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The Effect of Abnormal Iron Metabolism on Osteoporosis

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Abstract

Iron is one of the important trace elements in life activities. Abnormal iron metabolism increases the incidence of many skeletal diseases, especially for osteoporosis. Iron metabolism plays a key role in the bone homeostasis. Disturbance of iron metabolism not only promotes osteoclast differentiation and apoptosis of osteoblasts but also inhibits proliferation and differentiation of osteoblasts, which eventually destroys the balance of bone remodeling. The strength and density of bone can be weakened by the disordered iron metabolism, which increases the incidence of osteoporosis. Clinically, compounds or drugs that regulate iron metabolism are used for the treatment of osteoporosis. The goal of this review summarizes the new progress on the effect of iron overload or deficiency on osteoporosis and the mechanism of disordered iron metabolism on osteoporosis. Explaining the relationship of iron metabolism with osteoporosis may provide ideas for clinical treatment and development of new drugs.

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Abbreviations

DMT1:

divalent metal transporter 1

FPN:

ferroportin

Tf:

transferrin

TfR1:

transferrin receptor 1

STEAP:

six-transmembrane epithelial antigen of the prostate

FtMt:

mitochondria-specific Ft type

IRPs:

iron-regulatory proteins

IREs:

iron-responsive elements

BMP:

bone morphogenetic protein

RANKL:

receptor activator of nuclear factor κB

OPG:

osteoprotegerin

ALP:

Alkaline phosphatase

Runx2:

Runt-related transcription factor 2

OCN:

osteocalcin

BSP:

bone sialoprotein

ROS:

reactive oxygen species

MAPKs:

mitogen-activated protein kinase

ERK1/2:

extracellular signal-regulated kinases

JNK:

c-Jun-N-terminal kinase

BALP:

bone-specific alkaline phosphatase

OC:

osteocalcin

P1NP:

N-terminal propeptide of type I procollagen

OVX:

ovariectomized

BMD:

bone minimum density

MMP9:

matrix metalloproteinase 9

CTSK:

cathepsin K

DFO:

desferrioxamine

HIF:

hypoxia-inducible factor

References

  1. Muckenthaler MU, Rivella S, Hentze MW, Galy B (2017) A red carpet for iron metabolism. Cell 168(3):344–361. https://doi.org/10.1016/j.cell.2016.12.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Andrews NC, Schmidt PJ (2007) Iron homeostasis. Annu Rev Physiol 69:69–85. https://doi.org/10.1146/annurev.physiol.69.031905.164337

    Article  CAS  PubMed  Google Scholar 

  3. Shaw JG, Friedman JF (2011) Iron deficiency anemia: focus on infectious diseases in lesser developed countries. Anemia 2011:260380. https://doi.org/10.1155/2011/260380

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bo L, Liu Z, Zhong Y, Huang J, Chen B, Wang H, Xu Y (2016) Iron deficiency anemia’s effect on bone formation in zebrafish mutant. Biochem Biophys Res Commun 475(3):271–276. https://doi.org/10.1016/j.bbrc.2016.05.069

    Article  CAS  PubMed  Google Scholar 

  5. Klip IT, Voors AA, Swinkels DW, Bakker SJ, Kootstra-Ros JE, Lam CS, van der Harst P, van Veldhuisen DJ, van der Meer P (2017) Serum ferritin and risk for new-onset heart failure and cardiovascular events in the community. Eur J Heart Fail 19(3):348–356. https://doi.org/10.1002/ejhf.622

    Article  CAS  PubMed  Google Scholar 

  6. Li GF, Pan YZ, Sirois P, Li K, Xu YJ (2012) Iron homeostasis in osteoporosis and its clinical implications. Osteoporos Int 23(10):2403–2408. https://doi.org/10.1007/s00198-012-1982-1

    Article  CAS  PubMed  Google Scholar 

  7. Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L (2014) The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol 13(10):1045–1060. https://doi.org/10.1016/S1474-4422(14)70117-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. An J, Yang H, Zhang Q, Liu C, Zhao J, Zhang L, Chen B (2016) Natural products for treatment of osteoporosis: the effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci 147:46–58. https://doi.org/10.1016/j.lfs.2016.01.024

    Article  CAS  PubMed  Google Scholar 

  9. Balogh E, Tolnai E, Nagy B Jr, Nagy B, Balla G, Balla J, Jeney V (2016) Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin. Biochim Biophys Acta 1862(9):1640–1649. https://doi.org/10.1016/j.bbadis.2016.06.003

    Article  CAS  PubMed  Google Scholar 

  10. Chen B, Yan YL, Liu C, Bo L, Li GF, Wang H, Xu YJ (2014) Therapeutic effect of deferoxamine on iron overload-induced inhibition of osteogenesis in a zebrafish model. Calcif Tissue Int 94(3):353–360. https://doi.org/10.1007/s00223-013-9817-4

    Article  CAS  PubMed  Google Scholar 

  11. Zhang AS, Enns CA (2009) Iron homeostasis: recently identified proteins provide insight into novel control mechanisms. J Biol Chem 284(2):711–715. https://doi.org/10.1074/jbc.R800017200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Camaschella C (2015) Iron-deficiency anemia. N Engl J Med 372(19):1832–1843. https://doi.org/10.1056/NEJMra1401038

    Article  PubMed  Google Scholar 

  13. Fuqua BK, Vulpe CD, Anderson GJ (2012) Intestinal iron absorption. J Trace Elem Med Biol 26(2–3):115–119. https://doi.org/10.1016/j.jtemb.2012.03.015

    Article  CAS  PubMed  Google Scholar 

  14. Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC (2005) The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 1(3):191–200. https://doi.org/10.1016/j.cmet.2005.01.003

    Article  CAS  PubMed  Google Scholar 

  15. Frazer DM, Anderson GJ (2014) The regulation of iron transport. Biofactors 40(2):206–214. https://doi.org/10.1002/biof.1148

    Article  CAS  PubMed  Google Scholar 

  16. Theil EC (2013) Ferritin: the protein nanocage and iron biomineral in health and in disease. Inorg Chem 52(21):12223–12233. https://doi.org/10.1021/ic400484n

    Article  CAS  PubMed  Google Scholar 

  17. Drakesmith H, Nemeth E, Ganz T (2015) Ironing out ferroportin. Cell Metab 22(5):777–787. https://doi.org/10.1016/j.cmet.2015.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lakhal-Littleton S, Wolna M, Carr CA, Miller JJ, Christian HC, Ball V, Santos A, Diaz R, Biggs D, Stillion R, Holdship P, Larner F, Tyler DJ, Clarke K, Davies B, Robbins PA (2015) Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function. Proc Natl Acad Sci U S A 112(10):3164–3169. https://doi.org/10.1073/pnas.1422373112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mayle KM, Le AM, Kamei DT (2012) The intracellular trafficking pathway of transferrin. Biochim Biophys Acta 1820(3):264–281. https://doi.org/10.1016/j.bbagen.2011.09.009

    Article  CAS  PubMed  Google Scholar 

  20. Recalcati S, Gammella E, Buratti P, Cairo G (2017) Molecular regulation of cellular iron balance. IUBMB Life 69(6):389–398. https://doi.org/10.1002/iub.1628

    Article  CAS  PubMed  Google Scholar 

  21. Arosio P, Levi S (2010) Cytosolic and mitochondrial ferritins in the regulation of cellular iron homeostasis and oxidative damage. Biochim Biophys Acta 1800(8):783–792. https://doi.org/10.1016/j.bbagen.2010.02.005

    Article  CAS  PubMed  Google Scholar 

  22. Milto IV, Grishanova AY, Klimenteva TK, Suhodolo IV, Vasukov GY, Ivanova VV (2014) Iron metabolism after application of modified magnetite nanoparticles in rats. Biochemistry (Mosc) 79(11):1245–1254. https://doi.org/10.1134/S0006297914110121

    Article  CAS  Google Scholar 

  23. Recalcati S, Minotti G, Cairo G (2010) Iron regulatory proteins: from molecular mechanisms to drug development. Antioxid Redox Signal 13(10):1593–1616. https://doi.org/10.1089/ars.2009.2983

    Article  CAS  PubMed  Google Scholar 

  24. Wilkinson N, Pantopoulos K (2014) The IRP/IRE system in vivo: insights from mouse models. Front Pharmacol 5:176. https://doi.org/10.3389/fphar.2014.00176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Thompson JW, Bruick RK (2012) Protein degradation and iron homeostasis. Biochim Biophys Acta 1823(9):1484–1490. https://doi.org/10.1016/j.bbamcr.2012.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Xu W, Barrientos T, Andrews NC (2013) Iron and copper in mitochondrial diseases. Cell Metab 17(3):319–328. https://doi.org/10.1016/j.cmet.2013.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Peyssonnaux C, Nizet V, Johnson RS (2008) Role of the hypoxia inducible factors HIF in iron metabolism. Cell Cycle 7(1):28–32. https://doi.org/10.4161/cc.7.1.5145

    Article  CAS  PubMed  Google Scholar 

  28. Hou Y, Zhang S, Wang L, Li J, Qu G, He J, Rong H, Ji H, Liu S (2012) Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene 511(2):398–403. https://doi.org/10.1016/j.gene.2012.09.060

    Article  CAS  PubMed  Google Scholar 

  29. Park CH, Waring AJ, Ganz T (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver. https://doi.org/10.1074/jbc.M008922200

  30. Zhao N, Zhang AS, Enns CA (2013) Iron regulation by hepcidin. J Clin Invest 123(6):2337–2343. https://doi.org/10.1172/JCI67225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306(5704):2090–2093. https://doi.org/10.1126/science.1104742

    Article  CAS  PubMed  Google Scholar 

  32. Anderson GJ, Frazer DM (2017) Current understanding of iron homeostasis. Am J Clin Nutr 106(Suppl 6):1559S–1566S. https://doi.org/10.3945/ajcn.117.155804

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mendel GA (1961) Studies on iron absorption. I. The relationships between the rate of erythropoiesis, hypoxia and iron absorption. Blood 18:727–736

    Article  CAS  PubMed  Google Scholar 

  34. Ganz T (2019) Erythropoietic regulators of iron metabolism. Free Radic Biol Med 133:69–74. https://doi.org/10.1016/j.freeradbiomed.2018.07.003

    Article  CAS  PubMed  Google Scholar 

  35. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T (2014) Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 46(7):678–684. https://doi.org/10.1038/ng.2996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang CY, Core AB, Canali S, Zumbrennen-Bullough KB, Ozer S, Umans L, Zwijsen A, Babitt JL (2017) Smad1/5 is required for erythropoietin-mediated suppression of hepcidin in mice. Blood 130(1):73–83. https://doi.org/10.1182/blood-2016-12-759423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Murphy CJ, Oudit GY (2010) Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. J Card Fail 16(11):888–900. https://doi.org/10.1016/j.cardfail.2010.05.009

