Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice

The inbred strains of mice C57BL/6J (B6) and C3H/HeJ (C3H) have very differ ent femoral peak bone densities and may serve as models for studying the ge netic regulation of bone mass, Our objective was to further define the bone biomechanics and microstructure of these two inbred strains. Microarchitec ture of the proximal femur, femoral midshaft, and lumbar vertebrae were eva luated in three dimensions using micro-computed tomography (mu CT) with an isotropic voxel size of 17 mu m. Mineralization of the distal femur was det ermined using quantitative back-scatter electron (BSE) imaging, mu CT image s suggested that C3H mice had thicker femoral and vertebral cortices compar ed with B6, The C3H bone tissue also was more highly mineralized. However, C3H mice had few trabeculae in the vertebral bodies, femoral neck, and grea ter trochanter, The trabecular number (Tb.N) in the C3H vertebral bodies wa s about half of that in B6 vertebrae (2.8(-1) +/- 0.1 mm(-1) vs, 5.1(-1) +/ - 0.2 mm(-1);p < 0.0001), The thick, more highly mineralized femoral cortex of C3H mice resulted in greater bending strength of the femoral diaphysis (62.1 +/- 1.2N vs, 27.4 +/- 0.5N, p < 0.0001), In contrast, strengths of th e lumbar vertebra were not significantly different between inbred strains ( p = 0.5), presumably because the thicker cortices were combined with inferi or trabecular structure in the vertebrae of C3H mice, These results indicat e that C3H mice benefit from alleles that enhance femoral strength but para doxically are deficient in trabecular bone structure in the lumbar vertebra e.