Do steroids, conventional non-steroidal anti-inflammatory drugs and selective Cox-2 inhibitors adversely affect fracture healing?

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide. They are prescribed for orthopaedic conditions such as osteoarthritis, soft-tissue injuries and fractures. The new generation of NSAIDs, selective cyclooxygenase-2 (COX-2) inhibitors, exhibit analgesic and anti-inflammatory effects equivalent or superior to conventional NSAIDs, while reducing the prevalence of adverse gastrointestinal events. Several reports from animal and in vitro studies have demonstrated impaired bone healing in the presence of conventional NSAIDs, as measured by a variety of different parameters. More recently, initial studies investigating the effects of selective COX-2 inhibitors on bone healing have yielded similar results, while other reports showed minor or no impairment of the healing process. The purpose of the present review article is the thorough review and analysis of the past 50-year literature and the attempt to get some conclusions about the effect of NSAIDs and selective COX-2 inhibitors on fracture healing and the clinical significance of their use in the management of postoperative and post-fracture pain.

The effects of the short-term administration of low therapeutic doses of anti-COX-2 agents on the healing of fractures. An experimental study in rabbits.

We have evaluated the effect of the short-term administration of low therapeutic doses of modern COX-2 inhibitors on the healing of fractures. A total of 40 adult male New Zealand rabbits were divided into five groups. A mid-diaphyseal osteotomy of the right ulna was performed and either normal saline, prednisolone, indometacin, meloxicam or rofecoxib was administered for five days. Radiological, biomechanical and histomorphometric evaluation was performed at six weeks. In the group in which the highly selective anti-COX-2 agent, rofecoxib, was used the incidence of radiologically-incomplete union was similar to that in the control group. All the biomechanical parameters were statistically significantly lower in both the prednisolone and indometacin (p = 0.01) and in the meloxicam (p = 0.04) groups compared with the control group. Only the fracture load values were found to be statistically significantly lower (p = 0.05) in the rofecoxib group. Histomorphometric parameters were adversely affected in all groups with the specimens of the rofecoxib group showing the least negative effect. Our findings indicated that the short-term administration of low therapeutic doses of a highly selective COX-2 inhibitor had a minor negative effect on bone healing.