Bone 55 (2013) 16–22

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Original Full Length Article

3-year follow-up results of bone mineral content and density after aschool-based physical activity randomized intervention trial☆,☆☆

Ursina Meyer a,b,c,⁎, Dominique Ernst a,b, Lukas Zahner d, Christian Schindler a,b, Jardena J. Puder e,Marius Kraenzlin f, René Rizzoli g, Susi Kriemler a,b

a Swiss Tropical and Public Health Institute, 4053 Basel, Switzerlandb University of Basel, 4000 Basel, Switzerlandc Department of Human Movement Science, Maastricht University, 6229 ER Maastricht, The Netherlandsd Institute of Exercise and Health Sciences, University of Basel, 4052 Basel, Switzerlande Service of Endocrinology, Diabetes and Metabolism, Centre Hospitalier Universitaire Vaudoise, University of Lausanne, 1011 Lausanne, Switzerlandf Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Basel, 4031 Basel, Switzerlandg Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospitals and Faculty of Medicine of Geneva, 1211 Geneva, Switzerland

☆ Funding source: This study was funded by thePMPDB-114401). They had no role in the design and co☆☆ Author disclosures: UrsinaMeyer, Dominique Ernst,

⁎ Corresponding author at: Department of Human ME-mail addresses: ursina.meyer@maastrichtuniversi

(C. Schindler), jardena.puder@chuv.ch (J.J. Puder), mari

8756-3282/$ – see front matter © 2013 Elsevier Inc. Allhttp://dx.doi.org/10.1016/j.bone.2013.03.005

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 2 October 2012Revised 7 March 2013Accepted 9 March 2013Available online 17 March 2013

Edited by: Stuart Ralston

Keywords:ExerciseMechanical loadingChildrenGrowth and developmentPhysical activity

Background: As an important modifiable lifestyle factor in osteoporosis prevention, physical activity has beenshown to positively influence bone mass accrual during growth. We have previously shown that a ninemonth general school based physical activity intervention increased bone mineral content (BMC) and density(aBMD) in primary school children. From a public health perspective, a major key issue is whether these effectspersist during adolescence. We therefore measured BMC and aBMD three years after cessation of the interven-tion to investigate whether the beneficial short-term effects persisted.Methods: All children from 28 randomly selected first and fifth grade classes (intervention group (INT): 16 classes,n = 297; control group (CON): 12 classes, n = 205)who had participated in KISS (Kinder-und Jugendsportstudie)were contacted three years after cessation of the intervention program. The intervention included daily physicaleducationwith daily impact loading activities overninemonths.Measurements included anthropometry, vigorousphysical activity (VPA) by accelerometers, and BMC/aBMD for total body, femoral neck, total hip, and lumbar spineby dual-energy X-ray absorptiometry (DXA). Sex- and age-adjusted Z-scores of BMC or aBMD at follow-up wereregressed on intervention (1 vs 0), the respective Z-score at baseline, gender, follow-up height and weight,

pubertal stage at follow-up, previous and current VPA, adjusting for clustering within schools.Results: 377 of 502 (75%) children participated in baseline DXAmeasurements and of those, 214 (57%) participatedto follow-up. At follow-up INT showed significantly higher Z-scores of BMC at total body (adjusted groupdifference: 0.157 units (0.031–0.283); p = 0.015), femoral neck (0.205 (0.007–0.402); p = 0.042) and attotal hip (0.195 (0.036 to 0.353); p = 0.016) and higher Z-scores of aBMD for total body (0.167 (0.016 to0.317); p = 0.030) compared to CON, representing 6–8% higher values for children in the INT. No differencescould be found for the remaining bone parameters. For the subpopulation with baseline VPA (n = 163), effectsizes became stronger after baseline VPA adjustment. After adjustment for baseline and current VPA (n = 101),intervention effects were no longer significant, while effect sizes remained the same as without adjustmentfor VPA.Conclusion: Beneficial effects on BMC of a nine month general physical activity intervention appeared to persistover three years. Part of the maintained effects may be explained by current physical activity.

© 2013 Elsevier Inc. All rights reserved.

