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Bone remodelling is reduced by recovery from iron-deficiency anaemia in premenopausal women

Journal of Physiology and Biochemistry volume 69, pages 889–896 (2013)Cite this article

Abstract

Iron-deficiency anaemia (IDA), one of the most common and widespread health disorders worldwide, affects fundamental metabolic functions and has been associated with deleterious effects on bone. Our aim was to know whether there are differences in bone remodelling between a group of premenopausal IDA women and a healthy group, and whether recovery of iron status has an effect on bone turnover markers. Thirty-five IDA women and 38 healthy women (control group) were recruited throughout the year. IDA women received pharmacological iron treatment. Iron biomarkers, aminoterminal telopeptide of collagen I (NTx), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxyvitamin D, and parathormone (PTH) were determined at baseline for both groups and after treatment with pharmacological iron for the IDA group. IDA subjects were classified as recovered (R) or non-recovered (nR) from IDA after treatment. NTx levels were significantly higher (p <0.001), and P1NP levels tended to be lower in IDA women than controls after adjusting for age and body mass index (BMI), with no differences in 25-hydroxyvitamin D or PTH. After treatment, the R group had significantly lower NTx and P1NP levels compared to baseline (p <0.05 and p <0.001 respectively), whilst no significant changes were seen in the nR group. No changes were seen in 25-hydroxyvitamin D or PTH for either group. IDA is related to higher bone resorption independent of age and BMI. Recovery from IDA has a concomitant beneficial effect on bone remodelling in premenopausal women, decreasing both bone resorption and formation.

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References

  1. Adami S, Bianchi G, Brandi ML, Giannini S, Ortolani S, DiMunno O, Frediani B, Rossini M (2008) Determinants of bone turnover markers in healthy premenopausal women. Calcified Tissue Int 82:341–7

    Article  CAS  Google Scholar 

  2. Ardawi M-SM, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Raddadi RM (2010) Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study. Bone 47:804–14

    PubMed  Article  CAS  Google Scholar 

  3. Arnett TR, Gibbons DC, Utting JC, Orriss IR, Hoebertz A, Rosendaal M, Meghji S (2003) Hypoxia is a major stimulator of osteoclast formation and bone resorption. J Cell Physiol 196:2–8

    PubMed  Article  CAS  Google Scholar 

  4. Bendich A (2010) Iron deficiency and overload. From basic biology to clinical medicine. Humana, NY. ISBN 978-1-934115-22-0

    Google Scholar 

  5. Blanco-Rojo R, Pérez-Granados AM, Toxqui L, Zazo P, De la Piedra C, Vaquero MP (2013) Relationship between vitamin D deficiency, bone remodelling and iron status in iron-deficient young women consuming an iron-fortified food. Eur J Nutr 52:695–703

    PubMed  Article  CAS  Google Scholar 

  6. Cesari M, Pahor M, Lauretani F et al (2005) Bone density and hemoglobin levels in older persons: results from the InCHIANTI study. Osteoporosis Int 16:691–9

    Article  CAS  Google Scholar 

  7. D’Amelio P, Cristofaro MA, Tamone C et al (2008) Role of iron metabolism and oxidative damage in postmenopausal bone loss. Bone 43:1010–5

    PubMed  Article  Google Scholar 

  8. De Papp AE, Bone HG, Caulfield MP, Kagan R, Buinewicz A, Chen E, Rosenberg E, Reitz RE (2007) A cross-sectional study of bone turnover markers in healthy premenopausal women. Bone 40:1222–30

    PubMed  Article  Google Scholar 

  9. Del Campo MT, González-Casaus ML, Aguado P, Bernad M, Carrera F, Martínez ME (1999) Effects of age, menopause and osteoporosis on free, peptide-bound and total pyridinium crosslink excretion. Osteoporosis Int 9:449–54

