The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls

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1 OPEN Cittion: BoneKEy Reports 2, Article numer: 315 (213) doi:1.138/onekey & 213 Interntionl Bone & Minerl Society All rights reserved /13 ORIGINAL ARTICLE The reltionships mong totl ody ft, one minerl content nd one mrrow dipose tissue in erly-puertl girls Ann L Newton, Lyne J Hnks, Michelle Dvis nd Krist Cszz Deprtment of Nutrition Sciences, University of Alm t Birminghm, Birminghm, AL, USA. Investigtion of the physiologic relevnce of one mrrow dipose tissue (BMAT) during growth my promote understnding of the one-ft xis nd confluence with metolic fctors. The ojective of this pilot investigtion ws two-fold: (1) to evlute the reltionships mong totl ody ft, one minerl content (BMC) nd femorl BMAT during childhood nd underlying metolic determinnts nd (2) to determine if the reltionships differ y rce. Prticipnts included white nd non-hispnic lck girls (n ¼ 59) ges 4 1 yers. Femorl BMAT volume ws mesured y mgnetic resonnce imging, BMC nd ody ft y dul-energy X-ry sorptiometry. Metolic prmeters were ssessed in the fsted stte. Totl ft nd BMC were positively ssocited with BMAT; however, simultneous inclusion of BMC nd ody ft in the sttisticl model ttenuted the ssocition etween BMC nd BMAT. Differences in BMAT volume were oserved, non-hispnic lck girls exhiiting mrginlly greter BMAT t ge eight (P ¼.5) nd white girls exhiiting greter BMAT t ge ten (Po.1). Metolic prmeters conferred differentil impct y rce, such tht, positive ssocition for BMATnd leptin (P ¼.2) nd diponectin (P ¼.2) in white girls while BMATnd insulin were inversely relted in non-hispnic lck girls (P ¼.8). Our findings reveled positive reltionship etween BMAT, ody ft nd BMC, lthough ody ft, respective to leptin, contriuted prtly to the reltionship etween BMAT nd BMC. Despite lrge differences in totl ft etween non-hispnic lck nd white, the reltionship etween BMATnd BMC ws similr to white girls. However, this reltionship ppered to e impcted through different mechnisms ccording to rce. BoneKEy Reports 2, Article numer: 315 (213) doi:1.138/onekey Introduction A positive ssocition etween one minerl content (BMC) nd weight sttus hs een consistently documented. Thus, greter weight hs chrcteristiclly een recognized s protective fctor from one-relted injury. 1 However, contemporry investigtions hve reveled overrepresenttion in one frcture incidence t vrious ntomicl sites mong oese individuls, 2 4 suggesting tht ft ccrul in excess my pertur processes underlying one integrity. In essence, greter one size does not necessrily trnslte into stronger ones, 5 7 nd fctors tht my compromise one integrity wrrnt investigtion. Wheres under norml physiologic conditions, one minerl deposition nd resorption re tightly coupled, during growth, one formtion is fvored nd these developmentl (re)modeling processes ultimtely contriute to one strength. Seemingly counterintuitive, solute higher BMC with incresing ody size my not prllel enhnced properties of one uilding. 6,7 The extent to which excess diposity, during the growth period, my hve the cpcity to disrupt one (re)modeling nd long-term one helth hs not een well-descried. However, rpid growth secondry to oesity nd ssocited metolic perturtions (for exmple, hyperinsulinemi, hyperleptinemi, dyslipidemi) my lter the coupling etween one deposition nd resorption leding to imlnce in one remodeling processes (for exmple, intertreculr spce infusion t the epiphysis with lmellr one, intrcorticl porosity) This dysynchrony likely contriutes to volume of one mrrow dipose tissue (BMAT), s it hs een estlished tht the one mrrow depot is sensitive to metolic perturtions ensuing pthologicl conditions, which effect energy lnce, including metolic conditions Correspondence: Dr K Cszz, Deprtment of Nutrition Sciences, University of Alm t Birminghm, 1675 University Boulevrd, 2nd Avenue South, WEBB 439, Birminghm, AL , USA. E-mil: kristc@u.edu Received 7 Decemer 212; ccepted 21 Ferury 213; pulished online 1 April 213 BoneKEy Reports APRIL 213 1

