Osteonecrosis in a chemically induced rat model of human hemolytic disorders associated with thrombosis--a new model for avascular necrosis of bone.
Bone injury occurs in human hemolytic disorders associated with thrombosis, such as beta-thalassemia and sickle cell disease. Exposure of rats to 2-butoxyethanol (BE) has been associated with hemolytic anemia, disseminated thrombosis, and infarction in multiple organs including bone. This rat model apparently mimics acute hemolysis and thrombosis in humans. To elucidate the extent of bone injury, male and female Fischer F344 rats were given 4 daily doses of 250 mg BE/5 ml water/kg of body weight. Tail vertebrae were studied by histopathology and magnetic resonance imaging (MRI). Thrombosis and infarction were seen in both sexes, but females were more severely affected. Lesions were characterized by extensive medullary fat necrosis, granulomatous inflammation, fibroplasia, growth plate degeneration, and new woven bone formation adjacent to necrotic bone trabeculae. MRI mean and standard deviation tissue-density data for both sexes indicated a significant (P < or = 0.05) decrease following 4-days treatment and a significant increase (P < or = 0.05) following an additional 24 days without treatment. Thus, MRI was useful in revealing BE-induced bone injury, which was predominantly necrotic initially and subsequently regenerative with proliferation of connective tissue and bone following postischemia recovery.
D000818:Animals; D004195:Disease Models, Animal; D005026:Ethylene Glycols / Q000633:toxicity; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D012997:Solvents / Q000633:toxicity; D013131:Spine / Q000187:drug effects / Q000473:pathology; D013623:Tail / Q000187:drug effects / Q000473:pathology; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology
D005026:Ethylene Glycols; D012997:Solvents; C017096:n-butoxyethanol