Swiss Federal Office of Sports (grant number SWI05-013), the Swiss National Science Foundation (grant numbernduct of the study, collection, management, analysis and interpretation of the data. There was no industry sponsoring.Lukas Zahner, Christian Schindler, Jardena J. Puder, Rene Rizzoli,Marius Kraenzlin and Susi Kriemler have no conflicts of interest.ovement Science, Maastricht University, Universiteitssingel 50, NL-6229 ER Maastricht, The Netherlands.ty.nl (U. Meyer), dominique.ernst@unibas.ch (D. Ernst), lukas.zahner@unibas.ch (L. Zahner), christian.schindler@unibas.chus.kraenzlin@unibas.ch (M. Kraenzlin), rene.rizzoli@unige.ch (R. Rizzoli), susi.kriemler@unibas.ch (S. Kriemler).

rights reserved.

17U. Meyer et al. / Bone 55 (2013) 16–22

Introduction

There is growing evidence that osteoporosis has some origins inchildhood. Assuming that 60% of the risk of osteoporosis can beexplained by the amount of bone mass accrued by early adulthood[1], maximizing peak bone mass might be an important goal for theprevention of osteoporosis [2]. Although 60 to 80% of peak bonemass variance is explained by genetic factors [3–5], physical exercisebefore the end of growth has been shown to be a relevant behavioraland modifiable determinant of bone mass for children of both gendersand during different stages of puberty [2,6–8].

Results from physical activity interventions in children aimed atincreasing bonemasswere effective in increasing bonemineral content(BMC) and bone strength in the range of 1 to 8% [2,7,9]. While most ofthe existing intervention studies used targeted designs including de-fined jumping activities [10,11], we applied a general school basedphysical activity intervention over nine months to improve overallhealth of the children. While the aim to increase bone mass wasattained [12], the program also positively affected cardiovascular andpsychological health in these children [13].

Even though immediate data after the intervention were promising[12], the major key from a public health perspective is whether theseeffects persist over extended time periods, ideally up to adulthood.Longitudinal data show that physically active children maintainedtheir higher bone mass compared to less active peers into earlyadulthood, even independently of their actual physical activitylevel [14,15]. Follow-up results from tailored jumping interventionstudies support this finding [16,17] although intervention effectsseem to wear off over time [16,17]. Yet, it remains unclear, whetherthe effects of a more general physical activity intervention not exclu-sively targeting bone healthwould also bemaintained over a prolongedperiod.

We therefore measured bone variables three years after the end ofa school-based physical activity intervention which lasted ninemonths in initially first and fifth graders to investigate whether thebeneficial intervention effects on BMC and areal bone mineral density(aBMD) are maintained.

Material and methods

Study design and study population

The design and main intervention effects of this cluster randomizedcontrolled trial were previously published [13,18]. Briefly, the studywas performed between August 2005 and July 2006 in two (Aargau,Baselland) of the 26 provinces of Switzerland comprising about 10% ofthe Swiss population. Twenty-eight out of 190 eligible 1st and 5thgrade classes were selected and randomized by school in a 4:3 ratio toan intervention (n = 16) or control arm (n = 12) on the basis of acomputer generated random number table that was in the hands of aperson not involved in the study. A higher number of interventionclasses were chosen in order to gain more experiences with the inter-vention and to reduce the costs of the trial. The three year follow-upmeasurements were also performed at school. The younger children,now in fifth grade were contacted through and tested in the respectiveschools (June 2009). The 5th graders now attending different secondaryschools/collegeswere contacted individually and testingwas done in aneasily reachable, centrally located school (August to November 2009).All testing were done during active school time and children receiveda gift voucher of their choice for 30 CHF (younger children) or 50 CHF(older children). Assessors responsible for the measurements wereblinded to group allocation for anthropometric andDXAmeasurements,but not for accelerometry. None of the children had to be excludedbecause of any disease or medication that potentially alters boneand mineral metabolism. The study was approved by the local ethicscommittees. Written informed consent was provided by at least one

parent and all children gave their assent for participation to thewhole study and specifically for the DXA measurements.

