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High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes

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Abstract

Purpose

Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM.

Methods

Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model.

Results

OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9–31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time.

Conclusions

In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile.

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References

  1. Carnevale V, Romagnoli E, D’Erasmo E (2004) Skeletal involvement in patients with diabetes mellitus. Diabetes Metab Res Rev 20(3):196–204

    Article  PubMed  Google Scholar 

  2. Schwartz AV, Vittinghoff E, Bauer DC, Hillier TA, Strotmeyer ES, Ensrud KE, Study of Osteoporotic Fractures (SOF), the Osteoporotic Fractures in Men (MrOS), Health, Aging and Body Composition (Health ABC) et al (2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305(21):2184–2192. https://doi.org/10.1001/jama.2011.715

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporosis Int 18(4):427–444. https://doi.org/10.1007/s00198-006-0253-4

    Article  CAS  Google Scholar 

  4. Janghorbani M, Van Dam RM, Willett WC, Hu FB (2007) Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 166(5):495–505. https://doi.org/10.1093/aje/kwm106

    Article  PubMed  Google Scholar 

  5. Fan Y, Wei F, Lang Y, Liu Y (2016) Diabetes mellitus and risk of hip fractures: a meta-analysis. Osteoporos Int 27(1):219–228. https://doi.org/10.1007/s00198-015-3279-7

    Article  PubMed  CAS  Google Scholar 

  6. Centre for Metabolic Bone Diseases. University of Sheffield UK. https://www.sheffield.ac.uk/FRAX/tool.jsp?lang=it. Accessed Jun 2016

  7. Giangregorio LM (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27:301–308

    Article  PubMed  Google Scholar 

  8. Carnevale V, Morano S, Fontana A, Annese MA, Fallarino M, Filardi T et al (2014) Assessment of fracture risk by the FRAX algorithm in men and women with and without type 2 diabetes mellitus: a cross-sectional study. Diabetes Metab Res Rev 30:313–322

    Article  PubMed  CAS  Google Scholar 

  9. Chellaiah MA, Kizer N, Biswas R, Alvarez U, Strauss-Schoenberger J, Rifas L et al (2003) Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell 14(1):173–189

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Huang W, Carlsen B, Rudkin G, Berry M, Ishida K, Yamaguchi DT et al (2004) Osteopontin is a negative regulator of proliferation and differentiation in MC3T3-E1 pre-osteoblastic cells. Bone 34:799–808

    Article  PubMed  CAS  Google Scholar 

  11. Mazzali M, Kipari T, Ophascharoensuk V, Wesson JA, JohnsonR Hughes J (2002) Osteopontin—A molecule for all seasons. QJM 95:3–13

    Article  PubMed  CAS  Google Scholar 

  12. van der Leeuw J, Beulens JW, van Dieren S, Schalkwijk CG, Glatz JF, Hofker MH et al (2016) Novel biomarkers to improve the prediction of cardiovascular event risk in type 2 diabetes mellitus. J Am Heart Assoc 5:e003048. https://doi.org/10.1161/JAHA.115.003048

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hanwell HE, Vieth R, Cole DE, Scillitani A, Modoni S, Frusciante V, Ritrovato G, Chiodini I, Minisola S, Carnevale V (2010) Sun exposure questionnaire predicts circulating 25-hydroxyvitamin D concentrations in Caucasian hospital workers in southern Italy. J Steroid Biochem Mol Biol 121(1–2):334–337. https://doi.org/10.1016/j.jsbmb.2010.03.023 (epub 2010 Mar 16)

    Article  PubMed  CAS  Google Scholar 

  14. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

    Article  PubMed  PubMed Central  Google Scholar 

  15. Carnevale V, Romagnoli E, D’Erasmo L, D’Erasmo E (2014) Bone damage in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 24:1151–1157

    Article  PubMed  CAS  Google Scholar 

  16. Dobnig H, Piswanger-Solkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A et al (2006) Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab 91:3355–3363

    Article  PubMed  CAS  Google Scholar 

  17. Cho EH, Cho KH, Lee HA, Kim SW (2013) High serum osteopontin levels are associated with low bone mineral density in postmenopausal women. J Korean Med Sci 28(10):1496–1499. https://doi.org/10.3346/jkms.2013.28.10.1496 (epub 2013 Sep 25)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Fodor D, Bondor C, Albu A, Simon SP, Craciun A, Muntean L (2013) The value of osteopontin in the assessment of bone mineral density status in postmenopausal women. J Investig Med 61(1):15–21. https://doi.org/10.2310/jim.0b013e3182761264

    Article  PubMed  CAS  Google Scholar 

  19. Barbarossa G, Renzi A, D’Erasmo L, Gallo A, Grieco E, Rossetti M et al (2014) The relation between glycemic control and HDL-C in type 2 diabetes: a preliminary step forward? Diabetes Res Clin Pract 104:e26–e28

    Article  PubMed  CAS  Google Scholar 

  20. Nakhjavani M, Morteza A, Esteghamati A, Khalilzadeh O, Zandieh A, Safari R (2011) Serum lipoprotein(a) levels are greater in female than male patients with type 2 diabetes. Lipids 46:349–356

    Article  PubMed  CAS  Google Scholar 

  21. Kautzky-Willer A, Kamyar MR, Gerhat D, Handisurya A, Stemer G, Hudson S et al (2010) Sex-specific differences in metabolic control, cardiovascular risk, and interventions in patients with type 2 diabetes mellitus. Gend Med 7:571–583

    Article  PubMed  Google Scholar 

  22. Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847

    Article  PubMed  CAS  Google Scholar 

  23. Tamura A, Shingai M, Aso N, Hazuku T, Nasu M (2003) Osteopontin is released from the heart into the coronary circulation in patients with a previous anterior wall myocardial infarction. Circ J 67:742–744

    Article  PubMed  CAS  Google Scholar 

  24. Gravallese EM (2003) Osteopontin: a bridge between bone and the immune system. J Clin Invest 112:147–149

    Article  PubMed  PubMed Central  Google Scholar 

  25. Berezin AE, Kremzer AA (2013) Circulating osteopontin as a marker of early coronary vascular calcification in type two diabetes mellitus patients with known asymptomatic coronary artery disease. Atherosclerosis 229:475–481

    Article  PubMed  CAS  Google Scholar 

  26. Barchetta I, Alessandri C, Bertoccini L, Cimini FA, Taverniti L, Di Franco M et al (2016) Increased circulating osteopontin levels in adult patients with type 1 diabetes mellitus and association with dysmetabolic profile. Eur J Endocrinol 174:187–192

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or no-for-26 profit sectors.

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Authors and Affiliations

  1. Department of Experimental Medicine, Policlinico Umberto I, “Sapienza” University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    T. Filardi, F. Tavaglione, A. Lenzi, E. Romagnoli & S. Morano

  2. Unit of Internal Medicine, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy

    V. Carnevale

  3. Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy

    R. Massoud & C. Russo

  4. Faculty of Economics, UNINT University, Rome, Italy

    L. Nieddu

  5. Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy

    I. Turinese

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  1. T. Filardi
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  4. C. Russo
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  9. E. Romagnoli
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Correspondence to S. Morano.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Filardi, T., Carnevale, V., Massoud, R. et al. High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes. J Endocrinol Invest 42, 295–301 (2019). https://doi.org/10.1007/s40618-018-0914-0

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  • DOI: https://doi.org/10.1007/s40618-018-0914-0

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