2 Bone mrrow dipose tissue nd erly puerty AL Newton et l (for exmple type 2 dietes, oesity nd norexi nervos) Thus, the one mrrow comprtment represents unique niche providing direct interction etween one nd ft cells s it is here tht undifferentited stem cells cple of multiple linege pthwys meet their fte. 15 Investigtion including ssessment of the mrrow comprtment nd systemic interctions my provide some insight into the interreltionship etween the one-ft xis. A reciprocl reltionship exists etween the one nd dipose microenvironments, such tht energetic pthwys directed towrd the ltter verts cell linege wy from one remodeling. 16 As the foundtions of ody composition re lrgely estlished during growth nd development, with ctions of metolic fctors lrgely in ply, investigtive efforts to chrcterize one processes should e trgeted erly in the life course. In ddition, the mrrow is converted from red (hemtopoietic) to yellow (dipose) in predictle, progressive mnner such tht B1% is dipose t irth nd B9% of the mrrow is dipose t reproductive mturity. 17,18 However, it is speculted tht oesity nd relted metolic perturtions my ccelerte this conversion process. The ojective of this investigtion ws to evlute the reltionships mong totl ody ft, BMC nd BMAT during childhood, s well s underlying metolic determinnts, nd to determine if the reltionships differ y rce. Results Bseline chrcteristics. Descriptive chrcteristics of the totl smple popultion nd y rce re presented in Tle 1. Non-Hispnic lck girls were reproductively more mture likely contriuting to greter height, weight, diposity nd BMC. However, BMATws not significntly different etween groups. Metolic prmeters of the smple popultion re illustrted in Tle 2. Rce-relted differences in fsting glucose, lowdensity lipoprotein cholesterol nd prthyroid hormone (PTH) were oserved, such tht higher low-density lipoprotein cholesterol nd lower fsting glucose, nd PTH were pprent in non-hispnic lck girls compred with white girls. Additionlly, while not sttisticlly different etween rces, non- Hispnic lck girls did exhiit 25-hydroxy vitmin D levels elow tht which is considered sufficient (3 ng ml 1 ). BMAT nd ody composition correltions y ge nd rce. Figure 1 presents BMAT volume, totl ody ft nd BMC Tle 1 Descriptive chrcteristics of smple popultion Totl (n ¼ 59) Blck girls (n ¼ 25) White girls (n ¼ 34) Age (yers) 7.7±.3 8.±.4 7.5±.3 Tnner (I IV) 1.4±.1 1.8±.2 1.2±.1 Height (inches) 51.± ± ±1.1 Weight (l) 88.± ± ±5.6 Totl ft (kg) 15.2± ± ±1.3 Percent ft (%) 34.6± ± ±1.5 Totl BMC (g) 1169± ±98 113±61 BMAT (cm 3 ) 88.3± ± ±7.7 Arevitions: Blck, non-hispnic Blck; BMC, one minerl content; BMAT, one mrrow dipose tissue. Reproductive mturtion sttus I V sed on criteri of Mrshll nd Tnner. 42,43 Indictes significnt difference mong Blck nd White girls (Po.5). y ge for the totl smple. As ge incresed, progressive increse in BMAT volume, totl ody ft nd BMC ws oserved. Wheres no significnt difference ws oserved from ges four to six, nine-yer-old girls hd significntly greter Tle 2 Fsting metolic prmeters of smple popultion Totl (n ¼ 59) Blck girls (n ¼ 25) White girls (n ¼ 34) Insulin (uu ml 1 ) 8.3±.9 9.±1.6 8.±1.2 Glucose (mg dl 1 ) 91.1± ± ±1.7 Leptin (ng ml 1 ) 9.1± ± ±2.1 Triglycerides (mg dl 1 ) 69.3± ± ±6.9 HDL (mg dl 1 ) 5.8± ± ±3.8 LDL (mg dl 1 ) 82.4± ± ±4.3 Adiponectin (mcg ml 1 ) 14.1± ± ±1. PTH (pg ml 1 ) 35.1± ± ±2.3 Vitmin D (ng ml 1 ) 3.5± ± ±1.8 Arevitions: Blck, non-hispnic Blck; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; PTH, prthyroid hormone; Vitmin D,25-hydroxy vitmin D. Indictes significnt difference mong Blck nd White girls (Po.5). BMC (g) BMAT (cm 3 ) Totl Body Ft (kg) Age (yers) Age (yers) Age (yers) c c c c c Figure 1 BMAT volume, totl ody ft nd BMC y ge in smple popultion. Note:,,c denotes significnt difference (Po.5). N-vlues for ech ge group re s follows: 4 yers ¼ 6, 5 yers ¼ 6, 6 yers ¼ 7, 7 yers ¼ 6, 8 yers ¼ 1, 9 yers ¼ 14, nd 1 yers ¼ 1. 2 APRIL 213

