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Osteonecrosis in a Chemically Induced Rat Model of Human Hemolytic Disorders Associated with Thrombosis – A New Model for Avascular Necrosis of Bone

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Abstract

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 ≤ 0.05) decrease following 4-days treatment and a significant increase (P ≤ 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.

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Acknowledgements

The authors gratefully acknowledge Ms. JoAnne Johnson, NIEHS; Professor Issac Meller, National Unit of Orthopaedic Oncology, Sourasky Medical Center, Tel-Aviv, Israel; and Professor Charles Howard, Pediatric Orthopedic Unit, Hadassah University Hospital, Jerusalem, Israel, for their critical review of the manuscript. The authors have no conflict of interest.

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Authors and Affiliations

  1. Orthopaedic Surgery Department, Sapir Medical Center, 48 Tchernichovsky Street, Kfar-Saba, Israel 44281

    S. Shabat & M. Nyska

  2. Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA

    A. Nyska

  3. Pathology Associates - A Charles River Company, West Chester, Ohio 45069, USA

    P. H. Long

  4. MRI Lab, Human Biology Research Center, Department of Biophysics and Nuclear Medicine, Hadassah Hebrew University Hospital, Jerusalem, 91120, Israel

    G. Goelman & R. Abramovitch

  5. Harlan Biotech Israel Ltd., Kiryat Weizmann Building, Rehovot, 76326, Israel

    N. Ezov & T. Levin-Harrus

  6. Biostatistical Branch, National Institute of Environmental Sciences (NIEHS), Research Triangle Park, North Carolina 27709, USA

    S. Peddada

  7. Department of Orthodontics, Faculty of Dental Medicine, Hebrew University, Jerusalem, 91120, Israel

    M. Redlich

  8. Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel

    S. Yedgar

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  1. S. Shabat
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Shabat, S., Nyska, A., Long, P. et al. Osteonecrosis in a Chemically Induced Rat Model of Human Hemolytic Disorders Associated with Thrombosis – A New Model for Avascular Necrosis of Bone . Calcif Tissue Int 74, 220–228 (2004). https://doi.org/10.1007/s00223-003-0068-7

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