Fetuin-a and secondary osteoporosis in patients with rheumatoid arthritis

Abstract

Aim. To study the level of fetuin-A (FA), bone mineral density (BMD) and certain markers of bone remodeling in patients with rheumatoid arthritis (RA).

Materials and Methods. 110 Patients with RA and 30 conventionally healthy patients were examined. In both groups the levels of FA and BMD were determined. In the group of patients with RA the levels of C-telopeptide of type I collagen, N-terminal propeptide of procollagen I, 25-hydroxy-cholecalciferol, total alkaline phosphatase, total calcium of blood were determined.

Results. The mean concentration of FA in blood serum of patients with RA was 765.67±120.66 µg/mL, which was below the respective parameter in donors – 812.95±76.21 µg/mL (p=0.0437). In the group of patients with RA with osteoporosis (n=52) the mean level of FA was 733.65±135.84 µg/mL, and in the group without osteoporosis – 794.37±97.7 µg/mL (p=0.0044). The level of FA was also reduced in patients with osteoporotic fractures (n=24) – 694.79±110.47 µg/mL against 785.45±116.43 µg/mL in patients without osteoporotic fractures (n=86; p=0.00091). A positive correlation relationship was found between the level of FA and BMD of L1-L4 (r=0.194; p=0.042), femoral neck (r=0.328; p<0.0001) and proximal femur (r=0.293; p=0.002), and the level of 25-hydroxy-cholecalciferol (r=0.259; p=0.006), and the negative correlation relationship – with C-telopeptide of type I collagen (r=-0.203; p=0.033).

Conclusions. Patients with RA with reduced FA level were characterized by a higher detection rate of osteoporosis and of osteoporotic fractures, and by a lower BMD of L2-L4, femoral bone and proximal femur. Besides, a lower level of FA was associated with a lower level of 25-hydroxy-cholecalciferol and with a higher level of C-telopeptide of type I collagen which permits to suggest existence of osteoprotective function in this glycoprotein.

Keywords

fetuin-A / osteoporosis / bone metabolism / bone mineral density / rheumatoid arthritis

References

[1] Zavodovsky BV, Sivordova LE, Polyakova YV, et al. Study the prevalence of osteoporosis, its complications and a significant risk factor. Palliative Medicine and Rehabilitation. 2015;(2):9-12. (In Russ).

[2] Заводовский Б.В., Сивордова Л.Е., Полякова Ю.В., и др. Исследование распространенности остеопороза, его осложнений и значимости факторов риска // Паллиативная медицина и реабилитация. 2015. №2. С. 9-12.

[3] Melton LJ III, Chriscilles EA, Cooper C, et al. Perspective: how many women have osteoporosis? Journal of Bone and Mineral Research 1992;7(9): 1005-10.

[4] Melton L.J. III, Chrischilles E.A., Cooper C., et al. Perspective. How many women have osteoporosis? // Journal of Bone and Mineral Research. 1992. Vol. 7, №9. P. 1005-1010.

[5] Dydykina IS, Alekseyeva LI. Osteoporosis in rheumatoid arthritis: diagnosis, risk factors, fractures, treatment. Rheumatology Science and Practice. 2011;49(5):13-7. (In Russ). doi:10.14412/1995- 4484-2011-1454

[6] Дыдыкина И.С., Алексеева Л.И. Остеопороз при ревматоидном артрите: диагностика, факторы риска, переломы, лечение // Научно-практичес-кая ревматология. 2011. Т. 49, №5. C. 13-17. doi:10.14412/1995-4484-2011-1454

[7] Fedina TP, Bratygina EA, Starkova AS. Densito-metricheskaya otsenka kostnoy tkani bol'nykh revmatoidnym artritom. In: Tezisy II Vserossiys-kogo kongressa revmatologov Rossii. Yaroslavl'; 2011; (314):81. (In Russ).

[8] Федина Т.П., Братыгина Е.А., Старкова А.С. Денситометрическая оценка костной ткани больных ревматоидным артритом // Тезисы II Всероссийского конгресса ревматологов России. Ярославль; 2011. №314. С. 81.

[9] Kim SY, Schneeweiss S, Liu J, et al. Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Research & Therapy. 2010;12:154. doi:10.1186/ar3107

[10] Kim S.Y., Schneeweiss S., Liu J., et al. Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis // Arthritis Research & Therapy. 2010. Vol. 12. P. 154. doi:10.1186/ar3107

[11] Triffitt JT, Gebauer U, Ashton BA, et al. Origin of plasma α2HS-glycoprotein and its accumulation in bone. Nature. 1976;262:226-7. doi:10.1038/262226a0

[12] Triffitt J.T., Gebauer U., Ashton B.A., et al. Origin of plasma α2HS-glycoprotein and its accumulation in bone // Nature. 1976. Vol. 262. P. 226-227. doi:10.1038/262226a0

[13] Demetriou M, Binkert Ch, Sukhu B, et al. Fetuin/ alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist. Journal of Biological Chemistry 1996; 271:12755-61. doi:10.1074/jbc. 271.22.12755