Intervention

The intervention was described in detail previously [13,18]. Duringthe intervention time of nine months, children in both groups hadthree physical education lessons (45 min each) per week given by theclassroom teacherswhich are compulsory by the Swiss law. In addition,the intervention consisted of increasing physical activity during school,school breaks and at home. Classes of the intervention group received:(1) Two additional physical education lessons per week taught by aphysical education teacher which resulted in a daily physical educationlesson. Every physical education lesson of the intervention classes wasprepared by a team of expert physical education teachers and includedat least 10 min of jumping activities. (2) Several short activity breaksduring academic lessons comprising skill-oriented tasks such asjumping on one leg, balancing on one leg, power games or coordinativetasks were done every day. About every sixth task focused on boneloading. (3) The children received daily physical activity homework ofabout 10 min duration that included aerobic, strength or motor skilltasks like tooth brushing while standing on one leg, jumping up anddown the stairs, and rope jumping. Adherence to the program was notdirectly measured, as it was ensured by the mandatory curriculumthatwas integrated in the regular school schedule in all the interventionclasses with physical education teachers that provided the additionallessons.

The programhas been shown to positively influence bone health [12]as well as physical activity, aerobic fitness, body fat, and a compositecardiovascular risk score [13]. Initially, children and parents of thecontrol group were not informed of the existence of the interventionprogram in other schools. At the time of follow-up, all children wereaware of the design of the study although the exact content of the in-tervention was not communicated. Teachers of the control groupduring the intervention knew about the intervention arm, but werenot informed about its content. Teachers at the follow-up were in-formed about the previous study but were not involved other thanallowing the children to participate to the follow-up examinationduring school-time. Due to the curriculum dependent change in theintervention classes, teachers, parents and children of the interventionschools knew about the intervention and were therefore not blinded.After the intervention period, no further intervention steps weretaken and all classes returned to the normal curriculum of three weeklyphysical education lessons.

Measurements

Identical measurements were done at baseline and follow-up aspreviously described [13,18].

Anthropometry and physical activityChildren's height and body weight were measured in T-Shirt,

shorts and barefoot. Body mass index was calculated and transformedinto age and gender specific norm values [19]. According to thesenorm values, children with a BMI Z-score above the 85th percentilewere classified as overweight [19]. Parents and children were asked torate children's pubertal stage by a questionnaire with a simple explana-tion and line drawings of the Tanner stages which has been validatedand described as reasonably accurate [20]. Pubertal stage was catego-rized as prepubertal (Tanner stage 1), early pubertal (Tanner stages 2and 3) and late pubertal (Tanner stages 4 and 5) based on breast devel-opment for girls and pubic hair for boys. Girls were asked about theirage of menarche. Calcium intake was assessed by a validated question-naire [21], adapted to the Swiss nutrition and daily calcium intake wascalculated in milligrams per day. At baseline and follow-up, physicalactivity was monitored by an accelerometer (MTI/CSA 7164/GT1M,

18 U. Meyer et al. / Bone 55 (2013) 16–22

Actigraph, Shalimar, FL, USA)whichwasworn continuously around thehip for seven days. The sampling time was set to 1 min. Based on ourpilot work and other reports [22] time periodswith over 15 min of con-tinuous zero values were considered as not worn time and discarded.Individual child's physical activity data were included if at least threeweekdays and one weekend day of measurements with a minimum of12 h for a weekday and 10 h for a weekend day were recorded. Themean physical activity was calculated by weighing weekdays andweekend days 5:2. If included participants did not have seven days ofvalid data, data from monitored days were extrapolated to theremaining week by distinguishing weekdays and weekend days. Thiswas required in about 20% of baseline and 65% of follow-up measure-ments. Physical activity was expressed as daily minutes of vigorousphysical activity (VPA) above 3000 counts min−1 [23].

