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The attainment of peak bone mass: what is the relationship between muscle growth and bone growth?
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Bone
Volume 34, Issue 5, May 2004, Pages 767-770
A. M. Parfitt,
Division of Endocrinology and Center for Osteoporosis and Metabolic Bone Disease, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA
Received 13 June 2003; accepted 29 January 2004. Available online 30 April 2004.
It is a truism of our field that adult bone mass at any age is the difference between the amount gained during growth and the amount lost since growth stopped. Most efforts to prevent fracture focus on postponing, retarding, arresting, or reversing bone loss. The importance of bone gain has been recognized informally for a long time, but was first made explicit by Charles Dent in his keynote address at the symposium on Clinical Aspects of Metabolic Disease held at Henry Ford Hospital in 1972; he remarked "How far it can be said that 'senile osteoporosis' is a pediatric disease... clearly needs further study" [1]. The relative importance of gain and loss is still debated, but bone mass at age 50 (which is close to peak mass) and subsequent rate of loss contribute about equally to the variance in bone mass at age 70 [2].
The mass of a bone is the product of its volume and its apparent density, which is the weight of bone substance per unit external volume-the bone within the bone [3]. Total bone mass increases about 50-fold between birth and maturity, but the increase in apparent density is only about 15% in the vertebral body during the adolescent growth spurt and even less in the upper femur [4]. The accumulation of bone is largely driven by bodily growth; for example, long bone length is closely correlated with height, and bone shape, expressed as the ratio of width to length, varies within quite narrow limits [4]. The trajectory of growth, and hence eventual bone size, is to a great extent determined by age 1 year, but apparent density is more amenable to modification [5]. Men have higher bone mass than women because their bones are larger, not because they are more dense [6]. More generally, bigger people have bigger bones, and they also have bigger muscles. Muscles are attached only to bones and bones must be able to support the loads placed on them by muscles [7]. Not surprisingly, genetic factors account for most of the correlation between bone mass and muscle mass [8], since natural selection would have ensured that bone strength is closely matched to muscle strength.
An important question is whether there is physiologic adaptation of bone strength to muscle strength in individuals, as well as evolutionary adaptation in the population [9]. These two forms of adaptation are often confused, but as previously mentioned, the latter is responsible for most of the reported correlations [8]. The same explanation holds for much of the difference in bone mass between the sedentary and the athletic, who are self-chosen for particular sports by physique [9]. Based on data for a large healthy population aged 2 to 20 years [10], there was a high correlation between muscle mass and bone mass during growth [11]. But there was an even closer relationship between bone mass and body surface area (BSA), an estimate of skin mass (Fig. 1). I am unaware of an osteotrophic hormone secreted by skin, so it seems likely that all these correlations reflect no more than the commonality of growth and provide no evidence for a causal relationship.
Clearly, the existence and magnitude of physiologic adaptation of bone to muscle can be determined only by experiment, not by further observational studies. Many such experiments have been carried out in adults of various ages, prescribed various exercise regimens, but only small increases in bone mass have been achieved, representative mean values in different series ranging from 3.4% [12] to 4.3% [9]. These improvements are not negligible, but are far below the investigator's expectations. The persistent enthusiasm for such studies (3 reported in 2002) represents, as Samuel Johnson said about second marriages, the triumph of hope over experience. Many fewer studies have been carried out in children and adolescents but the results have been much more impressive [9]. The strongest evidence comes from racquet holding sports, in which the difference between the playing and nonplaying arms represents the response to the intervention in each subject. In tennis players who began serious competition before the adolescent growth spurt, there were substantial additions to humeral cortical bone, both periosteal and endocortical [13]. In both squash players [14] and tennis players [15], the playing-nonplaying arm difference increased progressively through the Tanner stages of puberty. Increased loading of the arm bones by muscular activity greatly augments the changes in apparent density that normally occur during the adolescent growth spurt, but does not affect the genetic target for bone length.
The greater responsiveness of the growing than the mature skeleton to the osteotrophic effect of physical activity reflects the need for bone acquisition during growth but the need only for maintenance after growth has ceased. For biological reasons discussed elsewhere, by the time growth has ceased the bones must be as strong as they will ever need to be-the system operates to get it right first time [9]! A mechanism to increase bone strength after skeletal maturity would serve no purpose; an immobilized adult animal in the wild dies quickly, and the ability to recover from disuse osteoporosis would have no survival value. Muscle contraction leads to bone deformation or strain, and the mechanism for individual adaptation of bone strength to muscle strength mediated by strain is called the mechanostat [16]. Its main biological purpose is to ensure that in every species, each individual grows the bones that will be needed to sustain the lifetime level and pattern of physical activity customary for that species. In this manner, physiologic adaptation to the loading consequent on physical activity in individuals will establish and maintain a property of the bone that is determined by evolutionary adaptation in populations. From this standpoint, the developing bone is the master, not the slave, of its cells and molecules [17].
