Abstract
Effects of dexamethasone, a representative of the steroidal anti-inflammatory drugs, and indomethacin, a non-steroidal anti-inflammatory drug, on the healing of wound holes made in the parietal bone of growing rats (4 weeks old) and on the growth of femurs were studied. Drugs were administered s. c., 0.5, 1, 2 mg/kg/day for 1, 2 and 4 weeks except Sunday. After the end of administration, the parietal bones and femurs were removed. The uncalcified area of the wound hole portion detected by alizarin red S staining was measured. New formation and rearrangement of blood vessels in the holes which were detected by India ink injection into the aorta, were also investigated. Femur length and width were measured from soft x-ray photographs, and changes in the degree of the film whitening of the femur image were determined with a microdensitometer. The results obtained were as follows: 1. Both dexamethasone and indomethacin delayed the reduction of the uncalcified area of the wound holes, and the effect of the former was stronger than that of the latter. 2. Administration of dexamethasone for one week resulted in a weak inhibition of new growth of blood vessels into the wound hole. However, the normal reduction of the amount of blood vessels seen without drug administration was more strongly inhibited by the second week of the drug treatment. These results suggest that dexamethasone inhibits bone wound healing by the retardation of mineralization, which is closedly linked to the inhibition of reconstruction of blood vessels in the wound hole. A similar result was obtained by indomethacin administration, but the effect was much weaker than that of dexamethasone. 3. The growth in length and width of the femur was greatly inhibited by dexamethasone administration, but the effect of indomethacin was weaker. And the normal time dependent increase in the film whitening of the femur image was cleary inhibited by both drugs. The result of microdensitometry of the soft x-ray films also showed stronger blackening of the film by dexamethasone administration for two weeks than one week admistration but not by indomethacin. These results suggest that the retardation effect of dexamethasone on bone wound healing and bone growth is stronger than that of indomethacin with some difference in action mechanism between the two drugs.
