Radiological Evaluation of the effects of varied doses of Celecoxib on fracture healing in dogs

To determine if Cyclooxygenase -2 (COX-2) functions in fracture healing, 10 dogs were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (Celecoxib) to reduce and stop COX-2-dependent prostaglandin production. Radiographic testing evaluation determined that fracture healing was not affected in dogs treated with a low dose of COX-2-selective NSAIDs (celecoxib) and delayed union was observed in dogs treated with a high dose of COX-2selective NSAIDs (celecoxib). Celecoxib dose of 5 mg/kg/day did not affect fracture callus formed in the study group and did not cause a significant increase in the proportion of delayed unions, however, at a dose of 10 mg/kg/day it reduced the rate of fracture callus formation and significantly increased the proportion of delayed unions for dogs in the group.


Material and Methods
Considerable evidence has shown that conventional nonspecific, non-steroidal, anti-inflammatory 10 mongrel dogs (12-18 months old) were used for the clinical study.All anaesthetic and surgical drugs, such as ibuprofen, ketoprofen, ketorolac and procedures were performed in conformity with the indomethacin, have an inhibitory effect on fractureexisting University of Nigeria, Nsukka, Faculty of healing as well as other forms of postoperative bone Veterinary Medicine ethics on animal handling and repair (Allen et al, 1980;Huo et al, 1991).In recent research.studies, comparing nonselective, non-steroidal, anti-Anaesthesia: Animals were premedicated with inflammatory drugs and COX-2-selective drugs in Atropine (Atrocare, Animal Care, UK) 50 mcg/kg IM rats, impaired fracture-healing was observed, with a and Xylazine (Xylacare 2%, Animalcare, UK) 1mg/kg greater effect seen in association with the COX-2-IM.Anaesthesia was induced with Ketamine selective drugs (Altman et al, 1995).Recent studies on (Vetalar-V, Pfizer, Germany) 10mg/kg IM and the use of selective prostaglandin-receptor agonists have shown that stimulation of the EP2 or EP4 maintained with Ketamine (Vetalar-V, Pfizer, UK) prostaglandin E2 (PGE2) receptor specifically 10mg/kg IM. promotes bone-healing (Gerstenfeld et al, 2003).Surgery: The femoral diaphysis was exposed by Prostaglandins play an important role in the regulation incision and blunt dissection.Using a bone saw, a of osteoblast and osteoclast functions, and inhibition simple transverse fracture was created at the mid shaft of Prostaglandin production retards bone formation. of the femoral diaphysis.Spatial re-alignment of the Therefore, non steroidal, anti-inflammatory drugs bone was achieved by insertion of a 4.5mm single (NSAIDs) could be expected to have significant armed IM pin.A post surgical radiograph was consequences in divergent clinical situations where immediately taken to assess fixation system and bone formation or remodelling is a contributory factor.confirm alignment of the fractured segment.

Post-operative Management and Care:
NSAIDs are used clinically to prevent ectopic bone Analgesics and Antimicrobials: Dogs in Group 1 were formation also known a heterotrophic ossification treated with Celecoxib (Celebrex®,Pfizer, Germany) (e.g. after total hip arthroplasty or trauma).The 5mg/kg P.O daily from day 0-14 and Enrofloxacin efficacy of NSAIDs in the avoidance of heterotrophic (Conflox® Animal Care, Nigeria) 10mg/kg IM; b.i.d ossification has been documented in controlled from day 0-5.Dogs in group 2 were treated with clinical trials, but the inherent risk on bone fracture Celecoxib (Celebrex®,Pfizer, Germany) 10mg/kg P.O healing processes and loosening of implants need daily from day 0-14 and Enrofloxacin (Conflox® further studies (Goodman et al, 2003).
drug was compared with a COX-2 selective drug in Radiography: Sequential radiographs were taken to terms of the inhibitory effects on fracture-healing, evaluate fracture healing at weeks 2, 4, 6 and 8 impaired fracture-healing was shown to be greater respectively.Development of periosteal callus when the COX-2 selective drug was used (Simon et al, indicated that indirect bone formation is occurring.2002).The study showed that at low dose celecoxib Filling of stable fracture lines with bone indicated did not inhibit the rate of callus formation and did not direct fracture healing.
inhibit fracture healing but at high dose, there was delay in callus formation up to four weeks after

Results
fixation of the fracture and there was a significantly Radiology: high rate of delayed union in the group.Finally, it is Radiographs of animals in group 1; that suggested that, use of celecoxib and other COX-2 received 5mg/kg celecoxib showed distinct line of selective inhibitors in fracture treatment should be facture and periosteal bridging callus formation at done with caution, and at the lowest effective dose for week 2.This was progressive at week 4 with cortical pain relief bearing in mind the benefits of pain relief bridging calluses.By week 6 the fractures in animals and inhibition of ectopic bone formation on one hand in this group had radiographic evidence of union with and the risk of non union and retarded union on the progressive healing observed at week 8 there was clear other hand.evidence of bridging in the fractures in animals in this group.At week 2 the radiographs from animals in