Bone and body compositionBody composition and bone parameters were measured using

dual-energy X-ray absorptiometry (DXA; Hologic QDR-4500;Waltham,MA, USA) located in a truck which traveled to each school. Within onetesting period (i.e. baseline and follow-up), the same trained technicianperformed all measurements and also analyzed the scans. Bodycomposition was assessed by the three compartment model, includ-ing fat mass, bonemineral content, and bonemineral free lean tissue.Bone mineral content (BMC, g) and areal bone mineral density(aBMD, g/cm2) were determined for total body, femoral neck, totalhip, and L1–L4 vertebrae in antero-posterior view. BMC and aBMDvalues were z-transformed using age- and sex-specific reference values[24]. The coefficient of variation of repeated measurements for femur,lumbar spine and total body determined in children ranged from 1.5to 3.7% [25].

Statistical analysis

All children who at least participated in baseline and 3-yearfollow-up measurements were included into analyses as “partici-pants”. Baseline comparisons were done using a multilevel linearor logistic regression model with the original schools as random ef-fect, using participation (1 = participants vs. 0 = non-participants),group (1 = intervention vs. 0 = control group) and the interactionparticipation × group as explanatory variables. Analyses were a prioriadjusted for gender and school grade. Descriptive results are reportedon the original scale, but all analyses were done using Z-scores ofBMC and aBMD parameters based on external sex- and age-relatedreference values [24]. Long-term effects of the interventionwere testedusing a multilevel linear regression model with Z-score of BMC andaBMD at follow-up as outcome and group, gender, pubertal stage atfollow-up (Tanner stage 1 vs. Tanner stages 2 and 3 vs. Tanner stages4 and 5), height and weight at follow-up and the respective baselineZ-score of the outcome as covariates. Original schools as the randomiza-tion unitwere introduced as randomeffect.We did not include baselinepubertal stage, baseline height and weight, change in height andweight, or calcium intake, since their addition did not improve themodel based on the Akaike Information Criteria (AIC). As we havepreviously shown that pre-pubertal children benefited more fromthe intervention than their early pubertal counterparts [12], we testedin a second step, whether the interaction between group and pubertalstage at the end of the intervention modified the effects. In a thirdstep, baseline and follow-up VPA were included stepwise as additionalcovariates. We calculated effect sizes by dividing effect estimate by re-sidual standard deviation. The initial power calculation of the studywas performed for the primary outcomes (i.e. physical activity, aerobicfitness, sum of four skinfolds and quality of life) during the first year[13]. Analyses were performed using Stata version 11.0 and the levelof significance was set at p b 0.05.

Results

Participants

A flow chartwith the number of participants is given in Fig. 1. A totalof 214 corresponding to 57% of children with baseline DXA also had3-year follow-up measurements and were included into analyses asparticipants. The main reasons for non-participating were emigration(n = 32) or non-willingness to participate (n = 199). None of the par-ticipants of the original intervention schools moved to a control schoolor vice versa. Tables 1 and 2 describe characteristics of the childrenaccording to participation and group at baseline and follow-up. Partici-pating children did not differ from non-participating children for boneoutcomes, anthropometric characteristics, age, and calcium intake.However, there were significantly more females than males amongthe current participants. Participating children showed higher physicalactivity levels at baseline than their non-participating counterpartswith lower levels for intervention group children compared to therespective controls. At follow-up, there were no differences betweenintervention and control group for anthropometric characteristics,age, menarcheal status (in both groups, one third of the girls werepost-menarcheal at follow-up), calcium intake, and physical activity.Of note, the two groups did not differ for baseline and follow-upmaturityor their changes in Tanner stages between baseline and follow-up.

Intervention effects at follow-up

Table 3 shows the main results of the intervention at follow-up.Intervention children showed significantly higher BMC values forwhole body, at femoral neck and total hip compared to controls cor-responding to a difference of 6.2%, 8.1%, and 7.7%, respectively. No sta-tistically significant group differences were found for lumbar spineBMC. Children of the intervention group showed also higher adjusteddifferences at follow-up for whole body aBMD compared to controls,corresponding to a difference of 6.6%. All other parameters were notstatistically significantly different and the intra-cluster correlation co-efficients (ICC) for school were small in all analysis (ICC b 0.01).

