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0021-972X/00/$03.00/0 The Journal of Clinical Endocrinology & Metabolism Copyright © 2000 by The Endocrine Society

Vol. 85, No. 10 Printed in U.S.A.

A 1-Year Prospective Study on the Relationship between Physical Activity, Markers of Bone Metabolism, and Bone Acquisition in Peripubertal Girls* ¨ TTO ¨ NEN, KERTTU IRJALA, MARJO LEHTONEN-VEROMAA, TIMO MO ILPO NUOTIO, AILA LEINO, AND JORMA VIIKARI Paavo Nurmi Center, Sport and Exercise Medicine Unit, Department of Physiology, University of Turku (M.L.-V.); Department of Medicine (M.L.-V., T.M., I.N., J.V.) and Central Laboratory (K.I., A.L.), Turku University Central Hospital, Turku, Finland ABSTRACT We conducted a 1-yr prospective study to evaluate the association between physical activity and biochemical markers of bone formation and resorption with bone mineral acquisition in 155 peripubertal Caucasian girls (51 gymnasts, 50 runners, and 54 nonathletic controls). The bone mineral density (BMD) of the femoral neck, the greater trochanter, and the lumbar spine were measured by dual energy x-ray absorptiometry. Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, aminoterminal propeptide of type I procollagen) and bone resorption (degradation product of C-terminal telopeptide of type I collagen) were measured. The 1-yr increase in BMD (adjusted for age, height, Tanner stage, BMD at baseline, and increases in height and weight) of the femoral neck was 0.037 g/cm2䡠yr [95% confidence interval (CI), 0.019 – 0.051 g/cm2䡠yr), and that of the greater trochanter was 0.020 g/cm2䡠yr (95% CI, 0.003– 0.039 g/cm2䡠yr) greater in gymnasts than in controls. The

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AXIMIZING skeletal mass and its quality has important implications for the individual and for the economics of the society. The risk of osteoporotic fractures in the elderly increases progressively as bone mineral density (BMD) declines, and a reduction of 1 sd in the BMD of the femoral neck is associated with a doubling of the risk of hip fractures (1). Although genetic factors may be the main determinants of bone mass and BMD, environmental factors also influence the quality and durability of bone. Several cross-sectional studies have shown that high impact weight-bearing activity is beneficial for the load-bearing sites of the skeleton (2– 6). There are few longitudinal data on the relationship between physical activity and bone mineral acquisition in prepubertal and pubertal girls (7–11). Several biochemical markers of bone formation and bone resorption have been introduced. Osteocalcin (OC) is the major noncollagenous protein of bone matrix. OC is syntheReceived March 13, 2000. Revision received July 5, 2000. Accepted July 11, 2000. Address all correspondence and requests for reprints to: Dr. Timo Mo¨tto¨nen, Department of Medicine of Turku University Central Hospital, Paimio Hospital, 21540 Paimio, Finland. E-mail: timo.mottonen@ tyks.fi. * This work was supported by the Medical Research Foundation of the Turku University Central Hospital, the Yrjo¨ Jahnsson Foundation, the Juho Vainio Foundation, and the Turku University Foundation.

corresponding figures for gymnasts compared with runners were 0.038 g/cm2䡠yr (95% CI, 0.009 – 0.041 g/cm2䡠yr) and 0.033 g/cm2䡠yr (95% CI, 0.006 to 0.043 g/cm2䡠yr). The figures for the lumbar spine did not differ significantly between study groups. The baseline serum concentrations of formation markers and resorption marker accounted for 2.3–12.8% (P ⬍ 0.05) of the variation in the 1-yr increase in BMD at the femoral neck and lumbar spine. However, there was no significant difference between the levels of adjusted baseline bone turnover markers of the gymnasts, runners, and controls. The present data add considerable support to the argument that high impact mechanical loading is extremely important and beneficial for the acquisition of BMD of the hip during peripubertal years. Our results indicate also that a high rate of bone turnover, reflected as elevated bone markers, is only weakly associated with the 1-yr bone gain in peripubertal girls. (J Clin Endocrinol Metab 85: 3726 –3732, 2000)

