overweight in childhood and bone density and size in adulthood

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1 23 Osteoporosis International With other metabolic bone diseases ISSN 0937-941X Volume 23 Number 4 Osteoporos Int (2012) 23:1453-1461 DOI 10.1007/s00198-011-1737-4 Overweight in childhood and bone density and size in adulthood K. Uusi-Rasi, M. Laaksonen, V. Mikkilä, S. Tolonen, O. T. Raitakari, J. Viikari, T. Lehtimäki, M. Kähönen & H. Sievänen

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Osteoporosis InternationalWith other metabolic bone diseases ISSN 0937-941XVolume 23Number 4 Osteoporos Int (2012) 23:1453-1461DOI 10.1007/s00198-011-1737-4

Overweight in childhood and bone densityand size in adulthood

K. Uusi-Rasi, M. Laaksonen, V. Mikkilä,S. Tolonen, O. T. Raitakari, J. Viikari,T. Lehtimäki, M. Kähönen & H. Sievänen

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ORIGINAL ARTICLE

Overweight in childhood and bone density and sizein adulthood

K. Uusi-Rasi & M. Laaksonen & V. Mikkilä & S. Tolonen &

O. T. Raitakari & J. Viikari & T. Lehtimäki &M. Kähönen & H. Sievänen

Received: 4 February 2011 /Accepted: 23 June 2011 /Published online: 18 August 2011# International Osteoporosis Foundation and National Osteoporosis Foundation 2011

AbstractSummary We evaluated the adult bone structural traits inrelation to childhood overweight in 832 men and women.Childhood overweight was associated with larger cross-sections at long bones in both sexes. Excess weight inchildhood may also lead to higher trabecular density infemales and somewhat lower cortical density in men.Introduction Excess body weight in childhood may imposemore loading on growing skeleton and thus lead to morerobust structure in adulthood.Methods This prospective cohort study evaluated the adultbone structural traits in relation to childhood overweight in asubgroup of 456 women and 376 men from the population-based cohort of Cardiovascular Risks in Young Finns Study.

Between-group differences were evaluated with analysis ofcovariance.Results According to established body mass index (BMI)criterion at the age of 12 years, 31 women and 34 men wereclassified overweight in childhood. At the mean age (SD)of 36.1 (2.7) years, total cross-sectional (ToA) and corticalarea (CoA) at the distal and shaft sites and cortical (shaftCoD) and trabecular (distal TrD) bone density of thenonweight-bearing radius and weight-bearing tibia wereevaluated with pQCT. Despite being taller in adolescence,the adult body height of overweight children was similar. Inboth sexes, childhood overweight was consistently associ-ated with 5–10% larger ToA at all bone sites measured inadulthood. CoA did not show such a consistent pattern.

K. Uusi-Rasi (*) :H. SievänenThe UKK Institute for Health Promotion Research,P.O. Box 30, 33501 Tampere, Finlande-mail: [email protected]

K. Uusi-RasiResearch Department of Tampere University Hospital,Tampere, Finland

M. Laaksonen :V. Mikkilä : S. TolonenDepartment of Food and Environmental Sciences,University of Helsinki,Helsinki, Finland

O. T. RaitakariResearch Centre of Applied and PreventiveCardiovascular Medicine,University of Turku,Turku, Finland

O. T. RaitakariDepartment of Clinical Physiology,University Hospital,Turku, Finland

J. ViikariDepartment of Medicine,University of Turku and University Hospital,Turku, Finland

T. LehtimäkiDepartment of Clinical Chemistry,Tampere, University Hospital,Tampere, Finland

M. KähönenDepartment of Clinical Physiology,Tampere University Hospital,Tampere, Finland

T. Lehtimäki :M. KähönenUniversity of Tampere Medical School,Tampere, Finland

Osteoporos Int (2012) 23:1453–1461DOI 10.1007/s00198-011-1737-4

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Women, who were overweight in childhood, had ~5%denser TrD with no difference in CoD. In contrast, TrD inmen who were overweight in childhood was not differentbut their CoD was ~1% lower.Conclusions Childhood overweight was consistently asso-ciated with larger long bone cross-sections in both sexes.Excess weight in childhood may also lead to highertrabecular density in women and somewhat lower corticaldensity in men. Specific mechanisms underlying theseassociations are not known.

