Ratlarda Opioidlerin ve Non-Steroidal Anti-Enflamatuvar İlaçların Kırık İyileşmesi Üzerine Etkilerinin Karşılaştırılması

Yıl 2018, , 933 - 947, 15.08.2018

Muhammet Zeki Gültekin , Serdar Yüksel Ender Alagöz , Şule Özsoy Ali Avcı , Mehmet Akif Güleç Oğuz Uğur

https://doi.org/10.30569/adiyamansaglik.444022

Öz

Amaç: Analjezik etkileri için kullanılan opioidlerin ve non-steroid
anti-enflamatuvar ilaçların kıkırdak harabiyetine yol açtığına ve kırık
iyileşmesini olumsuz etkilediği bilinmektedir. Bu çalışmada; ratlar üzerinde
deneysel modelde opioidler ve non-steroidal anti-enflamatuvar ilaçların kırık
iyileşmesine etkilerinin karşılaştırılması amaçlandı.

 

Yöntem: Çalışmamızda rastgele olarak 3 guruba ayrılan 60 adet Sprague
-Dawley cinsi rata femur kırığı oluşturulduktan sonra 2 hafta boyunca sırasıyla
serum fizyolojik, morfin ve karprofen verildi. Tüm gruplarda yarısını 4.
haftada diğer yarısını ise 8.haftada sarifiye ederek kırık kalluslarını akut ve
subakut dönemlerde biyomekanik, radyografik ve histopatolojik olarak
değerlendirildi.

 

Bulgular: Opioid kullanılan gruptaki
ratların 1.ay ve 2. aydaki kırık kalluslarının diğer iki gruptan histopatolojik
olarak olumsuz etkilendiğini fakat biyomekaniksel ve radyografik açıdan bir
fark olmadığı saptadı. Non-steroidal anti-enflamatuvar ilaç kullanılan grupta
ise kırık iyileşmesinin etkilenmediğini tespit edildi.

 

Sonuç: Gerek opioidler, gerekse non-steroidal anti-enflamatuvar
ilaçların kırık iyileşmesi sürecine etkileri ile ilgili yapılmış invitro ve
invivo çalışmalarda kırık iyileşmesini etkileri tartışmalıdır. Bizim çalışmamıza
göre kırık iyileşmesini olumsuz etkileyecek faktörleri (ileri yaş, açık kırık,
yumuşak doku hasarsı vs) olmayan hastalarda akut ağrı kontrolünde opioid ve
non-steroidal anti-enflamatuvar ilaçların rahatça kullanılabilir.

 

Anahtar Kelimeler

Opioid, Nonsteroid antienflamtuar ilaçlar, Kırık iyileşmesi, Rat, Fraktür

THE COMPARISON OF THE EFFECTS OF OPIOIDS AND ANTI-INFLAMMATORY DRUGS ON FRACTURE HEALING

Öz

Objective: Opioids and non-steroid anti-inlammatory drugs used
for analgesic effects are known to lead to cartilage destruction and to affect
cartilage healing negatively. In the present study, the effects of opioids and
non-steroid anti-inlammatory drugs on cartilage healing were aimed to be
compared on experimental model of rats.

Method: In our study, 60 Sprague –Dawley rats in which
femur fractures were intentionally formed were randomly divided into three groups
and then given physiological saline, morphine and carprofen for 2 weeks,
respectively. In all groups, half of the rats were sacrificed at week 4, and
the second half were sacrificed at week 8, and then fracture calluses were
assessed biomechanically, radiographically and histopathologically within the
acute and sub-acute periods.

Results: It was determined that the fracture calluses at 1st and 2nd
months of the rats given opioids were affected histopathologically negatively
from the other two groups, but there was no difference in
terms of biomechanical and radiographical effects. In the group treated with
non-steroidal anti-inflammatory drugs, however, no fracture healing was
detected to develop.

Conclusion: In in vitro and in vivo studies, the effects of both opioids and
non-steroid anti-inlammatory drugs on fracture healing period still remain
controversial. Based on our study findings, opioids and non-steroid
anti-inlammatory drugs can be conveniently used in pain control in the patients
not having factors (advanced age, open fracture, soft tissue injuries and so
on) to affect fracture healing.  

