Flbro-Osseous Lesions in Aged Mice

Fibro-osseous lesions arise commonly in the sternebrae, vertebrae, femurs, and other bones in a number of strains of mice. They arise most frequently in females, and they are age-related.

Female B6C3F1 mice appear to be espe­cially prone (100% at 110 week of age) to this lesion, when compared to B6 and CD-1 mice. Early changes have been detected as early as 32 weeks of age, but the proliferative lesions are more common (and more evi­dent) in mice examined at 50 or more weeks of age. Estrogens have been presumed to play a role in develop­ment of these lesions. Mice have been shown to be particularly responsive to estrogen that can alter the microenviroment of bone. However, they also arise in ovariectomized females and castrated males, suggesting that other factors are involved. Similar changes have been produced in selected strains of mice treated with estrogens or a prostaglandin E₁ analogue. In affected bones, there is partial to complete replacement of bone marrow by fibroblast-like cells in an eosinophilic matrix (Fig. 1.126). There is displacement of the hematopoietic elements of the marrow, and osteoblasts are present around bony spicules within the medullary cavity. In some cases, there is extension into the perios­teal region, but there is no evidence of malignant trans­formation. Differential diagnosis includes histiocytic sarcomas with intramedullary involvement, which typi­cally consist of a more anaplastic population of cells, including prominent multinucleated giant cells. We have observed a number of osteosarcomas arising from the vertebrae and long bones of p53⁺/^- heterozy­gotes on the B6C3F1 background, but we have not seen any convincing evidence of progression of fibro-osseous lesions to osteosarcomas.

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