One of the primary functions of bone is to transmit loads generated from body mass and muscle contractions, particularly during movement. Bone must therefore be strong enough to withstand tremendous loading, but not so massive as to require large amounts of energy to move. To ensure this is the case, an adaptive mechanism exists that alters the shape, distribution, and internal structure of bone to suit the demands of the mechanical environment. It is through this mechanism that exercise helps regulate osteogenesis, or bone formation.
Bone Response to Exercise
It is well established that mechanical loading from exercise and other physical activity regulates the growth of bone tissue. The primary cells involved in this regulatory process are osteocytes, which are embedded within bone tissue. Osteocytes are capable of transducing the energy from mechanical forces into biological signals that affect bone formation and resorption. As bone is mechanically deformed under loading, stretch-activated ion channels on osteocytes are activated, triggering the expression of genes that mediate bone growth and resorption.1 Each osteocyte has many (up to 80) processes that extend out through fluid-filled channels in bone that communicate, via gap junctions, with other osteocytes and with bone forming cells, osteoblasts, to regulate bone formation. Osteocytes and osteoblasts also communicate with bone resorbing cells, osteoclasts, by chemical signaling to regulate bone resorption. In general, high strains from mechanical loading induce or accelerate bone formation, low strains decelerate formation or result in bone loss, and intermediate strains maintain bone mass (Figure 1). This threshold-based mechanism, termed “mechanostat” by Harold Frost,2 adapts bone to the stresses exerted on it, thereby maintaining the capacity for load bearing and reducing the risk of fracture. Because the greatest forces exerted on bone come from muscle contractions due to the weak lever arms of muscles,3 exercise levels have a large influence on bone morphology and density.
Figure 1. Relationship between mechanical stimulus and bone formation/resorption. The strength of the mechanical stimulus is determined by the magnitude, frequency, and duration of the strain from mechanical loading.
Exercise has an osteogenic effect because it elevates the mechanical forces exerted on bone. The size of the effect depends on the strain rate, strain magnitude, and loading frequency of the exercise. Resistance exercises, like weightlifting, have a greater osteogenic effect than endurance exercises, like marathon running, because resistance exercises typically yield higher peak strains.4 This explains why resistance exercise is often prescribed to regain or maintain bone mass in conditions ranging from chronic disease to post-surgery recovery to osteoporosis.5-7 Periods of intermittent or cyclical loading interlaced with periods of rest promote osteogenesis more so than continuous loading or prolonged intermittent loading 8 because bone cells eventually become desensitized to mechanical stimuli.9 Thus, peak strains repeated in short duration provoke the greatest osteogenic response, while weak, static strains of long duration have the weakest effect. The absence or reduction of habitual peak strains result in bone resorption, which is observed in conditions such as paralysis, neuromuscular disorders, bed rest, fracture fixation, and weightlessness in space.10-13 Reduced bone strains trigger osteocyte apoptosis (likely from lack of strain-induced fluid flow to and from the cells), followed by osteoclastogenesis and bone resorption.14, 15 Decreased loading also stimulates the expression of signaling molecules, like RANKL, which promote osteoclastogenesis and bone resorption.16,17
Exercise, Age, and Location of Osteogenesis
The location of mechanically induced osteogenesis (inner vs. outer bone surface) varies with age (prepubertal vs. peripubertal vs. adult). The optimal location for osteogenesis at any age is on the periosteal (outer) surface of bone rather than the endosteal (inner or medullary) surface.18 While any addition of bone will increase the cross-sectional area, which increases resistance to compression, the addition of bone to the periosteal surface, and hence further from the long or bending axis of the bone, maximizes resistance to bending and resistance to torsion. Therefore, overall bone strength can be most effectively improved by adding bone adjacent to the periosteum.19 Bone naturally adapts to loading in this manner because the greatest strains occur farthest from the bending axis, which is along the periosteal surface.
