## 2 Left Hand and Wrist Bone Age Assessment  
### Traditional Approaches  
The ossification pattern in the hand and wrist bones is quite predictable and age-specific until the end of adolescence, when bone elongation is complete. Thus, the most widely used methods for estimating bone age are based on a comparison of the patient's level of maturation of hand and wrist bones to normal age standard levels. The radiograph of the left-hand wrist is the most used imaging technique for bone age assessment because it is fast and safe, widely available, and can obtain information from many bones included those in a small anatomical region. Despite the various attempts to avoid radiation using ultrasound (US) or magnetic resonance imaging (MRI), the antero-posterior hand radiograph is still the most popular method because the effective dose of radiation received is between 0.0001-0.1 mSv [1, 43]. Moreover, the quick acquisition of a radiograph is well suited to poor patient compliance, while US and MRI require more time and collaboration. The GP method is based on the comparison of the appearance of a standard left-hand wrist X-ray with the nearest matching reference images provided in the atlas \"The Radiographic Atlas of Skeletal Development of the Hand and Wrist\" by Dr. [PERSON] and Dr. [PERSON] (1959) [9]. This atlas contains reference standards of the left hand-left wrist radiography of subjects up to 18 years for females and 19 years for males. The GP method is simple and relatively fast, but it is based on radiographs of North American Caucasians of good socioeconomic status, therefore, it does not apply to different populations. This method demonstrated good reliability for Australian and Middle Eastern ethnicities, but it was imprecise when applied to Asian, especially males, and to African females [44; 45; 46; 47]  
Furthermore, recent studies have shown that bone age is advanced compared to chronological age, even in Caucasian populations, most likely because children nowadays mature faster than those reported in the GP Atlas, which was published in 1959 [48]. The GR Atlas [10] is a digital atlas, developed in 2005, including artificial and idealized standard hand-wrist radiographs images, specific for age and sex, created considering size, shape, morphology, and density as maturity characteristics of ossification centers in healthy children from 8 months to 18 years of age (at 6-month intervals between 2 and 6 years, and yearly intervals between 7 and 17 years). Compared to the older GP atlas, the new GR atlas provides images that are more precise and of a higher quality [49]. However, it also has more outliers [1] and it is affected by ethnic differences, as shown in a testing application on the Chinese population. According to this study, the GR atlas is not recommended in males aged 10-13 years, while the GP atlas does not fit properly for females aged 0-3 years [50]. The Tanner Whitehouse Method (1983) (TW2) [11] assesses the level of maturity of 20 selected regions of interest in specific bones of the hand and wrist in each age population. The development level for each region of interest is categorized into specific stages (from A to I) corresponding to a numerical score for every single bone. A global sex-specific maturity score is then obtained by summing all the individual scores and converting them into bone age [51]. In addition to the well-known ethical limitations, the TW2 method was affected by the evidence that new-generation children's bones were maturing more rapidly than in the past; therefore, a revised TW3 method was proposed in 2001 to assess the maturity of the radius, ulna, and short bones (RUS), with a new version of centile charts [11]. Regardless of this evidence, TW2 remains the most known and used method [52].