ERYTHROPOIETIN ACCELERATES FRACTURE HEALING AN EXPERIMENTAL ANIMAL STUDY

Abstract

Aim: The efficacy of erythropoietin (EPO) on wound healing has been shown before. There islimited data about the efficacy of EPO on fracture healing. In this study, the efficacy of EPO onclosed forearm fracture healing is searched by an experimental model. Material and method: Twenty eight rats were picked randomly and divided into EPO andControl groups. On the first day, fracture was performed on the right ulna and radius of all rats.500 U/kg daily low dose EPO was administered for each rat in EPO group and the same volumeof isotonic sodium chloride solution was given intraperitoneally in the control group for fivedays. Seven rats from each group were sacrificed at the end of the first week; the others weresacrificed at the end of the third week. Results: At the end of the first week and third week, bone healing scores of EPO group issignificantly higher than the control group according to the histological, clinic and radiologicanalysis. Conclusion: EPO could have positive effects on healing of forearm fracture on rats in acuteand subacute period. Low dose EPO may be a new protective agent against delayed union ornonunion in the risk population to go or not to go to surgical treatment

Keywords

• Erythropoietin,fracture healing,rat

Eritropoetin Kırık İyileşmesini Hızlandırıyor Deneysel Hayvan Çalışması

Abstract

Giriş: Eritropoetin’in yara iyileşmesi üzerine olan etkisi daha önce gösterilmiştir. Kırıkiyileşmesi üzerine olan etkisi üzerine sınırlı sayıda bilgi mevcuttur. Bu çalışmada eritropoetininkapalı kırık iyileşmesi üzerine olan etkileri deneysel bir model kullanılarak araştırılmıştır.Yöntem: Yirmisekiz rat alınıp rastgele sçilerek Eritropoetin ve Kontrol grupları oluşturuldu.Çalışmanın ilk gününde tüm ratların sağ önkollarında kapalı ulna ve radius cisim kırıklarıoluşturuldu. Beş gün boyunca Eritropoetin grubundaki ratlarda 500 U/kg düşük doz eritropoetinintraperitoneal olarak verilirken; Kontrol grubundaki ratlarda ise aynı hacimde izotonikintraperitoneal olarak verildi. Gruplardaki yedişer det rat ilk hafta sonunda, kalan yedişer adetratda üçüncü haftanın sonunda sakrifiye edildi.Bulgular: Birinci ve üçüncü hafta sonunda kırık iyileşme skorları histolojik, radyolojik ve klinikolarak değerlendirildiğinde Eritropoetin grubunda Kontrol grubuna gore belirgin olarak dahayüksek olduğu saptandı.Sonuç: Ratların kapalı önkol kırıklarının iyileşmesi üzerine akut ve subakut peryottaeritropoetinin pozitif etkileri olabilir. Düşük doz eritropoetin kullanımı cerrahiye gidecek veyagitmeyecek olan riskli hasta gruplarında kaynama gecikmesi veya kaynamamaya karşı koruyucuajan olarak verilebilir

Keywords

• Eritropoetin,kırık iyileşmesi,rat

References

1. Brinker RM, Miller MD. Basic sciences, Review of Orthopaedics.
2. nd ed. WB Saunders Co, Philadelphia, 1996: 1-26.
3. Murnaghan M, Li G, Marsh DR. Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis?. J Bone Joint Surg Am. 2006 Nov;88 Suppl 3:140-7.
4. Kertesz N, Wu J, Chen THP, Sucov HM, Wu H. The role of erythropoietin in regulating angiogenesis. Developmental Biology. 2004; 276: 101-110.
5. Buemi M, Galeano M, Sturiale A. Recombinant human erythropoietin stimulates angiogenesis and healing ischemic skin wounds. Shock, 2004; 22: 169-173.
6. Dimar JR, Ante WA, Zhang YP. The effect of nonsteroidal antiinflammatory drugs on posterior spinal fusions in the rats. Spine. 1996; 21: 1870-1876.
7. Huo MH, Troino NW, Pekler RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, histological, and histomorphometric parameters in rats. J Ortoph. Res. 1991; 9: 383-390.
8. Lane JM, Sandhu HS. Current approaches to experimental bone grafting. Orthop Clin North Am. 1987; 18: 213-225.

