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“To get back my youth I would do anything in the world, except take exercise… . ”

Oscar Wilde

The Picture of Dorian Gray, Chapter 19

INTRODUCTION

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

IN THIS ISSUE of the Journal, Petit et al.(1) report the structural changes accompanying exercise during growth.(1) During 7 months, 43 pre- and 43 early-pubertal girls, mean age 10-10.5 years, were exercised for 10 minutes three times weekly using a jumping program of gradually increasing intensity. Changes in these two intervention groups were compared with changes in 25 pre- and 63 early-pubertal controls matched by age, sitting height, leg length, and lean and fat mass from a different school. Structural changes occurred in all groups. However, in the prepubertal group (Tanner stage 1), the changes in the intervention group were no greater than in controls. In the early pubertal group (Tanner stages 2 and 3), the changes in femoral neck bone cross-sectional area (CSA), cortical thickness, and section modulus (a measure of bending and torsional strength) in the intervention group were greater than in controls. The study raises many issues regarding the rationale, hypothesis, design, execution, analysis, and interpretation of clinical trials of exercise during growth.

WHY EXERCISE?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

About 30-50% of women and 15-20% of men will suffer the consequences of fractures related to osteoporosis.(2) Drugs reduce fracture risk by about 40-50% in the subgroup of women at highest risk, that is, women with osteoporosis.(3) However, at least 50-75% of all fractures in the community come from the larger segment of the population at mild or moderate risk due to modest deficits in areal bone mineral density (aBMD) or younger age.(4) This distribution of event rates is well recognized in the cardiovascular field but underemphasized and poorly appreciated in the field of bone metabolism because of our obsession with fracture “thresholds.” Although persons with aBMD reduced by more than 2.5 SD below the young normal mean are at highest risk, this represents only a small proportion of the whole population, most of whom have aBMD above −2.5 SD. Thus, the population burden of fractures and events like stroke or myocardial infarction come from the larger population, not from the tail end of the population distribution containing the high risk group but smaller numbers of individuals.(5)

The public health burden of fractures cannot be solved with drugs, because drug trials have been done largely in women at highest fracture risk due to osteoporosis—those women with aBMD in the tail end of the population distribution (aBMD < −2.5 SD below the young normal mean). The risk of events such as fractures, strokes, and myocardial infarction is low in the larger segment of the population; to prevent one morbid event, large numbers need to be exposed to the costs of medical care, inconveniences, and side effects of drug therapy at no benefit whatsoever. The cost of treatment using this approach is greater than the cost of fractures.(6) We can reduce fracture risk in the subgroup of high risk individuals (case-finding), but they contribute only 25-50% of all fractures in the population. The solution to the public health burden of fractures remains an enigma, particularly as more and more of us are living longer to enjoy the fruits of old age.

Thus, nondrug related interventions are needed to reduce the population burden of fractures. For these population-based approaches to be successful, several criteria must be fulfilled. The interventions must be efficacious, safe, accessible to all, easily carried out, and inexpensive to implement. If it were possible to move the population distribution of the structural determinants of bone strength just a few percentage points using an intervention applied to the whole population, there is likely to be a profound benefit on the population burden of fractures.(5) Of all the modifiable lifestyle factors that influence the skeleton, such as nutrition, tobacco use, and exercise, it is exercise during growth that has the potential to fulfill all these criteria and therefore could reduce the public health burden of fractures.

DOES EXERCISE LIVE UP TO ITS POTENTIAL?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

The answer to this question is unknown. Inferences regarding the anti-fracture efficacy of exercise will never be based on the highest level of experimental evidence. There will obviously never be a double-blind trial of exercise. There will almost certainly never be a randomized open trial of exercise during growth or aging with fragility fractures in old age as an endpoint; the sample sizes needed to show a biologically worthwhile fracture risk reduction are similar to those needed in industry funded drug trials. Issues of design, compliance and funding almost certainly make these trials too difficult to execute successfully.

