Intracortical bone remodeling variation shows strong genetic effects

L. M. Havill, M. R. Allen, J. A.K. Harris, S. M. Levine, H. B. Coan, M. C. Mahaney, D. P. Nicolella

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    Abstract

    Intracortical microstructure influences crack propagation and arrest within bone cortex. Genetic variation in intracortical remodeling may contribute to mechanical integrity and, therefore, fracture risk. Our aim was to determine the degree to which normal population-level variation in intracortical microstructure is due to genetic variation. We examined right femurs from 101 baboons (74 females, 27 males; aged 7-33 years) from a single, extended pedigree to determine osteon number, osteon area (On.Ar), haversian canal area, osteon population density, percent osteonal bone (%On.B), wall thickness (W.Th), and cortical porosity (Ct.Po). Through evaluation of the covariance in intracortical properties between pairs of relatives, we quantified the contribution of additive genetic effects (heritability [h 2]) to variation in these traits using a variance decomposition approach. Significant age and sex effects account for 9 % (Ct.Po) to 21 % (W.Th) of intracortical microstructural variation. After accounting for age and sex, significant genetic effects are evident for On.Ar (h 2 = 0.79, p = 0.002), %On.B (h 2 = 0.82, p = 0.003), and W.Th (h 2 = 0.61, p = 0.013), indicating that 61-82 % of the residual variation (after accounting for age and sex effects) is due to additive genetic effects. This corresponds to 48-75 % of the total phenotypic variance. Our results demonstrate that normal, population-level variation in cortical microstructure is significantly influenced by genes. As a critical mediator of crack behavior in bone cortex, intracortical microstructural variation provides another mechanism through which genetic variation may affect fracture risk.

    Original languageEnglish (US)
    Pages (from-to)472-480
    Number of pages9
    JournalCalcified tissue international
    Volume93
    Issue number5
    DOIs
    StatePublished - Nov 1 2013

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    Keywords

    • Biomechanics
    • Bone histomorphometry
    • Osteoporosis
    • Population studies
    • Primate

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Orthopedics and Sports Medicine
    • Endocrinology

    Cite this

    Havill, L. M., Allen, M. R., Harris, J. A. K., Levine, S. M., Coan, H. B., Mahaney, M. C., & Nicolella, D. P. (2013). Intracortical bone remodeling variation shows strong genetic effects. Calcified tissue international, 93(5), 472-480. https://doi.org/10.1007/s00223-013-9775-x