3 Bone mrrow dipose tissue nd erly puerty AL Newton et l Totl Ft (kg) BMAT (cm 3 ) BMC (g) non-hispnic Blck White non-hispnic Blck White Age (yers) BMAT volume thn those o9 yers of ge, totl ody ft eginning t eight yers of ge, nd BMC eginning t seven yers. When ssessing differences in BMAT volume y ge, non-hispnic lck girls hd mrginlly greter BMAT t ge eight (P ¼.5), wheres white girls hd greter BMATt ge ten (Po.1; Figure 2). Additionlly, when ssessing differences in totl ft y ge, non-hispnic lck girls hd greter totl ft t ges seven, eight, nine nd ten yers thn white girls Age (yers) non-hispnic Blck White Age (yers) Figure 2 Rce differences for totl ft, BMAT volume nd BMC y ge. Note: denotes significnt differences. No BMAT dt provided for 9-yer-old non- Hispnic Blck ecuse none were present in the nlysis. N-vlues for ech ge group for non-hispnic Blck prticipnts re s follows: 4 yers ¼ 2, 5 yers ¼ 2, 6 yers ¼ 3, 7 yers ¼ 2, 8 yers ¼ 6, 9 yers ¼ nd 1 yers ¼ 4. N-vlues for ech ge group for white prticipnts re s follows: 4 yers ¼ 4, 5 yers ¼ 4, 6 yers ¼ 4, 7 yers ¼ 4, 8 yers ¼ 4, 9 yers ¼ 8 nd 1 yers ¼ 6. Independent ssocitions etween BMAT nd ody composition prmeters. The independent reltionships of BMAT with ody composition prmeters re presented in Tle 3 for the overll smple nd y rce. BMATws positively ssocited with totl ody ft (Po.5) nd BMC (Po.1). However, simultneous inclusion of totl ody ft nd BMC in the sttisticl model resulted in ttenution of the reltionship etween BMAT nd BMC, ut not totl ody ft (leit of mrginl significnce; P ¼.7). While ody ft ccounts for lrge proportion of the reltionship, our results, support t lest prtil involvement in the reltionship etween BMAT nd BMC. When nlyzed ccording to rce, the reltionship with BMAT ws mintined mong white girls for oth totl ody ft (P ¼.2) nd BMC (P ¼.1), ut only mrginlly with totl ody ft in non-hispnic lck girls (P ¼.5). Inclusion of oth totl ody ft nd BMC in the model resulted in ttenution of the reltionship etween BMC nd BMAT in white girls s it did in the overll smple; however, the reltionship etween totl ody ft nd BMAT remined significnt (Po.2). Independent ssocitions etween BMAT nd metolic prmeters. The independent ssocitions of BMAT with individul metolic prmeters, s well s the interctive effect of these ssocitions with the inclusion of totl ody ft nd BMC re presented in Tle 4. When investigting the reltionship etween BMAT nd individul metolic prmeters (tht is, insulin, leptin nd diponectin), positive ssocitions were only oserved etween BMAT nd leptin in the totl smple (P ¼.1). Additionlly, when totl ody ft ws included in the model circulting diponectin contriuted to the reltionship etween BMAT nd totl ft. However, when BMC ws included in the model the reltionship etween BMAT nd BMC ws ttenuted y leptin. When strtified y rce, mong white girls positive reltionship ws oserved for BMAT with leptin (P ¼.2), s well s with diponectin (P ¼.2), nd mrginl ssocition etween BMAT nd insulin (P ¼.7) ws oserved. However, the only oserved ssocition with metolic prmeters mong non-hispnic lck girls ws n inverse ssocition etween insulin nd BMAT (P ¼.8) when controlling for oth totl ft nd BMC. Inclusion of diponectin ttenuted the reltionship etween BMAT nd BMC, yet mong non-hispnic lck girls the reltionship etween BMAT nd BMC is mintined with the inclusion of insulin. Discussion During puerty, n understnding of the physiologicl events occurring in the one mrrow comprtment initited y interctions in the one-ft xis my provide insight into developmentl origins, which directly impct long-term skeletl helth. Norml mrrow conversion follows n orderly nd progressive mnner, in which red mrrow (predominntly comprised of hemtopoietic elements) is replced y yellow mrrow (BMAT; primrily dipogenic), such tht y erly dulthood the mrrow comprtment of the ppendiculr skeleton is comprised of virtully ll dipose tissue. 16 Accompnying the chrcteristic ccelerted tke off demrcting the liner growth spurt is significnt increse in the proportion of red mrrow to yellow mrrow. Indeed these processes re coupled, yet the mount, timing nd distriution of yellow nd red mrrow my increse in response to metolic stress. 19 Dysregultion, consequentil to ltertions in energy BoneKEy Reports APRIL 213 3