Keywords Body weight . bone strength . childhoodoverweight . cortical density . trabecular density

Introduction

Influence of childhood obesity on bone mineral accrual andsubsequent adult bone mass is not yet established. Somestudies have indicated that obese and overweight childrenhave normal or increased bone mass [1–3], but others havesuggested even lower bone mass for a given weight [4–7].Overweight children may also be susceptible to fragilityfractures [8–10]. Apparently, these contradictory findings inbone mass may at least partly be explained by the commonuse of dual-energy X-ray absorptiometry (DXA) in thesestudies. DXA assumes inherently that the body comprisestwo absorptiometrically disparate tissue components: ho-mogenous soft tissue representing the mix of all non-bonetissues (mainly muscle and adipose tissues) and bone tissue.Obviously this is not true in actual in vivo DXA scans andconsequently the violation of the two-component assump-tion can render the individual results inaccurate [11, 12].

Using quantitative computed tomography (QCT), a methodwhich does not make the above assumptions being thus freefrom inaccuracies inherent in DXA, Gilsanz et al. [13] foundthat body weight was the primary determinant of the femoralmidshaft total cross-sectional and cortical area in children. Inline with these findings, Ducher et al. observed withperipheral QCT (pQCT) that overweight prepubertal boysand girls had more bone mass, bigger bones and higher bonedensity both at the weight-bearing and nonweight-bearingbones than their healthy-weight peers [14]. Adulthood obesity,in turn, is associated with increased bone mass and strength inabsolute terms, but the bone traits appear to scale rather withlean (muscle) mass than body weight or fat mass [15].

Quite logically, thinness in adolescence is associatedwith low bone mass in adulthood [16], whereas obese adultwomen, who have been overweight since childhood, seemto have somewhat denser trabecular bone compared withtheir similarly obese counterparts, who had gained excessweight in adulthood [17]. To elaborate further the influenceof childhood overweight on bone structural traits in

adulthood, data from a population-based prospective cohortof the Young Finns Study was employed. Since the pubertalgrowth period provides the optimal time for bone accrual[18] and the excess body weight imposes proportionallymore load on the weight-bearing skeleton in similarlymoving individuals, we hypothesized that those personswho were overweight in childhood would have more robustbones in adulthood.

Methods

The Cardiovascular Risk in Young Finns Study is an ongoingmulti-centre follow-up of atherosclerosis risk factors foryoung Finns, started in 1980 [19]. The participants wererandomly selected from the national population register andthe baseline survey comprised 3,596 children and adoles-cents aged 3, 6, 9, 12, 15 and 18 years. Between the years1980 and 1992, these age cohorts were assessed in 3-yearintervals. Later, the surveys were performed in 2001 and2007, when the participants were aged 30–45 years.

Participants

In 2008, all subjects in the register of the Young Finns Study(n=3,386) received an invitation to pQCT measurements[20]. Altogether, 1,884 subjects (1,058 women and 826 men)were willing to participate and attended the measurementsorganized in five different study centers (Turku, Helsinki,Tampere, Oulu and Kuopio) between February and Decem-ber 2008. In each center, similarly trained technologistsperformed the measurements with the same pQCT device.The long-term performance of the pQCT scanner wasassessed by daily phantom measurements, which showedno significant drift in the density levels during the study. Inorder to compare adulthood differences in bone traits interms of being overweight in childhood, we collectedchildhood weight data from those follow-up surveys in 80’swhen the participants turned to 12 years of age.

Participants gave their written informed consent, and thestudy protocol was approved by the local ethics committeesof the participating universities and complied with nationallegislation.

A total of 832 participants (456 women and 376 men)with pQCT measurements and body weight data at the ageof 12 available were divided into healthy weight andoverweight groups by body mass index (BMI at the age of12.5 years) according to the scheme by Cole et al. [21]: thecut-off points were 22.14 for females and 21.56 for males.Height and weight were measured at each time point, andthree skinfolds (subscapularis, triceps and biceps) weremeasured in childhood. Body fat content (fat-%) wasestimated by skinfold measurements [22]. Information of

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health, injuries, medication, diseases, diet, lifestyle factors,such as physical activity, smoking and consumption ofalcohol were obtained in a questionnaire. In addition, thewomen were asked the age of menarche, menstrual statusand number of deliveries.