sized by osteoblasts in the bone, partly incorporated into the bone matrix, and partly delivered to the circulatory system. The bone-derived alkaline phosphatase (BAP) is an enzyme localized to the membrane of osteoblasts, and it is released into the circulation. Collagen type I is the most common protein of bone matrix, accounting for more than 90% of the total mass of protein. The amino-terminal propeptide of type I procollagen (PINP) is present in the circulation before the collagen molecules are assembled into fibers (12). Type I collagen peptides are present in the mature form of collagen. In the process of bone degradation, C-terminal telopeptide of type I collagen (CTX) is released into the circulation (13). Puberty is a time of large increases in bone mass over a relatively brief period. In females, the time of maximum bone acquisition occurs between 11–14 yr of age, a time that corresponds to pubertal stages Tanner 3–5 (14, 15). Careful evaluation of the factors associated with the increase in bone mass during this phase may be important for prevention of osteoporosis later in life. There has been little research on the association between biochemical markers of bone formation and resorption, and physical activity, especially in children and young adults (16 –20). Furthermore, little is known about the effects of various loading states on the formation and resorption of bone tissue or osteoblast-osteoclast activity in the growing skeleton. The aim of the present study was to evaluate the

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influence of physical activity on acquisition of bone mass during 1 yr with regard to biochemical markers of bone and type I collagen metabolism among peripubertal girls.

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of 1 yr was calculated. The number of years of training of the athletes was also recorded.

Laboratory studies Subjects and Methods Subjects The original study group comprised 191 healthy Caucasian girls, aged 9 –15 yr (66 competing gymnasts, 65 competing runners, and 60 nonathletic controls), who participated in a long-term health study. The participants were recruited from local sports clubs and schools in the city of Turku and its vicinity. Gymnasts, runners, and controls were studied to determine the difference in the impact of physical activity on the growing skeleton. Gymnastics is characterized by very high impact through repeated jumps and body contact with hard surfaces. Running, on the other hand, causes repetitive weight-bearing stress and impact loading mainly on the lower limbs. The intensity of the exercise was defined as competitive if the subject had participated regularly in competitive sports at a local, provincial, or national level for at least 1 yr. The group of the runners consisted of long distance runners and track runners. The controls were usually classmates of the athletes. Subjects in the control group did not participate in any kind of regular or organized sports activity. All participants were healthy, as assessed clinically and by questionnaire. All subjects were studied over an 8-week period from February to March 1997 and 1998. The study protocol was approved by the joint ethics committee of Turku University and Turku University Central Hospital. The study was carried out in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants and their parents.

Anthropometry Weight and height were recorded with subjects in minimal clothing and bare feet. Height was measured with a fixed stadiometer (Harpenden stadiometer, Holtain, Crymych, UK), and weight was measured with a regularly calibrated electronic scale (EKS Exclusive, EKS International, Sweden). The body mass index was calculated (kilograms per m2).

Bone mineral density (BMD) measurements The BMD (grams per cm2) and the projected bone area (square centimeters) of the nondominant hip and the lumbar spine (L2–L4) were measured by dual energy x-ray absorptiometry (QDR 4500C, Hologic, Inc., Waltham, MA). All measurements were performed and analyzed by the same 3 trained radiographers. Calibration was performed daily to assure quality, using a spine phantom supplied by the manufacturer. The coefficients of variation of two consecutive measurements for 10 girls were 1.3% for the spine, 0.8% for the hip, and 0.4% for the phantom over the study period.

Assessment of puberty stage The Tanner stage was examined and recorded by the researcher (M.L.-V.) according to the method of Tanner (21). When there were discrepancies between breast stage and pubic hair stage, greater emphasis was placed on the degree of breast development. The prepuberty group consisted of Tanner stage 1, the early puberty group consisted of Tanner stages 2–3, and the late puberty group consisted of Tanner stages 4 –5.