4 Bone mrrow dipose tissue nd erly puerty AL Newton et l Tle 3 The independent reltionships of BMAT nd totl ody ft nd BMC Totl ft BMC Totl ft BMC R 2 P R 2 P R 2 p P Totl (n ¼ 59) o Blck girls (n ¼ 25) White girls (n ¼ 34) Blck, non-hispnic Blck; BMC, one minerl content. Model 1: independent ssocition. Model 2: simultneous inclusion of one nd ft in sttisticl model with BMAT s dependent vrile. Vlues in old indicte significnt ssocitions. Tle 4 The independent ssocitions of BMAT with individul metolic prmeters with nd without the inclusion of totl ody ft nd/or BMC Leptin Adipo Insulin R 2 P-vlue R 2 P-vlue R 2 P-vlue Totl (n ¼ 59) Blck girls (n ¼ 25) White girls (n ¼ 34) Totft Leptin Totft Adipo Totft Insulin R 2 P-vlue R 2 P-vlue R 2 P-vlue Totl (n ¼ 41) o.1 o Blck girls (n ¼ 12) White girls (n ¼ 29) o.1 o BMC Leptin BMC Adipo BMC Insulin R 2 P-vlue R 2 P-vlue R 2 P-vlue Totl (n ¼ 41) o.1.8 Blck girls (n ¼ 12) White girls (n ¼ 29) Totft BMC Leptin Totft BMC Adipo Totft BMC Insulin R 2 P-vlue R 2 P-vlue R 2 P-vlue Totl (n ¼ 41) c o.1.3 o Blck girls (n ¼ 12) c d White girls (n ¼ 29) c Arevitions: Adipo, diponectin; Blck, non-hispnic Blck; BMAT, one mrrow dipose tissue; BMC, one minerl content; Totft, totl ft. Model 1: independent ssocition. Model 2: simultneous inclusion of Bone or Ft with metolic prmeters. c Model 3: the contriution of ody Ft nd BMC s modertors of the ssocition etween metolic prmeters nd BMAT. d Indictes negtive ssocition. Vlues in old indicte significnt ssocitions. Supercripts,, c indicte different regression models. provision (tht is, strvtion, oesity nd so on.), in the lnce etween dipogenesis, t the expense of ostelstogenesis, hs een shown to compromise one integrity in dults, 2 s well s in peditrics with norexi nervos. 13,21 During growth nd development, perturtions in this mechnism my exert ction on more highly susceptile common progenitor stem cell therey directing linege wy from osteogenesis. 22,23 While ssessment of cell linege is difficult in vivo, imging techniques llow for the quntifiction of BMAT volume, nd provide informtion regrding the function nd relevnce of the conversion of red mrrow to BMAT erly in the life course. In dults, mrrow diposity is independently ssocited with incresed frctures. 24 Childhood frctures hve een ssocited with ltertions in ody composition, tht is, incresed diposity nd impired one structure, 25 nd prevlence of frcture rtes hve incresed B2% (Pressley et l. 2 ). Recently, Shen et l. 26 reported n inverse reltionship etween BMD nd BMAT in young nd old dults, independent of rce or totl ody ft. Specultively, incresed dipose tissue within the mrrow comprtment could led to ltertions in the stem cell linege lloction involved in one remodeling, incresing dipogenesis therey impiring one integrity. 15 However, despite the reported effects of dipocyte infiltrtion within the one mrrow comprtment, 27 during growth the hormonl milieu promotes one formtion (tht is, increse in one size), explining the increse in BMC. In this peditric popultion, we show tht lthough the level of diposity my contriute to the positive reltionship etween BMATnd BMC, 4 APRIL 213

