Retinyl acetate-induced arthritis in C3H-A(vy) mice

Severely impaired musculoskeletal mobility in C3H-A(vy) mice was noted during a pharmacologic trial evaluating the antitumorigenic properties of retinyl acetate (RAc). To determine the etiology of this impairment, we studied 103 female C3H-A(vy) mice that were fed RAc in daily doses of 75-300 micrograms or placebo and were killed after 3-16 months. Whole-body radiographs and histologic sections of the hindlimbs were scored for presence and severity of arthritis. C3H-A(vy) mice treated with RAc in any dose had a significantly higher incidence of arthritis than placebo-treated mice. Histologic evidence of enthesopathic disease closely paralleled the radiographic changes and ranged from small enthesophytes at tendinous and capsular insertions to complete periarticular bony bridging. Articular cartilage was not grossly affected. The incidence and severity of arthritis were significantly correlated with the total dose of RAc administered. The bony metaplasia induced by RAc was similar to the pathologic changes caused by other retinoids. This model may be useful for studying the pathogenesis of periarticular bone formation in diffuse idiopathic skeletal hyperostosis and related syndromes.