Variation in bone biomechanical properties, microstructure, and density inBXH recombinant inbred mice

To test the hypothesis that factors associated with bone strength (i.e., vo lumetric bone mineral density [vBMD], geometry, and microstructure) have he ritable components, we exploited the 12 BXH recombinant inbred (RT) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high b one mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biom echanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomograph y (pQCT), and microcomputed tomography (mu CT). Segregation patterns of fem oral and vertebral biomechanical properties among the BXH RI strains sugges ted poll genic regulation, Femoral biomechanical properties sere strongly a ssociated with femoral width in the anteroposterior (AP) direction and cort ical thickness-geometric properties with complex genetic regulation. Verteb ral vBMD and biomechanical properties measured in BXH RI strains showed a g reater variability than either B6 or C3H progenitors, suggesting both proge nitor strains have independent subsets of genes that yield similar vBMD and strength. The mu CT and pQCT data suggested that the distribution of verte bral mineral into cortical and trabecular compartments is regulated genetic ally. Although the B6 and C3H progenitors had similar vertebral strength, t heir vertebral structures were markedly different: B6 had good trabecular b one structure and modest cortical bone mineral content (BMC), whereas C3H h ad high cortical BMC combined with a deficiency in trabecular structure. Th ese structural traits segregated independently in the BXH RI strains. Final ly, vertebral strength was not correlated consistently with femoral strengt h among the BSH RI strains, suggesting genetic regulation of bone strength is site specific.