5 Bone mrrow dipose tissue nd erly puerty AL Newton et l consistent with the notion tht incresed diposity in the mrrow comprtment my led to n increse in one modeling, qulittive explortion encompssing outer nd inner surfces extending eyond BMC is essentil. Contrry to findings in dults, our results show positive reltionships etween BMAT, totl ody ft, nd BMC, which is prticulrly impctful during growth. The reltionship is evident with proximity to puerty nd is plusily relted to the dditive effects of the metolic nd reproductive hormonl milieu intercting with diposity during this criticl period. Indeed non-hispnic lck girls in this cohort hve greter overll diposity, with greter BMAT t ge 8; however, greter BMAT is identified in white girls t ge 1, consistent with their puertl progression. Despite no differences in BMAT volume mong sujects, rce-dependent differentil effect ws oserved in regrd to intercting fctors linking the one-ft xis to BMAT volume. Similrly, differentil contriution of diponectin nd insulin ws oserved etween white nd non-hispnic lck girls. While these results were unexpected given differences in diposity, investigtors from our group hve recently reported higher leptin in Africn-Americn women tht ws not explined y differences in ody composition nd ft distriution. 28 These findings support mechnism in which inherent physiologic differences my underlie disprte outcomes in long-term chronic disese risk, prticulrly the noted impirments in one integrity despite greter one volume recently identified mong Africn-Americn dult women, 2 nd wrrnts further investigtion. Wheres the nolic effects of insulin on one re wellunderstood, 29 the interctive effects of insulin with diposity nd one formtion on BMAT re less cler. Insulin ws not independently ssocited with BMATcross the overll smple, nd lthough only mrginlly significnt, higher insulin ws independently ssocited with BMAT in white girls only. On the contrry, independent of totl ody ft nd BMC, insulin nd BMAT in non-hispnic lck girls displyed strong inverse ssocition. In this smple, non-hispnic lck girls were more hyperinsulinemic thn their white counterprts, ligning with tht commonly reported 3,31 nd suggestive tht elevted insulin levels my confer mitogenicity t lest during the growth period. 32 Additionlly, greter insulin utilizing cpcity y BMAT my function in upregultion of ftty cid metolism, wheres in the norml physiologic stte insulin s influence within the one mrrow would typiclly led to osteolst prolifertion. 33 Nonetheless, the divergent findings reported herein lend limited insight to underlying mechnisms, which my led to preferentil prolifertion of dipocytes. Adipokines my medite the reltionship pprent etween one nd diposity, s well s the composition of the mrrow comprtment. Elevted leptin nd low diponectin levels hve een independently ssocited with incresed risk of dverse outcomes (tht is, inflmmtion, crdiovsculr disese, type 2 dietes), 1,34 nd hve mjor role in one remodeling. 35,36 Herein, leptin ws positively ssocited with BMAT. In girls followed throughout puerty, leptin ws positively ssocited with chnge in one re, 37 despite niml models suggesting leptin functions through neurl pthwys inhiiting one formtion. It is plusile, given leptin s role in reproduction, 34 tht the ction of leptin my depend on current leptin sttus nd the mode of the ction (centrl or peripherl effects), s well s life stge. 1,38,39 Although counterintuitive, yet confined only to the white popultion, diponectin lso ssocited positively with BMAT. Adiponectin is cknowledged for its potentil insulin-sensitizing, nti-inflmmtory nd nti-therogenic effects. 4 Additionlly, the inverse reported reltionship of diponectin nd insulin sensitivity is thought to e independent of diposity levels. 34 Thus, the influence of dipokines in one regultion, prticulrly diponectin, my e life cycledependent. The use of roust ody composition mesures nd mgnetic resonnce imging (MRI) ssessment of BMAT llowed for greter precision eyond tht which hs een previously used to ssess rce-relted differences in mrkers of one turnover nd ody composition. Although this study genertes vlule insight regrding the contemporry one ft reltionship, limittions must e tken into considertion. Despite the cross-sectionl nture of this pilot study, with modest smple sizes in ech ethnic nd ge group, the interesting findings relting to BMAT ly the groundwork for future studies of longer durtion nd lrger smple size. Additionlly, in terms of BMAT volume, it must e relized tht