Genetic variations and physical activity as determinants of limb bone morphology: An experimental approach using a mouse model

Abstract

To gain insight into past human physical activity, anthropologists often infer functional loading history from the morphology of limb bone remains. It is assumed that, during life, loading had a positive, dose-dependent effect on bone structure that can be identified despite other effects. Here, we investigate the effects of genetic background and functional loading on limb bones using mice from an artificial selection experiment for high levels of voluntary wheel running. Growing males from four replicate high runner (HR) lines and four replicate nonselected control (C) lines were either allowed or denied wheel access for 2 months. Using μCT, femoral morphology was assessed at two cortical sites (mid-diaphysis, distal metaphysis) and one trabecular site (distal metaphysis). We found that genetic differences between the linetypes (HR vs. C), between the replicate lines within linetype, and between individuals with and without the so-called "mini-muscle" phenotype (caused by a Mendelian recessive gene that halves limb muscle mass) gave rise to significant variation in nearly all morphological indices examined. Wheel access also influenced femoral morphology, although the functional response did not generally result in enhanced structure. Exercise caused moderate periosteal enlargement, but relatively greater endocortical expansion, resulting in significantly thinner cortices and reduced bone area in the metaphysis. The magnitude of the response was independent of distance run. Mid-diaphyseal bone area and area moments, and trabecular morphology, were unaffected by exercise. These results underscore the strong influence of genetics on bone structure and the complexity by which mechanical stimuli may cause alterations in it.

Lumbar Vertebral Body Bone Microstructural Scaling in Small to Medium‐Sized Strepsirhines

“…This distribution approximates the inverse of the mean intercept length (MIL) directional distribution and is subsequently fit to an ellipsoid using a least square approach. This approach has been used in the anthropological literature by several investigators, including most recently Shaw and Ryan (2012), DeSilva and Devlin (2012), and Wallace et al (2012). In the crVOI and caVOI we measured Tb.BV/TV, Tb.Th, and Tb.N.…”

“…We also used the Quant3D analysis package developed by Ketcham and Ryan (Ryan and Ketcham, 2002) in the smaller cranial and caudal spherical VOI. Both of these methods have been validated and used in numerous publications in biomedicine (Rü egsegger et al, 1996;Hildebrand and Rü egsegger, 1997b;Bouxsein et al, 2005;Chappard et al, 2005;Glatt et al, 2007;Buie et al, 2008;Bouxsein et al, 2010;Fajardo et al, 2010) and biological anthropology (Fajardo and Mü ller, 2001;MacLatchy and Mü ller, 2002;Ryan and Ketcham, 2002;Ryan and Krovitz, 2006;Fajardo et al, 2007b;Griffin et al, 2010;Wang et al, 2010;DeSilva and Devlin, 2012;Shaw and Ryan, 2012;Wallace et al, 2012). The lower Tb.N values consistently reported in the vbVOI appear to result from architectural variability within the vertebral bodies.…”

Gradual decline in mobility with the adoption of food production in Europe

“…Although skeletal morphology is determined by a complex interplay between various genetic and environmental factors (18,19), there is abundant evidence that mechanical loading during life has a strong influence on skeletal structure (20)(21)(22)(23). Earlier studies identified declines in skeletal robusticity (strength relative to body size) in Homo throughout the Pleistocene (24,25), but recent analyses suggest that the major decrease in robusticity occurred later, at the end of the Pleistocene, between early anatomically modern H. sapiens and Holocene populations (26,27).…”

Inner structural organization of the distal humerus in Paranthropus and Homo

“…of recording relevant biomechanical information during life, but also of preserving the signature of their genetic-related evolutionary adaptive bauplan (Carlson and Marchi, 2014;Carlson et al, 2008;Currey, 2002;Gosman et al, 2011;Kivell, 2016;Lieberman et al, 2004;Lovejoy et al, 1999;Middleton et al, 2008;Nadell and Shaw, 2015;Pearson and Lieberman, 2004;Ruff et al, 2006;Ryan and Shaw, 2013;Smith-Adaline et al, 2004;Volkman et al, 2003;Wallace et al, 2010Wallace et al, , 2012, an increasing number of studies use high resolution imaging techniques to reveal the inner structure of the fossil hominin humerus (e.g., Kappelman et al, 2016;Ruff et al, 2016;Ryan and Sukhdeo, 2016).…”