However, osteogenesis is also influenced by other factors, such as hormones, calcium and vitamin D levels, cytokines, genetics, and gender.20 In particular, the effect of estrogen has been shown to significantly affect the location of bone formation in response to exercise because estrogen-specific receptors vary with location.21 This variation in receptor location serves to inhibit bone formation at the periosteal surface and promote osteogenesis at the endosteal surface, as well as in trabecular bone. Studies have shown that mechanically induced osteogenesis in response to exercise is greater at the periosteal surface before puberty, but greater at the endosteal surface during puberty and just after puberty when estrogen levels are higher.22,23 These skeletal changes correlate with estrogen level changes from childhood to adulthood. These findings suggest prepubertal children are able to increase the strength of their bones more effectively than pubertal juveniles and adults in response to exercise by adding more bone along the periosteal surface. However, the volume of bone mass that can be added is greatest during puberty when hormone levels surge.24
Adults and juveniles also vary in the manner of the osteogenic response. While the bones of both adults and juveniles are capable of adapting to the mechanical environment, the type of response is different. Because adults are not actively growing (although very minor appositional growth continues throughout life), the primary response is remodeling (addition of secondary osteons) with little modeling in comparison with juveniles.25 Osteogenesis from the modeling response is predominantly endosteal and trabecular rather than periosteal; however, bone mass gains from exercise are minimal in adults.26 Consequently, exercise is used to attenuate bone loss later in life rather than increase bone mass. In juveniles, both modeling and remodeling occurs and there is a much stronger osteogenic response to exercise (Figure 2).
Figure 2. Generalized schematic of the location and manner of the osteogenic response to mechanical loading in cross-sectional view of prepubertal, peripubertal, and adult individuals. Prepubertal growth is largely periosteal modeling, peripubertal growth is largely endosteal modeling, and adult response is largely remodeling.
Bone may also respond to exercise by changing its shape through bone formation on one side of the bone and resorption on the other (Figure 3). This “modeling drift” changes the curvature of a bone (most long bones are curved). Increasing the curvature of a bone makes the pathway of load transmission through the bone more predictable because it redirects bending loads into one plane.27 Greater load predictability is advantageous because it restricts the number of directions in which bending can occur and thus makes bone more resistant to loads that do not align with the normal loading orientation. Ultimately, this makes bone more resistant to fractures, which typically arise from large forces exerted in abnormal load orientations. 28
Figure 3. Bone modeling drift in response to mechanical loading in cross-sectional (left) and lateral (right) view. Arrows indicate the direction of the drift. Plus signs denote areas of bone formation and negative signs denote areas of bone resorption.
Exercise and Bone Mass
Mechanical loading also plays an important role in the determination of “peak bone mass”, ie, the greatest amount of bone one will have in one’s lifetime, which usually occurs in the third decade of life.29 While genetics, calcium intake, and other environmental factors clearly influence bone mass,30 there is a strong correlation between adult bone mass and activity levels during adolescence.31 Adolescents that are more physically active have significantly greater bone mass than their less active counterparts. In turn, bone mass is strongly correlated with the severity of bone loss later in life.32 Individuals with lower peak bone mass are more likely to develop osteopenia or osteoporosis, and are more prone to fractures later in life. In a longitudinal study of 178 women, peak bone mass was shown to predict post-menopausal bone loss rates and was associated with an increased risk of Colles’ fractures.33 Therefore, physical activity levels during adolescence are directly related to bone loss and fracture risk in adulthood.
Bone structure is well adapted to withstand the forces exerted on bone tissue. This is because osteogenesis and resorption are regulated by osteocytes, which are sensitive to changes in the localized strain environment of the tissue. The type and location of osteogenic response triggered by mechanical stimuli varies with age and with the magnitude, frequency, and duration of the stimulus, but is also influenced by a number of genetic and environmental factors. The adaptive mechanisms of bone modeling and remodeling help maintain bone integrity under varying loading conditions and minimize the risk of fracture while conserving bone mass.
- Iqbal J, Zaidi M. Molecular regulation of mechanotransduction. Biochemical and Biophysical Research Communications 2005;328:751-755.
- Frost HM. Perspectives: A proposed general model for the mechanostat (suggestions from a new skeletal-biologic paradigm). Anatomical Record 1996;244:139-147.
