Advertisement

Immunologic Research

, Volume 65, Issue 1, pp 423–427 | Cite as

Elevated ferritin and circulating osteoprotegerin levels as independent predictors of hip fracture in postmenopausal women admitted for fragility fracture: time for new screening strategies?

  • Y. Lipovetzki
  • G. Zandman-Goddard
  • Z. Feldbrin
  • M. Shargorodsky
Mechanism in Autoimmunity

Abstract

Identification of risk factors may help us to understand the pathogenesis of osteoporotic hip fracture as well as to formulate development of better diagnostic, prevention and treatment strategies. The present study was designed to determine the impact of multiple metabolic risk factors such as markers of systemic inflammation (C-reactive protein), immune responses–acute phase reactants (ferritin), insulin resistance (HOMA-IR) and bone remodeling (osteoprotegerin), for the prediction of hip fractures in postmenopausal osteoporotic women. The study group consisted of 115 postmenopausal women divided into two groups: Group 1 consisted of 49 women hospitalized in the Orthopedic Department, Wolfson Medical Center for the diagnosis of non-traumatic hip fracture and Group 2 contained 66 postmenopausal osteoporotic women without a history of hip fracture. Metabolic parameters were determined. Circulating OPG was significantly higher in Group 1 than in Group 2 (205.2 ± 177.1 vs 60.0 =/−22.3, p < 0.0001). While levels of hemoglobin (Hbg) as well as MCV and MCH did not differ between groups, circulating ferritin was significantly increased in Group 1 compared to the control Group 2 (217.9 ± 195.1 vs 49.7 ± 31.3, p < 0.0001). In multiple linear regression analysis, which explains about 40 % of the variability in CRP, 42 % in OPG, and 28 % in ferritin, significant by-group differences in terms of these parameters persisted even after adjustment. Elevated serum ferritin concentrations and bone remodeling marker, osteoprotegerin, are independent predictors of hip fracture in postmenopausal women hospitalized for fragility fracture.

Keywords

Osteoprotegerin Ferritin Hip fracture Postmenopausal women 

Notes

Compliance with ethical standards

Conflict of interest

Y. Lipovetzki has no conflicts of interest or financial or other contractual agreements that might cause conflicts of interest. G. Zandman-Goddard has no conflicts of interest or financial or other contractual agreements that might cause conflicts of interest. Z. Feldbrin has no conflicts of interest or financial or other contractual agreements that may couse conflicts of interest. M. Shargorodsky has no conflicts of interest or financial or other contractual agreements that might cause conflicts of interest.