    Article  CAS  PubMed  Google Scholar 

  38. Andrews NC (2008) Forging a field: the golden age of iron biology. Blood 112(2):219–230. https://doi.org/10.1182/blood-2007-12-077388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Sawicki KT, Shang M, Wu R, Chang HC, Khechaduri A, Sato T, Kamide C, Liu T, Naga Prasad SV, Ardehali H (2015) Increased heme levels in the heart lead to exacerbated ischemic injury. J Am Heart Assoc 4(8):e002272. https://doi.org/10.1161/JAHA.115.002272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Khechaduri A, Bayeva M, Chang HC, Ardehali H (2013) Heme levels are increased in human failing hearts. J Am Coll Cardiol 61(18):1884–1893. https://doi.org/10.1016/j.jacc.2013.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC (2015) Lethal cardiomyopathy in mice lacking transferrin receptor in the heart. Cell Rep 13(3):533–545. https://doi.org/10.1016/j.celrep.2015.09.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chang HC, Wu R, Shang M, Sato T, Chen C, Shapiro JS, Liu T, Thakur A, Sawicki KT, Prasad SV, Ardehali H (2016) Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med 8(3):247–267. https://doi.org/10.15252/emmm.201505748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kali A, Kumar A, Cokic I, Tang RL, Tsaftaris SA, Friedrich MG, Dharmakumar R (2013) Chronic manifestation of postreperfusion intramyocardial hemorrhage as regional iron deposition: a cardiovascular magnetic resonance study with ex vivo validation. Circ Cardiovasc Imaging 6(2):218–228. https://doi.org/10.1161/CIRCIMAGING.112.000133

    Article  PubMed  Google Scholar 

  44. Carberry J, Carrick D, Haig C, Ahmed N, Mordi I, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay M, Davie A, Mahrous A, Ford I, Sattar N, Welsh P, Radjenovic A, Oldroyd KG, Berry C (2018) Persistent iron within the infarct core after ST-segment elevation myocardial infarction: implications for left ventricular remodeling and health outcomes. JACC Cardiovasc Imaging 11(9):1248–1256. https://doi.org/10.1016/j.jcmg.2017.08.027

    Article  PubMed  PubMed Central  Google Scholar 

  45. Singh N, Haldar S, Tripathi AK, Horback K, Wong J, Sharma D, Beserra A, Suda S, Anbalagan C, Dev S, Mukhopadhyay CK, Singh A (2014) Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid Redox Signal 20(8):1324–1363. https://doi.org/10.1089/ars.2012.4931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rouault TA (2013) Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci 14(8):551–564. https://doi.org/10.1038/nrn3453

    Article  CAS  PubMed  Google Scholar 

  47. Fretham SJ, Carlson ES, Georgieff MK (2011) The role of iron in learning and memory. Adv Nutr 2(2):112–121. https://doi.org/10.3945/an.110.000190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Salazar J, Mena N, Hunot S, Prigent A, Alvarez-Fischer D, Arredondo M, Duyckaerts C, Sazdovitch V, Zhao L, Garrick LM, Nunez MT, Garrick MD, Raisman-Vozari R, Hirsch EC (2008) Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson’s disease. Proc Natl Acad Sci U S A 105(47):18578–18583. https://doi.org/10.1073/pnas.0804373105

    Article  PubMed  PubMed Central  Google Scholar 

  49. Boll MC, Sotelo J, Otero E, Alcaraz-Zubeldia M, Rios C (1999) Reduced ferroxidase activity in the cerebrospinal fluid from patients with Parkinson’s disease. Neurosci Lett 265(3):155–158

    Article  CAS  PubMed  Google Scholar 

  50. Martinez-Hernandez R, Montes S, Higuera-Calleja J, Yescas P, Boll MC, Diaz-Ruiz A, Rios C (2011) Plasma ceruloplasmin ferroxidase activity correlates with the nigral sonographic area in Parkinson’s disease patients: a pilot study. Neurochem Res 36(11):2111–2115. https://doi.org/10.1007/s11064-011-0535-x

    Article  CAS  PubMed  Google Scholar 

  51. Yamamoto A, Shin RW, Hasegawa K, Naiki H, Sato H, Yoshimasu F, Kitamoto T (2002) Iron (III) induces aggregation of hyperphosphorylated tau and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J Neurochem 82(5):1137–1147

    Article  CAS  PubMed  Google Scholar 

  52. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (2010) Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited by zinc in Alzheimer’s disease. Cell 142(6):857–867. https://doi.org/10.1016/j.cell.2010.08.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Williams R, Buchheit CL, Berman NE, LeVine SM (2012) Pathogenic implications of iron accumulation in multiple sclerosis. J Neurochem 120(1):7–25. https://doi.org/10.1111/j.1471-4159.2011.07536.x

    Article  CAS  PubMed  Google Scholar 

  54. Lassmann H, van Horssen J, Mahad D (2012) Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol 8(11):647–656. https://doi.org/10.1038/nrneurol.2012.168

    Article  CAS  PubMed  Google Scholar 

  55. Cooksey RC, Jouihan HA, Ajioka RS, Hazel MW, Jones DL, Kushner JP, McClain DA (2004) Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology 145(11):5305–5312. https://doi.org/10.1210/en.2004-0392

    Article  CAS  PubMed  Google Scholar 

  56. Gabrielsen JS, Gao Y, Simcox JA, Huang J, Thorup D, Jones D, Cooksey RC, Gabrielsen D, Adams TD, Hunt SC, Hopkins PN, Cefalu WT, McClain DA (2012) Adipocyte iron regulates adiponectin and insulin sensitivity. J Clin Invest 122(10):3529–3540. https://doi.org/10.1172/JCI44421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kukulj S, Jaganjac M, Boranic M, Krizanac S, Santic Z, Poljak-Blazi M (2010) Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer. Med Oncol 27(2):268–277. https://doi.org/10.1007/s12032-009-9203-2

