regulator of phosphate homeostasis, but the molecular mechanism of such regulation is not yet completely understood. Targeted disruption of the Fgf-23 gene in mice (Fgf-23-/-) elicits hyperphosphatemia, and an increase in renal sodium/phosphate co-transporter 2a (NaPi2a) protein abundance. To elucidate the pathophysiological role of augmented renal proximal tubular expression of NaPi2a in Fgf-23-/- mice and to examine serum phosphate-independent functions of Fgf23 in bone, we generated a new mouse line deficient in both Fgf-23 and NaPi2a genes, and determined the effect of genomic ablation of NaPi2a from Fgf-23-/- mice on phosphate homeostasis and skeletal mineralization. Fgf-23-/-/NaPi2a-/- double mutant mice are viable and exhibit normal physical activities when compared to Fgf-23-/- animals. Biochemical analyses show that ablation of NaPi2a from Fgf-23-/- mice reversed hyperphosphatemia to hypophosphatemia by 6 weeks of age. Surprisingly, despite the complete reversal of serum phosphate levels in Fgf-23-/-/NaPi2a-/-, their skeletal phenotype still resembles the one of Fgf23-/- animals. The results of this study provide the first genetic evidence of an in vivo pathologic role of NaPi2a in regulating abnormal phosphate homeostasis in Fgf-23-/- mice by deletion of both NaPi2a and Fgf-23 genes in the same animal. The persistence of the skeletal anomalies in double mutants suggests that Fgf-23 affects bone mineralization independently of systemic phosphate homeostasis. Finally, our data support (1) that regulation of phosphate homeostasis is a systemic effect of Fgf-23, while (2) skeletal mineralization and chondrocyte differentiation appear to be effects of Fgf-23 that are independent of phosphate homeostasis.
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Affiliation(s)
- Despina Sitara
- Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America
| | - Somi Kim
- Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America
| | - Mohammed S. Razzaque
- Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America
| | - Clemens Bergwitz
- Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Takashi Taguchi
- Department of Pathology, Nagasaki University School of Biomedical Sciences, Nagasaki, Japan
| | - Christiane Schüler
- Department of Natural Sciences, University of Veterinary Medicine, Vienna, Austria
| | - Reinhold G. Erben
- Department of Natural Sciences, University of Veterinary Medicine, Vienna, Austria
| | - Beate Lanske
- Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America
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Shaikh A, Berndt T, Kumar R. Regulation of phosphate homeostasis by the phosphatonins and other novel mediators. Pediatr Nephrol 2008; 23:1203-10. [PMID: 18288501 PMCID: PMC2441591 DOI: 10.1007/s00467-008-0751-z] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2007] [Revised: 11/29/2007] [Accepted: 12/03/2007] [Indexed: 01/23/2023]
Abstract
A variety of factors regulate the efficiency of phosphate absorption in the intestine and phosphate reabsorption in kidney. Apart from the well-known regulators of phosphate homeostasis, namely parathyroid hormone (PTH) and the vitamin D-endocrine system, a number of peptides collectively known as the "phosphatonins" have been recently identified as a result of the study of various diseases associated with hypophosphatemia. These factors, fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein 4 (sFRP-4), fibroblast growth factor 7 (FGF-7) and matrix extracellular phosphoglycoprotein (MEPE), have been shown to play a role in the pathogenesis of various hypophosphatemic and hyperphosphatemic disorders, such as oncogenic osteomalacia, X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemia and tumoral calcinosis. Whether these factors are true hormones, in the sense that they are regulated by the intake of dietary phosphorus and the needs of the organism for higher or lower amounts of phosphorus, remains to be firmly established in humans. Additionally, new information demonstrates that the intestine "senses" luminal concentrations of phosphate and regulates the excretion of phosphate in the kidney by elaborating novel factors that alter renal phosphate reabsorption.
