globalization is not a new trend in auxology . for decades , researchers have compared growth and maturation in populations across the world , exploring racial and regional differences and studying the effects of changes in lifestyle . in particular , there has been a longstanding interest in the differences in tempo of maturation among populations and their secular trend .
such studies have preferentially been performed using bone age ( ba ) determinations . unlike secondary sexual characteristics
, ba can reveal the entire course of maturation from birth to adulthood . however , bone age rating is associated with considerable operator variability , and it is particularly difficult to ensure consistency between raters from widely separated parts of the world .
the emergence of a fully automated and therefore rater - independent ba rating method   has the potential to overcome this problem and , thereby , revitalize comparative studies of maturation across the world .  
we present a reanalysis of a large study of hand radiographs involving modern , normal chinese children using this automated bone age system .  
due to the one - child policy , parents have a strong focus on growth and development of their child , and currently , there are more than 500.000 ba determinations in china per year .
this need is growing , but there is a shortage of persons qualified to do the rating .
adult height prediction in asian children based on automated ba will be reported in a separate paper .  
our study had the following objectives : to validate the automated method by assessing its ability to analyse these images and its agreement with manual tanner - whitehouse ( tw ) ratings ; to derive reference curves for greulich - pyle ( gp ) ba   of chinese children , to study their regional variation in china , and to compare the curves to american children studied with the same bone age method ; to construct a chinese ba scale ( called bx - china05 ) as an adaptation of the gp ba for the chinese population in 2005;to construct a chinese tw ba scale called tw - china05 .   to validate the automated method by assessing its ability to analyse these images and its agreement with manual tanner - whitehouse ( tw ) ratings ;   to derive reference curves for greulich - pyle ( gp ) ba   of chinese children , to study their regional variation in china , and to compare the curves to american children studied with the same bone age method ;   to construct a chinese ba scale ( called bx - china05 ) as an adaptation of the gp ba for the chinese population in 2005 ; to construct a chinese tw ba scale called tw - china05 .
left hand radiographs of 2883 males aged 220 years and 3143 females aged 219 years were extracted from a previous study of children of the han ethnicity from five different cities in china .
the full age range was covered in the children from dalian , wenzhou , and shijiazhuang , while the age range started at 5 years in guangzhou and at 7 years in shanghai .
the images were taken close to the children 's anniversaries ; in addition , images were taken at 2.5 and 3.5 years of age ( the age distribution can be appreciated from figure 2 ) .
the original study was approved by the ethical committee of the medical department , hebei sports science institute , in 2002 . before the study started ,
a questionnaire was given to children 's parents for surveying background such as parent 's occupation , education level , income , and the medical history of the children and their family , and a written informed consent was obtained from the parents and/or the children .
the films were scanned using a vidar diagnostic pro advantage scanner ( hemdon , usa ) in 150  dpi and 12  bits per pixel .
the radiographs formed a representative sample of the previous study which comprised 17,000 radiographs recorded on films .
these radiographs had previously been ba rated by the first author using the tw method .
the images were analysed using the bonexpert version 2.1 automated method for ba determination ( visiana , denmark , http://www.bonexpert.com ) , which determines gp and tw3 ba [ 57 ] . the method was developed on caucasian children and has been validated on asian children from japan and california [ 8 , 9 ] .
the tw ba rating , more specifically , the assignment of stages to each bone , was recently recalibrated in order to coincide with ratings from the first zurich longitudinal study .
this rating , called standard tw rating , has been shown to be consistent with tanner 's ratings of the so - called gold series of reference images .   in order to compare bone maturation in different regions , reference curves of ba  ca versus chronological age ( ca )
were derived for each city separately and for all cites combined , using gp ba .
it is fast and reliable , because the image is rated by direct comparison to reference images .
however , the gp ba scale refers to mid- to upper - class american caucasian children from the 1930s , a standard group remote from present - day chinese children .
we therefore developed a variant of gp ba called bx - china05 as follows .  
the gp ba is considered to be not an estimate of ca , but rather an abstract maturity measure , and for each age , we determined the median gp ba of chinese children .
the relationship between ca and median gp ba was tabulated and used to transform an observed gp ba value into an age value , defined as bx - china05 .
for example , if the median gp ba is 13.5 at a ca of 13 years , a child with a gp ba of 13.5 has a bx - china05 of 13 years .
this method of mapping a maturity measure to a population - specific bone age is not new ; it was originally conceived in the context of the tw method , and we also carried it through for the tw method in this study .
therefore , for each age , we derived the median sum maturity score ( sms ) of the automated tw rating in order to derive a table for transforming an observed sms value into a bone age , which we call tw - china05 ( such a table had been estimated before using the manual tw ratings of these image data . by reestimating the table using automated tw ratings , we ensured that the table was consistent with bonexpert 's standard tw rating of bone stages ) .
thirty images were rejected by bonexpert before arriving at the 6026 images of this study .
most of these rejections were due to poor image quality or a bone age below the lower limit of the intended range of bonexpert ( 2.5 years for boys and 2.0 years for girls ) , but 12 of the rejected images were of good quality , corresponding to 0.2% , so the observed efficiency of the method was 99.8% .  

