Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study

Bone

Volumn 98, Issue , 2017, Pages 1-8

  Lewerin, Catharina ^a   Ljunggren, Östen ^b   Nilsson Ehle, Herman ^a   Karlsson, Magnus K ^c   Herlitz, Hans ^a   Lorentzon, Mattias ^a   Ohlsson, Claes ^a   Mellström, Dan ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b UPPSALA UNIVERSITY   (Sweden)

^c LUND UNIVERSITY   (Sweden)

Author keywords

Bone mineral density; Elderly; Fibroblast growth factor 23; Intact FGF23; Iron; Men

Indexed keywords

25 HYDROXYVITAMIN D; APOLIPOPROTEIN A1; APOLIPOPROTEIN B; C REACTIVE PROTEIN; CALCIUM; CYSTATIN C; ERYTHROPOIETIN; FERRITIN; FIBROBLAST GROWTH FACTOR 23; HEMOGLOBIN; PARATHYROID HORMONE; PHOSPHATE; TRANSFERRIN; FIBROBLAST GROWTH FACTOR; IRON;

AGED; AGING; ANEMIA; ARTICLE; BODY MASS; BONE DENSITY; CONTROLLED STUDY; DISEASE ASSOCIATION; FERRITIN BLOOD LEVEL; GLOMERULUS FILTRATION RATE; HUMAN; IRON BLOOD LEVEL; IRON DEFICIENCY; LUMBAR SPINE; MAJOR CLINICAL STUDY; MALE; OBSERVATIONAL STUDY; POPULATION BASED CASE CONTROL STUDY; PREVALENCE; PROTEIN BLOOD LEVEL; SMOKING; TRANSFERRIN BLOOD LEVEL; VERY ELDERLY; VITAMIN BLOOD LEVEL; BLOOD; CLINICAL TRIAL; MIDDLE AGED; MULTICENTER STUDY; SWEDEN;

AGED; AGED, 80 AND OVER; FIBROBLAST GROWTH FACTORS; HUMANS; IRON; MALE; MIDDLE AGED; SWEDEN;

EID: 85013902911     PISSN: 87563282     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bone.2017.02.005     Document Type: Article

References (50)