Diet

The consumption of milk and milk products was assessedwith a dietary questionnaire on habitual eating behaviorsand food choices assessed at each follow-up time point. Thequestionnaire included always questions on the habitualamount of milk consumed (glasses/day) and the frequencyof consumption of cheese, sour milk products (buttermilk,sour whole milk, yoghurt and curd cheese) and ice cream.On the basis of questionnaire data, we calculated an indexof each participant’s habitual consumption of milk and milkproducts [23].

Physical activity

Physical activity was assessed by a short questionnaire at eachmeasurement point. Index of physical activity (PAI) wasestimated based on questions about intensity, frequency, timeper week, duration of each session and participating insupervised exercise [24]. In addition, adulthood physicalactivity was estimated in multiples of resting metabolic rate(MET) hours per week during leisure physical activities withand without commuting.

Bone mass and structure

The radius of the non-dominant arm and left tibia weremeasured with pQCT (XCT 2000R, Stratec, Medizintechnik,Pforzheim, Germany). The tomographic slices were takenfrom the shaft (a cortical-rich bone site) and distal part (atrabecular-rich bone site) of the weight-bearing tibia (30% and5% from the distal endplate of the tibia, respectively), and ofthe nonweight-bearing radius (30% and 4% from the distalendplate of the radius, respectively) according to our standardprocedures [25]. For the shaft regions, the analyzed bonetraits were total area (ToA, mm2), cortical area (CoA, mm2),cortical density (CoD, mg/cm3) and stress strain index(SSI, mm3), which represents bone strength againsttorsional loading. For the distal parts of the radius andtibia, the measured bone traits were ToA, CoA, trabeculardensity (TrD, mg/cm3), and bone strength index (BSI,mg2/cm4), which represents bone strength against com-pressive loading. BSI was calculated as a product of thetotal density squared and total cross-sectional area [26].The range of in vivo precision of the used pQCT-measuredtraits was from 0.5% (CoD of the radial shaft) to 4.4%(CoA of the distal radius) [20].

Statistical analyses

Mean and standard deviations (SD) were used as descriptivestatistics. Between-group differences were evaluated by ananalysis of covariance (ANCOVA) using adult body height,age at the time of pQCT measurements, and age at menarche(for females) as covariates. All analyses were done separatelyfor men and women because of the well-known effect ofestrogen on some bone traits [27, 28].

Results

Anthropometric characteristics in childhood and adulthoodare shown in Table 1 and absolute bone values in adulthoodare given separately for women and men in Table 2. Of 456women and 376 men, 31 women (6.8%) and 34 men (9.0%)were overweight at the age of 12 years. The mean skinfoldthickness among overweight boys and girls was more than50% greater indicating a substantially greater amount ofsubcutaneous fat tissue compared with their healthy weightcounterparts. For boys, the mean body fat-% was 14.0% inthe healthy weight group and 29.0% in the overweighgroup (p<0.001). For girls, the respective values were18.5% and 28.9% (p<0.001). The age of menarche was11.9 (1.3) years among overweight girls and 12.7 (1.3)years among healthy-weight girls (p<0.001). Overweight12-year-old girls and boys were not only heavier, but alsotaller, with the mean difference in height being about 6 cm(p<0.001). However, the initial height difference nearlydisappeared later in life being no more than 1–2 cm inadulthood (Table 1). More important, those who wereoverweight in childhood were more likely to remainoverweight in adulthood. Only four (13%) women and four(12%) men, who were overweight at the age of 12, werehealthy weight (i.e., BMI<25) in adulthood. On the otherhand, 43% of healthy weight girls and 60% of healthyweight boys in childhood had become overweight or obesein adulthood at the latest follow-up. There were nosignificant between-group differences in physical activityin childhood (p=0.63 for girls and 0.23 for boys) or inadulthood in either sex (p=0.66 for women and 0.32 formen). There was also no between-group difference in theuse of milk products throughout the study (p=0.25–0.87)(Table 1).