9. Altman RD, Latta LL, Keer R, Renfree K, Hornicek FJ, Banovac K. Effect of nonsteroidal antii-nflammatory drugs on fracture healing: a laboratory study in rats. J Orthop Trauma. 1995;9(5):392-400.
10. Erbayraktar Z, Erbayraktar S, Yilmaz O, Cerami A, Coleman T, Brines M. Nonerythropoietic tissue protective compounds are highly effective facilitators of wound healing. Mol Med. 2009 Jul-Aug;15(7- 8):235-41.
11. Kabak Ş, Balkar F, Duygulu F. Effect of fracture hematoma on fracture healing. Acta Orthop Traum Turc. 2001; 35: 252-259.
12. Lappin T. The cellular biology of erythropoietin receptors. The Oncologist. 2003; 8: 15-18.
13. Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakta EG; Talan MI. Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci. 2003; 100: 11612-11617.
14. Kumral A, Baskin H, Duman N, Yilmaz O, Tatli M, Ozer E, Gokmen N, Genc S, Ozkan H. Erythropoietin protects against necrotizing enterocolitis of newborn rats by the inhibiting nitric oxide formation. Biol Neonate. 2003; 84: 325-329.
15. Buemi M, Vacorro M, Sturiale A, Galeano MR, Sansotta C, Cavallari V, Floccari F, D’Amico D, Torre V, Calapai G, Frisina N, Guarneri F, Vermiglio G. Recombinant human erythropoietin influences revascularization and healing in a rat model of random ischemic flaps. Acta DermVenoreol. 2002; 82: 411-417.
16. Noyan T, Onem O, Ramazan Sekeroglu M, Koseoglu B, Dulger H, Bayram I, Yalcinkaya AS, Bakan V. Effects of erythropoietin and pentoxifylline on the oxidant and antioxidant systems in the experimental short bowel syndrome. Cell Biochem Funct. 2003; 21: 49-54.
17. Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines ML, Ghezzi P. Erythropoietin exerts an anti-inflammatory effect on the CNS in a model of experimental autoimmune encephalomyelitis. Brain. Res. 2002; 952:128-34.
18. Ribatti D, Vacca A, Roccaro AM, Crivelatto E, Presta M. Erythropoietin as an angiogenic factor. European Journal of Clinical İnvestigation. 2003; 33: 891-896.
19. Junk AK, Mammis A, Savitz Sİ, Singh M, Roth S, Malhotra S, Rosenbaum PS, Cerami A, Brines M, Rosenbaum DM. Erythropoietin administration protects retinal neurons from acute ischemia- reperfusion injury. Proc Natl Acad Sci. 2002; 99:10659-10664.
20. Hasegawa Y, Takamatsu J, Iwase T, Iwasada S, Kitamura S, Iwata H. Effects of recombinant human erythropoietin on thrombosis and fibrinolysis in autologous transfusion for hip surgery. Arch Orthop Trauma Surg. 1999; 119: 384-387.
21. Schmidt HA, Templeman CD, Kyle RF. Blood conservation in hip trauma. Clin. Orthop An Related Research. 1998; 357: 68-73.
22. Giglio MJ, Gorustovich A, Guglielmotti MB. Bone healing under experimental anemia in rats. Acta Odontol Latinoam. 2000; 13: 63- 72.
23. Chong ZZ, Kang JQ, Maiese K. Angiogenesis and plasticity: role of erythropoietin in vascular systems. J Hematother Stem Cell Res. 2002; 11: 863-871.
24. Frisina N. Wound care; recombinant human erythropoietin heals ischemic skin wounds. Drug week. 2004; 570.