Indomethacin inhibits bone formation in inductive allografts but not in autografts - Studies in rat

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are known to have inhibitory effects on new bone formation. We wanted to analyze some effects of the NSAID indomethacin on different inductive stimuli for bone formation. Methods We experimentally induced heterotopic new bone with demineralized allogeneic bone matrix (DABM) and with bone autografts in rats, in order to study the effects of indomethacin on new bone formation at 3 and 6 weeks. Results Indomethacin inhibited net bone formation in DABMs by 30% at 6 weeks. At 6 weeks, the mineral accretion rate was unaffected, indicating that it is at the early phase of the inductive process that mineral accretion is sensitive to inhibition by indomethacin, but not at the later stages. In traumatized skeletal bone, the Ca-45-specific activity was higher than in non-traumatized bone, while indomethacin significantly reduced the Ca-45 uptake at 3 weeks, but not at 6 weeks. In the autografts, a net mineral loss occurred, but neither mineral content nor Ca-45 incorporation was affected by Indomethacin treatment. Interpretation Indomethacin inhibited the early phase of new bone formation in heterotopic DABMs and the early bone healing process in traumatized skeletal bone, but did not affect resorption or bone formation in heterotopic autografts.