[14] Demetriou M., Binkert Ch., Sukhu B., et al. Fetuin/ alpha2-HS Glycoprotein Is a Transforming Growth Factor-Beta Type II Receptor Mimic and Cytokine Antagonist // Journal of Biological Chemistry. 1996. Vol. 271. P. 12755-12761. doi:10.1074/jbc. 271.22.12755

[15] Janssens K, ten Dijke P, Janssens S, et al. Transforming growth factor-beta1 to the bone. Endocrine Reviews. 2005;26(6):743-74. doi:10.1210/er.2004-0001

[16] Janssens K., ten Dijke P., Janssens S., et al. Transforming growth factor-beta1 to the bone // Endocrine Reviews. 2005. Vol. 26, №6. P. 743-774. doi:10.1210/er.2004-0001

[17] Binkert C, Demetriou M, Sukhu B, et al. Regulation of osteogenesis by fetuin. Journal of Biological Chemistry. 1999;274(40):28514-20. doi:10.1074/ jbc.274.40.28514

[18] Binkert C., Demetriou M., Sukhu B., et al. Regulation of osteogenesis by fetuin // Journal of Biological Chemistry. 1999. Vol. 274, №40. P. 28514-28520. doi:10.1074/jbc.274.40.28514

[19] Daveau M, Christian D, Julen N, et al. The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines on hepatoma HepG2 cells. FEBS Letters. 1988;241(1-2):191-4. doi:10.1016/ 0014-5793(88)81059-7

[20] Daveau M., Christian D., Julen N., et al. The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines on hepatoma HepG2 cells // FEBS Letters. 1988. Vol. 241, №1-2. P. 191-194. doi:10.1016/0014-5793(88)81059-7

[21] Tuttolomondo A, Di Raimondo D, Di Sciacca R, et al. Fetuin-A and CD 40 L plasma levels in acute ischemic stroke: differences in relation to TOAST subtype and correlation with clinical and laboratory variables. Atherosclerosis. 2010;208(1):290-6. doi:10. 1016/j.atherosclerosis.2009.07.032

[22] Tuttolomondo A., Di Raimondo D., Di Sciacca R., et al. Fetuin-A and CD 40 L plasma levels in acute ischemic stroke: differences in relation to TOAST subtype and correlation with clinical and laboratory variables // Atherosclerosis. 2010. Vol. 208, №1. P. 290-296. doi:10.1016/j.atherosclerosis.2009.07.032

[23] Dziegielewska KM, Andersen NA, Saunders NR Modification of macrophage response to lipopolysaccharide by fetuin. Immunology Letters. 1998; 60(1):31-5. doi:10.1016/S0165-2478(97)00126-0

[24] Dziegielewska K.M., Andersen N.A., Saunders N.R. Modification of macrophage response to lipopolysaccharide by fetuin // Immunology Letters. 1998. Vol. 60, №1. P. 31-35. doi:10.1016/S0165-2478 (97)00126-0

[25] Ozturk S, Keser M, Kozaci D, et al. Fetuin-A and Its Association with Disease Activity on Psoriatic Arthritis. Annals of the Rheumatic Diseases. 2014; 73(suppl 2):207. doi:10.1136/annrheumdis-2014-eular.4473

[26] Ozturk S., Keser M., Kozaci D., et al. Fetuin-A and Its Association with Disease Activity on Psoriatic Arthritis // Annals of the Rheumatic Diseases. 2014. Vol. 73, Supple 2. P. 207. doi:10.1136/ annrheumdis-2014-eular.4473

[27] Sato H, Kazama JJ, Wada Y, et al. Decreased levels of circulating α2-Heremans-Schmid glycoprotein/Fetuin-A (AHSG) in patients with rheumatoid arthritis. Internal Medicine. 2007;46(20):1685-92. doi:10.2169/internalmedicine.46.6269

[28] Sato H., Kazama J.J., Wada Y., et al. Decreased levels of circulating α2-Heremans-Schmid glycoprotein/Fetuin-A (AHSG) in patients with rheumatoid arthritis // Internal Medicine. 2007. Vol. 46, №20. P. 1685-1692. doi:10.2169/internalmedicine. 46.6269

[29] Inoue K, Ikeda Y, Yamanaka S, et al. Serum fetuin-A levels in patients with rheumatoid arthritis [abstract]. Atherosclerosis. 2002;9(Suppl 1):233. doi: 10-1016/s1567-5688(08)70930-9

[30] Inoue K., Ikeda Y., Yamanaka S., et al. Serum fetuin-A levels in patients with rheumatoid arthritis [abstract] // Atherosclerosis. 2002. Vol. 9, Supple 1. P. 233. doi:10-1016/s1567-5688(08)70930-9

RIGHTS & PERMISSIONS

Papichev E.V., Zavodovsky B.V., Seewordova L.E., Akhverdyan Y.R., Polyakova Y.V.