Assessment of physical activity The subjects completed a detailed questionnaire on their physical activity every 6 months. The competitive athletic history of the subjects and their leisure time physical activity (LTPA) during the past 6 months (weekly frequency, mean duration in minutes, and mean intensity of all bouts of physical activity) were reported retrospectively. On the basis of this information the LTPA was calculated as MET-hours per week by multiplying frequency, mean duration in minutes, and mean intensity of weekly physical activity and then dividing by 60 (22). The mean LTPA

All blood samples were obtained from the participants between 0800 – 0900 h after an overnight fast. The puncture site was anesthetized by local anesthetic patches (Emla, Astra USA, Inc., Sodertalje, Sweden). In menstruating subjects samples were collected during the early follicular phase of the menstrual cycle, defined as the time between the fifth and eighth days after the onset of menstrual bleeding. Blood samples were centrifuged (2100 ⫻ g, 10 min) within 2 h of venipuncture, and serum samples were stored frozen at ⫺20 C. Serum OC (S-OC) was measured by RIA (CIS-Bio International, Gifsur-Yvette, France). The intra- and interassay coefficients of variation were 1.7% and 3.1% at 22 ng/mL, respectively. Serum BAP (S-BAP) was measured by immunoassay (Metra Biosystems, Mountain View, CA), and the respective intra- and interassay coefficients of variation were 2.1% and 3.2% at 70 U/L, respectively. The serum concentration of PINP (S-PINP) was measured by RIA (Orion Diagnostica, Espoo, Finland), with intra- and interassay coefficients of variation of 5.2% and 2.0% at 106 ␮g/L, respectively. Serum CTX (S-CTX) was measured by enzyme immunological test (Osteometer Biotech, Herlev, Denmark), and the intra- and interassay coefficients of variation were 10.3% and 4.9% at 7387 pmol/L, respectively.

Statistical analyses Spearman’s correlation analyses, one-way ANOVAs, multivariate and regression analyses, Bonferroni tests, and nonparametric analyses were performed using version 6.12 of the SAS software (SAS Institute, Inc., Cary, NC). The normality of the variable distributions was tested using Shapiro-Wilk statistics and normality plots. The differences between exercise groups in baseline values were evaluated with one-way ANOVA followed by pairwise Bonferroni tests. In case of non-Gaussian distributions the Kruskal-Wallis test was used, followed by pairwise Wilcoxon analyses with Bonferroni correction. The homogeneity of slopes was assessed by studying the cross-product of Tanner stage and the independent bone formation or resorption marker with main effects in the model. The 1-yr changes in BMD of the femoral neck, greater trochanter, and lumbar spine were calculated to match the exact follow-up period. Multivariate analyses were applied in the adjustments of bone formation and resorption markers and 1-yr increases in BMD and in the assessment of the relationship between these markers and the 1-yr change in BMD.

Results Baseline variables

One hundred and ninety-one girls were originally evaluated. There were 6 dropouts from the follow-up during the year, and, in addition, 30 retired from sports and were therefore excluded from the analysis. After 1 yr of follow-up, 51 gymnasts and 50 runners who continued their sports career and 54 controls were available (n ⫽ 155). The absolute mean BMD values of the femoral neck, greater trochanter, and lumbar spine by pubertal stages and study groups at baseline are presented in Table 1. The body weight of the early pubertal gymnasts was significantly lower than that of the runners, but there were no differences in stature in the late puberty groups. Both athletic groups had significantly higher mean absolute BMD of the femoral neck than the controls in the early pubertal subgroup. The BMD of the femoral neck, greater trochanter, and lumbar spine of the late pubertal gymnasts differed significantly from those in the controls and the runners at baseline (Table 1). However, the projected area of the lumbar spine was comparable in each study group of three pubertal stages (data not shown).

MET, Ratio of work metabolic rate to resting metabolic rate. The MET index was calculated by multiplying frequency, mean duration, and mean intensity of weekly physical activity. a Gymnasts differ from runners. b P ⬍ 0.05. c P ⬍ 0.01. d Gymnasts differ from controls. e P ⬍ 0.001. f Runners differ from controls.