    Article  Google Scholar 

  10. Díaz-Castro J, López-Frías MR, Campos MS, López-Frías M, Alférez MJM, Nestares T, Ojeda ML, López-Aliaga I (2012) Severe nutritional iron-deficiency anaemia has a negative effect on some bone turnover biomarkers in rats. Eur J Nutr 51:241–7

    PubMed  Article  Google Scholar 

  11. Fujimoto H, Fujimoto K, Ueda A, Ohata M (1999) Hypoxemia is a risk factor for bone mass loss. J Bone Miner Metab 17:211–6

    PubMed  Article  CAS  Google Scholar 

  12. Glover SJ, Gall M, Schoenborn-Kellenberger O, Wagener M, Garnero P, Boonen S, Cauley JA, Black DM, Delmas PD, Eastell R (2009) Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium, and the United States. J Bone Miner Res 24:389–97

    PubMed  Article  Google Scholar 

  13. Groba M, Miravalle A, Gonzalez Rodriguez E, García Santana S, Gonzalez Padilla E, Saavedra P, Soria A, Sosa M (2010) Factors related to vitamin D deficiency in medical students in Gran Canaria. Rev Osteoporos Metab Miner 2:11–18

    Google Scholar 

  14. Harris MM, Houtkooper LB, Stanford VA, Parkhill C, Weber JL, Flint-Wagner H, Weiss L, Going SB, Lohman TG (2003) Dietary iron is associated with bone mineral density in healthy postmenopausal women. J Nutr 133:3598–602

    PubMed  CAS  Google Scholar 

  15. Heaney RP (2003) Is the paradigm shifting? Bone 33:457–65

    PubMed  Article  Google Scholar 

  16. Hercberg S, Preziosi P, Galan P (2001) Iron deficiency in Europe. Public Health Nutr 4:537–45

    PubMed  Article  CAS  Google Scholar 

  17. Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87:1080S–6S

    PubMed  CAS  Google Scholar 

  18. Ilich-Ernst JZ, McKenna AA, Badenhop NE, Clairmont AC, Andon MB, Nahhas RW, Goel P, Matkovic V (1998) Iron status, menarche, and calcium supplementation in adolescent girls. Am J Clin Nutr 68:880–7

    PubMed  CAS  Google Scholar 

  19. Jelkmann W (2011) Regulation of erythropoietin production. J Physiol 589:1251–8

    PubMed  Article  CAS  Google Scholar 

  20. Katsumata S, Katsumata-Tsuboi R, Uehara M, Suzuki K (2009) Severe iron deficiency decreases both bone formation and bone resorption in rats. J Nutr 139:238–243

    PubMed  Article  CAS  Google Scholar 

  21. Katsumata S, Tsuboi R, Uehara M, Suzuki K (2006) Dietary iron deficiency decreases serum osteocalcin concentration and bone mineral density in rats. Biosci Biotec Bioch 70:2547–2550

    Article  CAS  Google Scholar 

  22. Knott L, Bailey AJ (1998) Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. Bone 22:181–7

    PubMed  Article  CAS  Google Scholar 

  23. McLean E, Cogswell M, Egli I, Wojdyla D, De Benoist B (2009) Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993–2005. Public Health Nutr 12:444–54

    PubMed  Article  Google Scholar 

  24. Medeiros DM, Plattner A, Jennings D, Stoecker B (2002) Bone morphology, strength and density are compromised in iron-deficient rats and exacerbated by calcium restriction. J Nutr 132:3135–41

    PubMed  CAS  Google Scholar 

  25. 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 134:3061–7

    PubMed  CAS  Google Scholar 

  26. 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 231:378–86

    CAS  Google Scholar 

  27. Rodríguez Sangrador M, Beltrán de Miguel B, Cuadrado Vives C, Moreiras Tuny O (2010) Influence of sun exposure and diet to the nutritional status of vitamin D in adolescent Spanish women: the five countries study (OPTIFORD Project). Nutr Hosp 25:755–62

