I. Bone age (bone age, skeletal age) is the official name: skeletal age.
1, what is bone age: human growth and development can be expressed in two “age”, that is, the age of life (calendar age) and biological age (bone age). Bone age is short for skeletal age and is determined with the help of a specific image of the bone in an X-ray camera. To find out the bone age of a person, an X-ray of the wrist of the person’s left hand is usually taken, and the doctor determines the bone age by looking at the degree of development of the metacarpal phalanges, carpal bones and the ossification centers of the lower radius and ulna of the left hand. It is a biological age that reflects the degree of physical development by measuring the changes in size, form, structure and interrelationship of bones, and expresses it in the form of age in years through statistical processing.
2, standard bone age film shooting method: standard bone age film, only need to take a left hand orthopantomograph. When shooting, the left hand five fingers open naturally, palm down, middle finger and forearm keep in a straight line (try not to deviate from the left and right, arm flattened not to lift up), the X-ray bulb is aligned with the third metacarpal bone, the distance between the bulb and the X-ray film is about 80CM.
3, factors affecting bone development: many diseases affect bone development, making it into advance or backward, such as adrenal cortical hyperplasia or tumor, precocious puberty, hyperthyroidism, simple obesity with excessive growth in stature, ovarian granulosa cell tumor, etc. will lead to early bone age; and ovarian hypoplasia (Turner syndrome), chondrodysplasia, pituitary dwarf (growth hormone deficiency), low A, etc. will lead to significant lag in bone age. The most important factor is the hypothalamic-pituitary-gonadal axis system.
II. Clinical significance of bone age assessment
The changes of human skeletal development are basically similar, and the development process of each bone has continuity and stages, and the bones at different stages have different morphological characteristics. At present, the aspects of growth and development that often require the use of bone age evaluation are.
(1) Bone age assessment can reflect the level of growth and maturity of an individual more accurately (to determine the stage of growth and development, and to help distinguish between “early growth” or “late growth”, etc.);
②It can not only determine the biological age of the child, but also understand the growth potential of the child and the trend of sexual maturity through bone age at an early stage (determination of the remaining growth space and sexual maturity);
③Bone age can also be used to predict the adult height of a child (to determine whether a child with short stature or early growth needs treatment);
④The determination of bone age is also useful for the diagnosis of some endocrine diseases in children (e.g., children with growth hormone deficiency often lag behind in bone age, while children with precocious puberty often advance in bone age);
(5) To guide the clinical use of endocrine drugs and the judgment of treatment effects (e.g., children with precocious puberty need regular assessment of bone age to guide the adjustment of drug dosage);
⑥Bone age is also used in forensic medicine to determine the age of a particular individual as a basis for conviction;
(7) It is used for the selection of athletic, artistic and other special talents with different height requirements, as well as for the grouping of athletes in competitions, etc.
The difference between biological age (bone age) and life age within ±1 year is called normal development.
If the difference between biological age (bone age) and life age is >1 year, it is called early development.
If the difference between biological age (bone age) and life age is <1 year, it is called backward development.
Bone age determination plays an important role in the x-ray diagnosis of certain endocrine diseases, metabolic disorders and growth disorders. Abnormalities in bone age are often an aspect of the presentation of certain endocrine disorders in pediatrics.
According to the latest TW3 assessment method, when the bone age reaches 16.5 years for boys and 15.0 years for girls, the epiphysis basically closes, the skeleton reaches adulthood, and height basically stops growing. However, the bone age at which the epiphysis is completely closed is different for different bone age assessment methods. For example, for the TW2 method released in 1975, the epiphysis of boys is completely closed at 18.3 years old and reaches adulthood, which is 1.8 years different from TW3, and the epiphysis of girls is completely closed at 17.2 years old and reaches adulthood, which is 2.2 years different from TW3. There are still some differences, please refer to the growth curve in my website for the general prediction).
Third, the common bone age assessment methods at home and abroad
1.Bone age assessment methods
The traditional bone age assessment is usually done by taking X-rays of the subject’s hands and wrists, and then interpreted by a doctor based on the X-rays taken. The most commonly used methods are the G-P atlas method and the TW2 (TW3) scoring method; the prediction of adult height based on bone age includes the B-P method, the CHN method, the TW3 method, and so on. In recent years, a new technique of bone age assessment by ultrasound called BoneAge has also been developed in Israel.
1.1 Counting method
In the early 20th century, counting of ossification centers was dominant and consisted of.