0.833 (0.110) 0.707 (0.086) 0.896 (0.095) 0.862 (0.117)a,e 0.763 (0.103)a,e 0.953 (0.118)a,e 1.010 (0.156)d,e 0.880 (0.138)d,e 1.046 (0.143)d,e 0.689 (0.055)c,f 0.588 (0.060) 0.695 (0.074)b,f 0.784 (0.112) 0.680 (0.126) 0.791 (0.140) 0.796 (0.090)c,d 0.682 (0.127)b,d 0.783 (0.112)b,d

10.2 (8.3)e,f 8.4 (8.9)b,f

0.650 (0.069) 0.542 (0.062) 0.681 (0.071) 0.698 (0.106) 0.598 (0.111) 0.696 (0.093)

13.9 (11.5)e,f

14.1 (1.0) 166.0 (6.3) 54.0 (6.6) 19.6 (1.7) 5.9 (1.9)a,c 51.7 (30.1)a,c 14.3 (1.2) 163.5 (4.8) 53.5 (5.0) 20.0 (1.4) 7.9 (2.4) 81.6 (23.5)d,e 12.1 (1.1) 155.4 (8.9) 43.0 (7.8) 17.7 (1.9)

12.1 (1.6) 156.9 (10.0) 45.2 (9.1)a,b 18.3 (2.7) 3.5 (1.6)a,c 33.8 (21.3)a,e 12.3 (1.0) 152.7 (6.9) 39.4 (4.9) 16.9 (1.3) 5.4 (1.7) 84.6 (27.7)d,e 11.1 (1.4) 149.0 (3.6) 39.4 (6.2) 17.7 (2.4)

10.1 (0.8)a,b 147.6 (7.6) 35.3 (7.3) 16.0 (2.0) 3.2 (1.1)a,c 37.7 (26.3)

Age (yr) 11.4 (1.1) Height (cm) 146.1 (7.4) Weight (kg) 34.9 (4.5) BMI (kg/m2) 16.3 (1.0) Yr of training 5.4 (1.6) MET (h/wk) 64.3 (29.8)d,e BMD (g/cm2) Femoral neck 0.729 (0.090) Trochanter 0.587 (0.087) Lumbar spine (L2– 4) 0.686 (0.068)

Runners (n ⫽ 24) Runners (n ⫽ 18) Gymnasts (n ⫽ 12)

Controls (n ⫽ 9)

Gymnasts (n ⫽ 19) Runners (n ⫽ 8)

Controls (n ⫽ 16)

Gymnasts (n ⫽ 20)

Late puberty (Tanner 4 –5) Early puberty (Tanner 2–3) Prepuberty (Tanner 1)

Parameters

TABLE 1. Study population at baseline by Tanner stages and exercise group (n ⫽ 155). Results are expressed as unadjusted mean values (SD).

14.3 (1.0) 163.0 (4.7) 53.7 (6.4) 20.2 (2.3)

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Controls (n ⫽ 29)

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The concentrations of the markers of bone formation (SOC, S-BAP, and S-PINP) and bone resorption (S-CTX) were high among the prepubertal and early pubertal girls and decreased as puberty advanced (Table 2). The strongest correlations between formation markers were found between S-OC and S-PINP (r ⫽ 0.539 – 0.893) and between S-BAP and S-PINP (r ⫽ 0.612– 0.894). The correlations between various bone markers were stronger in the late pubertal group (r ⫽ 0.725– 0.894) than in the earlier stages (r ⫽ 0.175– 0.628). Accordingly, significant differences (P ⬍ 0.05) were noted in regression slopes between the pubertal stages, and slopes were 1.2–2 times greater in late puberty than in prepuberty or early puberty. There was no significant difference between the adjusted baseline bone turnover markers of the gymnasts, runners, and controls when the values were corrected for age, height, weight, and Tanner stage (data not shown). Physical activity and 1-yr increases in BMD

The changes in BMD of the femoral neck, greater trochanter, and lumbar spine over 1 yr among the different physical exercise groups are illustrated in Fig. 1. Compared with the controls, the 1-yr increase in BMD (adjusted for age, height, Tanner stage, BMD at baseline, and 1-yr increases in height and weight) of the femoral neck in the gymnasts was 0.037 g/cm2䡠yr [95% confidence interval (CI), 0.019 – 0.051 g/cm2䡠yr], and that of the greater trochanter was 0.020 g/cm2䡠yr (95% CI, 0.003– 0.039 g/cm2䡠yr) higher. In contrast, the 1-yr increase in the areas of the femoral neck and the lumbar spine did not differ significantly between gymnasts and controls. The corresponding figures compared to runners were 0.038 g/cm2䡠yr (95% CI, 0.009 – 0.041 g/cm2䡠yr) and 0.033 g/cm2䡠yr (95% CI, 0.006 – 0.043 g/cm2䡠yr). The rates of change at the lumbar spine did not differ significantly between the study groups. The mean percent increases in BMD of the femoral neck, greater trochanter, and lumbar spine over 1 yr in each exercise and pubertal group are described in Table 3. The mean rate of increase was high in the early pubertal subjects (5.9 – 13.5%/yr) and then decreased in the late pubertal participants (1.8 – 6.0%). The mean percent increase in the BMD of the femoral neck was significantly greater in the prepubertal and late pubertal gymnasts than in the runners or controls (Table 3). Relationship between 1-yr increases in BMD and biochemical markers