    Article  CAS  PubMed  Google Scholar 

  58. Babu KR, Muckenthaler MU (2016) miR-20a regulates expression of the iron exporter ferroportin in lung cancer. J Mol Med (Berl) 94(3):347–359. https://doi.org/10.1007/s00109-015-1362-3

    Article  CAS  Google Scholar 

  59. Fu Y, Chung FL (2018) Oxidative stress and hepatocarcinogenesis. Hepatoma Res 4. https://doi.org/10.20517/2394-5079.2018.29

  60. Raza M, Chakraborty S, Choudhury M, Ghosh PC, Nag A (2014) Cellular iron homeostasis and therapeutic implications of iron chelators in cancer. Curr Pharm Biotechnol 15(12):1125–1140

    Article  CAS  PubMed  Google Scholar 

  61. Jabara HH, Boyden SE, Chou J, Ramesh N, Massaad MJ, Benson H, Bainter W, Fraulino D, Rahimov F, Sieff C, Liu ZJ, Alshemmari SH, Al-Ramadi BK, Al-Dhekri H, Arnaout R, Abu-Shukair M, Vatsayan A, Silver E, Ahuja S, Davies EG, Sola-Visner M, Ohsumi TK, Andrews NC, Notarangelo LD, Fleming MD, Al-Herz W, Kunkel LM, Geha RS (2016) A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nat Genet 48(1):74–78. https://doi.org/10.1038/ng.3465

    Article  CAS  PubMed  Google Scholar 

  62. Oexle H, Kaser A, Most J, Bellmann-Weiler R, Werner ER, Werner-Felmayer G, Weiss G (2003) Pathways for the regulation of interferon-gamma-inducible genes by iron in human monocytic cells. J Leukoc Biol 74(2):287–294

    Article  CAS  PubMed  Google Scholar 

  63. Nairz M, Theurl I, Ludwiczek S, Theurl M, Mair SM, Fritsche G, Weiss G (2007) The co-ordinated regulation of iron homeostasis in murine macrophages limits the availability of iron for intracellular Salmonella typhimurium. Cell Microbiol 9(9):2126–2140. https://doi.org/10.1111/j.1462-5822.2007.00942.x

    Article  CAS  PubMed  Google Scholar 

  64. Weiss G (2002) Iron and immunity: a double-edged sword. Eur J Clin Investig 32(Suppl 1):70–78

    Article  CAS  Google Scholar 

  65. Camacho A, Simao M, Ea HK, Cohen-Solal M, Richette P, Branco J, Cancela ML (2016) Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress. Osteoarthr Cartil 24(3):494–502. https://doi.org/10.1016/j.joca.2015.09.007

    Article  CAS  Google Scholar 

  66. Marzetti E, Lees HA, Wohlgemuth SE, Leeuwenburgh C (2009) Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Biofactors 35(1):28–35. https://doi.org/10.1002/biof.5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Levi S, Rovida E (2009) The role of iron in mitochondrial function. Biochim Biophys Acta 1790(7):629–636. https://doi.org/10.1016/j.bbagen.2008.09.008

    Article  CAS  PubMed  Google Scholar 

  68. Medeiros DM, Stoecker B, Plattner A, Jennings D, Haub M (2004) Iron deficiency negatively affects vertebrae and femurs of rats independently of energy intake and body weight. J Nutr 134(11):3061–3067. https://doi.org/10.1093/jn/134.11.3061

    Article  CAS  PubMed  Google Scholar 

  69. Parelman M, Stoecker B, Baker A, Medeiros D (2006) Iron restriction negatively affects bone in female rats and mineralization of hFOB osteoblast cells. Exp Biol Med (Maywood) 231(4):378–386

    Article  CAS  Google Scholar 

  70. Toxqui L, Vaquero MP (2015) Chronic iron deficiency as an emerging risk factor for osteoporosis: a hypothesis. Nutrients 7(4):2324–2344. https://doi.org/10.3390/nu7042324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zofkova I, Davis M, Blahos J (2017) Trace elements have beneficial, as well as detrimental effects on bone homeostasis. Physiol Res 66(3):391–402

    Article  CAS  PubMed  Google Scholar 

  72. Lu W, Zhao M, Rajbhandary S, Xie F, Chai X, Mu J, Meng J, Liu Y, Jiang Y, Xu X, Meng A (2013) Free iron catalyzes oxidative damage to hematopoietic cells/mesenchymal stem cells in vitro and suppresses hematopoiesis in iron overload patients. Eur J Haematol 91(3):249–261. https://doi.org/10.1111/ejh.12159

    Article  CAS  PubMed  Google Scholar 

  73. Gattermann N (2009) The treatment of secondary hemochromatosis. Dtsch Arztebl Int 106(30):499–504, I. https://doi.org/10.3238/arztebl.2009.0499

    Article  PubMed  PubMed Central  Google Scholar 

  74. Chalès G, Guggenbuhl P (2003) When and how should we screen for hereditary hemochromatosis? Joint Bone Spine 70(4):263–270. https://doi.org/10.1016/s1297-319x(03)00035-6

    Article  PubMed  Google Scholar 

  75. Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS, American Association for the Study of Liver D (2011) Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 54(1):328–343. https://doi.org/10.1002/hep.24330

    Article  PubMed  Google Scholar 

  76. Pietrangelo A (2016) Iron and the liver. Liver Int 36(Suppl 1):116–123. https://doi.org/10.1111/liv.13020

    Article  CAS  PubMed  Google Scholar 

  77. Manz DH, Blanchette NL, Paul BT, Torti FM, Torti SV (2016) Iron and cancer: recent insights. Ann N Y Acad Sci 1368(1):149–161. https://doi.org/10.1111/nyas.13008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bystrom LM, Rivella S (2015) Cancer cells with irons in the fire. Free Radic Biol Med 79:337–342. https://doi.org/10.1016/j.freeradbiomed.2014.04.035