Observed bone characteristics are given in Table 2.Childhood overweight was associated with larger ToA inadulthood at both bone sites of the radius and tibia in bothsexes. Overweight women had larger CoA the distal tibiaexcluded, whereas in men only tibial shaft CoA differed(Figs. 1 and 2). In women, the greater body weight in earlyadolescence predicted denser trabecular but similar corticalbone density in adulthood. At the distal tibia, the difference

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was 5.7% (0.7–10.7%, p=0.025) (Fig. 2a), whereas themean 4.5% (−0.7% to 9.6%, p=0.09) difference in distalradius TrD did not reach statistical significance (Fig. 1a). Inmen, the greater body weight in early adolescence was notassociated with trabecular density at all but predicted 0.9%(0.2–1.6%, p=0.008) and 1.1% (0.5–1.8%, p=0.001) lowercortical density at the radius and tibia in adulthood,respectively (Figs. 1b and 2b).

Overweight in childhood predicted also strongerbones (BSI for distal sites and SSI for diaphyseal sites)in adulthood. At the radius, mean differences in womenwere 11.2% (1.2–21.9%, p=0.023) for the distal radiusBSI and 11.4% (4.7–18.3%, p<0.001) for the radial shaftSSI. At the tibia, the mean differences were 11.2% (2.3–20.8%, p=0.014) for the distal tibia BSI and 14.3% (7.9–21.1%, p<0.001) for the tibial shaft SSI (Fig. 2a). In menthere was no significant between-group difference in BSIat the distal sites, but the greater childhood body mass waspositively associated with SSI at the tibial and radialand shafts the mean differences being 11.7% (6.2–17.8%,

p<0.001) and 8.6% (1.9–16.1%, p=0.002), respectively(Figs. 1b and 2b).

Discussion

The main finding of this study was that overweight inchildhood was consistently associated with greater bonecross-sectional area both in men and women. In addition, astriking sex-specific difference in bone density was observed.In adult women, childhood overweight was associated withabout 5% higher trabecular density at the distal radius andtibia, but not at all in men. Cortical density, in turn, was similarin adult women, regardless of whether she was overweight orhealthy weight in childhood, whereas in men who wereoverweight in childhood had slightly lower cortical density atthe radial and tibial shafts. It should be noted that thedifference in some bone traits became somewhat greater ifthose who gained excess weight in adulthood were excludedand only those who apparently had been healthy weight over

Table 1 Background characteristics of the study groups according to overweight in childhood, mean (SD)

Women (n=456) Men (n=376)

Childhood overweight No (n=425) Yes (n=31) No (n=342) Yes (n=34)

At the age of 12

Height (cm) 154.3 (7.4) 160.5 (5.1) 152.9 (7.8) 158.3 (7.7)

Weight (kg) 42.8 (7.2) 62.4 (6.5) 41.1 (6.7) 58.7 (8.2)

Sum of three skinfolds (mm) 30.4 (10.8) 46.6 (17.1) 19.9 (6.6) 34.5 (13.0)

Body fat (%)a 18.5 (5.0) 28.9 (2.4) 14.0 (4.9) 29.0 (6.9)

BMI (Cole, 12.5 years) 17.9 (2.0) 24.1 (1.6) 17.5 (1.7) 23.31 (1.9)

Menarche (years) 12.7 (1.3) 11.9 (1.3) – –

PAIb 8.8 (1.4) 8.6 (1.0) 9.6 (1.6) 9.1 (1.2)

Milk indexc (portions/day) 4.4 (1.9) 4.5 (1.8) 4.9 (2.0) 5.1 (2.1)

In adulthood

Age (years) 36.3 (2.7) 36.4 (2.8) 36.0 (2.7) 35.6 (3.2)

Height (cm) 166.0 (6.0) 168.2 (6.5) 180.2 (6.7) 181.0 (5.9)

Weight (kg) 69.2 (13.0) 90.5 (19.1) 84.5 (13.1) 104.8 (19.7)

BMI 25.1 (4.6) 31.9 (6.2) 26.0 (3.5) 31.9 (5.1)

Ever use hormonal contraceptives [n (%)] 384 (96.5) 28 (90.3) – –

Parity [n (%)] 328 (71.9) 22 (71.0) – –

Number of deliveries (n) 1.8 (1.4) 1.7 (1.5) – –

PAIb 9.0 (1.8) 8.9 (1.5) 8.8 (1.8) 8.5 (2.6)

MET-h/weekd as adult (leisure) 14.1 (15.4) 10.2 (9.5) 15.6 (17.2) 17.6 (20.9)

MET-h/weekd as adult (leisure + commuting) 19.9 (21.5) 21.7 (29.6) 19.1 (20.1) 22.9 (26.9)

