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Morphological study of the femur in osteopetrotic (op/op) mice using microcomputed tomography
S Abe1, H Watanabe, A Hirayama
1Department of Anatomy, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.
Abstract:
Osteopetrosis is an inherited metabolic disorder in which normal bone remodelling is inhibited. Its primary cause is considered to be disruption of the functional balance between osteoblasts and osteoclasts as well as a reduction in the quantity of osteoclasts. The purpose of this study was to observe morphological characteristics of the femur in osteopetrotic (op/op) mice, in which the pathogenic mechanism of osteopetrosis has been shown to operate, using microcomputed tomography (micro-CT), in addition to macro-anatomical observations. Previously, micro-CT has been used mainly for morphometry of a small portion of cancellous bone. However, with recent improvements it has become possible for three-dimensional (3D) observations of bone using slightly larger samples to be made. In this study, the accuracy of reconstructed 3D images of the femur produced by micro-CT was confirmed by comparison with the original femur. In addition, an arbitrary cross-section could be displayed on the screen for detailed examination of its internal structure, and the volume percentage of trabecular bone in a particular region of interest could be measured in three dimensions. The results of this study revealed that the femur was smaller and malformed in the op/op mouse compared with the controls, and the differences were greater at the age of 18 weeks than at 5 weeks. In the control mice, bone marrow occupied a large space in the centre of the body of the femur, whereas this area was occupied by calcified bone tissue in the mutant mice. Moreover, when 3D bone density was measured in the region of interest, the value was greater in the mutants than in the controls at both 5 weeks and 18 weeks of age. This study also showed that micro-CT can be applied to 3D morphometric analyses.
Insights
Osteopetrosis in mice results in smaller, malformed femurs with increased bone density. Micro-computed tomography (micro-CT) effectively visualized these 3D morphological changes in bone.
Area of Science:
- Skeletal biology
- Medical imaging
- Genetics
Background:
- Osteopetrosis is an inherited metabolic bone disorder characterized by impaired bone remodeling due to disrupted osteoblast and osteoclast function.
- Understanding the morphological impact of osteopetrosis on long bones is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To investigate the morphological characteristics of the femur in osteopetrotic (op/op) mice using micro-computed tomography (micro-CT).
- To assess the utility of micro-CT for three-dimensional (3D) morphometric analysis of bone in a disease model.
Main Methods:
- Macro-anatomical observations and micro-CT scans of femurs from osteopetrotic (op/op) mice and control littermates.
- Validation of micro-CT accuracy by comparing reconstructed 3D images with original femur specimens.
- 3D morphometric analysis, including measurement of bone volume percentage and bone density in regions of interest.
Main Results:
- Osteopetrotic (op/op) mice exhibited smaller and malformed femurs compared to controls, with more pronounced differences at 18 weeks than at 5 weeks of age.
- The medullary cavity in control mice was filled with bone marrow, whereas in mutant mice, it was occupied by calcified bone tissue.
- 3D bone density measurements revealed significantly higher values in mutant mice compared to controls at both 5 and 18 weeks of age.
Conclusions:
- Micro-CT is a valuable tool for detailed 3D morphometric analysis of bone, enabling visualization of structural abnormalities in osteopetrosis.
- The study confirms significant femur malformations and increased bone density in op/op mice, highlighting the utility of this model for osteopetrosis research.