An X-ray analysis of adjuvant arthritis in the rat. The effect of prednisolone and indomethacin

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Abstract
A detailed evaluation has been made of the radiological changes occurring in the hindfeet of rats with adjuvant arthritis from 0 to 50 days after injection with Freund's Complete Adjuvant (FCA). The results were compared with concomitant foot swelling and the presence of histopathological abnormalities at the end of the experiment. In addition, the effects of oral administration of prednisolone and indomethacin administered either from one day before injection with FCA to 21 days afterwards, or from 21 to 35 days after injection with FCA, has been investigated on all these changes. The main radiological changes were osteoporosis of the tarsals and metatarsals, erosions of the tarsals and periosteral reactions in the metatarsals which were visible on day 10 and progressed up until 21–24 days after injection with FCA. Cystic fibrosis was noted in the metatarsals on day 14 and in the tibia, fibula and tarsals on day 21 and progressed to become the dominant abnormality by day 35. Cystic fibrosis and subsequent calcification, which was apparent on day 35, were the main features of the disease when the animals were killed on day 50. 10 and 30 mg/kg prednisolone and 0.3 and 3 mg/kg indomethacin both reduced the total X-ray score when administered either from day −1 to 21, or from day 21–35, but did not at any time inhibit the osteoporosis or erosions. Their effect was mainly on preventing the cystic fibrosis and calcification which occurred later in the disease. Prednisolone and indomethacin also reduced the periosteal reaction when administered from one day before injection with FCA, but they were inactive in this respect when dosing was started on day 21 when the periosteal reaction was well established. Therefore, the results suggest that prednisolone and indomethacin inhibit the later sequelae of the disease and do not interfere with either the initial events or the disease process itself. There was a good correlation between the total X-ray score, foot size and total histopathology score at the end of the experiment, and also an apparent correlation between total X-ray score and foot size throughout the experiment. Although this suggests that foot size is sufficient to indicate the overall reaction in adjuvant arthritis, X-ray analysis may detect clinically useful anti-rheumatoid activity which might not be evident from measurements of foot size alone.