The firm belief held by many that exercise reduces fracture risk is derived from lower levels of evidence—retrospective and prospective observational cohort and case-control studies that suggest active persons have fewer fractures than less active persons.(7–9) This inference may be correct, but these studies are subject to systematic healthy user bias and should be evaluated with skepticism and interpreted cautiously.(7) Healthier individuals may choose to be more active and are less prone to falls and fractures. Persons inheriting a larger musculo-skeletal size have higher bone mass and lower fracture risk before starting exercise. The exercise may be a consequence of the larger musculo-skeletal mass rather than the larger musculo-skeletal mass being a consequence of the exercise.

There is no strength in numbers. Meta-analyses of observational studies examining efficacy should not even be under taken, much less interpreted. At very best, they are hypothesis generating, not hypothesis testing. Recall the iconoclastic impact of the first randomized double-blind trial examining the effect of hormone replacement therapy (HRT) on cardiac events, and the more recently reported negative results concerning cerebrovascular morbidity and mortality using HRT.(10,11) One or two properly conducted studies shatter the dogma created by meta-analysis after meta-analysis of observational studies that claim HRT reduces cardiovascular events.

Thus, we are forced to make inferences within the constraints of the uncertainty imposed by even lower levels of evidence—the effect of exercise on surrogates of anti-fracture efficacy such as changes in bone mass, structure and derived measures of bone strength. These endpoints also have limitations that should be acknowledged. For example, a change in aBMD in response to drug therapy is a poor surrogate of the reduction in fracture risk.(12) What then are the effects of exercise on the surrogates of anti-fracture efficacy?

EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

There is little replicated and methodologically sound evidence to suggest that exercise during young adulthood, peri-menopause, late adulthood, or old age modifies bone size, prevents bone loss, or restores bone mass, architecture, or strength. Consistency in results is lacking; some studies suggest bone loss is prevented by exercise and others suggest bone loss is not prevented or is increased.(7–9,13) The increase in aBMD of a few percentage points reported in some studies is probably due to a reduction in the size of the reversible remodeling space.(14) There is little, if any, evidence of changes in bone tissue mass beyond that produced by reducing the remodeling space. There is no evidence that exercise in adults increases cortical thickness by increasing periosteal apposition, reducing endocortical resorption, or increasing endocortical bone formation. Whether exercise reduces intracortical porosity, increases trabecular thickness, connectivity or the mineral content of the matrix tissue mass (regrettably called “true” density), is not known. When exercise is stopped, bone loss accelerates,(15) probably due to an increase in the size of the reversible remodeling space. Exercise during adulthood may reduce the risk and severity of falls, but evidence that this translates into fewer fractures is lacking.(7)

It is during growth that exercise produces its most beneficial effects. Growth is the single most opportune time to modify the mass and geometry of the skeleton.(16–24) The studies of vigorous exercise during growth provide evidence that large increments in aBMD can be achieved in loaded compared with unloaded regions of the skeleton. High impact loading in gymnastics, weight lifting, and racket sports is associated with high regional aBMD. Differences of 1-3 SD are often reported in the playing arm compared with nonplaying arm in racket sports, increments that are an order of magnitude higher than produced by exercise in adults. These changes are the result of distinct structural changes in bone mass, size, and geometry, not just small changes in the remodeling space. The region specific differences in playing versus nonplaying arm cannot be the result of sampling bias or genetic factors so that this data provides one of the few “facts” in the bone field that is not controversial—vigorous competitive loading exercise during growth is good for bone.

All of this is hardly new. The original study comparing bone mass and structure of the playing and nonplaying arms of racket sports was published about 20 years ago.(17) The results have never been challenged on methodological grounds and have been replicated several times.(20–23) The skeleton adapts remarkably to local loading during growth by changing its size, shape, architecture, and mass. These changes are likely to produce biologically worthwhile differences in the bending, compressive, and torsional strength of bone that may well be the solution to the problem of fractures in old age, provided the changes can be maintained during the next six or seven decades of life.

METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

There are subtle issues in study design that need to be considered before the greater changes reported in an exercise compared with a control group can be legitimately inferred to be the result of the group differences in exercise (rather than being due to group differences in many other factors). Petit et al.(1) studied an intervention group of prepubertal and early pubertal girls matched with a control group by age, pubertal maturation, sitting height, leg length, and lean and fat mass. The authors are to be congratulated for this attention to design. Why?

These baseline characteristics may influence the outcome independent of the exercise. A small difference in baseline characteristics in an exercise and control group, even 2 to 3 months in age or pubertal maturation, can produce large changes. If controls are more advanced in maturity, and so are about to move into an accelerated phase of growth, then any benefit of exercise in the other, less mature group, will be obscured by the accelerated growth in controls. The investigator will falsely infer that exercise had no benefit. If the exercise group is more maturationally advanced, then the changes in the exercise group will be greater than the changes in the controls due to both the maturational difference and any independent benefit exercise may produce. This may have occurred in a 10-month study of exercise reported by Morris et al.(24) Bone mineral content (BMC) and bone area increased 2- to 8-fold more rapidly in the exercise than control group; large differences in growth rate better explained by a combination of differences in maturational progression and exercise, than differences in exercise alone.

Studies in which the participants are not confined to a single gender or racial/ethnic group also create difficulties in interpretation. Males and females of the same age differ by maturational status. If they are matched by maturational status, they will usually differ by age. The rate of maturational development may differ according to racial/ethnic group.(25) About 30% of the participants in the study by Petit et al.(1) were Asian. Although the data were not analyzed according to racial/ethnic group, in an earlier study of white and Asian girls and boys, these authors reported that the increase in total body and trochanteric aBMD was greater in the Asians than whites, and greater in the girls than boys.(26) In another study by these investigators, baseline exercise levels were lower in Asians than whites.(27) Whether the race- or gender- specific aBMD responses to exercise reflects race- and gender- specific differences in maturational rate, baseline differences in usual exercise (which may influence the response to exercise), or true race- and gender- specific responses to loading is not clear.

The difficulties in interpreting observations made in heterogenous samples comprising males and females of different racial/ethnic origin are not solved by reporting that baseline differences are “not significant.” Lack of statistical significance is assured by small sample sizes of males and females, different ethnic groups, and wide ranges in age, height, and weight in the exercise and control groups.

The importance of maturational stage is highlighted by a novel aspect in the design of the study by Petit et al.(1) Chronological age of all four groups was no different, about 10-10.5 years, yet there was about 1 SD difference in sitting height, leg length, and lean and fat mass in the prepubertal cohort than early pubertal cohort. The lesson is clear, matching an exercise group with controls only by chronological age in studies of growth is inadvisable.

The above addresses some issues in studies comparing an exercise group with a control group receiving no exercise. There are greater difficulties addressing the question of whether exercise is more efficacious in prepubertal than early-pubertal children, more efficacious in males than in females, or in one ethnic group compared with another. These comparisons require evidence that there is equivalent loading in these groups. Exercise in pre- versus early-pubertal girls may produce relatively less loading in the prepubertal girls.

Even if loading intensity is measured and is equivalent in two exercising groups, differences in the rate of maturational progression of the axial and appendicular skeleton between pre- and peripubertal groups, between genders, and between racial/ethnic groups introduces complexities in study design that cannot be easily controlled. In combined heterogeneous groups, most sample sizes will be too small for subanalyses and null observations are likely to be type 2 errors. The results, whether positive or negative, will be easy to challenge on methodological grounds and will lack credibility, no matter how clever the standard statistical analysis of covariance program.