    Article  CAS  PubMed  Google Scholar 

  79. Xiong W, Wang L, Yu F (2014) Regulation of cellular iron metabolism and its implications in lung cancer progression. Med Oncol 31(7):28. https://doi.org/10.1007/s12032-014-0028-2

    Article  CAS  PubMed  Google Scholar 

  80. Zhang C, Zhang F (2015) Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities. Protein Cell 6(2):88–100. https://doi.org/10.1007/s13238-014-0119-z

    Article  CAS  PubMed  Google Scholar 

  81. Orlandi R, De Bortoli M, Ciniselli CM, Vaghi E, Caccia D, Garrisi V, Pizzamiglio S, Veneroni S, Bonini C, Agresti R, Daidone MG, Morelli D, Camaschella C, Verderio P, Bongarzone I (2014) Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer. Ann Oncol 25(2):352–357. https://doi.org/10.1093/annonc/mdt490

    Article  CAS  PubMed  Google Scholar 

  82. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072. https://doi.org/10.1016/j.cell.2012.03.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Guan J, Lo M, Dockery P, Mahon S, Karp CM, Buckley AR, Lam S, Gout PW, Wang YZ (2009) The xc- cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine. Cancer Chemother Pharmacol 64(3):463–472. https://doi.org/10.1007/s00280-008-0894-4

    Article  CAS  PubMed  Google Scholar 

  84. Dixon SJ, Stockwell BR (2014) The role of iron and reactive oxygen species in cell death. Nat Chem Biol 10(1):9–17. https://doi.org/10.1038/nchembio.1416

    Article  CAS  PubMed  Google Scholar 

  85. Woo JH, Shimoni Y, Yang WS, Subramaniam P, Iyer A, Nicoletti P, Rodriguez Martinez M, Lopez G, Mattioli M, Realubit R, Karan C, Stockwell BR, Bansal M, Califano A (2015) Elucidating compound mechanism of action by network perturbation analysis. Cell 162(2):441–451. https://doi.org/10.1016/j.cell.2015.05.056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Beard JL (2001) Iron biology in immune function, muscle metabolism and neuronal functioning

  87. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L (2016) Iron deficiency anaemia. Lancet 387(10021):907–916. https://doi.org/10.1016/S0140-6736(15)60865-0

    Article  CAS  PubMed  Google Scholar 

  88. Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA (2013) Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 165(4):575–582 e573. https://doi.org/10.1016/j.ahj.2013.01.017

    Article  CAS  PubMed  Google Scholar 

  89. Youdim MB (2008) Brain iron deficiency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus. Neurotox Res 14(1):45–56

    Article  CAS  PubMed  Google Scholar 

  90. Kdoqi, National Kidney F (2006) KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis 47(5 Suppl 3):S11–S145. https://doi.org/10.1053/j.ajkd.2006.03.010

  91. Jonker FA, Boele van Hensbroek M (2014) Anaemia, iron deficiency and susceptibility to infections. J Inf Secur 69(Suppl 1):S23–S27. https://doi.org/10.1016/j.jinf.2014.08.007

    Article  Google Scholar 

  92. Sapir-Koren R, Livshits G (2017) Postmenopausal osteoporosis in rheumatoid arthritis: the estrogen deficiency-immune mechanisms link. Bone 103:102–115. https://doi.org/10.1016/j.bone.2017.06.020

    Article  PubMed  Google Scholar 

  93. Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC, Wang DD (2016) Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int 27(1):367–376. https://doi.org/10.1007/s00198-015-3386-5

    Article  CAS  PubMed  Google Scholar 

  94. Dresner Pollack R, Rachmilewitz E, Blumenfeld A, Idelson M, Goldfarb AW (2000) Bone mineral metabolism in adults with beta-thalassaemia major and intermedia. Br J Haematol 111(3):902–907

    CAS  PubMed  Google Scholar 

  95. Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283(2–3):65–87. https://doi.org/10.1016/j.tox.2011.03.001

    Article  CAS  PubMed  Google Scholar 

  96. Jeney V (2017) Clinical impact and cellular mechanisms of iron overload-associated bone loss. Front Pharmacol 8. https://doi.org/10.3389/fphar.2017.00077

  97. Matsushima S, Hoshimoto M, Torii M, Ozaki K, Narama I (2001) Iron lactate-induced osteopenia in male Sprague-Dawley rats. Toxicol Pathol 29(6):623–629. https://doi.org/10.1080/019262301753385951

    Article  CAS  PubMed  Google Scholar 

  98. Doyard M, Chappard D, Leroyer P, Roth MP, Loreal O, Guggenbuhl P (2016) Decreased bone formation explains osteoporosis in a genetic mouse model of hemochromatosiss. PLoS One 11(2):e0148292. https://doi.org/10.1371/journal.pone.0148292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Isomura H, Fujie K, Shibata K, Inoue N, Iizuka T, Takebe G, Takahashi K, Nishihira J, Izumi H, Sakamoto W (2004) Bone metabolism and oxidative stress in postmenopausal rats with iron overload. Toxicology 197(2):93–100. https://doi.org/10.1016/j.tox.2003.12.006

