The bones in the hand and wrist are the most suitable indicators of skeletal maturity during the different phases of postnatal development.
In the majority of healthy children,
there is an established sequence of ossification for the carpal,
metacarpal and phalangeal bones,
which is remarkably constant and the same for both sexes (Table 1 and Table 2).
The bone ossified from the primary center is the diaphysis,
while the bone ossified from the secondary center is the epiphysis.
As the secondary center is progressively ossified,
the cartilage is replaced by bone until only a thin layer of cartilage,
the epiphyseal plate,
separates the diaphyseal bone from the epiphysis.
The part of the diaphysis that abuts on the epiphysis is referred to as the metaphysis and represents the growing end of the bone.
As long as the epiphyseal cartilage plate persists,
both the diaphysis and epiphysis continue to grow,
but,
eventually,
the osteoblasts cease to multiply and the epiphyseal plate is ossified.
At that time,
the osseous structures of the diaphysis and epiphysis are fused and growth ceases (Figure 1).
Bone age,
the most common measure for biological maturation of the growing human,
derives from the examination of successive stages of skeletal development,
as viewed in hand-wrist radiographs.
Greulich and Pyle and Tanner-Whitehouse are the most prevalently employed skeletal age techniques today.
Greulich and Pyle.
The first ossification center to appear in hand and wrist radiographs is the capitate,
and the last is,
most often,
the sesamoid of the adductor pollicis of the thumb.
The first epiphyseal center to appear is that of the distal radius,
followed by those of the proximal phalanges,
the metacarpals,
the middle phalanges,
the distal phalanges,
and,
finally,
the ulna.
There are,
however,
two main exceptions to this sequence: the epiphysis of the distal phalanx of the thumb commonly appears at the same time as the epiphyses of the metacarpals,
and the epiphysis of the middle phalanx of the fifth finger is frequently the last to ossify (Figures 2,
3,
4).
Tanner-Whitehouse.
The Tanner-Whitehouse method is a bone-specific scoring technique in which a numerical score is assigned to selected hand-wrist bones depending on the appearance of certain well defined maturity indicators.
The advantage of this technique over previous Atlas methods is that the maturational differences between bones is statistically minimised thus reducing disagreement between bones. method is a bone-specific scoring technique in which a numerical score is assigned to selected hand-wrist bones depending on the appearance of certain well defined maturity indicators.
The advantage of this technique over previous Atlas methods is that the maturational differences between bones is statistically minimised thus reducing disagreement between bones.
The Tanner-Whitehouse method is a bone-specific scoring technique in which a numerical score is assigned to selected hand-wrist bones depending on the appearance of certain well defined maturity indicators.
The advantage of this technique over previous Atlas methods is that the maturational differences between bones is statistically minimised thus reducing disagreement between bones.
Bone age in the first two years of life.
Within the first two years of life,
the bone age is difficult to be calculated.
At birth,
there is no ossification nuclei in the x-ray of the hand,
because they appear until the first year of life.
However,
the numerical method SHS,
based on the lateral X-ray of the foot and left ankle,
evaluates five ossification nucleus (calcaneus,
cuboids,
third wedge and the distal epiphysis of the tibia and fibula) giving a score according to the maturity criteria they meet.
The sum of all of them gives the degree of bone maturation,
which must be compared with the standards of the general population.
As an approximation to bone maturation,
we look at the following ossification nuclei: at 3 months of life,
the large and hamate bone are appreciable and remains as the only ossification nucleus during the first 6 months and the distal epiphysis of the radius,
that usually appears around 10 months of age in girls and 15 months of age in boys (Figure 7).
Beyond hand and wrist.
Since 1950 when Greulich and Pyle developed and published the “Atlas of Skeletal Maturation of the Hand” this is well known worldwide to help clinicians in the study of the group of children with metabolic disorders or with prognostic reasons to know the final height of the pediatric population.
In 1952,
Girdany and Golden published a method to assess the bone age depending on the visualization of joints in the elbow,
shoulder,
hip,
knee,
and ankle,
as well as the spine (Figure 8).
The comparison versus standard images determines the approximate bone age and maturation in the patient depending on the appearance of ossification centers.
This method is used as an aid in the assessment of skeletal maturity,
there are some works that compared both methods and the results shows no significant differences in the final results.
Another aspect that is reliable is the use of some pneumonic like CRITOE that uses the moment of appearance of the ossification centers of the pediatric elbow (humerus capitelum,
radius head,
medial or internal epicondyle,
humerus trochlea,
olecranon,
lateral o external epicondyle),
(Figures 9,
10).
There are other methods including the Risser classification that predicts the skeletal maturity based on the level of ossification and fusion of the iliac crest apophysis.
This method is intended for the use in pediatric patients with scoliosis.
It is based on observations that the grade of ossification correlates with the spinal skeletal maturity.
In conclusion,
the skeletal maturity assessed in other regions than the hand and wrist is a very useful complement in the protocol of study of patients with obesity and endocrinologic diseases.
MRI (Figure 11).