We are really interested in the age-, sex-, race-, and site-specific effects of exercises. Thus, given the many variables that may influence outcome in heterogeneous samples, it may be more practical to simplify the design of these studies by recruiting single gender, racial/ethnic groups, groups with well-defined maturational stages, preferably with bone age measurements, rather than combining males and females or children of different racial/ethnic backgrounds.

IS MODERATE EXERCISE DURING GROWTH FEASIBLE?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

Although there are many cross-sectional studies showing that athletes have higher bone mass than sedentary controls, the Olympian effort needed to produce this skeleton tells us what is possible, not what is feasible in day-to-day life for “Everyman.” The question is, does moderate exercise produces biologically worthwhile changes in bone strength? What is “moderate” exercise? When is the best time during growth to exercise? What is the structural basis underlying any increase in bone strength produced by exercise during growth? Are the benefits lost when exercise is stopped?

Petit et al.(1) studied the effects of moderate exercise, an intervention that can easily be incorporated into a school exercise program. This study is part of a larger study in which the authors report the results of 177 of 483 students recruited by randomly allocating schools to be the source of intervention groups and other schools to be controls.(26–28) This is a nice approach because it avoids controls taking up exercise. However, the schools, not the individuals, were randomly allocated to exercise or no exercise.

Could self-selection to one of the groups have occurred and introduced a bias? For example, a sedentary child might volunteer at the school randomized to be the source of controls but may decline if attending a school randomized to be the source of the intervention group. A more active child may volunteer for the intervention group but decline to participate as a control, an effect that may result in a conservative bias. From the baseline exercise characteristics of the sample published in an earlier manuscript,(28) it does seem that there were no differences in baseline exercise characteristics in the intervention and control groups. Nevertheless, without random allotment of exercise to individuals, some sort of bias, conservative or otherwise, cannot be excluded. Socioeconomic differences in the schools that influence growth may also introduce a systemic bias. Random allotment of individuals rather than schools is one way of ensuring that covariates are equally represented in both groups.

Compliance is critical. The balance in covariates produced by random allotment may be lost if dropouts or poor compliance occur in exercise studies. The children were given a graded program of jumping 10 minutes three times per week. The authors reported compliance in the companion paper(28); only 14 of 177 left the study due to loss of follow-up or relocation. Two studies(29,30) reported an 86-100% compliance among 89 prepubertal boys and girls during 7 months. In this study, 100 two-footed jumps from 61-cm boxes were incorporated into the school schedule carried out during 20-minute sessions (5-minute warm-up, 5-minute cool down, 10-minute jumping) three times weekly. In another study of prepubertal boys aged 10 years, Bradney et al.(31) incorporated an exercise program consisting of 30-minute sessions of supervised weight-bearing physical education three times weekly during 8 months with all but 2 children participating throughout. Similar compliance was reported by Morris et al.(24) Adverse events were uncommon in all these trials. Thus, moderate exercise is feasible, accessible to all, accomplishable by the majority of children, safe, and inexpensive to institute, but does it work?

IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

As can be seen from the tables in the study by Petit et al.,(1) the CIs around the increase in most traits during 7 months did not overlap zero and so were significant in all four groups (except femoral shaft medullary diameter in the prepubertal groups). However, the increases in prepubertal intervention group were no greater than in the prepubertal controls. By contrast, the increases in the early pubertal intervention group in femoral neck bone CSA, cortical thickness and section modulus were greater than in early pubertal controls.

From these, and similar observations in aBMD changes,(28) the authors suggest that the most appropriate “window of opportunity” to exercise is during early puberty (Tanner stages 2 and 3), rather than during the prepubertal years. There are several reasons to suggest that this issue is unresolved. First, the authors have not tested whether the increments in bone mass, CSA, or section modulus in the early pubertal intervention group are greater than the increments in the prepubertal intervention group before, and most importantly, after adjusting for the large differences in baseline characteristics between these two maturationally different groups. A glance at the CIs around the mean changes suggests this is unlikely, so the inference that one period of growth is more favorable than another cannot be made.

