【作者】 赵仁清；

【导师】 王人卫； 程蜀琳；

【作者基本信息】 上海体育学院 ， 运动人体科学， 2008， 博士

【摘要】 研究目的:本课题是一项为期2年的纵向跟踪研究,旨在探讨青春期女孩骨骼生长发育特点及激素、肌肉力量和运动因素的调节作用,为实现在青春期最大骨量积累提供理论依据。本课题综合考虑主要的骨代谢调节激素(雌激素和类胰岛素生长因子I)、肌肉力量(以小腿肌肉含量和瘦体重含量分别代表局部和全身的肌肉力量发育情况)与骨骼生长发育的纵向相关性以及运动因素对骨骼生长发育的影响。研究方法:受试者为258名身体健康的芬兰女孩,平均年龄10-13岁,处于Tanner stageⅠ-Ⅲ阶段。实验历时二年共进行三次测量,分别在:第1个月、第12和第24个月,进行相关指标的测试。主要测试以下内容:①一般指标:身高(body height, H)、体重(body weight, W),每6个月测量一次,采用电子测量仪测定;②体成分及全身骨骼物理特性:脂肪含量(fat mass, FM)、瘦体重含量(lean mass, LM)及全身骨骼面积骨密度(areal bone mineral density, aBMD)、骨量(bone mineral content, BMC)和骨面积(bone area, BA) ,采用双能X线测量(dual energy X-ray absorptionometry, DEXA)测量;③四肢骨骼的密度和几何形态:胫骨、桡骨的体积骨密度(volumetric bone mineral density, vBMD)、骨量和横截面积(bone cross-sectional area, BCSA),皮质骨、骨松质的密度、骨量和横截面积,小腿肌肉含量(muscle mass, MM)等采用周围骨定量CT(peripheral quantitative computed tomography, pQCT)测量;④激素:血清雌二醇(estradiol, E2)和类胰岛素生长因子I (insulin-like growth factor I, IGF-I),分别采用免疫荧光法和放射免疫法测定;⑤运动状况的评估:女孩的运动状况的评估采用问卷形式确定。女孩第一次月经时间以问卷或电话方式获得,女孩的身体发育情况由社区护士根据Marshall和Tanner在1969年发表的青春期女孩评分方法来进行评估。数据采用MLwiN1.1软件进行统计分析。主要结果:1.青春期女孩身体一般状况的变化:女孩平均初潮年龄为12.9岁,从进入青春期到初潮期间,身高增加近10厘米,体重增加近8.8公斤,FM、LM和MM也明显增加。全身aBMD、BMC和BA随着年龄的增长表现为持续增加趋势。胫骨总vBMD比桡骨的vBMD增加明显,而BMC、BCSA的增加彼此之间却没有明显的差异。血清E2和IGF-I的分泌分别增加了49%和74%。2.青春期女孩身体各项指标的生长及增长速率曲线方程:⑴身高、体重、脂肪含量及瘦体重含量的生长曲线:从进入青春期到初潮期间,身高、体重增长十分迅速,身高大约在女孩初潮前的14个月(平均年龄11.7岁)达到最高增长速率,体重在初潮前的5个月,平均年龄为12.5岁时达到最高增长速率。表明身高要比体重大约提前9个月达到最快的增长速率。在整个青春期,FM一直在稳定的增加,LM却在初潮之前增加更明显。⑵桡骨vBMD、BMC和BCSA生长及增长速率曲线:从开始进入青春期vBMD呈现明显的下降趋势,大约在初潮之前27个月负增长速率达到最低值,平均年龄10.6岁,大约在初潮前6个月才出现正增长。BMC和BCSA从开始就呈现快速增长趋势,大约在初潮之前9个月桡骨BCSA达到增长速率的最高值,平均年龄12.1岁, BMC在初潮之后的2个月达到最高的增长速率,平均年龄13.1岁。桡骨的BCSA要比BMC提前大约一年达到最高增长速率。⑶胫骨及其皮质骨vBMD、BMC和BCSA生长及增长速率曲线:胫骨vBMD在整个青春期一直呈现增加趋势,在整个实验期间vBMD还没有达到最高增长速率。胫骨BMC的增长十分平稳,而胫骨BCSA的增长主要在初潮之前。胫骨BCSA在初潮之前17个月达到最高增长速率,平均年龄11.5岁;胫骨BMC在初潮之前3个月达到其最高的增长速率,平均年龄12.7岁。胫骨的BCSA要比BMC提前大约14个月达到最高增长速率。⑷血清E2、IGF-I的生长曲线:从进入青春期血清E2和IGF-I从较低的浓度迅速大量分泌达到很高的水平,在初潮稍后的时间达到各自的分泌高峰,此后,它们的分泌略有下降,并维持在较高的水平上。3.相关分析:⑴血清IGF-I、E2和LM与全身aBMD、BMC和BA的相关分析:平衡掉青春期生长因素的影响后,在女孩进入青春期到出现第一次月经这段期间血清IGF-I与全身的aBMD (r=0.36, p<0.001)、BMC (r=0.36, p<0.001)和BA (r=0.32, p<0.001)呈显著相关,血清E2与全身aBMD (r=0.18, p<0.01)和BMC (r=0.17, p<0.01)也具有显著相关性,在初潮之后IGF-I只与BA显著相关,而E2却没有显著的相关性。无论是在初潮之前还是之后,LM与全身aBMD, BMC和BA (BM: r=0.44, p<0.001; r=0.78, p<0.001; r=0.74, p<0.001,AM: r=0.18, p<0.01; r=0.29, p<0.001; r=0.29, p<0.001)都具有高度的相关性。⑵血清IGF-I、E2和MM与胫骨的vBMD、BMC和BCSA的相关分析:平衡掉青春期生长因素的影响后,在女孩进入青春期到出现第一次月经期间血清IGF-I与胫骨的BMC (r=0.31, p<0.001)和BCSA (r=0.25, p<0.01)有显著相关,血清E2与胫骨的BMC (r=0.19, p<0.01)和BCSA (r=0.15, p<0.05)呈现显著相关性,而在初潮之后血清IGF-I和E2与胫骨的vBMD、BMC和BCSA都没有显著的相关性。初潮之前MM与胫骨的vBMD、BMC和BCSA (r=0.21, p<0.001; r=0.79, p<0.001; r=0.75, p<0.001)高度相关,而初潮之后MM只与BMC、BCSA (r=0.72, p<0.001; r=0.70, p<0.001)有的显著的相关性,MM与vBMD没有显著的相关性。4.运动因素对青春期骨骼生长发育的影响:在基础测量时,经常运动组与不经常运动组之间身高、体重、FM、LM和总的aBMD、BMC等指标在开始时没有显著性的差异。