The cross-sectional correlations between muscle mass and bone mass during growth indicate that rates of muscle growth and bone growth are linked, but provide no information about their temporal relationships. This crucial information has now been supplied in a paper in the current issue. Rauch et al. [18] found that the curves relating the rates of gain (or velocity) to age for height, lean body mass (a surrogate for muscle mass), and bone mass are parallel but systematically out of step. In girls, peak velocity for height gain preceded by 0.39 years peak velocity for muscle gain, which preceded by 0.50 years peak velocity for bone gain; corresponding intervals for boys were 0.30 and 0.36 years. The authors are careful to point out that these data do not establish a causal relationship and it remains possible that genetic links between muscle growth, bone growth, and growth in height could account for all the data. However, the author's interpretation, that the sequential changes reflect the operation of the mechanostat to supplement genetic effects, is supported by the evidence previously reviewed for physiologic adaptation of bone to muscle in the growing skeleton. An increase in the rate of periosteal and endocortical apposition in cortical bone is the result of an increase in the rate of new osteoblast recruitment. There need only be a small delay between the detection of increased strain due to increased muscle strength and the generation of signals to increased proliferation of osteoblast precursor cells, which would take only a few months to produce a detectable increase in the rate of bone gain.
An important additional finding was that the relationship between muscle and bone during the pubertal growth spurt differed between the sexes. At peak velocities, the amount of bone added with each kilogram of muscle was 63 g in girls but only 47 g in boys, confirming the inference drawn from cross-sectional data ([11], Fig. 1). These data are open to several interpretations. Increasing BSA is an excellent index of growth in body size, and the relationship between BSA and bone mass is the same in both sexes (Fig. 1). Increases in bone mass and skin mass are both closely linked to bodily growth, but during adolescence, girls fill their skin with relatively more fat than muscle and boys with relatively more muscle than fat [19]. The discordance between muscle and bone in girls could represent insufficient muscle to move bone rather than too much bone to resist muscle. But although it is unclear which interpretation is correct, it is of interest to pursue the implications of the second interpretation, favored by the authors [18].
Many years ago, Albright et al. [20] interpreted postmenopausal bone loss as the discarding of bone no longer needed to supply calcium to the fetus and to the maternal breast. This notion was further developed by Garn [21] with the addition of anatomic localization. He proposed that the endocortical bone lost as the result of estrogen deficiency was the same bone that had been put there much earlier as the result of the estrogen surge of puberty; endocortical formation makes a larger contribution to cortical thickening in girls than in boys. Schiessel et al. [11] accepted this interpretation and proposed as a mechanism that estrogen altered the mechanical usage set-point, so that increased estrogen during adolescence deceived the cells into adding more bone than was needed for immediate use, a process reversed by estrogen deficiency [17]. In terms of the amounts of bone added and removed, this makes biologic sense, but it conceals an important structural difference between cortical and cancellous bone. During adolescence, trabeculae become thicker [9 and 22], but after menopause, they do not become thinner; instead, some disappear as a result of perforation ( [23]; Fig. 2). Even though the total amount of cancellous bone may be the same as before puberty, its disposition is less mechanically advantageous because the added and removed bone differ in location.
The Rauch study raises many interesting questions. The following is a personal selection: so far as I know, some may already have been answered! Muscles and tendons must elongate simultaneously with the increase in bone length, but the increase in muscle bulk is delayed for a few months; how is this accomplished? How much does strain increase as a result of increased muscle strength? And is the increase large enough to have the postulated effect? (This question is especially pertinent, since according to Frost [24], the mechanostat ignores small changes in strain). Does the response to loading depend on the number of osteoblasts present, which is much higher in the growing than in the mature skeleton? Do the levels of sex hormones influence the response? What signal pathways are involved, and why does their intensity differ between growing and non-growing bones? But whatever the answers to these questions, they must be of wide application, since the necessity of getting bone to full strength by the time of adulthood is a universal feature of vertebrate biology.
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Corresponding author. Division of Endocrinology and Center for Osteoporosis and Metabolic Bone Disease, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot 587, Little Rock, AR 72205-7199. Fax: +1-501-686-8148.
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