Second, the null observation in the prepubertal group is not supported by the results of several studies. In the study by Fuchs et al.,(30) femoral neck bone mass and bone area increased in prepubertal boys and girls of the exercise group more than in the controls. Whether there were gender specific changes is unclear. In a study of prepubertal boys, the increase in midfemoral aBMD was greater than controls and was the result of less expansion of the medullary canal.(31) In line with the views of Petit et al.,(1) Kannus et al.(21) suggest that the menarcheal, not premenarcheal period is a preferable period to exercise. However, this was a cross-sectional study and the menarcheal group had trained for a longer period of time.

Third, a small increase in periosteal diameter attributable to exercise may have been undetected for methodological, rather than biological, reasons. The numbers of controls in the early pubertal group was larger than in the prepubertal group (64 and 25, respectively). Progression from Tanner stages 1 and 2 occurred in 62% of controls and 41% of the intervention group, whereas more of the intervention group remained in Tanner stage 1.(1,28) Thus, maturational progression in greater numbers of controls than exercisers could obscure the benefit of the exercise.

In addition, periosteal and endocortical widths were measured at one point between the medial and lateral bone surfaces. Loading may result in periosteal expansion in the antero-posterior direction without change in the medio-lateral diameter producing a change in bone shape and area. Unpublished data cited in the Discussion of the paper by Petit et al.,(1) suggest that tibial periosteal expansion increased in prepubertal children to a variable extent along the tibia as assessed using magnetic resonance imaging (MRI). Bass et al.(32) report greater periosteal and endocortical expansion in the playing compared with nonplaying arm in prepubertal tennis players.

Fourth, without some measure of loading such as use of a force table or in vivo strain gauges, the possibility that loading produced by the jumping was relatively less in the pre- than early-pubertal girls cannot be excluded. (However, lean mass to weight ratio was no less in the prepubertal than in early pubertal girls.)

Thus, both periods of growth are likely to be opportune periods of life to build a stronger skeleton. Appendicular growth is more rapid than axial growth in the prepubertal years.(33,34) Around puberty most of the growth spurt is axial; appendicular growth accelerates slightly then slows down while accelerated axial growth dominates then slows but completes its growth later.

Perhaps asking whether one period of growth is more opportune than another is the wrong question. Is it possible that, for a given type of regional loading, the response of the appendicular skeleton may be favored by loading before puberty while the response of the axial skeleton might be favored by loading during puberty? Should exercise programs intended to develop appendicular skeleton in girls and boys be carried out in the prepubertal years while programs aimed at developing the axial skeleton be initiated later, and at a different chronological age in boys and girls, to account for the differences in axial maturational development?

PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

The greater changes in the intervention than control groups were detected by Petit et al.(1) in the early-pubertal group. The higher aBMD in the early-pubertal intervention group,(30) may be the result of one or both of two processes; greater subperiosteal bone formation than in controls or less medullary canal expansion or greater medullary canal contraction than in controls. Even a small change in CSA produced by periosteal bone formation confers a large change in the cross-sectional moment inertia because it is proportional to the fourth power of the radius. However, the increase in subperiosteal diameter in the early pubertal intervention group was 20% less than the increase in the controls (though not statistically significantly different). It was the increases in femoral neck bone CSA, cortical thickness, and section modulus, each derived, model-dependent data, that were statistically significantly greater in the intervention group than controls.

The greater increase in femoral cortical bone CSA is a “collapsed” measurement of bone mineral derived as if the tissue spaces were not there (it is not the CSA of the femoral neck). The increase in CSA and femoral cortical thickness is likely to be more the result of events on the endocortical than periosteal surface. This is consistently reported in exercise studies. Bass et al.,(35) in a prospective study of high impact exercise in gymnasts reported changes on the endocortical, not periosteal surface. Likewise, in the study of tennis players, Bass et al.(32) reported that the greater cortical volume in the playing compared with the nonplaying arm was the result of greater endocortical contraction in the postpubertal years and greater periosteal expansion in the prepubertal years. Similarly, Bradney et al.(31) report that the greater increase in aBMD in prepubertal boys participating in a supervised moderate exercise program at school was the result of greater endocortical contraction not greater periosteal expansion than observed in controls.