经过二年的生长发育之后,经常运动组和不经常运动组的女孩全身aBMD(p=0.002,t=3.134)、BMC(p=0.023,t=2.265)和LM(p=0.028,t=2.186)之间有显著性差异,而二组的BA和血清IGF-I、E2却没有显著性差异。主要结论:①初潮是女孩在身体、生理上逐渐成熟(physical and physiological maturation)的标志。在身体的发育上表现为身高、体重和骨骼的发育于初潮之前以快速生长为主,在此之后则是逐渐成熟为主,矿物质积累增加,骺软骨逐渐闭合;在生理上表现为激素的分泌在初潮后不久达到顶峰。②身高与体重最高增长速率不同步现象,说明在身体的快速增长时期机体蛋白质等营养物质的增长有滞后现象,这些物质是免疫等机制的物质基础,可能导致这个时期机体生理防御能力相对脆弱。③桡骨骨密度从进入青春期到初潮之前一直呈下降趋势,提示从进入青春期到初潮期间是女孩桡骨发育最脆弱的时期,桡骨矿物质的积累速度落后于骨骼生长速度,这是青春期桡骨骨折发生率十分高的一个重要原因。④与桡骨不同,胫骨密度在进入青春期就一直增高,在我们实验期间它没有达到最高增长速率,这主要反映机械负荷在促进矿物质的沉积中起到重要的作用。⑤血清E2、IGF-I只在初潮之前与全身aBMD高度相关,而与胫骨vBMD没有显著相关,这提示初潮之前E2、IGF-I对青春期女孩全身骨骼矿物质积累有着积极促进作用,反映全身与局部骨骼矿物质积累的机制不同,而初潮之后其它调节机制成为促进骨密度增长的重要因素。⑥只在初潮之前血清E2、IGF-I与胫骨和全身BMC有高度相关,提示初潮之前血清E2、IGF-I是促进全身和局部骨骼BMC增长的重要机制,初潮之后其它因素成为促进BMC增长的重要机制。⑦血清IGF-I在整个青春期与全身BA高度相关,表明在青春期IGF-I是促进全身骨骼面积增长的关键因素。IGF-I只在初潮之前与胫骨BCSA相关,提示初潮之前IGF-I对胫骨BCSA增长有促进作用,而之后来自其它机制更重要。初潮之前血清E2与胫骨BCSA高度相关,但没有发现与全身BA的显著相关。这个结果并不否定E2对全身BA的促进作用,由于E2是通过抑制骨髓腔的增长来实现对骨面积的调节,而全身BA反应的是全身各种骨的平均面积,由于大部分骨骼是没有专门的骨髓腔,所以即使骨的吸收变化很明显也不会表现在由DEXA测定的平均骨面积上。⑧无论初潮之前还是在此之后,反映机械负荷情况的指标MM和LM与反映胫骨及全身骨骼发育情况的指标有高度相关,说明机械负荷是促进全身和局部骨骼生长和矿物质积累的重要因素。⑨经常运动组比不经常运动组女孩有更高的全身aBMD、BMC和LM,而两组的激素水平没有显著差别,由此提示运动习惯是影响青春期女孩骨骼生长发育的重要因素,这种促进作用是通过机械负荷作用实现的,而不是通过内分泌调节机制。更多还原

【Abstract】 Purpose:The two year follow-up study aimed to investigate growth patterns of bone, and its correlations with serum estradiol, IGF-I and muscle strains as well as the effect of physical activity on bone growth in Finnish pubertal girls. Methods:The study population comprised 258 healthy Finnish girls aged 10-13 years at Tanner stage I-III maturational status at the time of recruitment. Bone geometry/density was measured annually: at baseline, and at 1-, and 2-years follow-up:①Body height (H) and body weight (W) were measured by electronic stadiometer every six months.②Body fat mass (FM) and lean mass (LM) together with whole body areal bone mineral density (aBMD), bone mineral content (BMC) and bone area (BA) were determined by dual energy X-ray absorptionometry (DEXA).③Tibial and raial, together with the cortical and trabecular bone, volumetric bone mineral density (vBMD), BMC, bone cross-sectional area (BCSA) and lower leg muscle mass (MM) were measured by peripheral quantitative computed tomography (pQCT).④Serum estradiol (E2) and IGF-I were assayed by fluoimmunoassay and radioimmunoassay, respectively.⑤The levels of physical activity of girls were determined by questionnaire. Menarche date was collected by questionnaire or retrospective phone call. The pubertal development was assayed by nurses according to the Tanner Stages published by Marshal and Tanner in 1969.Results:1. The changes of general characteristics: The average age of menarche was 12.9 years. The increment of body height was about 10 centimeters, with the body weight increasing 8.8 kilograms from pre-puberty to menarche. The FM, LM and MM increased significantly as