The Effects Of Celecoxib Applied In Different Durations On Fracture Healing In Rat Femur

Objective To investigate the effects of celecoxib,a selective COX-2 inhibitor,on bone healing in rats femur,when it is applied in different durations.Methods Opened non-displaced transverse mid-diaphyseal fractures in the middle of the left femoral shaft were generated in 36 skeletally mature male Sprague Dawley rats.The rats were then randomly assigned to three groups,Group A were treated with placebo,and Group B celecoxib (24 mg·kg-1·d-1,last for lweek), Group C celecoxib (24 mg-kg-1-d-1,last for 4weeks) after surgery. Bone union and average healing scores,callus formation were evaluated by radiographs in 2,3,4,6weeks after surgery.Half of these rats were put to death at 4 weeks after surgery and perform a histomorphometry,to evaluate the density of mean trabecular plate (MTPD) of each group.6 weeks after surgery,the mechanical strength of the fractured femur was evaluated by a three point bending test,the results of treatment group were compared with those of a vehicle control group.All results were analysed with statistical software SPSS17.0.Results (1)Radiological examination:The callus of normal group growed obviously and the fracture lines gradually blur in the second week after surgery,in the 3rd week some fractures got union and began to rebuild in the fourth week,6 weeks after surgery all fractures were healed.Compared with placebo,the callus of Group B grew later and less,the fracture line began to blur in 3 weeks and almost disappeared In 6 weeks with some callus grew around the fracture.3 weeks after surgery the average fracture healing score between group A and group B were significant differences (P<0.05),while in 4 and 6 weeks not significant (P>0.05).Few callus grew during the study of group C,the fracture line still clear 4 weeks after surgery and did not disappear in the 6th week.The average fracture healing score of group C were shown to be significantly lower than group A(P<0.005).(2)histological examinations:in Black group trabecula bone grew compact with vigorous growth of cartilage cells,while Group B sparser,and the bone trabecula density lower than group A(P<0.05).Trabecula bone grew very sparse, inordinate,and the bone trabecula density significantly lower than group A(P<0.005); (3)Biomechanical measurements:6 weeks after surgery the mechanical strength of the surgery side femurs were evaluated by a three point bending test,which showed no significant differences between group A and B (P>0.05).All of the fractures of group C,which is a long-term treatment group, were fiber healing with few Callus grown and unable to perform a bending test.Conclusions(1) Long-term,sustained use of Celecoxib,a selective COX-2 inhibitor,after fracture surgery in rats femur,will significantly reduce callus growth,delay fracture healing and increase the rate of nonunion;(2) Short-term,early use of Celecoxib,a selective COX-2 inhibitor,after fracture surgery in rats femur,will also reduce callus growth,impede the formation of bone trabecula,but these phenomenons were gradually recovered after drug withdrawal,and the process of bone healing were not obviously prolonged;(3) Short-term,early use of Celecoxib after fracture surgery in rats do not reduce the strength of fracture healing.