Group differences in BMC and aBMD parameters were not signif-icantly modified by pubertal status at the end of the intervention, in-dicating maintained effects in all pubertal groups (p-values ofinteraction all > 0.25). After adjustment for baseline VPA (i.e. beforethe start of the intervention), effects at follow-up (in a subsample ofn = 163) were maintained. Adjusted differences for BMC for wholebody, at femoral neck and total hip were 0.219 (0.067 to 0.372;p = 0.004, effect size (ES) = 0.52), 0.300 (0.071 to 0.530; p = 0.010,ES = 0.47) and 0.230 (0.029 to 0.431; p = 0.025, ES = 0.41)Z-score units, respectively, and adjusted group differences in wholebody aBMD at follow-up were 0.198 (0.019 to 0.378; p = 0.030,ES = 0.40). With adjustment for baseline and current VPA (in a sub-sample of n = 101 children), none of the bone measurementsremained statistically different among groups with adjusted differ-ences for BMC for whole body of 0.169 (−0.018 to 0.356; p = 0.08,ES = 0.43), at femoral neck of 0.263 (−0.060 to 0.586; p = 0.11,ES = 0.39), at total hip of 0.257 (−0.012 to 0.526; p = 0.06,ES = 0.46), and for whole body aBMD of 0.102 (−0.106 to 0.210;p = 0.36, ES = 0.23). Effect sizes which were moderate in general,were similar with and without adjustment for baseline and follow-upVPA, but were highest with adjustment for baseline VPA only.

Discussion

Our study showed that positive nine-month intervention effects onbone mineral of a general school-based physical activity interventionin pre- and early pubertal children were partially maintained overthree years, but part of the maintained effects could be explained bythe current amount of children's physical activity. From a public health

Fig. 1. Flow sheet of participants through the study. ⁎Loss due to a technical defect of the DXA unit.

19U. Meyer et al. / Bone 55 (2013) 16–22

perspective, these data are highly relevant as our school-based inter-vention led to multiple beneficial immediate health effects on bone[12] and cardiovascular health [13]. Hence, bone mineral mass gainswere maintained over three years at an extent corresponding to adifference in BMC of 7–8% in the intervention compared to the controlgroup irrespective of pubertal stage at the end of the intervention anddespite cessation of the program.

If one considers that a 10% increase in peak bonemass is expected todelay the onset of osteoporosis by 13 years [26] and reduce osteoporoticfracture risk by up to 50% in women after menopause [27], the 7–8%higher BMC at femoral neck and total hip in our children three yearsafter cessation of our intervention may be meaningful. This beneficialeffect was notable at the site where the most severe osteoporoticfractures occur [28].

The maintenance of BMC in hip and femur in favor of the interven-tion by 8% is higher compared to the few documented long-term effectsof tailored intervention studies [16,17,29,30] that were consistentand in the range of 1.4–4.4% seven month to eight years off training

[16,17,30]. The larger effects in our study compared to those from theliterature may be related (1) to a response of bone to loading by abroader variety of directions and magnitudes due to the highlystimulus-specific adaptation [31,32]. This could have led to morecomplex structural adaptations compared to simple drop jumps,and (2) by long-term behavioral changes in the children due to anattractive program, which is supported by the maintenance of VPA asfound in our secondary analyses.

Post-intervention as well as follow-up BMC at most sites were sig-nificantly higher in the intervention than control group. Adjustmentfor baseline VPA, hence for physical activity that was done prior to theintervention, increased intervention effects in favor of the intervention.The additional adjustment for current VPA, thus for actual physicalactivity unrelated to the intervention, led to still sustained interven-tion effects, but on a lower level. Although the latter model was nolonger statistically significant due to loss of power with a samplethat was about half of the original size (n = 101 vs. n = 216) weused the beta-coefficients and effect sizes, that both quantify the

Table 1Baseline characteristics of children according to treatment arm and participation at follow-up. Values are means (SD) unless otherwise stated.

