Phenotypic Characterization of Mice Bred for High and Low Peak Bone Mass

Authors

  • Robert F. Klein,

    Corresponding author
    1. Bone and Mineral Research Unit, Department of Medicine, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, Oregon, USA
    • Bone and Mineral Unit (CR113), Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201–3098, USA
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  • Marie Shea,

    1. Department of Orthopaedics, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, Oregon, USA
    2. These authors contributed equally to this work
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  • Michele E. Gunness,

    1. These authors contributed equally to this work
    2. Department of Pathology, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, Oregon, USA
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  • Geoffrey B. Pelz,

    1. Department of Orthopaedics, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, Oregon, USA
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  • John K. Belknap,

    1. Department of Behavioral Neuroscience, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, Oregon, USA
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  • Eric S. Orwoll

    1. Bone and Mineral Research Unit, Department of Medicine, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, Oregon, USA
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  • Preliminary data presented at the 21st Annual Meeting of The American Society of Bone and Mineral Research, St. Louis, MO, USA, September 30-October 4, 1999 (Poster SU474)

Abstract

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 have turned to animal models. In this study we examined the heritability of BMD acquisition and characterized differences in skeletal geometry, histomorphometry, and biomechanical competence between two lines of mice artificially selected for extremes of peak whole body BMD. F2 progeny from a cross between C57BL/6 and DBA/2 inbred strains was used as the foundation population 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 generation of selection, highest-scoring BMD (HiBMD) mice exhibited 14% greater peak BMD than lowest-scoring BMD (LoBMD) mice. The mean realized heritability of peak BMD was 36%. Femoral shaft cortical area and thickness and vertebral cancellous bone volume (BV) were significantly greater (16–30%) in the HiBMD 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 genetic mechanisms can affect skeletal structure and remodeling. Identification of the individual genes influencing peak BMD in this experimental system will likely reveal some of the genetic determinants of overall bone strength.

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