(i) observation of the number of ossification centers present at a certain age, mainly in the carpal bones;
② measuring the area of ossification centers and the ratio between bone and bone; ③ observing the fusion time of epiphysis. That is, the bone age counting method, such as Vogt and Vickers’ method published in 1938. Because of the early appearance of ossification centers in the wrist and the fact that increasing the area would result in excessive X-ray exposure, there have been few important developments in such studies since then.
1.2 Atlas method
After the discovery of X-rays in 1895, scholars began to use them in the study of skeletal development, and the first atlas of skeletal development was proposed by John Poland in 1898, and a more complete atlas of skeletal maturation was developed by Todd (1937). ), which was revised in 1959. The G-P Atlas is a longitudinal study based on children from middle and upper class families in the United States, from birth to adulthood.
The method is based on the order of appearance and disappearance of the ossification center and epiphysis of the wrist at different ages of children and adolescents, and establishes a standard bone age chart for both sexes. This method is simple, intuitive and easy to use, and countries or regions have established their own standard atlas, including Gu’s atlas in China.
1.3 Scoring method
The atlas method is subjective, deviates greatly, and the bone maturation rate is not clear, so Tanner and Whitehouse et al. (1962) proposed the TW1 bone age scoring method through their study, which was modified to the TW2 method in 1975. In this method, 20 wrist bones were taken from left wrist orthopantomographs, and each bone was divided into 8-9 stages according to different developmental grades and assigned different scores, and the total bone development score (SMS) was from 0-1000. The bone development score of each bone was accumulated from the wrist x-rays, and then the bone age score table or SMS an age curve was checked to obtain the bone age. Its scoring system has three series.
① R(radius, ulna and short finger bones, RUS) series, containing 13 distal ulnar radius, 1st, III and V metacarpals;
②C(carpals) series, containing 7 carpal bones, except pea bones;
③T(TW20 a bones) series, for the synthesis of R, C series. 2001 has been revised to TW3 method, which is currently the latest international assessment criteria, mainly the abolition of T series, that T series is only the synthesis of R, C series, no special use; as well as the reformulation of the R series of standards, that the standards are affected by the times, the population and other factors. China introduced the Li Guozhen percentage counting method (1979), the Chinese wrist bone development standard CHN method (1992), and the Ye’s score method (1991), which directly references TW2.
1.4 Other bone age assessment methods that have emerged in recent years
Bone age is mainly assessed with the help of higher modern technology.
① Computer-aided bone age assessment: mainly used for TW3 method, CHN method and other bone age scoring methods that require complex calculations. However, because it requires scanning of bone age films or can only be uploaded through the imaging department of our hospital, it increases the assessment procedure or is inconvenient to assess patients’ own films; at the same time, due to the imperfection of the current procedure, the score is fixed for each period, it is inconvenient to make appropriate adjustment of the score for those in between two periods, and only the same method can be used when predicting adult height, so the application is currently subject to some limitations.
② Ultrasound bone age assessment: In 1995, Castriota et al. used ultrasound to measure the thickness of femoral head articular cartilage (FHC) in children, showing a strong correlation between FHC thickness and bone age and life age, suggesting that ultrasound measurement is a meaningful method for assessing skeletal development in children and adolescents. It has also been reported that there is a significant correlation between heel bone broadband ultrasound attenuation values and age in children and adolescents aged 6 to 15 years. Ultrasonic bone age measurement instrument has been introduced, which is based on the structural changes in the process of cartilage ossification in the wrist, and the bone age is calculated by measuring the ultrasound velocity through the wrist, and the results are highly correlated with those obtained by the G-P method, suggesting that ultrasound technology has good application prospects in bone age assessment.
③Application of dual-energy X-ray absorptiometry (DXA): In 2002, some foreign scholars used the low-radiation measuring instrument DXA to image scans of the wrist to explore bone density to assess bone age . Pludowski et al. reported high agreement between DXA testing and X-ray testing for bone age assessment, and among 60 individuals, 40 cases had consistent bone age, and the difference between bone age in the other 16 cases was less than 0.5 years, and The image quality and resolution of DXM meet the requirements, but DXA is not yet able to achieve the accuracy of bone age within 0.5 years, and the high cost and relatively complicated operation limit its application.
2.The history of bone age assessment in China
①, Liang Duo (1937), Liu Huifang (1959), Gu Guangning (1962), and Zhang Naiju (1963) had successively proposed the standard of bone age calculation method for children in China. Liu Baolin (1983) and Xu Jida (1985) had proposed a bone age atlas for children in China, but none of them was widely used.