    Article  CAS  PubMed  Google Scholar 

  100. Tsay J, Yang Z, Ross FP, Cunningham-Rundles S, Lin H, Coleman R, Mayer-Kuckuk P, Doty SB, Grady RW, Giardina PJ, Boskey AL, Vogiatzi MG (2010) Bone loss caused by iron overload in a murine model: importance of oxidative stress. Blood 116(14):2582–2589. https://doi.org/10.1182/blood-2009-12-260083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Cheng Q, Zhang X, Jiang J, Zhao G, Wang Y, Xu Y, Xu X, Ma H (2017) Postmenopausal iron overload exacerbated bone loss by promoting the degradation of type I collagen. Biomed Res Int 2017:1–9. https://doi.org/10.1155/2017/1345193

    Article  CAS  Google Scholar 

  102. Zaidi M (2007) Skeletal remodeling in health and disease. Nat Med 13(7):791–801. https://doi.org/10.1038/nm1593

    Article  CAS  PubMed  Google Scholar 

  103. Fung EB, Harmatz PR, Milet M, Coates TD, Thompson AA, Ranalli M, Mignaca R, Scher C, Giardina P, Robertson S, Neumayr L, Vichinsky EP, Multi-Center Iron Overload Study G (2008) Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia. Bone 43(1):162–168. https://doi.org/10.1016/j.bone.2008.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Hofbauer LC, Kuhne CA, Viereck V (2004) The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact 4(3):268–275

    CAS  PubMed  Google Scholar 

  105. Ikeda K, Takeshita S (2016) The role of osteoclast differentiation and function in skeletal homeostasis. J Biochem 159(1):1–8. https://doi.org/10.1093/jb/mvv112

    Article  CAS  PubMed  Google Scholar 

  106. Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H, Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K (2009) Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med 15(3):259–266. https://doi.org/10.1038/nm.1910

    Article  CAS  PubMed  Google Scholar 

  107. Jia P, Xu YJ, Zhang ZL, Li K, Li B, Zhang W, Yang H (2012) Ferric ion could facilitate osteoclast differentiation and bone resorption through the production of reactive oxygen species. J Orthop Res 30(11):1843–1852. https://doi.org/10.1002/jor.22133

    Article  CAS  PubMed  Google Scholar 

  108. Doyard M, Fatih N, Monnier A, Island ML, Aubry M, Leroyer P, Bouvet R, Chales G, Mosser J, Loreal O, Guggenbuhl P (2012) Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells. Osteoporos Int 23(10):2435–2445. https://doi.org/10.1007/s00198-011-1871-z

    Article  CAS  PubMed  Google Scholar 

  109. Messer JG, Kilbarger AK, Erikson KM, Kipp DE (2009) Iron overload alters iron-regulatory genes and proteins, down-regulates osteoblastic phenotype, and is associated with apoptosis in fetal rat calvaria cultures. Bone 45(5):972–979. https://doi.org/10.1016/j.bone.2009.07.073

    Article  CAS  PubMed  Google Scholar 

  110. Yamasaki K, Hagiwara H (2009) Excess iron inhibits osteoblast metabolism. Toxicol Lett 191(2–3):211–215. https://doi.org/10.1016/j.toxlet.2009.08.023

    Article  CAS  PubMed  Google Scholar 

  111. Wynnyckyj C, Omelon S, Savage K, Damani M, Chachra D, Grynpas MD (2009) A new tool to assess the mechanical properties of bone due to collagen degradation. Bone 44(5):840–848. https://doi.org/10.1016/j.bone.2008.12.014

    Article  CAS  PubMed  Google Scholar 

  112. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89(5):747–754

    Article  CAS  PubMed  Google Scholar 

  113. Gammella E, Recalcati S, Cairo G (2016) Dual role of ROS as signal and stress agents: iron tips the balance in favor of toxic effects. Oxidative Med Cell Longev 2016:8629024. https://doi.org/10.1155/2016/8629024

    Article  CAS  Google Scholar 

  114. Zheng QQ, Zhao YS, Guo J, Zhao SD, Song LX, Fei CM, Zhang Z, Li X, Chang CK (2017) Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome. Leuk Res 58:55–62. https://doi.org/10.1016/j.leukres.2017.04.005

    Article  CAS  PubMed  Google Scholar 

  115. Filaire E, Toumi H (2012) Reactive oxygen species and exercise on bone metabolism: friend or enemy? Joint Bone Spine 79(4):341–346. https://doi.org/10.1016/j.jbspin.2012.03.007

    Article  CAS  PubMed  Google Scholar 

  116. Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24(5):981–990. https://doi.org/10.1016/j.cellsig.2012.01.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314(1):197–207

    Article  CAS  PubMed  Google Scholar 

  118. Lee DH, Lim BS, Lee YK, Yang HC (2006) Effects of hydrogen peroxide (H2O2) on alkaline phosphatase activity and matrix mineralization of odontoblast and osteoblast cell lines. Cell Biol Toxicol 22(1):39–46. https://doi.org/10.1007/s10565-006-0018-z

    Article  CAS  PubMed  Google Scholar 

  119. Fontani F, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT (2015) Glutathione, N-acetylcysteine and lipoic acid down-regulate starvation-induced apoptosis, RANKL/OPG ratio and sclerostin in osteocytes: involvement of JNK and ERK1/2 signalling. Calcif Tissue Int 96(4):335–346. https://doi.org/10.1007/s00223-015-9961-0

    Article  CAS  PubMed  Google Scholar 

  120. Grosbois B, Decaux O, Cador B, Cazalets C, Jego P (2005) Human iron deficiency. Bull Acad Natl Med 189(8):1649–1663 discussion 1663-1644

    CAS  PubMed  Google Scholar 

  121. Balogh E, Paragh G, Jeney V (2018) Influence of iron on bone homeostasis. Pharmaceuticals (Basel) 11(4). https://doi.org/10.3390/ph11040107