1. [1] Mirams, M., Robinson, B.G., Mason, R.S., Nelson, A.E., Bone as a source of FGF23: regulation by phosphate?. Bone 35:5 (2004), 1192–1199.
2. [2] Bhattacharyya, N., Wiench, M., Dumitrescu, C., Connolly, B.M., Bugge, T.H., Patel, H.V., Gafni, R.I., Cherman, N., Cho, M., Hager, G.L., Collins, M.T., Mechanism of FGF23 processing in fibrous dysplasia. J. Bone Miner. Res. 27:5 (2012), 1132–1141.
3. [3] Shimada, T., Hasegawa, H., Yamazaki, Y., Muto, T., Hino, R., Takeuchi, Y., Fujita, T., Nakahara, K., Fukumoto, S., Yamashita, T., FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J. Bone Miner. Res. 19:3 (2004), 429–435.
4. [4] Mirza, M.A., Karlsson, M.K., Mellstrom, D., Orwoll, E., Ohlsson, C., Ljunggren, O., Larsson, T.E., Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men. J. Bone Miner. Res. 26:4 (2011), 857–864.
5. [5] Lane, N.E., Parimi, N., Corr, M., Yao, W., Cauley, J.A., Nielson, C.M., Ix, J.H., Kado, D., Orwoll, E., Association of serum fibroblast growth factor 23 (FGF23) and incident fractures in older men: the Osteoporotic Fractures in Men (MrOS) study. J. Bone Miner. Res. 28:11 (2013), 2325–2332.
6. [6] Berndt, T.J., Craig, T.A., McCormick, D.J., Lanske, B., Sitara, D., Razzaque, M.S., Pragnell, M., Bowe, A.E., O'Brien, S.P., Schiavi, S.C., Kumar, R., Biological activity of FGF-23 fragments. Pflugers Arch. 454:4 (2007), 615–623.
7. [7] Wolf, M., White, K.E., Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr. Opin. Nephrol. Hypertens. 23:4 (2014), 411–419.
8. [8] Rodriguez-Ortiz, M.E., Lopez, I., Munoz-Castaneda, J.R., Martinez-Moreno, J.M., Ramirez, A.P., Pineda, C., Canalejo, A., Jaeger, P., Aguilera-Tejero, E., Rodriguez, M., Felsenfeld, A., Almaden, Y., Calcium deficiency reduces circulating levels of FGF23. J. Am. Soc. Nephrol. 23:7 (2012), 1190–1197.
9. [9] Marsell, R., Grundberg, E., Krajisnik, T., Mallmin, H., Karlsson, M., Mellstrom, D., Orwoll, E., Ohlsson, C., Jonsson, K.B., Ljunggren, O., Larsson, T.E., Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men. Eur. J. Endocrinol. 158:1 (2008), 125–129.
10. [10] di Giuseppe, R., Kuhn, T., Hirche, F., Buijsse, B., Dierkes, J., Fritsche, A., Kaaks, R., Boeing, H., Stangl, G.I., Weikert, C., Potential predictors of plasma fibroblast growth factor 23 concentrations: cross-sectional analysis in the EPIC-Germany Study. PLoS One, 10(7), 2015, e0133580.
11. [11] David, V., Francis, C., Babitt, J.L., Ironing out the crosstalk between FGF23 and inflammation. Am. J. Phys. Renal Phys., 2016 (ajprenal 00359 2016).
12. [12] David, V., Martin, A., Isakova, T., Spaulding, C., Qi, L., Ramirez, V., Zumbrennen-Bullough, K.B., Sun, C.C., Lin, H.Y., Babitt, J.L., Wolf, M., Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int., 2015.
13. [13] Clinkenbeard, E.L., Farrow, E.G., Summers, L.J., Cass, T.A., Roberts, J.L., Bayt, C.A., Lahm, T., Albrecht, M., Allen, M.R., Peacock, M., White, K.E., Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice. J. Bone Miner. Res. 29:2 (2014), 361–369.
14. [14] Farrow, E.G., Yu, X., Summers, L.J., Davis, S.I., Fleet, J.C., Allen, M.R., Robling, A.G., Stayrook, K.R., Jideonwo, V., Magers, M.J., Garringer, H.J., Vidal, R., Chan, R.J., Goodwin, C.B., Hui, S.L., Peacock, M., White, K.E., Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc. Natl. Acad. Sci. U. S. A. 108:46 (2011), E1146–E1155.
15. [15] Imel, E.A., Gray, A.K., Padgett, L.R., Econs, M.J., Iron and fibroblast growth factor 23 in X-linked hypophosphatemia. Bone 60 (2014), 87–92.
16. [16] Imel, E.A., Peacock, M., Gray, A.K., Padgett, L.R., Hui, S.L., Econs, M.J., Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J. Clin. Endocrinol. Metab. 96:11 (2011), 3541–3549.