Milk index,c portions/day 2.6 (1.5) 2.9 (1.5) 3.3 (2.2) 3.8 (2.1)

a Equation for girls = 1.33 (triceps + subscapular)−0.013(triceps + subscapular)2 −2.5; equation for boys=1.21 (triceps + subscapular)−0.008(triceps + subscapular)2 −3.4 (Slaughter et al. [22])bPAI physical activity index (range 5–14)cMilk index = habitual consumption of milk productsdMET metabolic equivalent in physical activity (1 MET=1 kcal/body weight in1 h)

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the life were compared with those who were overweightalready in childhood (data not shown). In other words,inclusion of those who gained weight in adulthood, as wasdone in the present study, slightly diminished the groupdifferences, especially in bone traits related to cortical density.

Obesity is known to accelerate growth in children [6,14], and the individual potential in height gain may beexploited earlier and possibly more efficiently. However,the initial difference in height may gradually decline duringpuberty, and the final mean adult height between over-weight and healthy weight people may not differ. Thepresent finding of equal height in adulthood is congruentwith an earlier paper [29], but contradictory to our recentfinding in premenopausal obese women [17]. However,besides being based on self-reported data of childhoodobesity the sample size of the earlier study was smallmaking the finding prone to chance [17]. Regarding bonegrowth, however, a more important factor may be thatoverweight children enter puberty at younger age than theirhealthy weight counterparts. Besides body height, earlymenarche may have positive influence on bone mineralmass accrual compared with girls who enter menarche later[30, 31]. Recent reports suggest that pubertal timing alsoplays a similar role in men [32, 33]. In the present study, the

overweight girls had their first menstruation nearly 1 yearearlier than the healthy weight girls. For boys the maturitycould not be defined as exactly, but overweight boys werealso taller than healthy weight boys in the year they turned12. However, by the time of adulthood the mean 6-cmheight benefit evident in early adolescence was virtuallyscaled down to 1–2 cm in both sexes.

The participants of the present study, young adults in their30s at the time of bone measurements, turned to 12 years oldin 1980s. In those days, children’s habitual leisure physicalactivity was generally higher due to frequent outdoor gamesand it was also more common to walk or cycle to school [34].This may partly explain the similar mean physical activityindex at each time point throughout the follow-up timeamong healthy weight and overweight groups. Besidesphysical activity, calcium is another important factor forappropriate bone accrual. Over the follow-up time, the use ofmilk products that provide about 80% of the calcium inFinnish diet [35], was abundant and did not differ betweenthe groups suggesting sufficient calcium intake.

The apparent fact that overweight children were equallyphysically active to their healthy weight peers duringchildhood, and received thus proportionally greater loadingstimulus, may have accounted for their consistently larger

Table 2 Absolute bone values at the trabecular-rich distal sites and cortical-rich shaft sites of the radius and tibia according to overweight inchildhood, mean (SD)

Women (n=456) Men (n=376)

Childhood overweight No (n=425) Yes (n=31) No (n=342) Yes (n=34)

Distal radius

ToA (mm2) 308.3 (43.2) 331.1 (45.1) 418.3 (66.8) 438.5 (56.6)

CoA (mm2) 70.2 (10.0) 75.2 (9.4) 101.8 (15.8) 101.4 (17.4)

TrD (mg/cm3) 207.8 (28.1) 218.3 (32.7) 251.0 (30.2) 249.0 (31.6)

BSI (g2/cm4) 0.32 (0.08) 0.36 (0.08) 0.57 (0.13) 0.58 (0.14)

Radial shaft

ToA (mm2) 92.1 (12.8) 103.9 (17.4) 138.9 (20.3) 147.4 (19.4)

CoA (mm2) 74.5 (7.7) 81.2 (10.3) 108.7 (13.3) 112.8 (13.4)

CoD (mg/cm3) 1,211.7 (20.5) 1,209.2 (15.6) 1,181.8 (20.8) 1,171.7 (31.7)

SSI (mm3) 202.3 (36.2) 232.1 (50.1) 345.5 (68.3) 375.2 (67.8)

Distal tibia

ToA (mm2) 805.3 (99.4) 879.7 (129.9) 988.6 (139.1) 1068.4 (137.7)