  122. Gorres KL, Raines RT (2010) Prolyl 4-hydroxylase. Crit Rev Biochem Mol Biol 45(2):106–124. https://doi.org/10.3109/10409231003627991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Goltzman D (2018) Functions of vitamin D in bone. Histochem Cell Biol 149(4):305–312. https://doi.org/10.1007/s00418-018-1648-y

    Article  CAS  PubMed  Google Scholar 

  124. Shayman JA (2014) Thematic review series: recent advances in the treatment of lysosomal storage diseases. J Lipid Res 55(6):993–994. https://doi.org/10.1194/jlr.E049817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Zhao GY, Zhao LP, He YF, Li GF, Gao C, Li K, Xu YJ (2012) A comparison of the biological activities of human osteoblast hFOB1.19 between iron excess and iron deficiency. Biol Trace Elem Res 150(1–3):487–495. https://doi.org/10.1007/s12011-012-9511-9

    Article  CAS  PubMed  Google Scholar 

  126. Katsumata S, Katsumata-Tsuboi R, Uehara M, Suzuki K (2009) Severe iron deficiency decreases both bone formation and bone resorption in rats. J Nutr 139(2):238–243. https://doi.org/10.3945/jn.108.093757

    Article  CAS  PubMed  Google Scholar 

  127. Diaz-Castro J, Lopez-Frias MR, Campos MS, Lopez-Frias M, Alferez MJ, Nestares T, Ojeda ML, Lopez-Aliaga I (2012) Severe nutritional iron-deficiency anaemia has a negative effect on some bone turnover biomarkers in rats. Eur J Nutr 51(2):241–247. https://doi.org/10.1007/s00394-011-0212-5

    Article  CAS  PubMed  Google Scholar 

  128. Toxqui L, Perez-Granados AM, Blanco-Rojo R, Wright I, de la Piedra C, Vaquero MP (2014) Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women. Eur J Nutr 53(2):441–448. https://doi.org/10.1007/s00394-013-0544-4

    Article  CAS  PubMed  Google Scholar 

  129. Chang K, Chang WH (2003) Pulsed electromagnetic fields prevent osteoporosis in an ovariectomized female rat model: a prostaglandin E2-associated process. Bioelectromagnetics 24(3):189–198. https://doi.org/10.1002/bem.10078

    Article  CAS  PubMed  Google Scholar 

  130. Sert C, Mustafa D, Duz MZ, Aksen F, Kaya A (2002) The preventive effect on bone loss of 50-Hz, 1-mT electromagnetic field in ovariectomized rats. J Bone Miner Metab 20(6):345–349. https://doi.org/10.1007/s007740200050

    Article  CAS  PubMed  Google Scholar 

  131. Jing D, Cai J, Wu Y, Shen G, Li F, Xu Q, Xie K, Tang C, Liu J, Guo W, Wu X, Jiang M, Luo E (2014) Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats. J Bone Miner Res 29(10):2250–2261. https://doi.org/10.1002/jbmr.2260

    Article  CAS  PubMed  Google Scholar 

  132. Zhou J, Li X, Liao Y, Feng W, Fu C, Guo X (2015) Pulsed electromagnetic fields inhibit bone loss in streptozotocin-induced diabetic rats. Endocrine 49(1):258–266. https://doi.org/10.1007/s12020-014-0439-z

    Article  CAS  PubMed  Google Scholar 

  133. Yan JL, Zhou J, Ma HP, Ma XN, Gao YH, Shi WG, Fang QQ, Ren Q, Xian CJ, Chen KM (2015) Pulsed electromagnetic fields promote osteoblast mineralization and maturation needing the existence of primary cilia. Mol Cell Endocrinol 404:132–140. https://doi.org/10.1016/j.mce.2015.01.031

    Article  CAS  PubMed  Google Scholar 

  134. Zhai M, Jing D, Tong S, Wu Y, Wang P, Zeng Z, Shen G, Wang X, Xu Q, Luo E (2016) Pulsed electromagnetic fields promote in vitro osteoblastogenesis through a Wnt/beta-catenin signaling-associated mechanism. Bioelectromagnetics 37(3):152–162. https://doi.org/10.1002/bem.21961

    Article  CAS  PubMed  Google Scholar 

  135. Chang K, Chang WH, Tsai MT, Shih C (2006) Pulsed electromagnetic fields accelerate apoptotic rate in osteoclasts. Connect Tissue Res 47(4):222–228. https://doi.org/10.1080/03008200600858783

    Article  PubMed  Google Scholar 

  136. Aydin N, Bezer M (2011) The effect of an intramedullary implant with a static magnetic field on the healing of the osteotomised rabbit femur. Int Orthop 35(1):135–141. https://doi.org/10.1007/s00264-009-0932-9

    Article  PubMed  Google Scholar 

  137. Taniguchi N, Kanai S (2007) Efficacy of static magnetic field for locomotor activity of experimental osteopenia. Evid Based Complement Alternat Med 4(1):99–105. https://doi.org/10.1093/ecam/nel067

    Article  PubMed  Google Scholar 

  138. Kotani H, Kawaguchi H, Shimoaka T, Iwasaka M, Ueno S, Ozawa H, Nakamura K, Hoshi K (2002) Strong static magnetic field stimulates bone formation to a definite orientation in vitro and in vivo. J Bone Miner Res 17(10):1814–1821. https://doi.org/10.1359/jbmr.2002.17.10.1814

