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

Research output: Contribution to journalArticle

15 Scopus citations


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
Issue number5
StatePublished - Nov 1 2013


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

ASJC Scopus subject areas

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

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    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.