Forgiveness of Genetic Variation: Functional Interactions Among Bone Traits in the Distal Femoral Epiphysis

We examined femora from adult female AXB/BXA recombinant inbred (RI) mouse strains to identify epiphyseal traits that are functionally related and to determine how interactions among these traits contribute to organ-level functionality. The results of this study validated that variation in bone morphology is linked to variation in trabecular architecture and tissue quality. More than 1/3 of the 36 correlations examined were significant, indicating that many bone traits covaried or were functionally related. Path analysis revealed novel interactions between traits defining epiphyseal volume, body weight, trabecular architecture and tissue quality. The causal relationship among these traits suggested a biological adaptation process, which allows for the forgiveness of genetic variation in physical bone traits, so that bone can be flexible in creating functional structures.

Year	Entry
2006	Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, .Peterson JM, Melton LJ III. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. January 2006;21(1):124-131.
2003	Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome. February 2003;14(2):97-104.
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1997	Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191-199.
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Year

Entry

2006

Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, .Peterson JM, Melton LJ III. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. January 2006;21(1):124-131.

2003

Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome. February 2003;14(2):97-104.

1996

Beck TJ, Ruff CB, Mourtada FA, Shaffer RA, Maxwell-Williams K, Kao GL, Sartoris DJ, Brodine S. Dual-energy X-ray absorptiometry derived structural geometry for stress fracture prediction in male u.s. marine corps recruits. J Bone Miner Res. May 1996;11(5):645-653.

1997

Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191-199.

1996

Beamer WG, Donahue LR, Rosen CJ, Baylink DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. May 1996;18(5):397-403.