MRI of the left hand,
using a single coronal sequence,
T1 VIBE-3D-WE,
in a routine scanner is a radiation-free alternative method feasible for skeletal age estimation of adolescents using the GP-based criteria.
The age of healthy adolescents could be correctly estimated by expert readers within 2 SD by hand MRI and the Greulich-Pyle atlas,
with a high agreement.
However,
when using only 1 SD,
bone ages tend to be estimated as older than the chronologic ages.
Disadvantages:
- High cost
- Accessibility
- Use of anesthesia
- Time
BoneXpert.
The BoneXpert method is a medical software that makes reconstructions,
from x-ray of the hand of the borders of 15 bones to calculate intrinsic bone ages for each of these bones (radius,
ulna,
and 11 short bones).
Finally,
it transforms the intrinsic bone ages into the Greulich Pyle or Tanner Whitehouse bone age (Figure 12).
It automatically rejects images with abnormal bone morphology or very poor image quality.
From the methodological point of view,
it contains the following innovations:
- A generative model (active appearance model) for the bone reconstruction.
- The prediction of bone age from shape,
intensity,
and texture scores from the principal component analysis.
- The consensus bone age concept that defines bone age of each bone as the best estimate of the bone age of the other bones in the hand.
- A common bone age model for all.
- The unified modeling of Tanner Whitehouse and Greulich Pyle bone age.
BoneXpert is developed on 1559 images and validated on the Greulich Pyle atlas in the age range of 2-17 years,
yielding a standard deviation of 0.42 years [0.37; 0.47] 95%,
and in 84 clinical Tanner Whitehouse rated images yielding a standard deviation of 0.80 years [0.68; 0.93] 95% conf.
The precision of the Greulich Pyle bone age determination (its ability to yield the same result on a repeated radiograph) is inferred under suitable assumptions from six longitudinal series of radiographs.
Factors that influence bone age.
The rhythm of maturation and growth is different in each individual,
as long as the plaque of epiphyseal cartilage persists,
both diaphysis and epiphysis continue to grow.
However,
the osteoblasts will stop multiplying over time and the epiphyseal plate is ossified,
this is when growth stops.
There are physiological and pathological reasons that modify delaying or accelerating the process of bone maturation.
Both obesity,
genetics,
environmental factors and hormones (thyroxine,
growth hormone and sex steroids) have an important role in bone maturation.
There is a disagreement between bone age and chronological age in children with obesity or with early puberty.
Primary and secondary delay of growth.
The primary delay of growth is the result of a genetic defect or prenatal damage that leads to a shortening of the diaphysis without a significant delay in epiphyseal maturation.
Secondary delay of growth is related to nutritional,
metabolic or unknown factors such as idiopathic (constitutional) growth retardation syndrome.
Bone age is frequently delayed in patients with idiopathic short height,
with an average of 1.5 - 2 years (range 0-4 years) at age of 8-11 years,
so whenever there is a delay in growth,
It will be related to a growth hormone deficit.
The absence of a delay in bone age is a strong argument against the existence of a growth hormone deficit,
although the delay in bone age does not always imply a delay of puberty.
Patients treated with growth hormone have an acceleration in bone age during prepuberty and puberty,
but bone age is usually delayed in most. Main causes of growth hormone deficiency( Table 3).
In those patients with short height and history of delayed intrauterine growth,
we found a delayed bone age up to 8 years.
However,
during the prepubertal stage,
rapid acceleration occurs with a premature and reduced liberal growth.
In Turner syndrome,
bone maturation is usually slightly delayed in the first assessment after birth which lasts until 10 years,
followed by a maturational delay due to the total or partial absence of estrogen.
In chronic kidney disease,
we found delayed bone age and delayed puberty.
However,
they have an acceleration in growth during puberty to subsequently lose height progressively (Figure 13).
Bone age advanced.
Given the presence of tall height,
a slightly advanced bone age is observed in patients with early puberty,
with a slow progression of bone maturation.
In other cases,
puberty is rapidly progressive and when it is diagnosed early,
bone age could be only minimally accelerated and must follow closely.
Sex steroids predominantly affect short bones rather than large bones,
so short bones are more useful for diagnosis.
Obesity is usually the most likely cause of high height and these are probably mediated by insulin and IGF-1.Excessive secretion of growth hormone in pituitary gigantism is known as McCune-Albright syndrome.
The presence of dysmorphic signs or asymmetries in the body segments in a tall height should make us think in syndromes associated with macrosomia (Beckwith-Wiedemann and Sotos syndrome),
which will show an advanced and fast-growing bone age that is later delayed.
In those patients with short height and history of delayed intrauterine growth,
we found a delayed bone age up to 8 years.
However,
during the prepubertal stage,
rapid acceleration occurs with a premature and reduced liberal growth.
In Turner syndrome,
bone maturation is usually slightly delayed in the first assessment after birth which lasts until 10 years,
followed by a maturational delay due to the total or partial absence of estrogen.
In chronic kidney disease,
we found delayed bone age and delayed puberty.
However,
they have an acceleration in growth during puberty to subsequently lose height progressively (Figure 14).
Examples (Figures 15,
16,
17,
18)