CoA (mm2) 142.1 (22.1) 149.4 (26.1) 197.3 (34.4) 201.0 (30.5)

TrD (mg/cm3) 229.7 (29.2) 246.2 (35.4) 258.2 (32.6) 255.8 (31.4)

BSI (g2/cm4) 0.85 (0.19) 0.98 (0.25) 1.30 (0.30) 1.35 (0.29)

Tibial shaft

ToA (mm2) 339.7 (42.0) 381.5 (43.0) 434.5 (51.7) 477.6 (63.6)

CoA (mm2) 246.8 (30.1) 273.5 (28.8) 320.8 (41.9) 347.1 (47.8)

CoD (mg/cm3) 1,169.5 (20.0) 1,162.5 (17.6) 1,146.8 (21.0) 1,134.2 (30.0)

SSI (mm3) 1,293.7 (225.6) 1,525.4 (250.9) 1,827.0 (315.7) 2,063.1 (379.7)

ToA total area, CoA cortical area, TrD trabecular density, CoD cortical density, BSI bone strength index, SSI stress strain index

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bone cross-sections in adulthood. In particular, the totalcross-sectional area of the long bone epiphysis of canincrease substantially only during the growing years [36].However, bearing a greater body weight seems not to be theonly explanation, since there was no difference between theweight-bearing tibia and the nonweight-bearing radius. Inwomen, the childhood overweight associated differences weresurprisingly similar being about 7% for both epiphyseal sitesand 10% for both diaphyseal sites. In physically stronger men,these differences were somewhat greater for the tibial sitesthan for the radial sites. Several studies suggest that lean mass(~muscle mass) is the most important predictor of bone massand strength [7, 15, 37–40].

Functionally, the most relevant property of bone is not itsmass, but its mechanical competence in terms of prevalent

loading. Accordingly, long bones are stiff to provide adequatelever arms for muscle contractions and strong enough to bear alocomotive loading without a risk of failure [41]. It has beenshown in several pQCT studies that overweight children havewider bones and greater absolute bone strength comparedwith healthy weight children [13, 38, 39, 42]. In addition, thetotal cross-sectional area of the tibia was found to enlargemore among overweight children than healthy weightchildren, and this change was associated with greater musclearea of overweight children [38]. Also, Gilsanz et al. [13]suggested with QCT that body weight was the primarydeterminant of the total cross-sectional area and the corticalbone area of the femoral midshaft in healthy prepubertalchildren in both sexes. All of the above findings support thenotion that childhood overweight results in larger and

a) Mean difference (95% CI) compared with healthy weight females

-10%

-5%

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25%

ToA CoA TrD BSI

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b) Mean difference (95% CI) compared with healthy weight males

ToA CoA TrD BSI

ToA CoA CoD SSI

ToA CoA CoD SSI

Distal tibia Tibial shaft

Distal tibia Tibial shaft

Fig. 2 Height-adjusted mean and 95% confidence intervals of thegroup differences (%) in bone traits at the tibia in women (a) and inmen (b) who were overweight at the age of 12 years (ToA total area,CoA cortical area, TrD trabecular density, BSI bone strength index, SSIstress strain index, CoD cortical density). The results are adjusted foradult height, age at the time of pQCT measurements, and age atmenarche (women). The reference line (0%) represents the mean levelof the healthy weight group in childhood

ToA CoA CoD SSI

ToA CoA CoD SSI

a) Mean difference (95% CI) compared with healthy weight females

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Distal radius Radial shaft

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b) Mean difference (95% CI) compared with healthy weight males

ToA CoA TrD BSI

Distal radius Radial shaft

ToA CoA CoD SSI

ToA CoA CoD SSI

Fig. 1 Mean and 95% confidence intervals of the group differences(%) in bone traits at the radius in women (a) and in men (b) who wereoverweight at the age of 12 years (ToA total area, CoA cortical area,TrD trabecular density, BSI bone strength index, SSI stress strainindex, CoD cortical density). The results are adjusted for adult height,age at the time of pQCT-measurements, and age at menarche (women).The reference line (0%) represents the mean level of the healthy-weight group in childhood

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stronger bones, and as the present study indicates, thesedifferences are maintained until adulthood.

