Influence of indomethacin on induced heterotopic bone formation in rats. Importance of length of treatment and of age.

The effect of indomethacin on heterotopic and orthotopic bone formation in rats was analyzed with respect to (1) length of treatment after implantation, (2) duration of the indomethacin induced inhibition of heterotopic bone formation, and (3) influence of age of the implant recipient. Three weeks after implantation of demineralized bone matrix, the ash weight of implants from rats receiving indomethacin 2 mg/kg body weight during the entire experiment was 31% lower than that of controls. Animals treated for only six days after implantation exhibited an almost equally pronounced inhibition. However, six weeks after implantation, the inhibition caused by six days of indomethacin treatment had almost dissipated. In older rats the implants of demineralized bone matrix induces smaller volumes of new bone than in younger rats, but indomethacin causes approximately the same degree of inhibition of osteoinduction. Orthotopic bone is not affected by indomethacin treatment. This study shows that a short period of indomethacin treatment at the time of implantation of demineralized bone matrix is sufficient to reduce experimental bone formation, but the inhibitory effect slowly diminishes if the inductive process is continuous. The results indicate that the inhibition of heterotopic new bone formation by indomethacin may be mediated through reduction of the initial inflammatory response or by reduced mesenchymal cell proliferation.