The effect of topical and systemic tranexamic acid on fracture healing in rats

Objective: The aim of the present study was to determine the effect of topical and systemic tranexamic acid (TXA) on fracture healing in a rat surgical model. Methods: We created standard, right-sided, open, diaphyseal femoral fractures with intramedullary Kirschner wire fixation in 48 male rats and divided them into three groups: a topical TXA (10 mg/kg) group, a systemic TXA (10 mg/kg) group, and a control group. Fracture healing was evaluated radiographically and histologically after early (week 2) and late (week 4) postoperative sacrifice. Results: The radiological scores differed significantly among the all groups (p=0.001), as did the week 2 and 4 scores (p=0.003 and p=0.010, respectively). Radiologically, the topical TXA group exhibited better bone healing at both 2 (p=0.001) and 4 (p=0.007) weeks than the control group, and the systemic group showed better healing at both 2 (p=0.027) and 4 (p=0.023) weeks than the control TXA group. Moreover, bone healing was better in the group treated with topical rather than systemic TXA on radiological examinations performed at 2 (p=0.001) and 4 (p=0.007) weeks postoperatively (p=0.001 and p=0.007, respectively). Histologically, the groups differed significantly (p=0.001). The histological scores differed significantly among the all groups (p=0.001). At 2 weeks, the topical TXA group exhibited significantly better bone healing than the control group (p=0.001). Conclusion: Our results suggested that topical application of TXA in fracture patients may accelerate healing, whereas systemic administration may adversely affect healing.

___

1. Collaborators C-. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.. 2011; 377: 1096- 101. [CrossRef]

2. Dunn CJ, Goa KL. Tranexamic acid. Drugs 1999; 57: 1005-32. [CrossRef]

3. Gausden EB, Garner MR, Warner SJ, et al. Tranexamic acid in hip fracture patients: a protocol for a randomised, placebo controlled trial on the efficacy of tranexamic acid in reducing blood loss in hip fracture patients. BMJ Open 2016; 6: e010676. [CrossRef]

4. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ 2012; 344: e3054. [CrossRef]

5. Benoni G, Fredin H. Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty. Bone Joint J 1996; 78: 434-40. [CrossRef]

6. Ho K, Ismail H. Use of intravenous tranexamic acid to reduce allogeneic blood transfusion in total hip and knee arthroplasty: a meta-analysis. Anaesth Intensive Care 2003; 31: 529-37. [CrossRef]

7. Sukeik M, Alshryda S, Haddad F, Mason J. Systematic review and meta-analysis of the use of tranexamic acid in total hip replacement. J Bone Joint Surg Br 2011; 93: 39-46 [CrossRef]

8. Gulabi D, Yuce Y, Erkal KH, Saglam N, Camur S. The combined administration of systemic and topical tranexamic acid for total hip arthroplasty: Is it better than systemic? Acta Orthop Traumatol Turc 2019; 53: 297-300. [CrossRef]

9. Emara WM, Moez KK, Elkhouly AH. Topical versus intravenous tranexamic acid as a blood conservation intervention for reduction of post-operative bleeding in hemiarthroplasty. Anesth Essays Res 2014; 8: 48-53. [CrossRef]

10. Wong J, Abrishami A, El Beheiry H, et al. Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg Am 2010; 92: 2503-13. [CrossRef]

11. Zufferey P, Miquet M, Quenet S, et al. Tranexamic acid in hip fracture surgery: a randomized controlled trial. Br J Anaesth 2009; 104: 23-30. [CrossRef]

12. Gausden EB, Qudsi R, Boone MD, O’gara B, Ruzbarsky JJ, Lorich DG. Tranexamic acid in orthopaedic trauma surgery: A meta-analysis. J Orthop Trauma 2017; 31: 513-9. [CrossRef]

13. Kolar P, Schmidt-Bleek K, Schell H, et al. The early fracture hematoma and its potential role in fracture healing. Tissue Eng Part B Rev 2010; 16: 427-34. [CrossRef]

14. Echeverri L, Herrero M, Lopez J, Oleaga G. Early stages of bone fracture healing: formation of a fibrin-collagen scaffold in the fracture hematoma. Bull Math Biol 2015; 77: 156-83. [CrossRef]

15. Einhorn TA. Enhancement of fracture-healing. J Bone Joint Surg Am 1995; 77: 940-56. [CrossRef]

16. Grundnes O, Reikerås O. The importance of the hematoma for fracture healing in rats. Acta Orthop Scand 1993; 64: 340-2. [CrossRef]

17. Brinker MR, O’Connor DP. The biological basis for nonunions. JBJS Rev 2016; 4. pii: 01874474-201606000-00001. [CrossRef]

18. Auer JA, Goodship A, Arnoczky S, et al. Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use. BMC Musculoskelet Disord 2007; 8: 72. [CrossRef]

19. Iwaki A, Jingushi S, Oda Y, et al. Localization and quantification of proliferating cells during rat fracture repair: detection of proliferating cell nuclear antigen by immunohistochemistry. J Bone Miner Res 1997; 12: 96-102. [CrossRef]

20. Bordei P. Locally applied platelet-derived growth factor accelerates fracture healing. J Bone Joint Surg Br 2011; 93: 1653-9. [CrossRef]

21. Suen PK, He YX, Chow DHK, et al. Sclerostin monoclonal antibody enhanced bone fracture healing in an open osteotomy model in rats. J Orthop Res 2014; 32: 997-1005 [CrossRef]

22. Lane JM, Sandhu H. Current approaches to experimental bone grafting. Orthop Clin North Am 1987; 18: 213-25.

23. Tägil M, McDonald MM, Morse A, et al. Intermittent PTH (1-34) does not increase union rates in open rat femoral fractures and exhibits attenuated anabolic effects compared to closed fractures. Bone 2010; 46: 852-9. [CrossRef]

24. Schwarzkopf R, Dang P, Luu M, Mozaffar T, Gupta R. Topical tranexamic Acid does not affect electrophysiologic or neurovascular sciatic nerve markers in an animal model. Clin Orthop Relat Res 2015; 473: 1074-82. [CrossRef]

25. Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res 1991; 9: 383-90. [CrossRef]

26. Lack WD, Crist BD, Seymour RB, Harvin W, Karunakar MA; TXA Study Group. Effect of tranexamic acid on transfusion: A randomized clinical trial in acetabular fracture surgery. J Orthop Trauma 2017; 31: 526-30. [CrossRef]

27. Lei J, Zhang B, Cong Y, et al. Tranexamic acid reduces hidden blood loss in the treatment of intertrochanteric fractures with PFNA: A single-center randomized controlled trial. J Orthop Surg Res 2017; 12: 124. doi: 10.1186/s13018-017-0625-9. [CrossRef]

28. Watts CD, Houdek MT, Sems SA, Cross WW, Pagnano MW. Tranexamic acid safely reduced blood loss in hemi-and total hip arthroplasty for acute femoral neck fracture: a randomized clinical trial. J Orthop Trauma 2017; 31: 345-51. [CrossRef]

29. Kashyap S, Mahajan S, Lal M. Effects of topical tranexamic acid during open reduction and internal fixation of acetabular fractures: A retrospective study. Acta Orthop Traumatol Turc 2019; 53: 175-9. [CrossRef]

30. Blanié A, Bellamy L, Rhayem Y, et al. Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study. Thromb Res 2013; 131: e6-e11. [CrossRef]

31. Mountziaris PM, Mikos AG. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng Part B Rev 2008; 14: 179-86 [CrossRef]

32. Xing Z, Lu C, Hu D, Miclau T, Marcucio RS. Rejuvenation of the inflammatory system stimulates fracture repair in aged mice. J Orthop Res 2010; 28: 1000-6. [CrossRef]

33. Benoni G, Lethagen S, Fredin H. The effect of tranexamic acid on local and plasma fibrinolysis during total knee arthroplasty. Thromb Res 1997; 85: 195-206. [CrossRef]

34. Carter G, Goss A, Lloyd J, Tocchetti R. Tranexamic acid mouthwash versus autologous fibrin glue in patients taking warfarin undergoing dental extractions: a randomized prospective clinical study. J Oral Maxillofac Surg 2003; 61: 1432-5. [CrossRef]

35. Soffer E, Ouhayoun JP, Anagnostou F. Fibrin sealants and platelet preparations in bone and periodontal healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003; 95: 521-8. [CrossRef]
Acta Orthopaedica et Traumatologica Turcica-Cover
  • ISSN: 1017-995X
  • Başlangıç: 2015
  • Yayıncı: Türk Ortopedi ve Travmatoloji Derneği
Sayıdaki Diğer Makaleler

Safety and efficacy of tranexamic acid with epinephrine for prevention of blood loss following surgery for trochanteric femoral fractures

Xinxian XU, Linghui XİE, Huachen YU, Yuezheng HU

The role of the platelet-to-lymphocyte ratio and neutrophilto-lymphocyte ratio in the prediction of length and cost of hospital stay in patients with infected diabetic foot ulcers: A retrospective comparative study

Mehmet Ali EREN, Ali Erdal GÜNEŞ, İdris KIRHAN, Tevfik SABUNCU

The effect of topical and systemic tranexamic acid on fracture healing in rats

Bilgehan ÇEVİK, Engin ECEVİZ, Özlem Tuğçe ÇİLİNGİR KAYA, Feriha ERCAN, Gültekin SITKI ÇEÇEN

Quantitative assessment of changes in lesser trochanter shapes in relation to femoral rotations

Ali TURGUT, Anıl KOCA, Melikşah UZAKGİDER, Sert HANCIOĞLU, Serkan ERKUŞ, Önder KALENDERER

Comparison of the clinical and radiological outcomes of arthroscopic transosseous and transosseous-equivalent double-row rotator cuff repair techniques

Ahmet FIRAT, Mustafa AYDIN, Osman TECİMEL, Ali ÖÇGÜDER, Yavuz SANİSOĞLU, Mahmut UĞURLU

Risk factors for mortality and survival rates in elderly patients undergoing hemiarthroplasty for hip fracture

Ahmet ASLAN, Tolga ATAY, Nevres Hürriyet AYDOĞAN

Comparison of operating time, fluoroscopy exposure time, and functional and radiological results of two surgical methods for distal forearm fractures of both-bones in pediatric patients: Is it necessary to fix both bones?

Hakan KOCAOĞLU, Mahmut KALEM, Mustafa KAVAK, Ercan ŞAHİN, Kerem BAŞARIR, Hakan KINIK

Effect of platelet-rich plasma and platelet-rich fibrin matrix on healing of vertical meniscal tears in a rabbit model

Recep Kurnaz, Orhan BALTA

Comparison of two methods for coracoclavicular ligament reconstruction: A finite element analysis

Emre ÇALIŞAL, Levent UĞUR

Reliability and validation of the Turkish version of the Low Back Outcome Score

Ghofran ALHOMEDAH, Seyit ÇITAKER, Gürkan GÜNAYDIN, Refia SEZER, Furqan KHAN