17. [17] Larsson, T., Nisbeth, U., Ljunggren, O., Juppner, H., Jonsson, K.B., Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 64:6 (2003), 2272–2279.
18. [18] Braithwaite, V., Jones, K.S., Assar, S., Schoenmakers, I., Prentice, A., Predictors of intact and C-terminal fibroblast growth factor 23 in Gambian children. Endocr Connect. 3:1 (2014), 1–10.
19. [19] Braithwaite, V.S., Prentice, A., Darboe, M.K., Prentice, A.M., Moore, S.E., The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism. Bone 83 (2016), 1–8.
20. [20] Braithwaite, V., Jarjou, L.M., Goldberg, G.R., Prentice, A., Iron status and fibroblast growth factor-23 in Gambian children. Bone 50:6 (2012), 1351–1356.
21. [21] Bozentowicz-Wikarek, M., Kocelak, P., Owczarek, A., Olszanecka-Glinianowicz, M., Mossakowska, M., Skalska, A., Wiecek, A., Chudek, J., Plasma fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population?. Clin. Biochem. 48:6 (2015), 431–436.
22. [22] Isakova, T., Cai, X., Lee, J., Katz, R., Cauley, J.A., Fried, L.F., Hoofnagle, A.N., Satterfield, S., Harris, T.B., Shlipak, M.G., Sarnak, M.J., Ix, J.H., Associations of FGF23 with change in bone mineral density and fracture risk in older individuals. J. Bone Miner. Res. 31:4 (2016), 742–748.
23. [23] Weinberg, E.D., Role of iron in osteoporosis. Pediatr. Endocrinol. Rev. 6:Suppl. 1 (2008), 81–85.
24. [24] Lopez, A., Cacoub, P., Macdougall, I.C., Peyrin-Biroulet, L., Iron deficiency anaemia. Lancet 387:10021 (2016), 907–916.
25. [25] Mellstrom, D., Vandenput, L., Mallmin, H., Holmberg, A.H., Lorentzon, M., Oden, A., Johansson, H., Orwoll, E.S., Labrie, F., Karlsson, M.K., Ljunggren, O., Ohlsson, C., Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J. Bone Miner. Res. 23:10 (2008), 1552–1560.
26. [26] Nutritional anaemias, Report of a WHO scientific group, World Health Organ Tech Rep Ser. 405, 1968, 5–37.
27. [27] Yamazaki, Y., Okazaki, R., Shibata, M., Hasegawa, Y., Satoh, K., Tajima, T., Takeuchi, Y., Fujita, T., Nakahara, K., Yamashita, T., Fukumoto, S., Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J. Clin. Endocrinol. Metab. 87:11 (2002), 4957–4960.
28. [28] Lewerin, C., Ljungman, S., Nilsson-Ehle, H., Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly. J. Intern. Med. 261:1 (2007), 65–73.
29. [29] Lewerin, C., Nilsson-Ehle, H., Jacobsson, S., Johansson, H., Sundh, V., Karlsson, M.K., Lorentzon, M., Barrett-Connor, E., Vandenput, L., Ohlsson, C., Mellstrom, D., Serum estradiol associates with blood hemoglobin in elderly men: the MrOS Sweden study. J. Clin. Endocrinol. Metab. 99:7 (2014), 2549–2556.
30. [30] Johansson, H., Oden, A., Lerner, U.H., Jutberger, H., Lorentzon, M., Barrett-Connor, E., Karlsson, M.K., Ljunggren, O., Smith, U., McCloskey, E., Kanis, J.A., Ohlsson, C., Mellstrom, D., High serum adiponectin predicts incident fractures in elderly men: osteoporotic fractures in men (MrOS) Sweden. J. Bone Miner. Res. 27:6 (2012), 1390–1396.
31. [31] Haghsheno, M.A., Mellstrom, D., Behre, C.J., Damber, J.E., Johansson, H., Karlsson, M., Lorentzon, M., Peeker, R., Barret-Connor, E., Waern, E., Sundh, V., Ohlsson, C., Hammarsten, J., Low 25-OH vitamin D is associated with benign prostatic hyperplasia. J. Urol. 190:2 (2013), 608–614.
32. [32] Mirza, M.A., Alsio, J., Hammarstedt, A., Erben, R.G., Michaelsson, K., Tivesten, A., Marsell, R., Orwoll, E., Karlsson, M.K., Ljunggren, O., Mellstrom, D., Lind, L., Ohlsson, C., Larsson, T.E., Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler. Thromb. Vasc. Biol. 31:1 (2011), 219–227.
