This study represents to our best knowledge the first comparison of observed near final heights and the recent adult height calculation method based on automated bone age determination (BoneXpert™) with the conventional PAH method by Bayley-Pinneau based on bone age determination according to Greulich and Pyle in children with various chronic endocrinopathies. In general, there was a good agreement of automated BX in girls, regardless of bone age deviations from chronological age. The recent method of automate BX implements a nonlinear growth potential function . This is more graduated and therefore more precise than the conventional BP using the tables of Bayley-Pinneau which rates only for three ranges namely advanced ( BA > CA > 1 year), normal BA(CA = BA ± 1 year) and retarded ( BA < CA < -1 year). Our results applying automated BX in girls are in accordance with the results of Unrath et al.,  and Thodberg et al. , who investigated healthy children with short stature. Martin et al. reported a slight underprediction of automated BX in girls with short stature by 0,8 cm when bone age was younger than 12 years . This observation was explained by an individual, unpredictable growth pattern of six included girls.
Remarkably, automated BX overestimated adult heights in boys, especially, when bone ages were severely retarded. This observation was confirmed by Thodberg et al. . In their study, height predictions in boys using automated BX did not outperform the conventional method in boys indicating an inherent weak spot. It is known, that conventional BP systematically overestimates adult height in boys, especially when bone age is retarded [26, 27] or in constitutional tall stature .
These observations cannot be explained by a systematic error in bone age determination of automated BA, because our study and all other studies reported a good accordance with the conventional BA assessment (Fig. 1 and Table 2) [12, 19]. This difference is similar to the deviation between two manual raters . Further, this remarked effect is not caused by incorrect bone age determination due to dysmorphic bones, because none of the images were rejected by BoneXpert™.
The residual errors of growth prediction in both methods arise from various sources: a) conventional growth prediction models presumed a linear dependence between adult height and BA, but puberty and its growth spurt are dynamic processes and not concordant with bone age advancement. Each child experiences an individual growth pattern. The tables of Bayley and Pinneau were initially evaluated in healthy children but thereafter adapted as benchmark to children with various growth disorders and treatments. Implementation in clinical routine of growth disorders revealed a valuable tool in treatment control and expectations ([29, 30]), b) incorrect measurements of height and (near) adult heights, c) unpredictable influences on growth and pubertal development, such as nutrition, genetic, and environmental factors. But a clear advantage using automated BX is that the bone age determination is not impaired by rater variability and can be therefore easily used for clinical studies. Automated bone age determination by BoneXpert™ can be used as a reliable tool and efficient method, because it is time- and cost saving. It is reliable also when bone age is accelerated or retarded [7, 8, 12, 9]. Apart from children with chronic kidney disease, in which automated BA tended to underestimate acceleration or retardation of bone age , this difference can be probably explained by the renal osteodystrophy in this cohort.
For evaluation of bone morphology a rating of the x-ray by an expert remains mandatory and cannot be replaced by computerization. A limitation of this study is the small numbers of patients in each group. Therefore, future multi-centre-studies with a larger sample size are needed to evaluate accuracy of automated BX.
Taking the described limitations into account, the new prediction method is superior to the conventional BP in girls, regardless of bone age deviation from chronological age. Automated BX tends to overestimate PAH in boys, especially, when bone age is retarded.
Bone age determination is a standard investigation in the work up of growth disturbances in children with various paediatric diseases , but also in orthodontics and paediatric orthopaedics . Further it is used for legal issues, especially to determine a person's age based on skeletal radiographs. However, according to the statement of the European Society of Paediatric Radiology musculoskeletal task force group exact determination of chronological age of a person cannot be done with sufficient accuracy with existing methods . Based on the bone age determination several prediction models for adult heights were established. The accuracy of the predicted adult heights is limited due to the growth pattern that can be influenced by medication, nutrition, individual variation in pubertal height gain and environmental factors . This biological variation is not possible to overcome with mathematical prediction models. Therefore the accuracy of bone age assessment should be optimized to improve the accuracy of height prediction methods. Using automated bone age determination an inter- and intrarater error is eliminated and consecutively improves reproducibility of adult height prediction.