In the present study, childhood overweight was associatedwith bone density in adulthood. However, in healthyprepubertal children, both trabecular and cortical bonedensities have been reported to be similar irrespective of theirbody weights [13]. Likewise, a Canadian study [38] did notfind any difference in cortical density between healthyweight and overweight boys and girls. Obviously, theinfluence of age on the relationship between bone densityand body weight is not a straightforward issue. In adulthood,trabecular bone density was about 5% higher in women whowere overweight in childhood, whereas in men such abeneficial association was not indicated. In contrast, over-weight in boyhood predicted somewhat lower cortical densityin manhood. In a recent study of 7- to 19-year-old boys andgirls divided into thirds by their body fat, the intermediatetertile had 3% higher cortical density at the radial shaft thanthe low tertile adjusted for lean body mass, maturity, calciumintake and physical activity [43]. Unfortunately, boys andgirls were analyzed together making it impossible to assesswhether the difference was more pronounced among boys, asthe present study indicates.

In general, premenopausal women have higher corticaldensity than men [27, 28], which was also confirmed in thisstudy. It has been suggested that premenopausal femaleskeleton restores bone mineral for the development of fetusduring pregnancy and lactation after delivery [44, 45], andfor this reason fertile-aged women have more bone massrelative to their mechanical needs than men [45]. Estrogenhas also a stronger association with cortical density thanphysical activity but not with trabecular density [46].Adipose tissue acts as a source of aromatase enzymes thatconvert estrogen and might thus enhance the effect ofestrogen on bone [47]. In children, estradiol level has beenreported to be similar in obese and healthy weight boys andgirls [6, 48]. However, in adult women, several factors, suchas the use of hormonal contraceptives, number of deliveriesor breast-feeding, may confound the influence of adiposetissue on bone traits, but there were no significant groupdifferences in these factors in the present study. On the otherhand, it remains unclear, why the childhood obesity was notpositively associated with trabecular density in men, as wasthe apparent case in women. One explanation could pertainto sex-specific hormonal differences that are differentlyassociated with body and skeletal development [49].

The greatest strength of the present study is the largepopulation-based cohort of adult men and women, and the useof pQCT for bone assessments, which allowed specificevaluation of bone geometry and separation of trabecularand cortical densities without inherent limitations of DXAarising from the two-component assumption [11, 12]. Thisstudy also has limitations, the biggest one being the cross-

sectional design: bone measurements were done only inadulthood, and we do not have any information aboutgrowing bones, and cannot show any temporal and poten-tially causal relationships. However, a recent study suggeststhat young girls with low bone mass also are prone to lowbone mass in young adulthood the heritability accountingmore for bone mass than soft tissue [50]. Moreover, physicalfitness and muscle strength were not measured, and we couldnot assess the influence of exercise loading on bones.

For the assessment of childhood obesity, the participantswere divided into healthy weight and overweight groups at12 years of age. This was considered a reasonable age pointfor the division since the growing skeleton is sensitive andhighly responsive to loading [18]. Girls have peak bonemineral accrual after peak height velocity approximately atthe age of 12 [51]. Although boys mature later, we decidedto use the same age criterion for boys, since in the presentsurvey height and weight were measured in 3-yearintervals. At the age of 15 years, boys would also haveclearly crossed the age of peak height velocity and peakbone mineral accumulation [51].

In conclusion, body weight in early adolescence modulatesbone phenotype in adulthood. In particular, childhood over-weight was consistently associated with larger cross-sectionsat long bone diaphyseal and epiphyseal sites in both sexes.Also, excess weight in childhood may contribute to highertrabecular density in women and somewhat lower corticaldensity in men. Obviously, there are several direct and indirectfactors affecting bone growth, and the underlying mechanismsbetween body weight and bone involve contributions of bodycomposition, various hormones, neuronal inputs, loading oringested nutrients. Exact physiological mechanisms thataccount for these differences need further studies.

Acknowledgements The Young Finns Study has been financiallysupported by the Academy of Finland (grants no. 117797, 126925,121584, 117941), the Social Insurance Institution of Finland, theTurku University Foundation, the Finnish Cultural Foundation, theYrjö Jahnsson Foundation, the Emil Aaltonen Foundation (TL),Competitive Research Funding of Tampere University Hospital (grant9M048), Turku University Central Hospital Medical Fund, the JuhoVainio Foundation, and the Finnish Foundation for CardiovascularResearch and Tampere Tuberculosis Foundation.

Conflicts of interest None.

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