Dynamic histomorphometry is needed to define the effects of exercise on the cellular activity on the endocortical surface. If exercise reduces remodeling (activation frequency), this may reduce the extent of medullary expansion during growth compared with controls, leaving a narrower medullary canal and a thicker cortex. Loading may alter the volumes of bone removed and replaced in each basic multicellular unit (BMU) by altering the number, work, or lifespan of the osteoblasts and osteoclasts. This may result in either less medullary expansion or a net medullary contraction. Finally, exercise may produce bone formation independent of the BMU remodeling cycle. The effects of exercise on secondary mineralization of newly formed matrix are unknown.

In all of these studies, the dimensions of bone were measured at one point along the bone and in the medio-lateral direction. The relative contributions of periosteal and endocortical modeling and remodeling varies along the whole length of a limb. Local loading will modify each part of the geometry of the bone in accordance with the imposed load. In racket sports, the greater humoral cortical area of the playing versus nonplaying side is the result of both greater periosteal expansion and greater endocortical contraction. The relative contributions of periosteal expansion and endocortical contraction to the greater cortical thickness in the playing than nonplaying arm in a study by Haapasalo et al.(22) were 75:25 at the proximal humerus and 10:90 at both mid- and distal humerus. In the study by Jones et al.,(23) the respective relative contributions of greater periosteal expansion and greater endosteal contraction to the greater cortical thickness were 60:40 in the antero-posterior dimension and 80:20 in the medio-lateral dimension in men and women. Thus, loading affects both the periosteal and endocortical surfaces, but the magnitude of the effects vary according to whether the surface is anterior, posterior, medial, or lateral and whether the region is proximal, central, or distal along the bone's length.

These levers are not perfect tubes with a single diameter and cortical thickness along their length. Thus, as pointed out by Petit et al.,(1) inferences about surface-specific effects, or lack of effects, must be made cautiously given only one dimension was measured and calculations of cortical dimensions and whole bone strength were then derived.(36) We need noninvasive, safe, and low-cost methods that accurately measure the size and contours of the levers that propel us against gravity.

DOES EXERCISE DURING GROWTH REDUCE STATURE?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

Although greater periosteal expansion in the playing arm than nonplaying arm is reported by several investigators, why might periosteal expansion at long bone sites be less in the intervention than control group in the above studies?(1,31,35) By contrast, Fuchs et al.(30) reported greater increase in bone size in prepubertal boys and girls. How can this be explained?

In the studies by Petit et al.(1) and Fuchs et al.,(30) the changes in the periosteal diameter were adjusted for changes in height. This is important. If the change in height in an exercise and control group is the same, any difference in the change in periosteal diameter can be reasonably attributed to the exercise. If height increases less in an exercise group than control group due to reduced longitudinal growth of the tibia, femur, or axial skeleton, then this may be accompanied by lesser periosteal expansion of the corresponding region independent of any local loading that may be taking place. This must be taken into account in the analysis and requires knowledge of the behavior of the bone that is affected; adjusting for total height may introduce errors if longitudinal growth is region specific (which of course it is).

In one study by McKay et al.(26) involving boys and girls, height did increase less in the exercise than control group. Baseline sitting height and leg length did not differ in the study by Petit et al.,(1) and the changes in these segments, reported in the companion paper,(28) also did not differ significantly in intervention or control groups in either the prepubertal or early pubertal cohorts. Although not statistically significant, leg length increased by about 0.5 SD less in the prepubertal intervention than control group.

