Title: Association of Serum Fetuin-A Concentration and Bone Mineral Density in Women with Postmenopausal Osteoporosis
Authors: Marwa A. Saad*, Sally S. El-Tawab, Marwa H. Mahmood, Amr M. El-Abd
DOI: http://dx.doi.org/10.18535/jmscr/v3i11.18
Abstract
Osteoporosis is a chronic, progressive, skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility. Biological pathways leading to osteoporosis remain incompletely understood. The discovery of novel pathways for osteoporosis could lead to new preventive strategies or therapeutic targets. Fetuin-A is a hepatic-derived, serum protein that regulates calcium mineralization. We aimed to evaluate the correlation between serum fetuin-A concentrations and bone mineral density (BMD) in postmenopausal women.52 postmenopausal women were enrolled in the current study, divided to 2 groups; Group I: 31 postmenopausal osteoporotic women, not on osteoporotic treatment, group II(controls): 21age-matched post-menopausal women with normal BMD. Exclusion criteria included; females with surgical menopause or secondary osteoporosis, those with acute infection, malignancy, myocardial infarction (MI) within the previous month, a history of severe trauma, surgery, burns, diabetes mellitus (DM), liver or kidney disease, hormone replacement therapy (HRT), a history of smoking or alcoholism, patients taking steroids, anticonvulsants, chemotherapy, and L-Thyroxine. Basic laboratory investigations were done, plus parathyroid hormone, serum vitamin D3 levels, and serum fetuin-A levels. Women in osteoporotic group had significantly lower BMI, vitamin levels, and higher PTH levels. Also, women in osteoporotic group had significantly lower Fetuin-A levels. BMD of femur neck and lumbar spine were significantly lower in osteoporotic group. Fetuin-A was significantly correlated to BMD of femur neck and lumbar spine. We concluded that serum fetuin-A might be related to osteoporosis and it may provide necessary information on its pathogenesis. Fetuin-A can be used as a biochemical parameter within the scope of the diagnosis and treatment of postmenopausal osteoporosis.
Keywords: Osteoporosis, Fetuin-A, Postmenopausal, Bone mineral density.
References
1. Ahmed SF, Elmantaser M. Secondary osteoporosis. Endocr Dev 2009; 16:170-9.
2. Majumdar SR, Lier DA, Beaupre LA, Hanley DA, Maksymowych WP, Juby AG, et al. Osteoporosis case manager for patients with hip fractures: results of a cost-effectiveness analysis conducted alongside a randomized trial. Arch Intern Med 2009 Jan 12; 169(1):25-31.
3. National Osteoporosis Foundation. Gallup survey: women's knowledge of osteopo-rosis. Am Fam Physician 1991. 44:1052.
4. Czerwinski E, Badurski JE, Marcinowska-Suchowierska E, Osieleniec J. Current understanding of osteoporosis according to the position of the World Health Organization (WHO) and International Osteoporosis Foundation. Ortop Traumatol Rehabil 2007; 9(4):337-56.
5. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ 3rd, Khaltaev N. A reference standard for the description of osteoporosis. Bone 2008 Mar; 42(3):467-75.
6. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. OsteoporosInt 1992 Nov; 2(6):285-9.
7. NOF Releases Updated Data Detailing the Prevalence of Osteoporosis and Low Bone Mass in the U.S. 54 Million Americans Affected by Osteoporosis and Low Bone Mass. By NOF; Monday, June 2, 2014.
8. Wright NC1, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 2014; 29(11):2520-6.
9. Omaima Abo Elfatth Mohammed1, Hala Mohammed El Moselhey Shaheen2, Yasmin El GamilKaoud. Role of family medicine in the early detection and management of osteoporosis. Menoufia Medical Journal 2014; 27,(4): 833-9.
10. Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003; 81(9):646-56.
11. Bethel M, Kristine M Lohr, Laura D Carbone, Machua W, Herbert S Diamond. Osteoporosis. Medscape reference. Updated: Feb 26, 2015.
12. Lyles KW, Schenck AP, Colón-Emeric CS. Hip and other osteoporotic fractures increase the risk of subsequent fractures in nursing home residents. OsteoporosInt 2008 Aug; 19(8):1225-33.
13. Fink HA, Kuskowski MA, Taylor BC, Schousboe JT, Orwoll ES, Ensrud KE. Association of Parkinson's disease with accelerated bone loss, fractures and mortality in older men: the Osteoporotic Fractures in Men (MrOS) study. OsteoporosInt 2008 Sep; 19(9):1277-82.
14. Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y AcadSci 2006; 1068:173-9.
15. Ix JH, Chertow GM, Shlipak MG, Brandenburg VM, Ketteler M, WhooleyMA.Fetuin-A and kidney function in persons with coronary artery disease–data from the Heart and Soul Study. Nephrol Dial Transplant 2006; 21:2144–51.
16. Joanne L. Reynolds,Jeremy N. Skepper,† Rosamund McNair, Takeshi Kasama, Kunal Gupta,Peter L. Weissberg, WilliJahnen-Dechent, Catherine M. Shanahan. Multifunctional Roles for Serum Protein Fetuin-A in Inhibition. J Am SocNephrol 2005; 16: 2920 –30.
17. Alia A. Maharema, , , Salwa H. Gomaab, Marwa K. El Ghandorb, Ehab I. Mohamedc, Khaled A. Matrawyd, Sameh S. Zaytoune, Hanan M. Nomeirf. Association of serum fetuin-A and fetuin-A gene polymorphism in relation to mineral and bone disorders in patients with chronic kidney disease. Egyptian Journal of Medical Human Genetics 2013; 14 (4):337–52.
18. Brandenburg V, Kruger T, Westenfeld R, Schafer C, JahnenDechentW, Floege J, Martin D, Shalhoub V, Ketteler M. Administration of calcimimmetic AMG 641 improves osteomalacia in fetuin-A2/2 mice with mild renal insufficiency. AmSocNephrol 2007 (Abstract).
19. Toroian D Price PA .The essential role of fetuin in the serum-induced calcification of collagen. Calcif Tissue Int 2008; 82: 116–26.
20. Chailurkit L, Kruavit A, Rajatanavin R, OngphiphadhanakulB.The relationship of fetuin-A and lactoferrin with bone mass in elderly women. OsteoporosInt 2011; 22: 2159–64.
21. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ . "Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging.” Fertility and Sterility 2012; 97 (4): 398–406.
22. Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Böhm R, et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003; 361:827-33.
23. Schinke T, Amendt C, Trindl A, Pöschke O, Müller-Esterl W, Jahnen-Dechent W. The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J BiolChem 1996; 271:20789-96.
24. Adams CS, Mansfield K, Perlot RL, Shapiro IM. Matrix regulation of skeletal cell apoptosis. Role of calcium and phosphate ions. J BiolChem 2001; 276:20316-22.
25. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am SocNephrol 2004; 15:2857-67.
26. Toroian D, Price PA. The essential role of fetuin in the seruminduced calcification of collagen. Calcif Tissue Int 2008; 82:116–26.
27. Triffitt JT, Owen ME, Ashton BA, Wilson JM. Plasma disappearance of rabbit alpha2HS-glycoprotein and its uptake by bone tissue. Calcif Tissue Res 1978; 26: 155– 61.
28. Schinke T, Amendt C, Trindl A, Pöschke O, Müller-Esterl W, Jahnen-Dechent W. The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem. 1996; 271: 20789– 96.
29. Binkert C, Demetriou M, Sukhu B, Szweras M, Tenenbaum HC, Dennis JW. Regulation of osteogenesis by fetuin. J BiolChem 1999; 274: 28514–20.
30. Ix JH, Wassel CL, Bauer DC, Toroian D, Tylavsky FA, CauleyJA, Harris TB, Price PA, Cummings SR, Shlipak MG. Fetuin-Aand bone mineral density in older persons: The Health Agingand Body Composition (Health ABC) study. J Bone Miner Res2009; 24: 514–21.
31. EsinÖzkan, Hüseyin Ö, Serkan B, Ersin O, Nuray C, Emin ÖA, İbrahim Y, Yüksel Y, Mustafa K, Mustafa B, Mehmet KE. Serum fetuin-A levels in postmenopausal women with osteoporosis. Turkish Journal of Medical Sciences 2014; 44: 985-8.
32. Aylin S, Turan U. The Relationship between Fetuin-A and Bone Mineral Density in Postmenopausal Osteoporosis. Archives of Rheumatology 2013; 28(3): 195-201.
33. Jahnen-Dechent W, Schinke T, Trindl A, Müller-Esterl W, Sablitzky F, Kaiser S, et al. Cloning and targeted deletion of the mouse fetuin gene. J BiolChem 1997; 272:31496-503.
34. Binkert C, Demetriou M, Sukhu B, Szweras M, Tenenbaum HC, Dennis JW. Regulation of osteogenesis by fetuin. J BiolChem 1999; 274: 28514– 20.