figure 1 shows the agreement between the manual tw3 rating and bonexpert 's tw3 rating , expressed as a bland - altman plot , that is , the difference is plotted versus tw3mid , the average of the two tw3 bone ages .
focusing on the tw3mid range of 2.516 years for boys and 2.514.5 years for girls , the average difference between automated and manual tw3 ratings was 0.00 years for boys and 0.37 years for girls .
the root mean square ( rms ) deviations were 0.64 for boys and 0.68 years for girls in the same tw3mid range .
to study the difference in tempo of maturation across various populations and ethnicities , we used the gp ba minus the age ( ca ) .
figure 2 displays the observed ba  ca data , and the mean and 2 sd curves are indicated .
the sd for boys within the age range of 817 years was 1.26 years , and the sd for girls aged 7 to 15 years was 1.12 years ( the sd curve was computed in 1-year intervals , and the quoted sd numbers are the averages over the entire age interval ) .  

figure 3 shows the average curves for each of the five cities , and figure 4 compares the ba  ca curves with data on four ethnicities from los angeles , usa . the new bone age , bx - china05 , is reported in table 1 . to calculate bx - china05 for a new image
, one should first determine the bonexpert gp ba and then apply the correction from table 1 .
it is seen that the average difference was close to zero for all ages as expected .
the sd for boys over the age range of 814 years was 1.08 years , and for girls aged 712 years , the sd was 1.01 years . 

table 2 shows the relationship between bonexpert 's sms and tw - china05 , the new tw ba adapted to this population , and figure 6 compares bonexpert 's tw - china05 ba and the manual tw - china05 ba . the sd of tw - china05  ca for boys aged 814 years was 1.09 , and for girls aged 712 years , it was 1.01 years .
we found that bonexpert was able to determine bone age for 99.8% of the good - quality images of chinese children .
this result compares well with previous results in caucasian children , despite that this is a new ethnic group , and the similar performance is probably due to fact that the variation between the average caucasian and asian child is much smaller than the variation within the caucasian population itself .
there was good agreement between automated standard tw3 rating and manual tw3 as shown in figure 1 .
firstly , there was only a small average difference ( bias ) of 0.00 years in the boys and 0.37 years in the girls , which indicates that the chinese tw rater was largely consistent with the european raters underlying the calibration of bonexpert 's standard tw rating .
this agreement was in contrast to that reported in   where a japanese rater had a bias of up to 1.19 years .   secondly , the rms deviation ( 0.64 years for boys and 0.68 years for girls ) was smaller than that observed for the zurich raters .
one reason for this slightly better result may lie in the fact that the chinese children were rated by a single rater while the zurich images were rated by one of two raters .   the chinese rater was never trained by authoritative raters on the tw gold series radiographs in london or on other series .
he learned the rating from the book   but still achieved good agreement with the automated rating .
the most striking aspect is that , at the end of puberty , the average ba  ca has reached approximately 1 year . in other words ,
chinese children reach maturity around one year earlier than the children that made up the gp ba reference , in agreement with previous studies .
this dramatic deviation was the main motivation for setting up the bx - china05 ba scale . 