The baseline serum concentrations of OC and PINP correlated significantly with the adjusted 1-yr changes in BMD of the femoral neck and the lumbar spine (r ⫽ 0.280 – 0.478), but none of the biochemical markers correlated with the adjusted 1-yr change in BMD of the greater trochanter among late pubertal group. The baseline serum formation markers accounted for 5.0 – 6.9% (P ⬍ 0.001) of the variation in the 1-yr increase of BMD at the femoral neck in multivariate analyses. The corresponding figures were 7.3–12.8% (P ⬍ 0.001) at the lumbar spine. In contrast, the serum resorption marker CTX accounted for only 2.3% (P ⬍ 0.05) of the variation in the 1-yr increase in

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TABLE 2. The baseline concentrations of bone formation and resorption markers in prepubertal (n ⫽ 29), early pubertal (n ⫽ 53), and late pubertal (n ⫽ 73) girls Variable

Prepuberty (n ⫽ 29)

Early puberty (n ⫽ 53)

Late puberty (n ⫽ 73)

Group difference

S-OC (ng/mL) S-BAP (U/L) S-PINP (␮g/L) S-CTX (nmol/L)

107 (29) 83 (24) 613 (178) 14.9 (3.6)

112 (32) 80 (23) 639 (231) 15.4 (3.8)

78 (31) 47 (24) 327 (240) 12.0 (4.3)

⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001

OC, Osteocalcin; BAP, bone-specific alkaline phosphatase; PINP, aminoterminal propeptide of type I procollagen; CTX, C-terminal telopeptide of type I collagen. Concentrations are expressed as means (SD).

FIG. 1. One-year increases in BMD (adjusted for age, height, Tanner stage, BMD at baseline, and 1-yr increases in height and weight) of the femoral neck, greater trochanter, and lumbar spine among gymnasts, runners, and controls. Results are adjusted means (SEM). Bonferroni difference: *, P ⬍ 0.05; **, P ⬍ 0.01; ***, P ⬍ 0.001.

BMD at the femoral neck and only 4.9% (P ⬍ 0.001) at the lumbar spine. Discussion

The results of this 1-yr follow-up study provide evidence of an association between high impact loading of the type encountered in gymnastics training and positive adaptive responses in the growing skeleton. This association seems to be particularly strong at the femoral neck subjected to repetitive loading. The 1-yr increase in adjusted BMD at the femoral neck of the gymnasts was 115% larger than that of the controls and 125% larger than that of the runners. At baseline, the BMD of the femoral neck was 11–22% greater in gymnasts than controls. The amount of bone accrued during growth may be a major determinant of future susceptibility to fractures. Whether this osteogenic effect of high

impact loading is maintained into adulthood remains a key issue. Bass et al. reported that retired gymnasts had 6 –16% higher BMD at the weight-bearing sites of the skeleton than controls (9). This amount of increment should be sufficient to halve the fracture risk (1). The influence of exercise on the femoral neck was more evident than that on the lumbar spine in both the longitudinal and cross-sectional data of our study. The 1-yr increases in adjusted BMD at the femoral neck and greater trochanter of the gymnasts were 115% and 49% larger than those of the controls; at the lumbar spine there was only a tendency toward higher BMD values in the gymnasts. In a very recent study McKay et al. (11) reported that an 8-month schoolbased jumping program augmented BMD at the greater trochanter, but not at the lumbar spine, in prepubertal and early pubertal children (11). In an earlier study Bass et al. reported

