Analysis Tools
skeleton
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• all mice develop fibrous dysplasia that progresses from an initial stage in which excess primary bone formation occurs at endosteal surfaces and within medullary cavities, to an intermediate stage during which enhanced remodeling occurs, and a final stage during which marrow fibrosis and overall bone deformation and/or fractures are established
• lesions in the tail vertebrae first appear at 2 months of age
• 70% of mice develop multiple lesions at other skeletal sites, resulting in a polyostotic pattern of skeletal disease
• femur is the second earliest and second most common site of involvement, followed by tibia, spine, humerus, acropodial short bones, cranium, ribs, and pelvis
• however, mice exhibit normal bone development and embryonic bone cell differentiation
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• early skeletal changes result in narrow and distorted marrow cavities
• in intermediate lesions (2-6 months from appearance), the marrow cavity is obliterated or narrowed and distorted
• in late lesions, the internal bone architecture is effaced, such that the cortical bone and marrow cavity can no longer be discerned
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• in the femur, early lesions consist in localized endosteal thickening at the midshaft or the metadiaphyseal junction, with thickening extending proximally and distally progressively and lytic changes developing within the thickened bone
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• intermediate lesions show large, focal structural gaps within an abnormally expanded cortical bone, however no fibrosis is seen
• vertebra show intracortical gaps at sites of ectopic intracortical remodeling
• in late lesions, the internal bone architecture is effaced, such that the cortical bone and marrow cavity can no longer be discerned
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• early changes consist of endosteal thickening, associated with an excess of abnormal bone trabeculae leading to narrowed and distorted marrow cavities
• endosteal/medullary bone trabeculae are irregular in shape and mode of woven bone, do not contain a cartilage core (not endochondrally formed) and are separated from each other by a cellular tissue
• a characteristic Chinese writing pattern of abnormal bone trabeculae is seen in late lesions
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• increasing hyperostosis and deformity of vertebrae, which progresses steadily after 1 year of age
• distal metaphyses become hyperostotic and deformed after 1 year of age
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• progressive sclerosis in vertebrae, femur and other bones
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• excess bone of intermediate lesions is undermineralized
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• early changes are dominated by abnormal and excessive bone formation, however excessive osteoclast activity is not seen at this time
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• a complex system of cement lines indicates the occurrence of multiple, recurrent cycles of intracortical remodeling in intermediate lesions
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• intermediate lesions show prominent osteoclastic resorption
• intense osteoclastic activity extends up to the outer regions of the cortex causing microfractures
• florid osteocalstogenesis is obvious in resorptive lacunae
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• spontaneous fractures of tail vertebrae in 9.1% of mice between 12 and 18 months
• spontaneous partial fractures of the distal femur are seen in 2 of 89 mice
• in late lesions (more than 10 months from appearance), individual bones are grossly deformed and/or fractured
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limbs/digits/tail
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• in the femur, early lesions consist in localized endosteal thickening at the midshaft or the metadiaphyseal junction, with thickening extending proximally and distally progressively and lytic changes developing within the thickened bone
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| McCune Albright syndrome | DOID:1858 |
OMIM:174800 |
J:240241 | |
