Ontogenetic and genetic influences on bone’s responsiveness to mechanical signals

Introduction The human skeleton is able to alter its structure and strength throughout life in response to the loads it sustains during the physical activities to which we subject our bodies. Typically, skeletal loading shifts the balance in bone turnover toward net formation, which can lead to bigger, stronger bones, whereas decreased loading causes net resorption, which can result in more slender, fragile bones. This phenomenon, commonly referred to as “bone functional adaptation” (Ruff et al., 2006), has fascinated biologists and clinicians for well over a century (Wolff, 1892), for it is an exquisite example of the capacity of organisms to adjust to their environments (West-Eberhard, 2003), and harnessing the sensitivity of our skeletons to mechanical signals provides opportunities for promoting bone health and treating skeletal injuries and degenerative diseases (Ozcivici et al., 2010). The responsiveness of bone to loading is an ancient and widespread evolutionary trait among vertebrates, observable in animals as distantly related to humans as reptiles and birds (e.g., Rubin and Lanyon, 1984). Biological anthropologists have long been interested in bone’s responsiveness to loading, because if our bones are shaped by our physical activity, then it might be possible to infer the lifestyles of ancient human populations by analyzing their skeletal remains (Ruff, 2005). Ancient peoples characterized by thick, strong bones would be interpreted as having been highly active, whereas those with slender, gracile bones would be interpreted as having been more sedentary. Over the last few decades, this model has been the foundation for numerous reconstructions of past human behavior (e.g., Ruff et al., 1984, 1993, 2015; Bridges, 1989; Trinkaus, 1997; Holt, 2003; Marchi et al., 2006; Sládek et al., 2006; Maggiano et al., 2008; Shaw and Stock, 2013). Strong empirical support for this model has been provided by controlled experiments involving animal models such as sheep, pigs, rodents, and fowl that have demonstrated the potential for skeletal loading activities (e.g., running) to promote bone formation, retard bone loss, and, ultimately, enhance structure and strength (e.g., Biewener and Bertram, 1994; Lieberman, 1996; Judex et al., 1997; Lieberman et al., 2001, 2003; Joo et al., 2003; Hamrick et al., 2006; Barak et al., 2011).