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Affiliation(s)
- Aisha Shaikh
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905 USA
| | - Theresa Berndt
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905 USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, Rochester, MN USA
| | - Rajiv Kumar
- Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905 USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN USA
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Marcucci G, Masi L, Brandi ML. Phosphatonins: new hormones that control phosphorus homeostasis. Expert Rev Endocrinol Metab 2008; 3:513-526. [PMID: 30290433 DOI: 10.1586/17446651.3.4.513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Phosphorus (Pi) plays an important role in nucleic acid synthesis, energy metabolism, bone mineralization and cell signaling, and is also present in sugars, phospholipids and phosphoproteins. Phosphate homeostasis is controlled by processes that regulate the intestinal absorption and renal excretion of Pi, and bone turnover. These processes are influenced by peptide and sterol hormones, such as parathyroid hormone and 1α,25-dihydroxyvitamin D (1α,25[OH]2D3). Recently, a new class of phosphate-regulating peptides has been discovered: phosphatonins. These factors, such as FGF-23, secreted frizzled-related protein-4, matrix extracellular phosphoglycoprotein and FGF-7, are circulating peptides with potent phosphaturic activity. These peptides inhibit Na/Pi transporters in renal epithelial cells and, therefore, increase renal Pi excretion. In addition, FGF-23 and secreted frizzled-related protein-4 inhibit 25-hydroxyvitamin D 1α-hydroxylase activity, reducing 1α,25(OH)2D3 synthesis and, thus, intestinal Pi absorption. Phosphatonins have been associated with hypophosphatemic diseases, such as tumor-induced osteomalacia, X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets and hyperphosphatemic disease (e.g., tumoral calcinosis). The aim of this article is to review the role of phosphatonins in Pi metabolism in normal and pathologic conditions and also to investigate the correlations among the various phosphatonins.
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Affiliation(s)
- Gemma Marcucci
- a Department of Internal Medicine and # De Gene Spin-off, University of Florence, Medical School, Florence, Italy
| | - Laura Masi
- a Department of Internal Medicine and # De Gene Spin-off, University of Florence, Medical School, Florence, Italy
| | - Maria Luisa Brandi
- b Department of Internal Medicine, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
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Thomas L, Kumar R. Control of Renal Solute Excretion by Enteric Signals and Mediators. J Am Soc Nephrol 2008; 19:207-12. [DOI: 10.1681/asn.2007101122] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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Isakova T, Gutierrez O, Shah A, Castaldo L, Holmes J, Lee H, Wolf M. Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD. J Am Soc Nephrol 2008; 19:615-23. [PMID: 18216315 DOI: 10.1681/asn.2007060673] [Citation(s) in RCA: 125] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Normophosphatemia and normocalcemia are maintained in chronic kidney disease (CKD) by increased levels of fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH), but the stimuli for secretion of these hormones in early CKD are incompletely understood. Most human physiologic studies have focused on random or fasting measurements of phosphorus, calcium, FGF-23, and PTH, but in this study, the hypothesis was that measurements in the postprandial state may reveal intermittent stimuli that lead to increased FGF-23 and PTH levels. The 4-h postprandial response in 13 patients with CKD and fasting normophosphatemia and normocalcemia (mean GFR 41 +/- 8 ml/min per m(2)) was compared with 21 healthy volunteers. Compared with healthy subjects, fasting patients with CKD had significantly higher levels of FGF-23 and fractional excretion of phosphorus; lower fractional excretion of calcium; and no difference in serum calcium, phosphorus, and PTH levels. After standardized meals, urinary phosphorus excretion in both groups increased despite unchanged serum phosphorus and FGF-23 levels. Postprandial urinary calcium excretion also increased in both groups, and this was accompanied by significantly reduced serum calcium and increased PTH levels in patients with CKD only; therefore, FGF-23 does not seem to be an acute postprandial regulator of phosphaturia in CKD or in health, but inappropriate postprandial calciuria with episodic, relative hypocalcemia may represent a previously unreported mechanism of secondary hyperparathyroidism in CKD.
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Affiliation(s)
- Tamara Isakova
- Renal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
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Sadideen H, Covic A, Goldsmith D. Mineral and bone disorder after renal transplantation: a review. Int Urol Nephrol 2007; 40:171-84. [PMID: 18085426 DOI: 10.1007/s11255-007-9310-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2007] [Accepted: 11/13/2007] [Indexed: 02/07/2023]
Abstract
Chronic kidney disease-mineral bone disorder is a common clinical picture encountered in patients with end-stage renal disease and is the result of additive pathophysiological processes. Renal transplantation remains the treatment of choice for these patients, especially as advances in this field have allowed for enhanced allograft survival. However, with increasing success of renal transplantation has come a greater appreciation of some of its subsequent complications, such as posttransplantation bone disease. Recently, persistent hyperparathyroidism and osteopenia-osteoporosis have been given specific attention. Traditionally, persistent hyperparathyroidism has been treated with parathyroidectomy, although the role that calcimimetics may play in the future is promising. Newer aspects to medical management of osteopenia-osteoporosis, such as the efficacy of bisphosphonate therapy and early steroid withdrawal, are becoming apparent and some of the newer drugs for the treatment of osteoporosis are yet to be investigated in this subgroup of patients.