33. [33] Siilin, H., Lundgren, E., Mallmin, H., Mellstrom, D., Ohlsson, C., Karlsson, M., Orwoll, E., Ljunggren, O., Prevalence of primary hyperparathyroidism and impact on bone mineral density in elderly men: MrOs Sweden. World J. Surg. 35:6 (2011), 1266–1272.
34. [34] Methods to Estimate and Measure Renal Function (Glomerular Filtration Rate): A Systematic Review. Stockholm: 2013 by the Swedish Council on Health Technology Assessment.; 2011.
35. [35] Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23, Nat Genet. 26 (3) (2000) 345-8.
36. [36] Kapelari, K., Kohle, J., Kotzot, D., Hogler, W., Iron supplementation associated with loss of phenotype in autosomal dominant hypophosphatemic rickets. J. Clin. Endocrinol. Metab. 100:9 (2015), 3388–3392.
37. [37] Imel, E.A., Liu, Z., McQueen, A.K., Acton, D., Acton, A., Padgett, L.R., Peacock, M., Econs, M.J., Serum fibroblast growth factor 23, serum iron and bone mineral density in premenopausal women. Bone 86 (2016), 98–105.
38. [38] Deger, S.M., Erten, Y., Pasaoglu, O.T., Derici, U.B., Reis, K.A., Onec, K., Pasaoglu, H., The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients. Clin. Exp. Nephrol. 17:3 (2013), 416–423.
39. [39] Marsell, R., Mirza, M.A., Mallmin, H., Karlsson, M., Mellstrom, D., Orwoll, E., Ohlsson, C., Jonsson, K.B., Ljunggren, O., Larsson, T.E., Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos. Int. 20:7 (2009), 1167–1173.
40. [40] Bhattacharyya, N., Chong, W.H., Gafni, R.I., Collins, M.T., Fibroblast growth factor 23: state of the field and future directions. Trends Endocrinol. Metab. 23:12 (2012), 610–618.
41. [41] Holecki, M., Chudek, J., Owczarek, A., Olszanecka-Glinianowicz, M., Bozentowicz-Wikarek, M., Dulawa, J., Mossakowska, M., Zdrojewski, T., Skalska, A., Wiecek, A., Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly. Clin. Endocrinol. 82:6 (2015), 900–909.
42. [42] Braithwaite, V., Prentice, A.M., Doherty, C., Prentice, A., FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study. Int. J. Pediatr. Endocrinol., 2012(1), 2012, 27.
43. [43] Evstatiev, R., Gasche, C., Iron sensing and signalling. Gut 61:6 (2012), 933–952.
44. [44] Jovanovich, A., Buzkova, P., Chonchol, M., Robbins, J., Fink, H.A., de Boer, I.H., Kestenbaum, B., Katz, R., Carbone, L., Lee, J., Laughlin, G.A., Mukamal, K.J., Fried, L.F., Shlipak, M.G., Ix, J.H., Fibroblast growth factor 23, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study. J. Clin. Endocrinol. Metab. 98:8 (2013), 3323–3331.
45. [45] Murali, S.K., Andrukhova, O., Clinkenbeard, E.L., White, K.E., Erben, R.G., Excessive osteocytic Fgf23 secretion contributes to pyrophosphate accumulation and mineralization defect in Hyp mice. PLoS Biol., 14(4), 2016, e1002427.
46. [46] Wang, H., Yoshiko, Y., Yamamoto, R., Minamizaki, T., Kozai, K., Tanne, K., Aubin, J.E., Maeda, N., Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J. Bone Miner. Res. 23:6 (2008), 939–948.
47. [47] Katsumata, S., Katsumata-Tsuboi, R., Uehara, M., Suzuki, K., Severe iron deficiency decreases both bone formation and bone resorption in rats. J. Nutr. 139:2 (2009), 238–243.
48. [48] Yanovich, R., Merkel, D., Israeli, E., Evans, R.K., Erlich, T., Moran, D.S., Anemia, iron deficiency, and stress fractures in female combatants during 16 months. J Strength Cond Res. 25:12 (2011), 3412–3421.
49. [49] Doyard, M., Chappard, D., Leroyer, P., Roth, M.P., Loreal, O., Guggenbuhl, P., Decreased bone formation explains osteoporosis in a genetic mouse model of Hemochromatosiss. PLoS One, 11(2), 2016, e0148292.
50. [50] He, Y.F., Ma, Y., Gao, C., Zhao, G.Y., Zhang, L.L., Li, G.F., Pan, Y.Z., Li, K., Xu, Y.J., Iron overload inhibits osteoblast biological activity through oxidative stress. Biol. Trace Elem. Res. 152:2 (2013), 292–296.