    PubMed  Google Scholar 

  28. Schulze KJ, Dreyfuss ML (2005) Iron-Deficiency Anemia. In: Caballero B (ed) Encyclopedia of human nutrition, 2nd edn. Elsevier, Oxford, pp 101–109

    Chapter  Google Scholar 

  29. Scientific Advisory Committee on Nutrition (2010) Iron and health. TSO, London

    Google Scholar 

  30. Seeman E (2003) Invited review: pathogenesis of osteoporosis. J Appl Physiol 95:2142–51

    PubMed  Google Scholar 

  31. Shin JY, Shim JY (2013) Low vitamin D levels increase anemia risk in Korean women. Clin Chim Acta 421:177–180

    PubMed  Article  CAS  Google Scholar 

  32. Shiozawa Y, Jung Y, Ziegler AM et al (2010) Erythropoietin couples hematopoiesis with bone formation. PLoS One 5:e10853

    PubMed  Article  Google Scholar 

  33. Sim JJ, Lac PT, Liu IL, Meguerditchian SO, Kumar VA, Kujubu DA, Rasgon SA (2010) Vitamin D deficiency and anemia: a cross-sectional study. Ann Haematol 89:447–52

    Article  CAS  Google Scholar 

  34. Toxqui L, Pérez-Granados A, Blanco-Rojo R, Wright I, González-Vizcayno C, Vaquero MP (2013) Intake of an iron or iron and vitamin D-fortified skimmed milk and iron metabolism in women. Ann Nutr Metab (in press)

  35. Tuderman L, Myllylä R, Kivirikko KI (1977) Mechanism of the prolyl hydroxylase reaction. 1. Role of co-substrates. Eur J Biochem 80:341–8

    PubMed  Article  CAS  Google Scholar 

  36. Watts NB (1999) Clinical utility of biochemical markers of bone remodeling. Clin Chem 45:1359–68

    PubMed  CAS  Google Scholar 

  37. World Health Organisation (2004) Assessing the iron status of populations: including literature reviews: report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the assessment of iron status at the population level. WHO, Geneva

    Google Scholar 

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Acknowledgments

This study was financed by Project AGL2009-11437. RBR and LT were supported by a JAE pre-doc grant from CSIC and European Social Fund. The authors are grateful to the volunteers who participated in the study, and to the staff of the anaemia section at Complejo Hospitalario de Toledo.

Conflict of interest

The authors have declared no conflict of interest.

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Affiliations

  1. Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CISC), C/José Antonio Novais 10, 28040, Madrid, Spain

    Ione Wright, Ruth Blanco-Rojo, Laura Toxqui, Ana M. Pérez-Granados & M. Pilar Vaquero

  2. Complejo Hospitalario de Toledo, Toledo, Spain

    M. Cristina Fernández, Gemma Moreno & Ángel F. Remacha

  3. Department of Biochemistry Investigation, Fundación Jiménez Díaz Institute for Medical Research (IIS-FJD), Madrid, Spain

    Concepción de la Piedra

Authors
  1. Ione Wright
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  2. Ruth Blanco-Rojo
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  3. M. Cristina Fernández
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  4. Laura Toxqui
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  5. Gemma Moreno
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  6. Ana M. Pérez-Granados
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  7. Concepción de la Piedra
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  8. Ángel F. Remacha
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  9. M. Pilar Vaquero
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Correspondence to M. Pilar Vaquero.

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Wright, I., Blanco-Rojo, R., Fernández, M.C. et al. Bone remodelling is reduced by recovery from iron-deficiency anaemia in premenopausal women. J Physiol Biochem 69, 889–896 (2013). https://doi.org/10.1007/s13105-013-0266-3

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  • DOI: https://doi.org/10.1007/s13105-013-0266-3

Keywords

  • Bone turnover markers
  • Iron-deficiency anaemia
  • Menstruating women
  • Vitamin D status
  • Bone resorption
  • PTH