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Affiliation(s)
- Hazim Sadideen
- Department of Nephrology and Transplantation, New Guy's House, Guy's Hospital, St. Thomas' Street, London SE1 9RT, UK
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Garabedian M. Regulation of phosphate homeostasis in infants, children, and adolescents, and the role of phosphatonins in this process. Curr Opin Pediatr 2007; 19:488-91. [PMID: 17630616 DOI: 10.1097/mop.0b013e328270b902] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
PURPOSE OF REVIEW Unlike calcium metabolism, the control of phosphate homeostasis has long been poorly understood. The identification of 'phosphatonins' in the serum of hypophosphatemic patients, the unveiling of the genetic causes of hypo and hyperphosphatemic diseases in patients, and the creation of finely adapted animal models have revolutionized our understanding of phosphate homeostasis. RECENT FINDINGS Original reports published in 2006/2007 bring valuable pieces of information that enable better understanding of the physiological regulation of phosphate homeostasis by more precisely defining the interplay between PHEX, vitamin D, and phosphatonins; identification of new genes causing hypophosphatemic rickets, aside from PHEX and fgf23, namely the genes encoding for a renal sodium-phosphate cotransporter, NaPiIIc, and for a bone matrix protein, DmpI; and improved diagnosis of tumor-induced osteomalacia with more precise imaging techniques for tumor localization and more precise fibroblast growth factor 23 assays. SUMMARY From a clinical point of view, these findings offer new tools for the diagnosis of hypophosphatemic rickets (biologic, genetic, imaging techniques) and open the way to new treatment strategies.
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Berndt T, Thomas LF, Craig TA, Sommer S, Li X, Bergstralh EJ, Kumar R. Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption. Proc Natl Acad Sci U S A 2007; 104:11085-90. [PMID: 17566100 PMCID: PMC1891094 DOI: 10.1073/pnas.0704446104] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The mechanisms by which phosphorus homeostasis is preserved in mammals are not completely understood. We demonstrate the presence of a mechanism by which the intestine detects the presence of increased dietary phosphate and rapidly increases renal phosphate excretion. The mechanism is of physiological relevance because it maintains plasma phosphate concentrations in the normal range after ingestion of a phosphate-containing meal. When inorganic phosphate is infused into the duodenum, there is a rapid increase in the renal fractional excretion of phosphate (FE Pi). The phosphaturic effect of intestinal phosphate is specific for phosphate because administration of sodium chloride does not elicit a similar response. Phosphaturia after intestinal phosphate administration occurs in thyro-parathyroidectomized rats, demonstrating that parathyroid hormone is not essential for this effect. The increase in renal FE Pi in response to the intestinal administration of phosphate occurs without changes in plasma concentrations of phosphate (filtered load), parathyroid hormone, FGF-23, or secreted frizzled related protein-4. Denervation of the kidney does not attenuate phosphaturia elicited after intestinal phosphate administration. Phosphaturia is not elicited when phosphate is instilled in other parts of the gastrointestinal tract such as the stomach. Infusion of homogenates of the duodenal mucosa increases FE Pi, which demonstrates the presence of one or more substances within the intestinal mucosa that directly modulate renal phosphate reabsorption. Our experiments demonstrate the presence of a previously unrecognized phosphate gut-renal axis that rapidly modulates renal phosphate excretion after the intestinal administration of phosphate.
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Affiliation(s)
- Theresa Berndt
- *Division of Nephrology and Hypertension, Department of Internal Medicine
| | - Leslie F. Thomas
- *Division of Nephrology and Hypertension, Department of Internal Medicine
| | - Theodore A. Craig
- *Division of Nephrology and Hypertension, Department of Internal Medicine
| | - Stacy Sommer
- *Division of Nephrology and Hypertension, Department of Internal Medicine
| | - Xujian Li
- Division of Biostatistics, Department of Health Sciences Research, and
| | | | - Rajiv Kumar
- *Division of Nephrology and Hypertension, Department of Internal Medicine
- Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905
- To whom correspondence should be addressed. E-mail:
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