Bond strength and related traits in HcB/Dem recombinant congenic mice

Fracture susceptibility depends jointly on bone mineral content (BMC), gros s bone anatomy, and bone microarchitecture and quality. Overall, it has bee n estimated that 50-70% of bone strength is determined genetically. Because of the difficulty of performing studies of the genetics of bone strength i n humans, we have used the HcB/Dem series of recombinant congenic (RC) mice to investigate this phenotype. We performed a comprehensive phenotypic ana lysis of the HcB/Dem strains including morphological analysis of long bones , measurement of ash percentage, and biomechanical testing. Body mass, ash percentage, and moment of inertia each correlated moderately but imperfectl y with biomechanical performance. Several chromosome regions, on chromosome s 1, 2, 8, 10, 11, and 12, show sufficient evidence of linkage to warrant c loser examination in further crosses. These studies support the view that m ineral content, diaphyseal diameter, and additional nonmineral material pro perties contributing to overall bone strength are controlled by distinct se ts of genes. Moreover, the mapping data are consistent with the existence o f pleiotropic loci for bone strength-related phenotypes. These findings sho w the importance of factors other than mineral content in determining skele tal performance and that these factors can be dissected genetically.