Efficacy of specific versus non-specific cyclooxygenase-2 inhibitors in the healing of rabbit models of tibial fractures / 中国组织工程研究

ABSTRACT

BACKGROUND: Non-specific cyclooxygenase inhibitor and specific cyclooxygenase inhibitor are commonly used nonsteroidal anti-inflammatory and analgesic drugs, but there is a lack of experimental evidence concerning the effect of these drugs on the fracture healing and the administration time. OBJECTIVE: To investigate the effect of non-specific cyclooxygenase-2 inhibitor versus specific cyclooxygenase-2 inhibitor on the healing of tibial fractures in rabbits. METHODS: Thirty-six 3-5-month-old New Zealand rabbits either in sexes were selected (provided by Laboratory Animal Center of Guangxi Medical University). Rabbit models of unilateral tibial fractures (3 mm) were established and randomly divided into modeling group (same volume of distilled water via gavage), specific cyclooxygenase-2 inhibitor group (1.15 mg/kg?d etoricoxib via gavage), and non-specific cyclooxygenase-2 inhibitor group (7.6 mg/kg?d aspirin via gavage), with 12 rabbits in each group. At 2, 4 and 8 weeks postoperatively, the fracture healing was observed and assessed by gross observation and histopathological sections. The serum level of osteocalcin, and levels of transforming growth factor β1 and vascular endothelial growth factor were detected. RESULTS AND CONCLUSION: (1) The non-specific cyclooxygenase-2 inhibitor group was superior to the other two groups in the formation and remodeling of callus and healing. (2) The serum level of osteocalcin in the non-specific cyclooxygenase-2 inhibitor group was significantly higher than that in the specific cyclooxygenase-2 inhibitor group (P ＜ 0.05). (3) Hematoxylin-eosin staining results: the non-specific cyclooxygenase-2 inhibitor group was earlier than the specific cyclooxygenase-2 inhibitor group in the formation of collagen fibers, cartilage tissue, trabecular bone and bone matrix. (4) The average absorbance value of transforming growth factor and vascular endothelial growth factor in the non-specific cyclooxygenase-2 inhibitor group was significantly higher than those in the specific cyclooxygenase-2 inhibitor group at 4 weeks postoperatively (P ＜ 0.05). (5) These results suggest that specific cyclooxygenase-2 inhibitor for rabbit tibia fractures took longer time than non-specific cyclooxygenase-2 inhibitor, indicating that cyclooxygenase-2 specific inhibitor is less effective than non-specific cyclooxygenase-2 inhibitor in fracture healing.