figure 2 also shows that the spread in maturity is rather large in chinese children .
this is partly due to the fact that the children were from several cities , separated by large distances . to illustrate this effect ,
figure 2 shows the average ba  ca for the two cities at either end of the ba  ca spectrum , dalian , a middle - size city in the north , and shanghai , a large city in the south .
our pooling of all five cities contributed to a larger sd of ba  ca . even within each city , there was a relatively large spread , presumably due to differences between social classes .  

figure 3 reveals the significant differences between the five cities , with shanghai being the most advanced in ba and dalian the most delayed , and the other cities lie in between these two extremes . in principle , these data could be used to set up city - specific reference curves for ba  ca .
however , we believe that this would be impractical , and one would be faced with ambiguities when a child moves from one city to another , or if the child is from a city not among the five investigated here . we prefer to pool all children and treat city differences as a statistical uncertainty .
a limitation of this sample is that all data come from urban regions and middle and upper social classes , so the sample might not be representative for children from a rural community or children living under poor social conditions . 

figure 4 compares the chinese ba  ca curves with data on four ethnicities from los angeles , usa .
this comparison exploits the strength of the automated method . for the first time , one is able to compare maturity of chinese children with children in the west using a method guaranteed to have no rater bias .
the upper part of the figure compares los angeles children of different ethnicities , showing that asians and hispanics in los angeles have similar maturation tempo , while the lower plot compares asian children from los angeles and china .
we see that asians , averaged over the two sexes , reach maturity 0.6 years before american caucasians .
this comparison of the populations with each other is more interesting than a comparison to the outdated gp standard . in
, it was reported that american caucasians reach maturity 0.4 years before europeans , so we infer that asians reach maturity a full year ahead of european caucasians .
the new bone age bx - china05 is defined by table 1 , which can conveniently be built into the automated method .
the table can also be used to transform a manually determined gp ba to bx - china05 .
the table can even be used to adjust the ages of each plate of the gp atlas , thereby  translating  it to chinese .
for instance , the female plate with gp ba 12.0 years can be labelled 11.5 years for chinese females .
the new bx - china scales end 1.2 years earlier than the original gp ba scale .
the new tw - china05 scale ends at ages 16.1 years for boys and 15.1 years for girls , similar to the endings of the corresponding manual tw - china05 scale   of 16 and 15 years , respectively , as also illustrated in figure 6 .
both are adapted to agree , on average , with the age in the chinese population . however , there are important differences , because bx - china05 is based on the gp method whereas tw - china05 is based on the tw method .  
gp and tw ba rating represent two rather different methods . when used for manual rating , the tw method has the advantage that it employs an explicit procedure that ensures that the same bones are used , with the same weights , by all raters .
the gp method , on the other hand , has the advantage that it easier to learn and can be performed in a fast and intuitive manner . furthermore , its reliance on a direct comparison of the image with the plates in the atlas ensures that raters are constantly  calibrated  to the correct level .  
the tw method based on manual rating has been used extensively in china , rather than the gp method , because the latter refers to pre - ww ii ohio children which are far removed from modern chinese children .
this paper has introduced bx - china05 for chinese children , based on the gp method .
the gp atlas is both a method and a ba standard . with bx - china05 ,
one uses the gp method but escapes its ba standard by employing the corrections in table 1 .   with the introduction of automated methods , and the  recalibration  of gp ba in the shape of bx - china05 , the balance between the tw and the gp methods changes in favour of the gp method , which has several advantages relative to the tw method . in the automated method used in this paper ,
the tw and gp methods are both based on the 13 rus bones ( radius , ulna , and 11 short bones ) chosen by tanner for the tw method .
the gp method assigns a uniform weight of 7.7% to all 13 bones , while the tw method places a larger weight of 20% on both radius and ulna .
any uncertainty in the interpretation of radius and ulna will , therefore , have a disproportionately large effect on the tw ba , and , indeed , the precision of the automated gp ba is considerably better ( 0.18 years sd ) than that of the automated tw ba ( 0.30 years ) .adult height prediction has been found to be more accurate using gp compared to tw ba , primarily due to the large weight of the radius and ulna in the tw method .
