Effects of a cyclooxygenase-2 inhibitor (rofecoxib) on bone healing

In the study reported here, we determined the effects on bone healing of rofecoxib, one of the selective cyclooxygenase-2 (Cox-2) inhibitors that has been used for post-surgical analgesia, and compared these effects with those of nonselective ibuprofen and placebo. Each of 66 male rats received a closed, nondisplaced femoral fracture and was fed rofecoxib, ibuprofen, or placebo for 4 weeks. Results of postsacrifice evaluation showed gross nonunions in 64.7% of rofecoxib rats (P<.0001), 17.6% of ibuprofen rats (P =.007), and 0% of placebo rats. Compared with ibuprofen, rofecoxib was significantly more likely to produce nonunions (P =.007). Mean callus width was 8.9 mm (SD, 1.3 mm) for rofecoxib (P =.03), 8.9 mm (SD, 1.2 mm) for ibuprofen (P =.03), and 8.0 mm (SD, 1.3 mm) for placebo. Mean healing maturity (Goldberg classification) was 1.6 (SD, 0.7) for rofecoxib (P<.0001), 1.7 (SD, 0.8) for ibuprofen (P =.0001), and 2.7 (SD, 0.6) for placebo. Mean fracture angulation was 30.8° (SD, 16.7°) for rofecoxib (P =.003), 14.3° (SD, 14.4°) for ibuprofen (NS), and 13.4° (SD, 10.3°) for placebo. Mean histologic healing was 5.75 for rofecoxib (P =.02), 6.35 for ibuprofen (P =.05), and 8.25 for placebo. Cox-2 inhibitors should be used with caution when bone healing is necessary. Further study is warranted to determine whether the adverse effects occur in humans.