Proliferative Bone Lesions in Rats Fed a Diet Containing Glucocorticoid for up to Two Years

Abstract

A glucocorticoid was fed in the diet to 50 Sprague-Dawley rats/sex at 0, 0.03, 0.06, 0.12, 0.25, 0.50, and 1.0 mg/kg/day for up to 2 yr. A total of 1,400 rats were examined. Bone neoplasms (5 osteosarcomas and 2 osteomas), involving the head, occurred in 7 males that were fed the test compound at the highest dose (0.25 mg/kg) with long-term survivors. One osteoma and 1 hyperostotic lesion were seen in 2 males receiving lower doses (0.06 mg/kg and 0.12 mg/kg, respectively); 1 female rat that received the highest dose (1 mg/kg) had an osteosarcoma. The results suggest, but do not confirm, a relationship between glucocorticoid exposure and bone proliferations in male Sprague-Dawley rats. Other proliferative bone lesions included hyperostosis in a 0.12-mg/kg male, osteoma in a 0.06-mg/kg male, and osteosarcoma in 1 female at 1.0 mg/kg. The purpose of this report is to characterize the incidence and morphology of primary bone proliferative lesions found in rats of 1-yr glucocorticoid toxicity and 2-yr carcinogenicity studies conducted in our laboratory.