well. The total body aBMD, BMC and BA increased with the age accrual and the increment of tibial vBMD exceeded the increment of radial vBMD significantly, without any patent difference in BMC and BCSA between tibia and radius. The tibial cortical bone grew about 0.38 centimeter during this period. Serum estradiol and IGF-I gained about 49% and 74%, respectively.2. The growth and growth velocity models:⑴Growth models of H, W, FM and LM: After entering puberty, growth of H and W was significantly, but W continued to increase and H slowed down its growth speed. The peak height velocity (PHV) was attained 14 months prior to menarche about 11.7 years, and the highest growth velocity of W was 5 months before menarche, which indicated that the H preceded W to reach highest growth velocity about 9 months. During the whole puberty, FM increased constantly while the main increment of LM was before menarche.⑵Growth and growth velocity models of radial vBMD, BMC and BCSA: Up to menarche, the radial vBMD continually decreased with lowest growth velocity about 27 months prior to menarche, averaging 10.6 years. It did not show increment until 6 months before menarche. With very high growth speed before menarche, BMC continued to increase and reached highest growth velocity about 2 months after menarche(average age13.1 years), while BCSA attained its highest growth velocity about 9 months before menarche (average age12.1 years) indicating BMC lag behind BCSA to reach highest growth velocity about 1 year.⑶Growth and growth velocity models of tibial vBMD, BMC and BCSA: The tibial vBMD increased continually without attaining its highest growth velocity during experiment. Tibial BCSA reached its highest growth velocity about 17 months prior to menarche (average age 11.5 years) with 20 months preceding BMC which attained its highest growth velocity about 3 months after menarche.⑷Growth models of estradiol and IGF-I: From pre-puberty to menarche, serum estradiol and IGF-I promoted their secretion and reached their individual’s highest concentration near after menarche.3. Correlation:⑴Longitudinal relationships between serum IGF-I, E2 and LM, and whole body aBMD, BMC and BCSA: After adjustment for pubertal growth effect, serum IGF-I significantly correlated with aBMD (r=0.36, p<0.001), BMC (r=0.36, p<0.001) and BA (r=0.32, p<0.001), while erum E2 associated with whole body aBMD (r=0.18, p<0.01)and BMC (r=0.17, p<0.01) before menarche. Serum IGF-I correlated to BA only, without any relationship between E2 with aBMD, BMC and BA after menarche。Both before and after menarche,LM significantly correlated with whole body aBMD, BMC and BA (BM: r=0.44, p<0.001; r=0.78, p<0.001; r=0.74, p<0.001,AM: r=0.18, p<0.01; r=0.29, p<0.001; r=0.29, p<0.001)。