In the 1960s, Li Guozhen proposed the “Chinese bone age percentage counting method”, which was widely used for a certain period of time.
In 1992, the National Sports Commission organized relevant professionals to revise the TW2 bone age according to the characteristics of Chinese children, removing the ulna and adding the cephalic bone and hook bone. And scored by similar method, called CHN method. In recent years, it was revised by Hebei Sports Institute.
④, In 1991, Yeyin Ye et al. made the adult height prediction method of TW2 bone age by first converting Chinese height to British height, and then converting back to Chinese height after making annual height prediction by TW2 method. Because of its high accuracy, it has been widely used in the field of pediatric endocrinology and is referred to as the “TW2 Ye method”.
Advantages and disadvantages of various bone age assessment
1.GP atlas method: The advantages are concise, intuitive and easy to evaluate; different data of advanced bone age, normal bone age and backward bone age are available for adult height prediction, which is helpful for predicting the height of people with endocrine diseases. The main disadvantages are the lack of accuracy, the carpal bone morphology is easier to distinguish by the atlas method, while the long bones are more difficult to distinguish, but the adult height prediction is mainly based on the bone age of the long bones, so the accuracy is often felt to be insufficient in clinical practice. And the original data came from the 50’s American middle and upper class family children, but after all, it was not updated after 1959, the age is older.
2, CHN method: Since the 80s, according to the current development of children, China has improved the TW2 method and developed a unified bone age standard in China – CHN standard, which is more suitable for the evaluation of bone age of children in China and is common in China, but not common internationally, causing inconvenience in communication. And it is as complicated as the TW method. At the same time, because it is derived from the results of cross-sectional studies (the same period, the collection of different age groups of normal children, adolescents bone age data), the reliability is lower than that of longitudinal studies (the same group of normal children, from birth to adulthood, regular bone age film).
3. TW3 bone age: In 2001, the TW2 bone age scoring method, updated to the TW3 method, and the RUS score was adjusted to correspond to the bone age of male and female children according to the changing times. Adult height prediction is no longer predicted by bone age, which is more obviously influenced by race, era and region, but by direct prediction of bone development score, and after 9 years of longitudinal observation of 3300 children in North America and Europe, it is found that this method is more accurate than other methods in adult height prediction, and it is not restricted by race and region, so it is worth to promote vigorously.
Currently, the National Endocrinology Group’s “Guidelines for the Management of Children with Short Stature” recommends either the BP method or the TW3 method. However, the TW3 method is definitely more accurate and more up-to-date.
V. Adult height prediction
1.The significance of adult height prediction
At present, most hospitals assess the bone age based on the radiology bone age report or the bone age assessed by the pediatric endocrinologist against the chart, and very few hospitals make the adult height prediction for the patients. However, adult height prediction is very important for the diagnosis, treatment and efficacy observation of pediatric endocrine diseases.
(1) Adult height prediction is an important basis for clinical intervention
(2) Adult height prediction is the main indicator of whether to continue intervention
(3) Adult height prediction is one of the bases for the effectiveness of treatment.
(4) Adult height prediction is an important basis for differentiating pathological shortening from pubertal growth retardation.
⑤ The adult height prediction is the most important indicator for parents.
2.Methods of adult height prediction
B-P (Bayley-Pinneau) method: The proportion (%) of children reaching adult height at that bone age is closely related to the proportion of children reaching adult height at that bone age. Calculation method: Adult predicted height = height at that time / P x 100
By bone age (BA ) developmental rate.
Normal BA – CA = < 1y
Fast BA – CA = > 1y
Slow BA – CA = < - 1y
Bone age was measured by the G-P method, and PH was performed using the B-P form.
(ii), CHN method to predict height with the same principle as B-P method, with different reference tables (Chinese children, divided into northern, central and southern, but without values when there is a difference between bone age and age).
③, HtSDs (BA) trajectory extension method (curve method): the height shown in the trajectory extension of the HtSD locus at the present BA equivalent of the growth curve marker.
(iv) TW3 method for adult height prediction is the latest method available (bone age from European children in Belgium, Spain and Texas, USA, and adult height prediction from children born in the late 1970s and early 1980s in Zurich, Switzerland), calculated based on RUS bone age score, current height, current age, and height gain in the previous year. Calculations ± 2 standard deviations included 95% of the population range. Since the bone development score is not affected by race, region and era, it can be used for different ethnic groups in theory.
3. Prediction of timing of menarche in girls.
TW3 girl menarche method: age at menarche = 12.6-0.68*(years of bone age – years of age) ± 0.625 years.
