Phenotypic characterization of mice bred for high and low peak bone mass

In humans, peak bone mineral density (BMD) is a highly heritable trait and a strong determinant of subsequent osteoporotic fracture risk. To identify the genetic factors responsible for variation in peak BMD, investigators ha ve turned to animal models. In this study we examined the heritability of B MD acquisition and characterized differences in skeletal geometry, histomor phometry, and biomechanical competence between two lines of mice artificial ly selected for extremes of peak whole body BMD, F-2 progeny from a cross b etween C57BL/6 and DBA/2 inbred strains was used as the foundation populati on to develop lines selected for either high or low BMD, Whole body BMD was measured by dual-energy X-ray absorptiometry (DXA), By the third generatio n of selection, highest-scoring BMD (HiBMD) mice exhibited 14% greater peak BMD than lowest-scoring BMD (LoBMD) mice. The mean realized heritability o f peak BMD was 36%, Femoral shaft cortical area and thickness and vertebral cancellous bone volume (BV) were significantly greater (16-30%) in the HiB MD line compared with the LoBMD line, Mean cancellous bone formation rates (BFRs) were 35% lower in HiBMD mice compared with LoBMD mice. Failure load and stiffness in the femoral shaft, femoral neck, and L6 vertebrae were all substantially greater (by 25-190%) in HiBMD mice, Thus, these divergently selected murine lines serve to illustrate some of the means by which geneti c mechanisms can affect skeletal structure and remodeling. Identification o f the individual genes influencing peak BMD in this experimental system wil l likely reveal some of the genetic determinants of overall bone strength.