Spontaneous Fibro-osseous Proliferative Lesions in the Sternums and Femurs of B6C3F1 Mice

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Abstract
Bone morphology associated with fibro-osseous proliferation in the femurs and sternums of 98 female B6C3F1 mice were compared morphologically and quantitatively to femurs and sternums from 100 male B6C3F1 and 79 CF1 mice (48 female and 31 male). In addition, sternal samples from five B6C3F1 mice per sex were collected and processed for electron microscopy. Fibro-osseous proliferation was present in female B6C3F1 mice, but not male B6C3FI or female CF1 mice. In female B6C3F1 mice at 32 weeks of age, the marrow spaces in the region of the proximal and distal epiphyseal plate were lined by large osteoblasts and had large vascularized centers. At 58 weeks, metaphyseal fibrovascular proliferative areas containing multinucleated cells and new cancellous bone delineating the lesion were seen. At 84 weeks, fibro-osseous tissue occupied the outer third of the sternal marrow cavity and by 110 weeks, more than two thirds of the marrow cavity. Fibroosseous proliferation was present in 100 and 94% of the examined sternums and femurs, respectively, of female B6C3F1 mice at 110 weeks of age, but not in male B6C3F1 or female CF1 mice. Ultrastructural examination of the sternal changes at 110 weeks showed numerous osteoblasts, irregular bony spicules, and fibrocyte-like cells. By morphometry, the normal marrow cavity in B6C3F1 females occupied 35% of a longitudinal section of the whole sternebra compared with 70% and 75% of the whole sternebra in B6C3F1 males and CF1 female, respectively. The area of the whole sternum in B6C3F1 females did not change despite extensive fibro-osseous proliferation. The bony changes were associated with significant increase in plasma alkaline phosphatase activity. A comparable incidence of cystic endometrial hyperplasia and cystic ovaries were seen in both B6C3F1 and CF1 females. The results of this study suggest that B6C3F1 females may be more sensitive than females of other strains to age-related hormonal changes that alter the bone microenvironment.