the bonexpert method for adult height prediction is , therefore , based on gp ba ( this is also true for the method for chinese children , presented in a separate paper).the tw3 ba terminates at 16.5 and 15 years for boys and girls , respectively , while the gp ba terminates at 19 and 18 years . in other words ,
this also holds for the automated versions where tw3 and gp agree well up to the ba where tw3 saturates .
the same findings are noted in the chinese version where tw - china05 stops 1.7 years before bx - china05 .
when rating the maturity of adolescents , the gp method is the more powerful method .
notice , however , that the automated method has the general limitation that it becomes more uncertain above a certain maturity level , which is 17 and 15 years of gp ba for boys and girls , respectively .
this translates to the limits of 15.8 and 13.8 years , respectively , on the bx - china05 scale . above these limits , there are only small maturity - related changes in the appearance of the short bones .   in the automated method used in this paper , the tw and gp methods are both based on the 13 rus bones ( radius , ulna , and 11 short bones ) chosen by tanner for the tw method .
the gp method assigns a uniform weight of 7.7% to all 13 bones , while the tw method places a larger weight of 20% on both radius and ulna . any uncertainty in the interpretation of radius and ulna
will , therefore , have a disproportionately large effect on the tw ba , and , indeed , the precision of the automated gp ba is considerably better ( 0.18 years sd ) than that of the automated tw ba ( 0.30 years ) .
adult height prediction has been found to be more accurate using gp compared to tw ba , primarily due to the large weight of the radius and ulna in the tw method .
the bonexpert method for adult height prediction is , therefore , based on gp ba ( this is also true for the method for chinese children , presented in a separate paper ) .
the tw3 ba terminates at 16.5 and 15 years for boys and girls , respectively , while the gp ba terminates at 19 and 18 years . in other words ,
this also holds for the automated versions where tw3 and gp agree well up to the ba where tw3 saturates .
the same findings are noted in the chinese version where tw - china05 stops 1.7 years before bx - china05 .
when rating the maturity of adolescents , the gp method is the more powerful method .
notice , however , that the automated method has the general limitation that it becomes more uncertain above a certain maturity level , which is 17 and 15 years of gp ba for boys and girls , respectively .
this translates to the limits of 15.8 and 13.8 years , respectively , on the bx - china05 scale . above these limits
, there are only small maturity - related changes in the appearance of the short bones .   in rare cases where the automated method fails ,
it is recommended to record a new x - ray , unless the child has abnormal bone structure .
one can also perform a manual rating using the gp atlas and then use table 1 to correct the gp ba to the bx - china05
. it would even be acceptable to apply the manual tw - china05 method , in case the rater is more familiar with this method .
we have presented an important step toward the application of automated ba assessment to asian populations around the world .
we have found that asian children in los angeles , and in mid- to large - sized cities in china , have approximately the same maturation rates .
asians reach full maturity 1.2 years before the age indicated by the gp ba reference , and , thus , the use of this standard in china is considered misleading by some . on the other hand , as we have pointed out , there are many advantages of the gp atlas methodology , and we have presented an adaptation of the gp ba to chinese children , called bx - china05 .
 
 rationale and objective . 
 large studies have previously been performed to set up a chinese bone age reference , but it has been difficult to compare the maturation of chinese children with populations elsewhere due to the potential variability between raters in different parts of the world . 
 we re - analysed the radiographs from a large study of normal chinese children using an automated bone age rating method to establish a chinese bone age reference , and to compare the tempo of maturation in the chinese with other populations . 
 materials and methods . 
 x - rays from 2883 boys and 3143 girls aged 220 years from five chinese cities , taken in 2005 , were evaluated using the bonexpert automated method . 
 results . 
 chinese children reached full maturity at the same age as previously studied asian children from los angeles , but 0.6 years earlier than caucasian children in los angeles . 
 the greulich - pyle bone age method was adapted to the chinese population creating a new bone age scale bx - china05 . 
 the standard deviation between bx - china05 and chronologic age was 1.01 years in boys aged 814 , and 1.08 years in girls aged 712 . 
 conclusion . by eliminating rater variability 
 , the automated method provides a reliable and efficient standard for bone age determination in china . 
 
1. Introduction 
2. Subjects and Methods
3. Results
4. Discussion 
5. Conclusion 