The effects of non-selective and cyclooxygenase-2-selective non-steroidal anti-inflammatory drugs on heterotopic ossification in rats.

Background: Review of the literature revealed several experimental studies on the effects of selective COX-2 inhibitors on fracture healing, but no reports were encountered regarding the effects of these compounds on experimental heterotopic bone formation, so the present study was conducted.

Material/methods: Thirty adult male Wistar rats were divided into three groups of ten animals each. Tibial and femoral bones were collected from the rats, cleaned and demineralized, and diaphyseal parts were implanted in muscle pouches created in the right gluteal region, one into each rat. Group 1 received DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), a highly selective COX-2 inhibitor, at a dose of 1.1 mg/kg/day. Group 2 received 2 mg/kg/day of indomethacin. The drugs were administered by oral gavage with 0.5% methyl cellulose as a delivery vehicle for eleven days, beginning on the first postoperative day. Group 3 received only methyl cellulose.

Results: Thirty days after the implantation of the demineralized bone matrix, 6/10 of DFU-treated, 9/9 of the indomethacin-treated, and 8/9 of the control rats displayed new bone formation.

Conclusions: The results of this study suggest that no form of non-steroidal anti-inflammatory drug has inhibitory effects on heterotopic bone formation in rats. In our opinion, bone formation is a quite complex process that requires several events and is regulated by several factors, so further investigations other than those using non-steroidal anti-inflammatory drugs are required.