Exercise may be associated with reduced growth in animals and human subjects, and may be confined to one region.(19,35,37–40) The implication is that the behavior of the periosteum is dependent on the local effects of the exercise as well as possible systemic factors, local growth plate cellular activity and other factors that regulate longitudinal and radial growth of the limb.

The study by McKay et al.(26) was confined to changes in the femur. In the companion paper, aBMD of the spine increased more in the early pubertal exercise than control group. An analysis of the changes in vertebral body dimensions was not done, probably because of the difficulties in accurately measuring the dimensions of this structure. This information is needed if statements are going to be made about the anti-spine fracture efficacy of exercise.

VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

BMC and aBMD increase during growth because bone size increases. As the densitometry “sees” three-dimensional objects in a two-dimensional projected area, the increase in “density” may be the result of an increasing bone size and not necessarily an increase in the mass per unit external volume of bone.(39) Why would the skeleton want to be heavier if it can adapt to greater loads equally well by changing its shape?

vBMD will increase during growth if the increase in the amount of bone within the periosteal envelope is proportionally greater than the increase in the size of the bone. The results of changes in vBMD were reported in the study by MacKelvie et al.(28) vBMD increased at the femoral neck, consistent with the notion that there was minimal change on the periosteal surface so external diameter of the bone remained unchanged while endocortical remodeling favored either contraction of the medullary canal by net bone formation or less endocortical resorption so there was more bone “inside” the same sized bone. vBMD did not increase at the spine. In the study by Bradney et al.,(31) vertebral height increased in the exercise group whereas vertebral width increased in controls so that the increase in vertebral area were no different in the two groups. BMC of the third lumbar vertebra increased by similar amounts in both groups with no change in vertebral vBMD in either. Haapasalo et al.(40) reported that the difference in aBMD in a playing versus a nonplaying arm was due to differences in bone size produced by greater periosteal apposition, not due to an increase in vBMD.(40) These studies all suffer from the methodological limitations; we can't measure bone size accurately, and so we can't derive vBMD accurately.

IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

If all the benefits of exercise achieved during growth are lost when exercise is stopped, why bother?(41) This question is critical. The answer to this question determines whether or not recommendations can be made regarding exercise as a public health measure. There is evidence that when exercise stops bone loss occurs.(15,40) Whether this occurs at the endocortical and trabecular surfaces alone while any periosteal apposition is maintained is not known.

In athletes such as gymnasts, residual benefits are maintained for many years, but these subjects are still young adults.(35,41–43) The residual benefits are about 1-1.5 SD, lower than the 2-3 SD benefits seen in active athletes, but this may reflect secular changes in training intensity where the older athletes may have achieved a lower peak bone size and mass than the contemporary athlete. In older athletes, retired international soccer players aged 70-80 years, benefits seem to be lost or largely lost.(43) Fracture rates were no less in the retired athletes than in controls, but the study may have been underpowered. These are cross-sectional studies, but surely that's as good as it is going to get! We will not have prospective studies of young athletes followed until they reach the door to the nursing home. There is no evidence of a persisting benefit of exercise during growth on bone structure or strength in old age when falls and fracture risk increases.

The evidence regarding persisting skeletal benefits, no matter how slight, or how interpreted, is based on studies in retired elite athletes, not based on studies of moderate exercise. There is no data to support or refute the notion that the modest benefits achieved by moderate exercise during growth are sustained into adulthood when activities are stopped. There is only one study, by Fuchs et al.,(44) published in abstract form, that suggests the benefits derived from 7 months of exercise were maintained 7 months after ceasing the jumping program. This study must await peer review before the veracity of the results can be evaluated. Nor is their data addressing the most important question: whether any benefits achieved during growth will be sustained by a less frequent or less intense exercise “maintenance” program. If the benefits are lost, is it better to never have exercised at all?

WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES

There is progress; we are moving away from impenetrably complex traits such as BMC and aBMD and heading toward a greater understanding of skeletal heterogeneity. The skeleton is not an entity that can be squeezed into a single number or single phenotype like aBMD. Height is an inadequate phenotype; its axial and appendicular components behave differently during growth because they are regulated differently. The appendicular skeleton is not a single entity. The growth patterns of the distal (tibia, radius, ulna) and proximal (femur, humerus) segments behave differently. Individual long bones are not single elements that grow equally at each end like stretching an elastic band, the distal segment of the long bone grows more rapidly than the proximal section. The epiphyses don't close at the same time despite being exposed to the same circulating concentrations of sex steroids. There is no one cortical thickness; heterogeneity in bone shape, size, and cortical thickness is present at every point around its perimeter and along its length and these are adaptive changes to loading.

Each region of the axial and appendicular skeleton, each point on the external and internal surfaces along a bone's length and circumference is fashioned by genetic factors, local mechanical and hormonal factors, into a structure adapted to loading. The effect of exercise may depend on the stage of growth when exercise is undertaken, as well as the intensity and pattern (compressive, torsional, bending) of loading. Do we need methods of measuring all of these surfaces, at every point along the bone? I don't know. We must get away from BMC and aBMD when we ask questions about the physiology of growth and aging. We have recognized that the effects of loading are region specific and the anatomical changes are the result of the absolute and relative behavior of the periosteal and endosteal surfaces. So, yes, measure them and the cellular activity that fashions them in space.

Do we know that moderate exercise during growth builds a skeleton composed of long bones with a wider diameter, a thicker cortex, and thicker or more connected trabeculae? If so, do we know that this skeleton will remain just a little less eroded and a little less fragile after decades of a sedentary life in elevators, escalators, moving platforms, four-wheel drives, infrared fingertip controls, the ravages of time, tobacco, Tabasco, tomato juice, and alcohol than would otherwise have occurred had moderate exercise not been undertaken during growth? Perhaps, but somehow, I don't think so.

So, further research is needed. There are many fine and instructive aspects of the studies reported by Petit et al.(1) and MacKelvie et al.,(28) and these papers should be studied together. Meticulous attention to study design is paramount in all studies, but the standards needed are particularly challenging in studies of growth.

We need studies that are designed simply, in a single gender and single ethnic group, with well-documented pubertal staging including bone age. We need techniques that measure bone size and its contours and bone loading. If the design is simple the studies will be easy to understand, and so, the results, positive or negative, will be easy to interpret and difficult to refute on methological grounds. When statistical packages can do everything, we will not need clinical trials. But until then, we need study design rather than statistical packages that “adjust” colinear covariates by multiple regression in small sample sizes to squeeze out the truth with the confidence given to us by a storm in a p cup.

REFERENCES

  1. Top of page
  2. INTRODUCTION
  3. WHY EXERCISE?
  4. DOES EXERCISE LIVE UP TO ITS POTENTIAL?
  5. EXERCISE DURING GROWTH, NOT AGING, ALTERS BONE STRUCTURE AND STRENGTH
  6. METHODOLOGICAL ISSUES IN THE DESIGN AND EXECUTION OF STUDIES OF EXERCISE DURING GROWTH
  7. IS MODERATE EXERCISE DURING GROWTH FEASIBLE?
  8. IS MODERATE EXERCISE IN THE PREPUBERTAL AND PERIPUBERTAL PERIOD EFFICACIOUS?
  9. PERIOSTEAL AND ENDOCORTICAL SURFACE CHANGES IN RESPONSE TO EXERCISE
  10. DOES EXERCISE DURING GROWTH REDUCE STATURE?
  11. VOLUMETRIC BMD—WHY WOULD THE GROWING OR EXERCISED SKELETON WANT TO BE HEAVIER?
  12. IS IT BETTER TO HAVE EXERCISED AND LOST, THAN NEVER TO HAVE EXERCISED AT ALL?
  13. WHAT'S IT ALL ABOUT ALFIE—SURFING THE SKELETON'S SURFACES?
  14. REFERENCES
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