Parecoxib and indomethacin delay early fracture healing: a study in rats

Nonsteroidal antiinflammatory drugs (NSAIDs) are used to reduce inflammatory response and pain. These drugs have been reported to impair bone metabolism. Parecoxib, a specific COX-2 inhibitor, exerts an inhibitory effect on the mineralization of fracture callus after a tibial fracture in rats. Decreased bone mineral density (BMD) at a fracture site may indicate impairment of early healing, casting doubt on the safety of using COX-2 inhibitors during the early treatment of diaphyseal fractures. Forty-two female Wistar rats were randomly allocated to three groups. They were given parecoxib, indomethacin, or saline intraperitoneally for 7 days after being subjected to a closed tibial fracture stabilized with an intramedullary nail. Two and 3 weeks after surgery, the bone density at the fracture site was measured using dual energy xray absorptiometry (DEXA). Three weeks after the operation the rats were euthanized and the healing fractures were mechanically tested in three-point cantilever bending. Parecoxib decreased BMD at the fracture site for 3 weeks after fracture, indomethacin for 2 weeks. Both parecoxib and indomethacin reduced the ultimate bending moment and the bending stiffness of the healing fractures after 3 weeks. These results suggest COX inhibitors should be avoided in the early phase after fractures.