References

  1. 1.
    Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporos Int. 2004;15:897–902.CrossRefPubMedGoogle Scholar
  2. 2.
    Kanis JA, Johnell O, de Laet C, Jönsson B, Odén A, Ogelsby AK. International variations in hip fracture probabilities: implications for assessment guidelines. J Bone Miner Res. 2002;17:1237–44.CrossRefPubMedGoogle Scholar
  3. 3.
    Gullberg B, Johnel O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int. 1997;7:407–13.CrossRefPubMedGoogle Scholar
  4. 4.
    Mussolino ME, Madans JH, Gillum RF. Bone mineral density and mortality in women and men: the NHANES I epidemiologic follow-up study. Ann Epidemiol. 2003;13:692–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Kado DM, Browner WS, Blackwell T, Gore R, Cummings SR. Rate of bone loss is associated with mortality in older women: a prospective study. J Bone Miner Res. 2000;15:1975–80.CrossRefGoogle Scholar
  6. 6.
    Adami S, Braga V, Zamboni M. Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif Tissue Int. 2004;74:136–42.CrossRefPubMedGoogle Scholar
  7. 7.
    Cappuccio FP, Meilahn E, Zmuda JM, Cauley JA. High blood pressure and bone-mineral loss in elderly white women: a prospective study. Study of Osteoporotic Fractures Research Group. Lancet. 1999;354:971–5.CrossRefPubMedGoogle Scholar
  8. 8.
    Schwartz AV. Diabetes mellitus: does it affect bone? Calcif Tissue Int. 2003;73:515–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Stern A, Laughlin GA, Bergstrom J, Barrett-Connor E. The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study. Eur J Endocrinol. 2007;156:555–62.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Asaba Y, Ito M, Fumoto T, Watanabe K, Fukuhara R, Takeshita S, Nimura Y, Ishida J, Fukamizu A, Ikeda K. Activation of renin-angiotensin system induces osteoporosis independently of hypertension. J Bone Miner Res. 2009;24:241–50.CrossRefPubMedGoogle Scholar
  11. 11.
    Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y. Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res. 1999;14:518–27.CrossRefPubMedGoogle Scholar
  12. 12.
    Kim B-J, Ahn SH, Bae SJ, Kim EH, Lee S-H, Kim H-K, Choe JW, Koh J-M, Kim GS. Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3 year retrospective longitudinal study. J Bone Miner Res. 2012;27:2279–90.CrossRefPubMedGoogle Scholar
  13. 13.
    Yang Q, Jian J, Abramson SB, Huang X. Inhibitory effects of iron on bone morphogenetic protein 2-induced osteoblastogenesis. J Bone Miner Res. 2011;26:1188–96.CrossRefPubMedGoogle Scholar
  14. 14.
    Guggenbuhl P, Deugnier Y, Boisdet JF, Rolland Y, Perdriger A, Pawlotsky Y, Chales G. Bone mineral density in men with genetic hemochromatosis and HFE gene mutation. Osteoporos Int. 2005;16:1809–14.CrossRefPubMedGoogle Scholar
  15. 15.
    Vogiatzi MG, Macklin EA, Fung EB. Bone disease in thalassemia: a frequent and still unresolved problem. J Bone Miner Res. 2009;24:543–57.CrossRefPubMedGoogle Scholar
  16. 16.
    Zarjou A, Jeney V, Arosio P, Poli M, Zavaczki E, Balla G, Balla J. Ferritin ferroxidase activity: a potent inhibitor of osteogenesis. J Bone Miner Res. 2010;25:164–72.CrossRefPubMedGoogle Scholar
  17. 17.
    Ahn SH, Lee S, Kim H, Lee SH, Kim BJ, Koh JM. Higher serum ferritin level and lower femur neck strength in women at the age of bone loss. Endocr Res. 2016. doi: 10.3109/07435800.2016.PubMedGoogle Scholar
  18. 18.
    Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, Carvalho JF, Doria A, Shoenfeld Y. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007;1109:385–400.CrossRefPubMedGoogle Scholar
  19. 19.
    Zandman-Goddard G, Shoenfeld Y. Ferritin in autoimmune diseases. Autoimmun Rev. 2007;6:457–63.CrossRefPubMedGoogle Scholar
  20. 20.
    Rosário C, Zandman-Goddard G, Meyron-Holtz EG, D’Cruz DP, Shoenfeld Y. The hyperferritinemic syndrome: macrophage activation syndrome, still’s disease, septic shock and catastrophic antiphospholipid syndrome. BMC Med. 2013;11:185.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Bonfils L, Ellervik C, Friedrich N, Linneberg A, Sandholt CH, Jorgenson ME, Jorgnson T, et al. Fasting serum levels of ferritin are associated with impaired pancreatic beta cell function and decreased insulin sensitivity: a population-based study. Diabetologia. 2015;58:523–33.CrossRefPubMedGoogle Scholar
  22. 22.
    Kim BJ, Lee SH, Koh J-M, Kim GS. The association between higher serum ferritin level and lower bone mineral density is prominent in women ≥45 years of age (KNHANES 2008–2010). Osteoporos Int. 2013;24(10):2627–37.CrossRefPubMedGoogle Scholar
  23. 23.
    Chon SJ, Choi YR, Roh YH, Yun BH, Cho SH, Choi YS, et al. Association between levels of serum ferritin and bone mineral density in Korean premenopausal and postmenopausal women: KNHANES 2008–2010. PloS One. 2014. doi: 10.1371/journal.pone.0114972.Google Scholar
  24. 24.
    Stern A, Laughlin GA, Bergstrom J, Barrett-Connor E. The sex-specific association of serum osteoprotegerin and receptor activator of nuclear factor kappaB legend with bone mineral density in older adults: the Rancho Bernardo study. Eur J Endocrinol. 2007;156:555–62.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Oh KW, Rhee EJ, Lee WY. Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system are associated with bone metabolism in middle-aged males. Clin Endocrinol (Oxf). 2005;62:92–8.CrossRefGoogle Scholar
  26. 26.
    Barbour KE, Boudreau R, Danielson ME, Youk MO, Wactawski-Wende J, Greep NC, Lacroix AZ, Jackson RD, Wallace RB, Bauer DC, Allison MA, Cauley JA. Inflammatory markers and the risk of hip fracture: the women’s health initiative. J Bone Miner Res. 2012;27:1167–76.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Y. Lipovetzki
    • 1
  • G. Zandman-Goddard
    • 1
    • 4
  • Z. Feldbrin
    • 2
    • 4
  • M. Shargorodsky
    • 3
    • 4
  1. 1.Department of Internal MedicineWolfson Medical CenterHolonIsrael
  2. 2.Department of OrtopedicsWolfson Medical CenterHolonIsrael
  3. 3.Department of EndocrinologyWolfson Medical CenterHolonIsrael
  4. 4.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations