Rat tibia diyafiz kırıklarında deksketoprofen trometamolün kırık iyileşmesi üzerine etkisi

Öz

Amaç: Bu çalışmanın amacı bir non-steroid ve anti-enflamatuar ilaç olan deksketoprofen trometamolün kırık iyileşmesi üzerine etkisini araştırmaktı. Çalışma planı: Altmış adet Wistar tipi albino erkek ratın sağ tibiasında kapalı kırık oluşturuldu. Kapalı redüksiyon ve 0.5 mm’lik intramedüller çivi ile tespit sağlandı. Deney grubundaki 30 rata kas içi 5 mg/kg/gün deksketoprofen trometamol verildi. Ratlar kırık sonrası 2., 4. ve 6. haftalarda onarlı gruplar halinde sakrifiye edildi. İyileşmekte olan kırık tibialar mekanik, radyolojik ve histopatolojik olarak karşılaştırıldı. Bulgular: İkinci, 4. ve 6. hafta deney ve kontrol gruplarının ortalama radyolojik ve histopatolojik inceleme değerleri arasındaki fark istatistiksel olarak anlamlı değildi (p>0.05). Erken dönemdeki kırık iyileşmesi nedeniyle 2. hafta deney ve kontrol grubundaki tüm rat tibialarında biyomekanik değerlendirme yapılamadı. Dördüncü ve 6. hafta deney ve kontrol gruplarının ortalama biyomekanik inceleme değerleri arasındaki fark da istatistiksel olarak anlamlı bulunmadı (p>0.05). Çıkarımlar: Deksketoprofen trometamolün ratlarda oluşturulan ve intramedüller çivi ile tespit edilen kapalı tibia kırıklarının iyileşmesi üzerine, uzun süreli kullanımında radyolojik, biyomekanik veya histolojik bir etkisi görülmedi. Deksketoprofen trometamol travma sonrası kırığı olan ve cerrahi tespit yapılan hastalarda beraber verilen diğer ilaçlar da göz önünde bulundurularak kullanılabilir.

Anahtar Kelimeler

• Deksketoprofen trometamol; hayvan deneyi; kapalı kırık; kırık iyileşmesi; tibia kırığı

The effect of dexketoprofen trometamol on the healing of diaphysis fractures of rat tibia

Abstract

Objective: The aim of this study was to analyze the effect of dexketoprofen trometamol, a nonsteroidal anti-inflammatory drug, on fracture healing.
Methods: Closed tibia fracture was created in the right tibia of 60 male Wistar albino rats. Fixation was achieved by closed reduction and 0.5 mm intramedullary nails. Intramuscular dexketoprofen trometamol was administered at a dose of 5 mg/kg daily to the 30 rats in the study group. Rats were sacrificed in groups of 10 at the 2nd, 4th, and 6th weeks following the fracture. Fracture healing was compared mechanically, radiologically, and histopathologically between the groups.
Results: There was no statistically significant difference between the study and control groups in terms of mean values of radiological or histopathological scores at the 2nd, 4th and 6th weeks (p>0.05). Biomechanical evaluation could not be conducted in all rats in the study and control groups at the 2nd week due to early stage fracture healing. Mean biomechanical examination values were not statistically significant at the 4th and 6th weeks between the study and control groups (p>0.05).
Conclusion: No radiological, biomechanical, and histological effects were detected in the healing of closed fractures of the tibia fixed with intramedullary nail with the long-term use of dexketoprofen trometamol. Dexketoprofen trometamol may be used in patients undergoing surgical fixation for traumatic fractures, taking into account other drugs administered together. 

Keywords

• Animal experiment
• closed fracture
• dexketoprofen trometamol
• fracture healing
• tibial fracture

References

1. Einhorn TA. The cell and molecular biology of fracture heal- ing. Clin Orthop Relat Res 1998;(355 Suppl):S7-21.
2. Allen HL, Wase A, Bear WT. Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. Acta Orthop Scand 1980;51:595- 600.
3. Elves MW, Bayley I, Roylance PJ. The effect of indomethacin upon experimental fractures in the rat. Acta Orthop Scand 1982;53:35-41.
4. Törnkvist H, Lindholm TS, Netz P, Strömberg L, Lindholm TC. Effect of ibuprofen and indomethacin on bone metabo- lism reflected in bone strength. Clin Orthop Relat Res 1984; (187):255-9.
5. More RC, Kody MH, Kabo JM, Dorey FJ, Meals RA. The effects of two nonsteroidal antiinflammatory drugs on limb swelling, joint stiffness, and bone torsional strength following fracture in a rabbit model. Clin Orthop Relat Res 1989;(247): 306-12.
6. Lane JM, Sandhu HS. Current approaches to experimental bone grafting. Orthop Clin North Am 1987;12:213-25.
7. Huo MH, Troiano NW, Pelker RR, Gundberg CM, Friedlaender GE. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomor- phometric parameters in rats. J Orthop Res 1991;9:383-90.
8. Phillips AM. Overview of the fracture healing cascade. Injury 2005;36S:S5-7.

9. Evans AM. Enantioselective pharmacodynamics and pharma- cokinetics of chiral non-steroidal anti-inflammatory drugs. Eur J Clin Pharmacol 1992;42:237-56.
10. Zegpi C, Gonzalez C, Pinardi G, Miranda HF. The effect of opioid antagonists on synergism between dexketoprofen and tramadol. Pharmacol Res 2009;60:291-5.
11. Giordano V, Giordano M, Knackfuss IG, Apfel MI, Gomes RD. Effect of tenoxicam on fracture healing in rat tibiae. Injury 2003;34:85-94.
12. Fracon RN, Teófilo JM, Satin RB, Lamano T. Prostaglandins and bone: potential risk and benefits related to the use of non- steroidal anti-inflammatory drugs in clinical dentistry. J Oral Sci 2008;50:247-52.
13. Sweetman BJ. Development and use of the quick acting chiral NSAID dexketoprofen trometamol (keral). Acute Pain 2003;4: 109-15.
14. Keller J, Bünger C, Andreassen TT, Bak B, Lucht U. Bone repair inhibited by indomethacin. Effects on bone metabolism and strength of rabbit osteotomies. Acta Orthop Scand 1987; 58:379-83.
15. Ozaki A, Tsunoda M, Kinoshita S, Saura R. Role of fracture hematoma and periosteum during fracture healing in rats: interaction of fracture hematoma and the periosteum in the initial step of the healing process. J Orthop Sci 2000;5:64-70.
16. Hausman MR, Schaffler MB, Majeska RJ. Prevention of frac- ture healing in rats by inhibitor of angiogenesis. Bone 2001; 29:560-4.
17. Tuncer S, Tavlan A, Köstekçi H, Reisli R, Otelcio¤lu S. Dexketoprofen use in postoperative pain. Agri 2006;18:30-5.
18. Ho AM, Phillips NW, Friedlaender GE. The effect of ketoro- lac on fracture repair: biomechanical, histologic, and histo- morphometric parameters in rats. J Orthop Res 1995;3:461- 72.
19. Turk C, Halici M, Guney A, Akgun H, Sahin V, Muhtaroglu S. Promotion of fracture healing by vitamin E in rats. J Int Me Res 2004;32:507-12.
20. Miranda HF, Puig MM, Dursteler C, Prieto JC, Pinardi G. Dexketoprofen-induced antinociception in animal models of acute pain: synergy with morphine and paracetamol. Neuropharmacology 2007;52:291-6.
21. Moore RA, Barden J. Systematic review of dexketoprofen in acute and chronic pain. BMC Clin Pharmacol 2008;8:11.
22. Simon AM, Manigrasso MB, O’Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res 2002;17:963-76.
23. Cabré F, Fernández MF, Calvo L, Ferrer X, García ML, Mauleón D. Analgesic, antiinflammatory and antipyretic effects of S(+)-ketoprofen in vivo. J Clin Pharmacol 1998;38: 3S-10S.
24. Dimmen S. Effects of Cox inhibitors on bone and tendon healing. Acta Orthop Suppl 2011;82:1-22.
25. Marsh DR, Li G. The biology of fracture healing: optimizing outcome. Br Med Bull 1999;55:856-69.
26. Sandberg O, Eliasson P, Andersson T, Agholme F, Aspenberg P. Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury. Acta Orthop 2012;83:305-10.
27. Urrutia J, Mardones R, Quezada F. The effect of ketoprophen on lumbar spinal fusion healing in a rabbit model. Laboratory investigation. J Neurosurg Spine 2007;7:631-6.
28. Matsushita T, Cornell CN. Biomechanics of bone healing: editorial comment. Clin Orthop Relat Res 2009;467:1937-8.