Genetic variations in bone density, histomorphometry, and strength in mice

The purpose of this study was to assess breed-related differences in bone h istomorphometry, bone biomechanics, and serum biochemistry in three mouse b reeds shown to differ in bone mineral density (BMD) las measured by DXA) an d bone mineral content (BMC). Femurs, tibiae, and sera were collected from 16-week-old C3H/HeJ {C3H}, C57BL/6J {BL6}, and DBA/2J {DBA} mice (n = 12/br eed). Data collected included BMC and BMD (femora), histomorphometry of can cellous (distal femur) and cortical bone (diaphyseal tibiae and femoral, bo ne strength (femora), and serum alkaline phosphatase (ALP). Consistent with previous reports, BMC and BMD were higher in C3H than in BL6 or DBA mice. The higher BMD in the C3H breed was associated with greater cancellous bone volume, cortical bone area, periosteal bone formation rate, biomechanical strength, and serum ALP. However, mid-diaphyseal total femoral and tibial c ross-sectional area and moment of inertia were greatest in BL6, intermediat e in C3H, and lowest in DBA mice. The specific distribution of cortical bon e in C3H, BL6, DBA mice represents a difference in adaptive response to sim ilar mechanical loads in these breeds. This difference in adaptive response may be intrinsic to the adaptive mechanism, or may be intrinsic to the bon e tissue material properties. In either case, the bone-adaptive response to ordinary mechanical loads in the BL6 mice yields bones of lower mechanical efficiency (less stiffness per unit mass of bone tissue) and does not adap t as well as that of the C3H mice where the final product is a bone with gr eater resistance to bending under load. We suggest that the size, shape, an d BMD of the bone are a result of breed-specific genetically regulated cell ular mechanisms. Compared with the C3H mice, the lower BMD in BL6 mice is a ssociated with long bones that are weaker because the larger cross-sectiona l area fails to compensate completely for their lower BMD and BMC.