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TABLE 3. The 1-yr mean increase of BMD (⌬BMD) (%) at the femoral neck (FN), greater trochanter (Troch), and lumbar spine (L2– 4) in the prepubertal, early pubertal, and late pubertal gymnasts, runners, and controls. ⌬BMD values are adjusted for mean baseline age, height, BMD, and 1-yr increase of height and weight in each pubertal group Groups Prepuberty (Tanner 1)

⌬BMD

FN Troch L2– 4

Gymnasts (n ⫽ 12)

Runners (n ⫽ 8)

7.5 11.7 10.4

1.2 6.3 6.4

Group difference

Controls (n ⫽ 9)

4.0 7.9 7.5

⬍0.05 NS ⬍0.05

Early puberty (Tanner 2–3)

FN Troch L2– 4

Gymnasts (n ⫽ 19)

Runners (n ⫽ 18)

Controls (n ⫽ 16)

10.8 13.5 11.5

5.9 7.5 8.2

6.7 10.7 9.9

NS ⬍0.05 NS

Late puberty (Tanner 4 –5) Gymnasts (n ⫽ 20)

FN Troch L2-4

6.0 4.4 5.6

Runners (n ⫽ 24)

3.8 1.8 4.1

Controls (n ⫽ 29)

3.2 2.7 3.6

⬍0.05 NS NS

that growth is region specific; the growth spurt was more evident at the spine than at the lower limbs during puberty. The growth of the lower limbs was more rapid than that of the trunk before puberty (23). Although the cross-sectional data regarding late pubertal gymnasts showed significantly higher BMD values of the lumbar spine than in the controls or the runners, a follow-up of only 1 yr was too short to observe any significant difference in the increase in BMD of the lumbar spine. The BMD of the lumbar spine, however, is more sensitive to the negative effect of hormonal disturbances, which are common in athletes (5, 24). In our baseline data the runners had a tendency toward higher BMD values of the femoral neck and lumbar spine than the controls, whereas the 1-yr increases in BMD were similar in the two groups. However, we did not find any negative effect of running on BMD as has been described previously in collegeaged women (5, 25). The influence of physical activity on the BMD of children has been explored in a few follow-up studies (7–11, 20, 26). In general, the studies have concentrated on prepubertal subjects. We chose a more extensive age span that allowed us to study the effect of sexual maturation, and therefore we adjusted analyses for the Tanner stage. Our results are in agreement with those reported by Bass et al., whose 12-month follow-up study showed an increase in BMD of the total body, lumbar spine, and legs that was 30 – 85% greater in gymnasts than in controls in a population of prepubertal girls (9). However, in a recent cross-sectional study, Haapasalo et al. found that the benefit of physical activity became evident during the growth spurt or Tanner stage III–IV (27). Bailey et al. (10) reported that the increase in total body bone mineral content reached its peak velocity in girls at the age of 12.5 yr (10). According to our results the mean 1-yr increase in BMD was highest (5.9 –13.5%) in early pubertal girls.

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In our prepubertal group the average number of training years was 5.4 for gymnasts and 3.2 for runners, and the amount of exercise was far above moderate, particularly in the group of gymnasts. Prospective studies of prepubertal children have shown that a 10- to 30-min exercise session three times per week for less than 1 yr increased BMD significantly (8, 11, 26). In the present study the baseline projected bone area and annual increase in that bone area at the femoral neck and lumbar spine were comparable in gymnasts and controls. This fact did not explain the higher BMD values in the gymnasts than in the controls. In contrast to our results, Morris et al. reported that exercise also significantly increased the projected bone area of the femoral neck in prepubertal girls (8). Our results are in line with those reported by Nordstro¨m et al. (28), who found that exercise affected primarily the BMD and not the bone area of adolescent boys. According to our results there were significant correlations in the serum concentrations of bone formation markers (OC, BAP, and PINP) and a bone resorption marker (CTX), which were associated with the positive response to the annual change in BMD, particularly at the lumbar spine and partly at the femoral neck of the growing skeleton. Our results stand in contrast to previous results for older subjects, in which the concentrations of bone turnover markers did not predict changes in bone mass (17, 29). Our findings disagreed also with the study by Slemenda et al. (30), who reported that low concentrations of formation and resorption markers in children predicted high BMD values. Puberty is associated with the high values of bone turnover markers (31–33). Mora et al. found that the concentrations of biochemical markers reach a zenith at pubertal stage 2 (32). Our findings for all measured formation markers were consistent with previous results (23, 31–33). All four bone turnover markers we studied correlated significantly with the 1-yr increase in BMD at the lumbar spine, and both OC and PINP also correlated with the increase in BMD at the femoral neck. Mora et al. (33) found in their cross-sectional study of 7- to 18-yr-old subjects that serum BAP and OC correlated inversely with the material density of bone, and markers of bone resorption were related to the volume of bone. Borderie et al. (34) found that the values of the biochemical markers correlated with the change in BMD at the lumbar spine, but not at the femoral neck. This might have been due to higher biological activity of trabecular bone than that of cortical bone; the lumbar spine consists mostly of trabecular bone (35). It is likely that estradiol is the primary ovarian steroid maintaining bone health, whereas in exercising women with luteal phase abnormalities, BMD and biochemical markers of bone turnover are unaffected (36). However, in recent studies there has been no significant difference in bone turnover markers among amenorrheic and eumenorrheic athletes and controls (24, 37). In pubertal children there is a significant negative correlation between the serum concentration of estrogen and bone turnover markers (23, 31). Biochemical markers of bone turnover have large diurnal and seasonal variation (38 – 40). Therefore, the sampling time is crucial for the interpretation of the results, and understandably the single measurements may be misleading. In