sttisticlly significnt difference is not necessrily of iologicl significnce; tht is, sttisticlly significnt group difference in one mss my not e trnsferred to difference in frcture risk. Further, the independent nd interctive effects of diposity nd puerty re difficult to delinete. While the reltionship etween BMC/D nd BMAT in dults my e independent of totl ody ft, the interply during growth nd development when lrge proportion of BMAT conversion occurs hs not een fully investigted. However, finding n effect in erly-puertl girls cn e regrded s promising in the quest to understnd the reciprocl reltionship etween ft nd one, nd the implied idirectionl influence of the one mrrow comprtment. Although we exmined only the ppendiculr skeleton, specificlly the femur, tht of the xil skeleton my lso e relevnt nd wrrnts investigtion. Future studies should include lrger smple size, inclusion of multiple rces/ethnicities, s well s inclusion of individuls with wider rnge of ody hitus. Wheres in dults the presence of BMAT is ssocited with impirments in metolic nd skeletl helth reminiscent of ging, 19,36,41 the timing of conversion of hemtopoietic mrrow to BMAT is suggestive of physiologic relevnce for liner growth, minerliztion nd osteolst function. Accordingly, one-ft interply hs profound implictions for developmentl origins of helth nd disese. Ft within one my cquire different metolic sttus dictted y energy metolism nd certin locl demnds of physiologicl importnce. Our findings reveled positive reltionship etween BMAT, ft mss nd BMC, lthough ft mss, respective to leptin, contriuted in lrge prt to the reltionship etween BMATnd BMC. Additionlly, despite lrge differences in totl ft mss etween non-hispnic lck nd white girls, the reltionship etween ft mss, BMAT nd BMC ws similr to white girls. However this reltionship ppered to e impcted through different mechnisms ccording to rce. Indeed, long-term skeletl nd metolic helth is significntly influenced y physiologic chnges during the puertl trnsition. Accordingly, further investigtions re wrrnted to elucidte the extent to which greter BMAT volume erlier in the prepuertl trnsition my underlie lifelong interctions mong the one-ft xis. BoneKEy Reports APRIL 213 5

6 Bone mrrow dipose tissue nd erly puerty AL Newton et l Mterils nd Methods Prticipnts. This pilot study represents n ongoing cohort comprised of helthy prticipnts enrolled in clinicl studies, including dietry nd physicl ctivity interventions, nd oservtionl studies imed t investigting ody composition during the puertl trnsition 42,43 conducted t the University of Alm t Birminghm (UAB). Prticipnts were recruited through newspper dvertisements, flyers posted t vrious community prtnerships nd y word-of-mouth. Irrespective of study enrollment, the present investigtion is limited to crosssectionl nlyses of seline dt for prticipnts who underwent dul-energy X-ry sorptiometry (DXA) nd MRI scns nd venipuncture over the period of The totl smple included 59 girls ges 4 1 yers (42% non-hispnic lck). All the procedures were pproved y the UAB Institutionl Review Bord nd informed consent nd ssent (where pproprite) were otined. Anthropometric ssessment. Weight ws mesured using digitl scle to the nerest.1 kg in miniml clothing without shoes. Height ws lso recorded without shoes using digitl stdiometer. Wist circumference ws mesured t the nrrowest pprent prt of the torso etween the ris nd ilic crest s descried y Lohmn et l. 44 Wist circumference mesures were otined using flexile tpe mesure (Gulick II; Country Technology, Inc., Gys Mills, WI, USA) nd recorded to the nerest.1 cm. Body composition. Adipose tissue distriution nd ody composition were ssessed y MRI nd DXA, respectively. Wheres DXA mesures totl tissue content sed upon rel estimte, mgnetic resonnce through delinetion nd simple signl thresholding llows contrst etween tissue comprtments, thus providing more sensitive quntifiction of ft nd one. MRI imging nd nlysis. Mesures for femorl BMAT were cquired using MRI. MRI which involves no ionizing rdition is emerging s comprehensive tool for ft quntifiction. For MRI, children were scnned using Philips 3T system in the UAB Division of Crdiology. 