Histological studies in male C 57 black mice revealed a high incidence (39–61 %) of osteo-arthrotic changes in the knee joint from about the 17th month of life. In animals of the same strain aged 15½ months the incidence was only 19 %. The incidence of gonarthroses in 16-month-old female mice was considerably lower (4 %). In male mice aged 17–20 months, the oral administration of tribenoside in doses of 500 and 1,200 mg/kg weekly led to a significant (p < 0.05) reduction in the overall arthrotic involvement. A possible relation between the effect of tribenoside and other anti-inflammatory agents on osteo-arthroses in the mouse and their influence on mucopolysaccharide metabolism in connective tissue is discussed. The incidence of the formation of gaps in the epiphyseal growth zones and of osteoporosis of the femur and tibia in the same strain increases distinctly with advancing age. Except in animals treated with the highest dosage tested, in which there was a significant decrease in the development of osteoporosis, tribenoside in the range of doses used had no influence on these skeletal changes.

Experiments in rats of different ages have shown that juvenile animals are less sensitive than adults to the gastric irritant effects of non-steroid anti-inflammatory drugs, such as acetylsalicylic acid, oxyphenbutazone and phenylbutazone, although the anti-oedematous activity ofthese drugs is equally potent in all agegroups.

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(1) In the different vertebrates studied (mammals, amphibians, birds and fish) phenylbutazone, which was selected as a representative anti-inflammatory agent, was found to exert a varying degree of gastroulcerogenic activity. (2) The four anti-inflammatory agents, phenyl-butazone, oxyphenbutazone, indomethacin and flufenamic acid displayed a potent, acute ulcerogenic effect when administered orally to the rat. In the guinea pig and the mouse, a similar effect was only observed in response to higher (in some cases considerably higher) doses. (3) The margin between the median ulcerogenic and median lethal doses of phenylbutazone, oxyphenbutazone and flufenamic acid was narrow in the guinea pig and the mouse, but wide in the rat. In the case of indomethacin, it was wide in the mouse and narrow in the other two species. (4) The anti-inflammatory activity of the four preparations against acute oedema in the same species differed. (5) In the guinea pig, all four preparations showed a favourable therapeutic ratio, i.e. relation between anti-inflammatory and ulcerogenic activity; in the mouse and the rat, no consistent relationship was demonstrable. The most important finding emerging from these experiments is that ulcerogenicity and anti-inflammatory potency – in terms of the doses required to elicit these effects -need not necessarily parallel each other.

Mice of the C57 Black strain, aged 11–12 weeks, were treated once daily on 5 days a week for 4 months with C21 524-Su (pirprofen) in doses of 10 and 30 mg/kg p.o. In this genetically predisposed strain of mice, increases in the incidence of gonarthrosis have been observed after the administration of certain anti-inflammatory agents such as acetylsalicylic acid. Radiography and in particular exact histological examination of the knee joints revealed, however, that neither the overall incidence nor the severity of osteoarthrosis was greater in the mice treated with C 21 524-Su than in the controls. On the contrary, in the treated animals there was a tendency for the incidence and the intensity of gonarthrosis to be lower.