EFFECT OF TIMING OF COX-2-SELECTIVE NSAIDS USE ON FRACTURE HEALING IN AN ADULT RAT MODEL

Abstract

Introduction: Fractures are common in the old and are associated with increased morbidity. The pain of fractures and surgery can be managed using NSAIDs, but this may result in impaired healing. The inflammatory stage of bone healing is responsible for laying the foundation for subsequent proliferative stages. This may be the stage when NSAIDs may have their greatest impact and it is unclear if avoiding NSAIDs in this stage would result in differences in healing or whether different molecules have varied responses. This study sought to determine the differences in the histomorphometry of fracture callus in older rats when diclofenac and celecoxib were avoided in the first week after a fracture. Methods: Fractures of the tibia were induced in 43 15-month-old (equivalent to 50 human years) rats which were then allocated to receive either diclofenac or celecoxib. Each group was further subdivided into early or late subgroups of 10 animals each receiving the study medication from the day after the fracture or eight days later, respectively. Histological and stereological examination of the callus on days 21 and 42 enabled comparison of histological grades, tissue proportions and cellular densities. Results: The histological grade and amount of bone increased and the amount of cartilage reduced in all groups. The group that received celecoxib early had the least proportion of bone. The osteocyte and chondrocyte cellular densities increased in all groups across both time points. Conclusion: Administration of celecoxib in the early fracture period in the old is associated with poorer histological grades, lower proportions of bone and increased cellularity which may result in delayed union of the fracture. Use of selective COX-2 inhibitors is discouraged for the management of pain in older patients with fractures especially in the first seven days.