    Article  PubMed  Google Scholar 

  139. Qian AR, Gao X, Zhang W, Li JB, Wang Y, Di SM, Hu LF, Shang P (2013) Large gradient high magnetic fields affect osteoblast ultrastructure and function by disrupting collagen I or fibronectin/alphabeta1 integrin. PLoS One 8(1):e51036. https://doi.org/10.1371/journal.pone.0051036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Yang J, Zhang J, Ding C, Dong D, Shang P (2018) Regulation of osteoblast differentiation and iron content in MC3T3-E1 cells by static magnetic field with different intensities. Biol Trace Elem Res 184(1):214–225. https://doi.org/10.1007/s12011-017-1161-5

    Article  CAS  PubMed  Google Scholar 

  141. Zhang J, Ding C, Shang P (2014) Alterations of mineral elements in osteoblast during differentiation under hypo, moderate and high static magnetic fields. Biol Trace Elem Res 162(1–3):153–157. https://doi.org/10.1007/s12011-014-0157-7

    Article  CAS  PubMed  Google Scholar 

  142. Wu D, Wen X, Liu W, Hu H, Ye B, Zhou Y (2018) Comparison of the effects of deferasirox, deferoxamine, and combination of deferasirox and deferoxamine on an aplastic anemia mouse model complicated with iron overload. Drug Des Devel Ther 12:1081–1091. https://doi.org/10.2147/DDDT.S161086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Zhao Q, Shen X, Zhang W, Zhu G, Qi J, Deng L (2012) Mice with increased angiogenesis and osteogenesis due to conditional activation of HIF pathway in osteoblasts are protected from ovariectomy induced bone loss. Bone 50(3):763–770. https://doi.org/10.1016/j.bone.2011.12.003

    Article  CAS  PubMed  Google Scholar 

  144. Chung JH, Kim YS, Noh K, Lee YM, Chang SW, Kim EC (2014) Deferoxamine promotes osteoblastic differentiation in human periodontal ligament cells via the nuclear factor erythroid 2-related factor-mediated antioxidant signaling pathway. J Periodontal Res 49(5):563–573. https://doi.org/10.1111/jre.12136

    Article  CAS  PubMed  Google Scholar 

  145. Zhang J, Zheng L, Wang Z, Pei H, Hu W, Nie J, Shang P, Li B, Hei TK, Zhou G (2019) Lowering iron level protects against bone loss in focally irradiated and contralateral femurs through distinct mechanisms. Bone 120:50–60. https://doi.org/10.1016/j.bone.2018.10.005

    Article  CAS  PubMed  Google Scholar 

  146. Xu Z, Sun W, Li Y, Ling S, Zhao C, Zhong G, Zhao D, Song J, Song H, Li J, You L, Nie G, Chang Y, Li Y (2017) The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss. Bone 94:152–161. https://doi.org/10.1016/j.bone.2016.09.023

    Article  CAS  PubMed  Google Scholar 

  147. Chiu PF, Ko SY, Chang CC (2012) Vitamin C affects the expression of hepcidin and erythropoietin receptor in HepG2 cells. J Ren Nutr 22(3):373–376. https://doi.org/10.1053/j.jrn.2011.09.007

    Article  CAS  PubMed  Google Scholar 

  148. Deyhim F, Strong K, Deyhim N, Vandyousefi S, Stamatikos A, Faraji B (2019) Vitamin C reverses bone loss in an osteopenic rat model of osteoporosis. Int J Vitam Nutr Res:1–8. https://doi.org/10.1024/0300-9831/a000486

  149. Shen CL, Chyu MC, Wang JS (2013) Tea and bone health: steps forward in translational nutrition. Am J Clin Nutr 98(6 Suppl):1694S–1699S. https://doi.org/10.3945/ajcn.113.058255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Shen CL, Yeh JK, Cao JJ, Wang JS (2009) Green tea and bone metabolism. Nutr Res 29(7):437–456. https://doi.org/10.1016/j.nutres.2009.06.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Chen K, Qiu P, Yuan Y, Zheng L, He J, Wang C, Guo Q, Kenny J, Liu Q, Zhao J, Chen J, Tickner J, Fan S, Lin X, Xu J (2019) Pseurotin A inhibits osteoclastogenesis and prevents ovariectomized-induced bone loss by suppressing reactive oxygen species. Theranostics 9(6):1634–1650. https://doi.org/10.7150/thno.30206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Jing X, Du T, Chen K, Guo J, Xiang W, Yao X, Sun K, Ye Y, Guo F (2019) Icariin protects against iron overload-induced bone loss via suppressing oxidative stress. J Cell Physiol 234(7):10123–10137. https://doi.org/10.1002/jcp.27678

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Dr. Xu-Hui Li for the suggestions and comments. We thank Dr. Debiroundtree for the language support.

Funding

This review is supported by the National Natural Science Foundation of China (51777171), the Fundamental Research Funds for the Central Universities (3102017OQD111), the Northwestern Polytechnical University Foundation for Fundamental Research (3102018JGC012), and the Science and Technology Planning Project of Shenzhen of China (JCYJ20170412140904406).

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Authors and Affiliations

  1. Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, 518057, Guangdong, China

    Jingmin Che & Peng Shang

  2. School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072, Shaanxi, China

    Jingmin Che, Jiancheng Yang & Bin Zhao

  3. Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, 710072, Shaanxi, China

    Jingmin Che, Jiancheng Yang, Bin Zhao & Peng Shang

  4. Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, SAR, China

    Ge Zhang & Luyao Wang

  5. Department of Spine Surgery, Shenzhen People’s Hospital, Shenzhen, 518000, Guangdong, China

    Songlin Peng

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Che, J., Yang, J., Zhao, B. et al. The Effect of Abnormal Iron Metabolism on Osteoporosis. Biol Trace Elem Res 195, 353–365 (2020). https://doi.org/10.1007/s12011-019-01867-4

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