Anahtar Kelimeler

Fracture, opioids, non-steroid anti-inflammatory drugs, fracture healing, rat

Kaynakça

• 1- Pountos I, Georgouli T, Blokhuis TJ, Pape HC, Giannoudis PV. Pharmacological agents and impairment of fracture healing: what is the evidence?. Injury 2008; 39(4): 384–394.
• 2- Augat P, Margevicius K, Simon J, Wolf S, Suger G, Claes L. Local tissue properties in bone healing: influence of size and stability of the osteotomy gap. Journal of Orthopaedic Research 1998;16(4): 475–481.
• 3- Castell´a FB, Garcia FB, Berry EM, Perello EB, Sanchez-Alepuz E, Gabarda R. Nonunion of the humeral shaft: long lateral butterfly fracture—a nonunion predictive pattern?. Clinical Orthopaedics and Related Research 2004; 42: 227–230.
• 4- Buckwalter AJ. Bone and Joint Healing. In: R. Bucholz, J. Heckman, Court- Brown C (Eds) Rockwood and Green’s Fractures in Adults, Lippincott Williams and Wilkins, Philadelphia, 2006;Vol 1: 297-307.
• 5- Chrastil J, Sampson C, Jones KB, Higgins TF. Postoperative opioid administration inhibits bone healing in an animal model. Clin Orthop Relat Res 2013; 471(12):4076-4081.
• 6- Müller M, Raabe O, Addicks K, Wenisch S, Arnhold S. Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells. Cell Biology International 2011; 35(3): 235–248.
• 7- Karachalios T, Boursinos L, Poultsides L, Khaldi L, Malizos KN. The effects of the short-term administration of low therapeutic doses of anti-COX-2 agents on the healing of fractures: an experimental study in rabbits. Journal of Boneand Joint Surgery B 2007; 89(9):1253–1260.
• 8- O’Connor JP, Capo JT, Tan V et al. A comparison of the effects of ibuprofen and rofecoxib on rabbit fibula osteotomy healing. Acta Orthopaedica 2009; 80(5): 597–605.
• 9- Endo K, Sairyo K, Komatsubara K et al. Cyclooxygenase-2 inhibitor delays fracture healing in rats. Acta Orthopaedica 2005;76(4) : 470–474.
• 10- Dodwell ER, Latorre JG, Parisini E, et al. NSAID exposure and risk of nonunion: a meta-analysis of case-control and cohort studies. Calcif Tissue 2010;87:193–202.
• 11- Bhattacharyya T, Levin R, Vrahas MS, Solomon DH. Nonsteroidal antiinflammatory drugs and nonunion of humeral shaft fractures. Arthritis Rheum 2005; 53:364–367.
• 12- Jeffcoach DR, Sams VG, Lawson CM et al. Nonsteroidal anti-inflammatory drugs’ impact on nonunion and infection rates in long-bone fractures. J Trauma Acute Care Surg 2014;76:779–783.
• 13- Geusens P, Emans PJ, De Jong JJA, Van den Bergh J. NSAIDs and fracture healing. Curr Opin Rheumatol 2013; 25:524–531.
• 14- Huo MH, Troiano NW. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic and histomorphometric parameters in rats. J Orthop Res 1991; 9(3): 383-390.
• 15- Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB Journal2004; 18(7):790–804.
• 16- Horn PL, Wrona S, Beebe AC, Klamar JE. A retrospective quality improvement study of ketorolac use following spinal fusion in pediatric patients, Orthopaedic Nursing 2010; 29(5): 342–343.
• 17- Fracon RN, Te´ofilo JM, Moris LC, Lamano T. Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats. Journal of Applied Oral Science 2010;18(6): 630–634.
• 18- Hak DJ, Schulz KS, Khoie B, Hazelwood SJ. The effect of Cox-2 specific inhibition on direct fracture healing in the rabbit tibia. Journal of Orthopaedic Science 2011;16(1): 93–98.
• 19- Chang JK, Li CJ, Wu SC et al. Effects of antiinflammatory drugs on proliferation, cytotoxicity and osteogenesis in bone marrow mesenchymal stem cells. Biochemical Pharmacology 2007; 74(9):1371–1382.
• 20- Chang JK, Li CJ, Liao HJ, Wang CK, Wang GJ, Ho ML. Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts. Toxicology 2009; 258(2):148–156.
• 21- Bhandari M, Tornetta III P, Sprague S et all. Predictors of reoperation following operative management of fractures of the tibial shaft. Journal of Orthopaedic Trauma 2003;17(5): 353–361.
• 22- Pountos I, Georgouli T, Bird H, Kontakis G, Giannoudis PV. The effect of antibiotics onbone healing: current evidence. Expert Opinion on Drug Safety 2011; 10(6):. 935–945.
• 23- Leonelli SM, Goldberg BA, Safanda J, Bagwe MR, Sethuratnam S, King SJ. Effects of a cyclooxygenase-2inhibitor (rofecoxib) on bone healing. American Journal of Orthopedics 2006;35(2): 79–84.
• 24- Reikeraas O, Engebretsen L. Effects of ketoralac tromethamine and indomethacin on primary and secondary bone healing. An experimental study in rats. Archives of Orthopaedic and Trauma Surgery 1998;118(1-2): 50– 52.
• 25- Long J, Lewis S, Kuklo T, Zhu Y, Riew KD. The effect of cyclooxygenase-2 inhibitors on spinal fusion. Journal ofBone and Joint Surgery 2002; 84(10): 1763–1768.
• 26- Pountos I, Georgouli T, Calori GM, Giannoudis PV. Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis. ScientificWorldJournal. 2012:60-64
• 27- Fransen M , Neal B. Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. Cochrane Database of Systematic Reviews 2004; 3: Article ID CD001160.
• 28- Miller M, Sturmer T, Azrael D, Levin R, Solomon DH. Opioid analgesics and the risk of fractures in older adults with arthritis. J Am Geriatr Soc 2011; 59:430–438.
• 29- King T, Vardanyan A, Majuta L, Melemedjian O, Nagle R, Cress AE, Vanderah TW, Lai J, Porreca F. Morphine treatment accelerates sarcoma-induced bone pain, bone loss, and spontaneous fracture in a murine model of bone cancer. Pain 2007; 132:154–168.