⑵Longitudinal relationships between serum IGF-I, E2 and MM, and whole body aBMD, BMC and BCSA: After adjustment for pubertal growth effect, serum IGF-I significantly correlated with tibial BMC (r=0.31, p<0.001) and BCSA (r=0.25, p<0.01),while serum E2 associated with tibial BMC (r=0.19, p<0.01) and BCSA (r=0.15, p<0.05) before menarche. After menarche, however, both serum IGF-I and E2 did not show significant relationship with vBMD、BMC and BCSA。MM correlated to tibial vBMD、BMC and BCSA (r=0.21, p<0.001; r=0.79, p<0.001; r=0.75, p<0.001) before menarche,but MM associated with tibial BMC、BCSA (r=0.72, p<0.001; r=0.70, p<0.001) only after menarche,without any association of MM with vBMD。4. Effect of physical activity on bone growth: There were no differences in H, W, FM, LM, aBMD, BMC, and BCSA between low physical activity and high physical activity at baseline. After two year’s development, significant differences in whole body aBMD(p=0.002,t=3.134)、BMC(p=0.023,t=2.265) and LM(p=0.028,t = 2.186) were found between the two groups,but there were no differences in BA and serum IGF-I and E2。Conclusions:①Puberty was crucial period for girl development during which girls gradually attained physical and physiological maturation.②W lagged behind H to reach the highest growth velocity about 9 months during puberty, which suggested that the immune system may be weaken during this period.③Radial vBMD continued to decrease up to menarche and reached the lowest growth velocity about 27 months prior to menarche, which suggested that radius had a weak period during grow spurt which may be the key factors causing radius fracture.④Tibial vBMD continued to increase during puberty unlike radial vBMD indicating the the mechanical load promotes bone mineral accumulation. The asynchrony between growth of tiabial BMC and BCSA suggested that the weak bone during pubertal growth spurt can not be recovered by mechanical load.⑤The association of serum E2 and IGF-I with whole body aBMD before menarche suggested that the two hormones promoted the bone formation during puberty. No significant correlation between the two hormones and aBMD and vBMD after menarche indicated that other factors may be contribution to bone formation.⑥Serum E2 and IGF-I associated with whole body and tibial BMC mainly as the result of both increase of BMD and bone size before menarche, and no such association after menarche suggested that other factors were more important for BMC accrual.⑦Serum E2 mediates the bone formation mainly by depressing the marrow cavity and the anomalous bones have not marrow cavity so serum E2 only associated with tibial bone size but not whole body bone area.⑧LM and MM were the determinants of whole body and local bone formation and mineralization during pubertal growth.⑨Pubertal bone growth benefit from physical activity, and it act the function by mechanical mechanism but not system endocrine.更多还原