3. Discussion of adult height prediction problems
①, each kind of adult height prediction has its advantages and disadvantages, TW3 method into the original data of annual height prediction, after all, from Western countries, although the appointment of height by bone development score (response to the degree of bone growth) can be independent of the era, region, race, but after all, the era is different, the average height of normal people or differences, and again, there is a lack of a large sample size of domestic verification data. ②, growth curve method to predict height for bone age and age similar or slightly older children are relatively accurate, bone age is significantly less than the age of accuracy.
③, TW2 Ye’s adult height prediction method has been widely accepted in the past.
(iv) The BP method predicts height with data on bone age matching age, bone age greater than age 1 year or more and bone age less than age 1 year or more. It is relatively more meaningful in the presence of childhood endocrine diseases when bone age does not match age. However, the GP chart method is less accurate in assessing bone age, and the proficiency of the assessing physicians varies greatly, which obviously affects the accuracy of the prediction results, and after all, the age is long ago, and the average height of normal people has changed a lot.
It is best to evaluate all bone age assessment methods for each child when available, and to make adult height predictions for all methods for them.
VI. Special tips.
①. Except for a very small number of prediction methods for a specific disease, the raw data for the majority of adult height prediction methods are derived from normal individuals. The difference between bone age and age in normal people is generally less than 1 year. When the bone age and age match, the height prediction is relatively accurate; when the bone age and age differ by 1 to 2 years, the height prediction is for reference only; when the bone age and age differ by more than 2 years, the height prediction is not based on, but can be used as a comparison for observing the efficacy of treatment before and after.
②, the prediction of height can only be based on the height and bone age at the time of examination and predicted future height according to the normal growth trajectory. For children with short stature, if they did not grow according to the normal growth trajectory in the past and without any treatment, there is little possibility that they can grow according to the normal growth trajectory from the time of prediction, and their actual height without treatment is often lower than the predicted height. The same is true for children with precocious puberty, who cannot grow according to their normal growth trajectory because of their early development. The premature development, bone age often changes faster, and later on the prediction may be decreased.
7. How can we generally judge the reliability of adult height prediction?
Recently, when answering online inquiries, I often saw some adult height prediction results after bone age assessment, but many of them are very unreliable. For example, there is “an 11.5-year-old boy with a current height of 150 cm and a bone age of 13.1 years, but the predicted adult height is over 176 cm. The average height of boys at age 13 is 159.5cm, the average adult height of normal men is only 172.1cm, the average late growth space of 13-year-old boys is less than 13cm, the bone age is already 13.1 years, even if the age is slightly younger, the late growth space may be slightly greater than 13cm, but there is more than 26cm of growth space is impossible, if we consider the rapid progress of bone age, the late growth space Less than 13cm is still possible.
1, for the bone age and age equivalent and normal growth, after excluding precociousness, dwarfism, etc., can be based on the normal height table of each age group (although it is an age table, because normal children and adolescents bone age and age is equivalent, can be compared by bone age), to see the average height of the corresponding bone age and adult average height gap, to compare the late growth space. You can also consider using the growth curve to do a rough comparison.
2, for the bone age in advance of more than 1 year, can also be compared according to the above method, however, the late growth space may be slightly larger than the corresponding bone age segment growth space, because the prediction of adult height also has an age factor. However, the older the bone age, the lower the weight of age in predicting adult height and the smaller the magnitude greater than the average growth space. However, if one considers the possibility of rapid progression of bone age in early growers, there is also the possibility of a later growth space below the normal average growth space. In the case of girls, the above method cannot be used to compare directly after menarche, while if a girl has menarche too early, it will also obviously affect the later growth space.
3, for the bone age behind the age of more than 1 year, especially the bone age behind the normal age of more than 2 years, the presence of diseases affecting growth and development of children, it is best to roughly according to the age to compare the corresponding age of late growth space. Although theoretically the actual growth space should be greater than that of the corresponding age due to the younger bone age, the actual annual growth will be less than that of a normal child due to the presence of growth abnormalities, and the later growth space will be limited. Of course, the comparison is more reliable by calculating the corrected bone age, but it is not possible to calculate the corrected bone age without a very experienced professional.
With the development of our society and the improvement of people’s health, the growth and development of children has received great attention from the society. Bone age, as an important indicator of an individual’s level of development and maturity, should be promoted and applied in clinical practice. And familiarity, mastery, and selection of appropriate methods are required to guide and help the work.