Participants Non-participants

Intervention Control Intervention Control Baseline differencesa

N Mean (SD) N Mean (SD) N Mean (SD) N Mean (SD) Ppart Pgroup Ppart ∗ group

Age (y) 149 8.8 (2.1) 65 8.8 (2.2) 148 9.6 (2.1) 140 9.2 (2.3) 0.937 0.145 0.517Height (cm) 149 133.3 (13.1) 65 134.2 (14.2) 141 137.5 (11.8) 128 136.2 (13.8) 0.168 0.874 0.2Weight (kg) 149 30.7 (8.7) 65 30.4 (9.8) 141 33.5 (9.4) 128 33 (10.3) 0.554 0.718 0.919Body mass index (kg/m2) 149 16.9 (2.2) 65 16.4 (2.4) 141 17.4 (3.0) 128 17.3 (2.6) 0.081 0.968 0.325Gender, n (%) girls 78 (52%) 40 (62%) 75 (51%) 65 (46%) 0.044 0.486 0.158Grade, n (%) 1st grade 78 (52%) 36 (55%) 54 (37%) 65 (46%) 0.258 0.562 0.513n (%) overweightb 32 (22%) 10 (15%) 33 (23%) 35 (27%) 0.064 0.468 0.207n (%) pre-pubertal 116 (78%) 52 (80%) 96 (65%) 102 (73%) 0.138 0.181 0.766Calcium intake (mg/wk) 144 5911 (2471) 62 5796 (3000) 127 6394 (3483) 101 5530 (2487) 0.444 0.116 0.238Vigorous physical activity (min/d) 111 43.1 (21.7) 49 52.2 (21.2) 110 42.8 (23.1) 103 44.8 (22.7) 0.005 0.734 0.013Bone mineral content

Total body (g) 143 732 (222) 65 750 (257) 96 818 (175) 69 898 (260) 0.752 0.002 0.325Femoral neck (g) 149 2.33 (0.77) 65 2.39 (0.78) 98 2.67 (0.64) 69 2.88 (0.76) 0.824 0.021 0.653Total hip (g) 149 14.37 (5.59) 65 14.72 (5.69) 98 16.63 (4.5) 69 18.63 (6.11) 0.569 0.006 0.199Lumbar spine (g) 148 22.26 (6.1) 65 22.99 (7.09) 97 24.8 (5.23) 69 27.44 (8.37) 0.257 0.001 0.171

Areal bone mineral densityTotal body (g/cm2) 143 0.65 (0.1) 65 0.65 (0.11) 96 0.69 (0.08) 69 0.72 (0.1) 0.771 0.002 0.28Femoral neck (g/cm2) 149 0.65 (0.09) 65 0.66 (0.1) 98 0.67 (0.08) 69 0.71 (0.1) 0.773 0.011 0.473Total hip (g/cm2) 149 0.68 (0.09) 65 0.69 (0.1) 98 0.7 (0.08) 69 0.74 (0.12) 0.727 0.011 0.211Lumbar spine (g/cm2) 148 0.59 (0.1) 65 0.6 (0.11) 97 0.62 (0.08) 69 0.65 (0.11) 0.499 0.134 0.341

a Regression or logistic regression analyses were done based on age-group and gender based Z-Scores to compare data for group, participation and group ∗ participation differencesafter adjustment for cluster (school).

b Overweight based on WHO references.

20 U. Meyer et al. / Bone 55 (2013) 16–22

intervention outcomes rather than providing only a conditionalprobability with p-values [33]. These findings suggest in accordanceto other long-term follow-ups [16,17,29,30] that maintenance ofbone mineral in favor of the intervention was present, but some ofthese sustained effects seemed also to be a consequence of continuedmechanical loading. This could also explain why the reported differencesin BMC at follow-up seem to be greater than the immediate effectsreported earlier [12]. One has to be cautious when comparing the im-mediate and long-term effects of the intervention due to a decrease insample size, the higher dropout rate of older males, or the highersport club participation at follow-up in the intervention group.