BONE TURNOVER AND BONE ACQUISITION

the present study the samples were collected at the same time of the morning and at the same early follicular phase of the menstrual cycle. To avoid seasonal variation we used only samples collected in the winter. The effect of physical activity on bone turnover markers in the growing skeleton has been poorly studied. Bass et al. reported that prepubertal gymnasts had significantly lower serum concentrations of OC and BAP than did sedentary controls (9). In our opinion this may have been due to delayed growth in regard to strenuous exercise. Our results for peripubertal girls are in line with the recent study by NickolsRichardson et al. (20), who did not find differences in turnover markers between female gymnasts and controls aged 8 –13 yr. Instead, short exercise trials have been shown to increase serum concentrations of formation markers, particularly OC (16, 19, 41). There have been several attempts to evaluate the influence of exercise on the bone turnover of adult athletes, but the results have remained conflicting (18, 42– 44). The present study is particularly important because it examines and establishes certain effects of common physical activities on health in adolescent girls. Our results confirm that participation in physical exercise remarkably affects BMD. Cross-sectional comparisons cannot establish a causal relationship between exercise and bone density, because selfselection may confound athlete-control studies. Thus, this 1-yr follow-up study is especially valuable; peripubertal female gymnasts have greater increases in BMD of both the femoral neck and the greater trochanter than runners or controls. This adds considerable support to the argument that high impact mechanical loading is indeed responsible for the differences in BMD, not selection bias. The biochemical markers reflect the status of overall skeletal health and not of a particular site as does dual energy x-ray absorptiometry. High bone turnover is associated with the high annual bone gain in peripubertal girls. High impact mechanical loading during the peripubertal years is apparently extremely important and beneficial, particularly for the acquisition of BMD of the femoral neck. An important question remains: are osteoporotic fractures in senescence reduced by increasing the magnitude of high impact exercise during peripubertal years? Therefore, it is important to conduct long-term follow-up studies to explain whether the beneficial effect of physical activity on bone accumulation is sustained. References 1. Cummings SR, Black DM, Nevitt MC, et al. 1993 Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet. 341:72–75. 2. Grimston SK, Willows ND, Hanley DA. 1993 Mechanical loading regime and its relationship to bone mineral density in children. Med Sci Sports Exerc. 25:1203–1210. 3. Fehling PC, Alekel L, Clasey J, Rector A, Stillman RJ. 1995 A comparison of bone mineral densities among female athletes in impact loading and active loading sports. Bone. 17:205–210. 4. Heinonen A, Oja P, Kannus P, et al. 1995 Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone. 17:197–203. 5. Robinson TL, Snow Harter C, Taaffe DR, Gillis D, Shaw J, Marcus R. 1995 Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea. J Bone Miner Res. 10:26 –35. 6. Dyson K, Blimkie CJ, Davison KS, Webber CE, Adachi JD. 1997 Gymnastic training and bone density in pre-adolescent females. Med Sci Sports Exerc. 29:443– 450.

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