45,46 A series of T1-weighted slices (llowing for rpid scns with strong ft-wter tissue contrst) were cquired t the upper-leg regions with dt cquisition eginning t the ilic crest nd continuing to the knee (superior order of the ptell). Scns were nlyzed off-site in the lortory t the University of Southern Cliforni using SliceoMtic (Tomovision, Inc., Mgog, Queec, Cnd) softwre. The technique used for nlysis hs een descried elsewhere. 47,48 Briefly, the procedure involves the trnsfer of imges to n offline worksttion, followed y the use of SliceOMtic softwre tht requires mnul intervention. Dul-energy X-ry sorptiometry. Totl ody composition (ody ft mss nd BMC) ws mesured y DXA using GE Lunr Prodigy densitometer (GE LUNAR Rdition Corp., Mdison, WI, USA). Prticipnts were scnned in light clothing, while lying flt on their cks with rms t their sides. DXA scns were performed nd nlyzed using peditric softwre (encore 22 Version ). In our lortory, the coefficient of vrition (CV) for repeted mesures of totl ody ft mss is 6.55%. Assy of metolites. The puertl trnsition is ccompnied y vrious chnges in the metolic hormonl milieu, which my e disrupted y oesity. Accordingly, the contriution of insulin/glucose homeostsis, lipid profile nd circulting dipokines to the reltionship etween BMAT, BMC nd totl ft were evluted. Glucose ws mesured in 12 ml ser with the glucose oxidse method using SIRRUS nlyzer (inter-ssy CV 2.56%). Insulin ws nlyzed using TOSOH AIA-6 II Automted Immunossy Anlyzer (TOSOH Bioscience, South Sn Frncisco, CA, USA). Assy sensitivity is pmol l 1, men intr-ssy CV is 4.69%, nd inter-ssy CV is 6.%. Triglycerides were ssessed with the glycerylphosphte method. High-density lipoprotein cholesterol ws nlyzed using two-regent system involving stiliztion of lowdensity lipoprotein cholesterol, very low-density lipoprotein cholesterol, nd chylomicrons using cyclodextrin nd dextrin sulfte, nd susequent enzymtic-colorometric detection of high-density lipoprotein cholesterol. Further, leptin nd diponectin, oth integrl components of one remodeling were nlyzed y rdioimmunossy s descried (ELISA Immuno Assy (EIA); ImmunoDignostic Systems (IDS), Fountin Hills, AZ, USA). 49,5 Serum 25-hydroxy vitmin D nd PTH were ssyed either in the UAB Core Lortory or commercilly (Quest Dignostics, Sn Jun Cpistrno, CA, USA). In the UAB Core Lortory, serum 25-hydroxy vitmin D ws ssessed y EIA immunossy (Immunodignostics Systems Inc, Fountin Hills, AZ, USA) nd PTH y two-site immunordiometric ssy. The intr-ssy CV for the nlysis of PTH nd 25- hydroxy vitmin D were 7.76 nd 4.83, nd the men inter-ssy c.v. were 2.7% nd 4.94%, respectively. Sttisticl nlysis. Generl liner models were used to evlute demogrphic chrcteristics of the smple popultion. Multiple liner regression nlysis ws used to evlute the reltionship etween BMAT, ody composition nd metolic prmeters. All models were djusted for ge, height nd rce (where pproprite). Sttisticl significnce ws set t Po.5. All dt were nlyzed using SAS 9.1 softwre (SAS institute Inc., Cry, NC, USA). Conflict of Interest The uthors declres no conflicts of interest. Acknowledgements This study ws supported y Grnt no. RDK8333. References 1. Co JJ. Effects of oesity on one metolism. J Orthop Surg Res 211;6:3. 2. Pressley JC, Kendig TD, Frencher SK, Brlow B, Quitel L, Wqr F. Epidemiology of one frcture cross the ge spn in lcks nd whites. J Trum 211;71:S541 S Yng L, Burton AC, Brdurn M, Nielson CM, Orwoll ES, Estell R. Distriution of one density in the proximl femur nd its ssocition with hip frcture risk in older men: The MrOS study. 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J Clin Endocrinol Met 2;85: This work is licensed under Cretive Commons Attriution- NonCommercil-NoDerivs 3. Unported License. To view copy of this license, visit BoneKEy Reports APRIL 213 7