- Currey JD. The mechanical adaptations of bones. Princeton, NJ: Princeton University Press; 1984.
- Frost HM. Why do marathon runners have less bone than weight lifters? A vital-biomechanical view and explanation. Bone 1997;20:183-189.
- Feigenbaum MS, Pollock ML. Prescription of resistance training for health and disease. Medicine and Science in Sports and Exercise 1999;31:38-45.
- Sharkey NA, Williams NI, Guerin JB. The role of exercise in the prevention and treatment of osteoporosis and osteoarthritis. Nursing Clinics of North Ameica 2000;35:209-221.
- Braith RW, Mills RM, Welsch MA, Keller JW, Pollock ML. Resistance exercise training restores bone mineral density in heart transplant recipients. Journal of the American College of Cardiology. 1996;28:1471-1477.
- Robling AG, Duijvelaar KM, Geevers JV, Ohashi N, Turner CH Modulation of appositional and longitudinal bone growth in the rat ulna by applied static and dynamic force. Bone 2001;29:105-113.
- Robling AG, Hinant FM, Burr DB, Turner CH. Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts. J Bone Miner Res 2002;17:1545-1554.
- Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tissue Int 1985;37:411-417.
- Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 2004;19:1006-1012.
- Rittweger J, Gerrits K, Altenburg T, Reeves N, Maganaris CN, de Haan A. Bone adaptation to altered loading after spinal cord injury: a study of bone and muscle strength. J Musculoskelet Neuronal Interact 2006;6:269-276.
- Gross TS, Poliachik SL, Prasad J, Bain SD. The effect of muscle dysfunction on bone mass and morphology. J Musculoskelet Neuronal Interact 2010;10:25-34.
- Knothe Tate Ml, Niederer P, Knothe U. In vivo tracer transport through the lacuna-canalicular system of rat bone in an environment devoid of mechanical loading. Bone 1998;22:107-117.
- Aguirre JI, Plotkin LI, Stewart SA, et al. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res 2006;21:605-615.
- Rubin J, Murphy TC, Fan X, Goldschmidt M, Taylor WR. Activation of extracellular signal-regulated kinase is involved in mechanical strain inhibition of RANKL expression in bone stromal cells. J Bone Miner Res 2002;17:1452--1460.
- You L, Temiyasathit S, Lee P, Kim CH, Tummala P, Yao W, Kingery W, Malone AM, Kwon RY, Jacobs CR. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone 2008;42:172-179.
- Turner CH, Burr DB. Basic biomechanical measurements of bone: A tutorial. Bone 1993;14:595-608.
- Lieberman DE, Pearson OM, Polk JD, Demes B, Crompton AW. Optimization of bone growth and remodeling in response tapered mammalian limbs. J Exp Biol 2003;206:3125-3138.
- McLean FC, Urist MR. Bone, 2nd ed. University of Chicago Press, Chicago, 1961.
- Saxon LK, Turner CH. Estrogen receptor beta: the antimechanostat? Bone 2005;36:185-192.
- Plochocki JH. Mechanically-induced osteogenesis in the cortical bone of pre- to peripubertal stage and peri- to postpubertal stage mice. Journal of Orthopaedic Surgery and Research 2009;4:22.
- Bass SL, Saxon L, Daly RM, Turner CH, Robling AG, Seeman E, Stuckey S. The effect of mechanical loading on the size and shape of bone in pre-, peri, and postpubertal girls: a study in tennis players. J Bone Miner Res 2002;17:2274-2280.
- Khan K, McKay HA, Haapasalo H, Bennell KL, Forwood M, Kannus P, Wark JD. Does childhood and adolescence provide a unique opportunity for exercise to strengthen the skeleton? J Sci Med Sport 2000;3:150-164.
- Lieberman DE, Pearson OM, Polk JD, Demes B, Crompton AW. Optimization of bone growth and remodeling in response to loading in tapered mammalian limbs. J Exp Biol 2003;206:3125-3138.
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- Lanyon LE. The success and failure of the adaptive response to functional load-bearing in averting bone fracture. Bone 1992;Suppl 2:S17-21.
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