Summary
The effect of the two nonsteroidal antiinflammatory drugs Diclofenac and Indomethacin on the formation of heterotropic and orthotopic bone in rats was compared. Experimental heterotopic bone formation was induced by implanting demineralized bone matrix into the abdominal wall of rats. Indomethacin (3 mg/kg), Diclofenac (3, 6 or 12 mg/kg), or saline were given as daily subcutaneous injections. 3H-proline and 45Ca were given 24 h before the animals were killed. The net amount of bone formed by induction after three weeks was decreased by 15% by Indomethacin and Diclofenac in a dose of 3 mg/kg. The higher dose of 6 mg/kg of Diclofenac caused a higher degree of inhibition (30%), while 12 mg/kg produced toxic effects. Orthotopic bone was not affected by treatment with Indomethacin or Diclofenac.
Although both drugs inhibit prostaglandin synthesis to a different degree, they exert similar effects on induced heterotopic bone, suggesting that this action is caused by an inhibition of the inflammatory response to trauma.
Résumé
Comparaison de l'effet de deux anti-inflammatoires non stéroïdiens, le Diclofénac et l'Indométhacine, sur la formation d'os hétérotopique et orthotopique chez le rat. La formation expérimentale d'os hétérotopique a été provoquée par implantation de matrice osseuse déminéralisée dans la paroi abdominale du rat. L'Indométhacine (3 mg/kg), le Diclofénac (3, 6, 12 mg/kg) ou du sérum salé ont été administrés quotidiennement par voie sous-cutanée. 24 heures avant que les animaux soient sacrifiés on leur injecte une quantité connue de 3H-proline et de Ca45. La quantité d'os formé par induction après 3 semaines est diminuée de 15% par l'Indométhacine ou le Diclofénac à la dose de 3 mg/kg. Une dose plus élevée, de 6 mg/kg de Diclofénac, entraîne une inhibition plus importante, de 30%, tandis qu'une dose de 12 mg/kg a des effets toxiques. L'os orthotopique n'est pas influencé par l'Indométhacine ou le Diclofénac.
Bien que ces deux médications inhibent à différents degrés la synthèse des prostaglandines, elles ont le même effet vis-à-vis de l'induction de l'os hétérotopique, ce qui conduit à penser que cette action relève de l'inhibition de la réponse inflammatoire aux traumatismes.
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Nilsson, O.S., Bauer, H.C.F., Brosjö, O. et al. A comparison of Indomethacin and Diclofenac in the inhibition of experimental heterotopic new bone formation. International Orthopaedics 11, 283–287 (1987). https://doi.org/10.1007/BF00271462
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DOI: https://doi.org/10.1007/BF00271462