Whereas short-term effects of our intervention program showedsignificant benefits on BMC and on aBMD [12], long-term effects couldmainly be observed for BMC. The interpretation of aBMD in the growingskeleton is much more challenging than in adults. Measured by DXA,

Table 2Baseline and follow-up characteristics and their changes of children with baseline and follo

Intervention group (n = 149)

Baseline Follow-up

Mean (SD) Mean (SD)

Age (y) 8.8 (2.1) 12.7 (2.2)Height (cm) 133.3 (13.1) 155.7 (14.4)Weight (kg) 30.7 (8.7) 47.3 (13.8)Body mass index (kg/m2) 16.9 (2.2) 19.1 (2.9)Gender, n (%) girls 78 (52%)Grade, n (%) original 1st graders 78 (52%)n (%) overweighta 32 (22%) 34 (23%)

Became normal weightb

Became overweightb

Pubertal stagesc, n (%)Prepubertal 116 (78%) 42 (28%)Early pubertal 32 (21%) 50 (34%)Late pubertal 1 (1%) 56 (38%)Became pubertalb

Became late pubertalb

Calcium intake (mg/wk) 5911 (2471) 6287 (3449)Vigorous physical activity (min/d) 43.1 (21.7) 33.4 (18.5)

a Overweight based on WHO references.b Only those with a change in weight category or pubertal categories reported.c Pubertal stages are based on Tanner stages: Prepubertal (Tanner 1), early pubertal (Tan

aBMD is an areal rather than a true volumetric density. Thus, the truedepth of bone is not taken into account. In DXA scans, larger bonesproduce higher BMC and aBMD values even if they do not havehigher volumetric density [34]. This size-dependence is of particularrelevance in the three-dimensional growth of children. Consequently,bone mineral mass or content rather than density might be more suit-able to understand the effects of exercise on bone health during thegrowing years [35]. Further, it has been shown that bone area and min-eralization do not develop simultaneously [36] which further compli-cate the interpretation of aBMD. For a deeper understanding of howthe intervention effects on BMC and total body aBMDwere maintained,future studies should also include an analysis of bone structure, ratherthan only bone mineral mass. Animal studies have shown that me-chanical loading derived from weight-bearing exercise generatedincreases in bone strength without substantial increases in bone

w-up data according to treatment arm. Values are means (SD) unless otherwise stated.

Control group (n = 65)

Δ Baseline Follow-up Δ

Mean (SD) Mean (SD) Mean (SD) Mean (SD)

3.9 (0.2) 8.8 (2.2) 12.7 (2.3) 3.9 (0.2)22.5 (4.4) 134.2 (14.2) 154.9 (14.1) 20.7 (5.3)16.7 (6.6) 30.4 (9.8) 46.3 (15.4) 16 (7.4)2.2 (1.7) 16.4 (2.4) 18.7 (3.6) 2.3 (1.7)

40 (62%)36 (55%)10 (15%) 13 (20%)

9 (6%) 1 (2%)11 (7%) 4 (6%)

52 (80%) 17 (26%)10 (15%) 24 (37%)3 (5%) 24 (37%)

50 (34%) 24 (37%)55 (37%) 21 (32%)

373 (3786) 5796 (3000) 6025 (2672) −202 (3135)−9.3 (20.2) 52.2 (21.2) 33.2 (19) −20.8 (25)

ners 2 and 3), pubertal (Tanners 4 and 5).

Table 33-year follow-up effects of a nine-month physical activity intervention on bone mineral content and density. Values at baseline and follow-up are means (SD).

Variables Intervention (n = 149) Control (n = 65) Adjusted difference at follow-up⁎

Baseline Follow-up Baseline Follow-up Coefficient (95% CI) P value Effect sizes

Bone mineral contentTotal body (g) 732 (223) 1196 (458) 750 (257) 1153 (424) 0.157 (0.031 to 0.283) 0.015 0.37Femoral neck (g) 2.33 (0.77) 3.67 (1.03) 2.39 (0.78) 3.54 (0.92) 0.205 (0.007 to 0.402) 0.042 0.30Total hip (g) 14.37 (5.59) 24.98 (10.8) 14.72 (5.69) 23.53 (8.37) 0.195 (0.036 to 0.353) 0.016 0.36Lumbar spine (g) 22.26 (6.1) 39.07 (16.09) 22.99 (7.09) 37.86 (14.99) 0.107 (−0.121 to 0.335) 0.357 0.19

