GENETIC-VARIABILITY IN ADULT BONE-DENSITY AMONG INBRED STRAINS OF MICE

More than 70% of the variability in human bone density has been attrib uted to genetic factors as a result of studies with twins, osteoporoti c families, and individuals with rare heritable bone disorders. We hav e applied the Stratec XCT 960M pQCT, specifically modified for small s keletal specimens, to analyses of bones from 11 inbred strains (AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, NZB/B1NJ, SM/J, SJL/BmJ , SWR/BmJ, and 129/J) of female mice to determine the extent of herita ble differences in peak bone density. pQCT scans were taken of femurs from (a) 12-month-old inbred strain females and (b) a subset of four s trains (C3H/HeJ, DBA/2J, BALB/cByJ, C57BL/6J) at 2, 4, and 8 months. I n addition, pQCT scans were also obtained from L5-L6 vertebrae and pro ximal phalanges from the same subset of four inbred strains at 12 mont hs of age. Comparison of bone parameters among inbred strains revealed significant differences at each of the three sites investigated. Femo ral and phalangeal bones differed among strains with respect to total and cortical density, mineral, and volume. Only cortical bone paramete rs were significantly different among strains at the vertebral site. W ith respect to strain differences, the highest value for any given bon e parameter was found in the C3H/HeJ strain, whereas C57BL/6J values w ere absolutely, or statistically, the lowest. Similarly, with respect to bone sites, cortical bone density was significantly correlated amon g strains. On the other hand, we found that none of the femur, vertebr al, or phalangeal parameters correlated with body weight, even though body weight varied by 86% among these inbred strains. The developmenta l studies of femurs conducted at 2, 4, and 8 months of age with C3H/He J, DBA/2J, BALB/cByJ, and C57BL/6J females showed differences in total density among strains at 2 months and thereafter. Adult peak bone den sity was typically achieved by 4 months, whereas femurs continued to l engthen for 4 to 8 months thereafter. We conclude that (1) major genet ic effects on femoral, vertebral, and phalangeal bone density are dete ctable among inbred strains of mice; (2) cortical bone density shares common genetic regulation at the three measured sites; and (3) within the femur, genes that regulate length and density are different.