From the Cover: Physical activity when young provides lifelong benefits to cortical bone size and strength in men

The skeleton shows greatest plasticity to physical activity-related mechanical loads during youth but is more at risk for failure during aging. Do the skeletal benefits of physical activity during youth persist with aging? To address this question, we used a uniquely controlled cross-sectional study design in which we compared the throwing-to-nonthrowing arm differences in humeral diaphysis bone properties in professional baseball players at different stages of their careers (n = 103) with dominant-to-nondominant arm differences in controls (n = 94). Throwing-related physical activity introduced extreme loading to the humeral diaphysis and nearly doubled its strength. Once throwing activities ceased, the cortical bone mass, area, and thickness benefits of physical activity during youth were gradually lost because of greater medullary expansion and cortical trabecularization. However, half of the bone size (total cross-sectional area) and one-third of the bone strength (polar moment of inertia) benefits of throwing-related physical activity during youth were maintained lifelong. In players who continued throwing during aging, some cortical bone mass and more strength benefits of the physical activity during youth were maintained as a result of less medullary expansion and cortical trabecularization. These data indicate that the old adage of “use it or lose it” is not entirely applicable to the skeleton and that physical activity during youth should be encouraged for lifelong bone health, with the focus being optimization of bone size and strength rather than the current paradigm of increasing mass. The data also indicate that physical activity should be encouraged during aging to reduce skeletal structural decay.Physical activity is recommended for skeletal health because bones adapt to elevated mechanical loading. However, a disparity exists between the time when the skeleton shows greatest plasticity to mechanical loads (during youth) and when it is most at risk for failure (during aging) (1, 2). Do the skeletal benefits derived from physical activity-related loading during youth persist with aging? A popular hypothesis is that physical activity increases peak bone mass to prime the skeleton against the bone loss occurring during aging (3). Prospective observational studies suggest some of the benefits in bone mass generated through physical activity during youth persist into early adulthood (4–9); however, the prospective assessment of lifelong benefits is not practically feasible. Instead, the lifelong skeletal benefits of physical activity during youth can be explored using cross-sectional studies comparing former athletes with controls. Although cross-sectional studies typically do not control for selection bias and secular variations in activity levels, current data suggest that cessation of physical activity after youth is associated with the eventual return of bone mass to control levels (10).Although the benefits in bone mass acquired through physical activity during youth may be lost, some of the benefits in bone size and strength may persist throughout life. For the purposes of the current work, “bone size” refers to total cross-sectional area, and “bone strength” refers to torsional rigidity. The torsional rigidity of a tubular bone is dependent on its polar moment of inertia, which is calculated from the radii of its outer periosteal (r_p) and inner endocortical (r_e) surfaces as π(r_p⁴ − r_e⁴)/2. This relationship demonstrates that a bone is stronger if its material is distributed further from its central axis and that periosteal surface changes have a greater influence on strength than changes on the endocortical surface. For example, assuming constant bone material properties and a typical r_p: r_e ratio of 1.8, a 5% increase in r_p (equating to 10% and 15% increases in bone size and mass, respectively) results in a 24% increase in strength. If the same mass of bone added to the periosteal surface was simultaneously removed from the endocortical surface, r_e would increase by 15%, but the bone would still be 16% stronger because of its 5% greater r_p (i.e., size). Because physical activity during youth preferentially deposits new bone on the outer periosteal surface to increase bone size (11–13), and bone loss during aging occurs primarily on the endocortical surface to decrease mass (14, 15), the benefits in bone size and strength acquired through physical activity during youth have the potential to remain independent of the maintenance of benefits in bone mass.Cross-sectional and prospective observational studies have suggested that some of the benefits in bone size and strength acquired through physical activity during youth persist into early adulthood (5, 8, 16, 17), but whether these benefits persist throughout life remains unanswered. We demonstrated that mechanical loading during a period of rapid skeletal growth conferred lifelong benefits in bone size and strength in rodent models (18, 19). To explore whether the same phenomenon occurs in humans, the current study used a uniquely controlled cross-sectional study design that compared differences in humeral diaphysis properties between the throwing and nonthrowing arms of professional Major (MLB) and Minor (MiLB) League Baseball players at different stages of their careers with the differences between the dominant and nondominant arms in age-matched controls. The use of baseball players was inspired by the bilateral asymmetry initially observed in tennis players by Jones et al. (20) and minimizes the influence of selection bias because the unilateral upper extremity loading and humeral adaptation associated with overhand throwing (21–23) enables the nonthrowing arm to serve as an internal control site for inherited and other systemic traits. Similarly, use of MLB/MiLB players reduces secular variations in physical activity levels because individuals who reached professional level baseball typically threw with high volume from a young age, with throwing being the primary unilateral dominant training modality. Also, the game of baseball has not changed in more than 100 y, and the ball weight and the distance and speed at which the ball is thrown have remained relatively constant across generations. Another distinct advantage of studying former MLB/MiLB players (compared with even tennis players) is that they often retire completely from throwing activities once they stop professional play, allowing us to explore the skeletal benefits of physical activity long after the subjects’ return to habitual loading. By comparing the differences between the throwing and nonthrowing arms in throwing athletes with the differences between the dominant and nondominant arms in age-matched controls, we isolated the skeletal benefits of throwing from the differences caused by the elevated habitual unilateral loading associated with simple arm dominance.Using professional baseball players as a model, we addressed: (i) the magnitude and location of adaptations associated with throwing-related physical activity; (ii) whether the skeletal benefits of throwing-related physical activity persist lifelong once throwing is ceased; and (iii) whether there are skeletal benefits of continued throwing-related physical activity in later adulthood.