Areal bone mineral densityTotal body (g/cm2) 0.649 (0.096) 0.794 (0.128) 0.654 (0.109) 0.781 (0.127) 0.167 (0.016 to 0.317) 0.030 0.33Femoral neck (g/cm2) 0.647 (0.087) 0.775 (0.123) 0.659 (0.101) 0.781 (0.137) −0.019 (−0.163 to 0.126) 0.799 −0.04Total hip (g/cm2) 0.681 (0.094) 0.834 (0.149) 0.687 (0.103) 0.827 (0.144) 0.015 (−0.127 to 0.157) 0.836 0.03Lumbar spine (g/cm2) 0.588 (0.097) 0.782 (0.165) 0.596 (0.11) 0.774 (0.173) 0.079 (−0.088 to 0.247) 0.353 0.15

⁎ Adjusted difference in average Z-Score of respective outcome at follow-up between intervention and control group with 95% confidence interval and p value, adjusted for sex,grade, follow-up weight, follow-up height, pubertal stage at follow-up and Z-Score of baseline bone mineral content/density, and school as cluster.

21U. Meyer et al. / Bone 55 (2013) 16–22

mass. Importantly, these structural changes of bone persisted intoadulthood while loading-induced changes in bone mass diminishedover time [37,38].

Even if we could showmaintained intervention effects over a periodof three years post-intervention, it is still questionable if a nine monthintervention can induce sustained benefits into adulthood. Ideally,daily school-based physical activity should be provided during wholechildhood. In this regard, feasibility and adherence are highly importantpoints in the long-term implementation of such a project. To ensurecompliance of such a program, it needs to be implemented on curricularlevel and therefore governmentally supported. The Canadian projectAction Schools! BC is thereby an impressive example that this mightbe possible. The project started with a small efficacy trial in a fewschools of one province in Canada [39]. In response to the positiveresults of the intervention [40,41], the program was implementedthroughout the province with the help of the government that imposed30 min of daily physical activity in schools by law [42].

Our study has significant strengths and some potential limitations.A major strength is the well-designed randomized controlled trial in arelatively large sample of children that cover thewhole period of puberty.Since the physical activity programwas standardized and integrated intothe school curriculum, dose and compliance of the program was givenand sufficient to induce multiple immediate health effects [12,13].Despite the nature of physical activity being a highly variable behavior,the use of accelerometers allowed one to quantify loading of bonesmuch better than by the use of questionnaires. Nevertheless, measure-ment error based on validations bymetabolic rather than impact forces[43], smoothing of the single accelerations over the measurement in-terval of oneminute [43,44] or inability of themonitor to assess somerelevant activities such as weight training, should be considered. De-spite a lack of relevant baseline differences between participating andnon-participating children and adolescents, lower participation rateat follow-up with a higher dropout of older males and those with a mi-grant background and loss of baseline DXA data in the control groupdue to a technical defect, selection bias could have occurred. Yet, theoverall level of drop-out was comparable [17] or lower [30] totime-wise similar follow-ups of school-based interventions, but stilllower than long-term follow-ups of extended timewindows [16]. Finally,limitations of DXA with its two-dimensional approach in documentingaBMD have been addressed extensively [34,37,38]. This problem wasminimized by the use of sex- and age-adjusted Z-scores and the adjust-ment of the statistical models for children's body height and mass.

In conclusion, our randomized, controlled study reports sustainedeffects on BMC of total body, femoral neck and hip from a generalschool-based physical activity intervention that led to multiple im-mediate and sustained general health effects. The effects three yearsafter the intervention were independent of pubertal stage and itsevolution over the study period. However, they were influenced by

current physical activity. It still remains unclear whether mechanicalloading during the pre- and early pubertal years can induce sustainedbenefits on bone structure and mass that last into adulthood.

Acknowledgments

The authors thank the foundation AETAS, Switzerland, for the use oftheir DXA-bus and we greatly appreciate the help of Giuglio Conicella,Chantal Genet and Claude Kränzlin for their competent help in thebone measurements. Finally, we sincerely thank all children, teachersand parents for taking part in the study. We also thank the FederalCouncil of Sports, Magglingen, Switzerland (grant number SWI05-013), and the Swiss National Foundation (grant number PMPDB-114401) for the financial support of the study.

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