Estimating the Biological Age in Children: Multiple Methods and Their Clinical Utility.

The biological age (BA) is an estimates of how old cells, tissues and organs are at the time of observation. How one determines the BA depends on the chronological age of interest, fetal to adult. In this historical mini-review we provide an overview of various methods for the determination of BA in children. Through the ages the eruption and maturation of the dentition (observation) and then radiographic methods have been used. Later the use of radiographs to track the appearance of ossification centers and the appearance and maturation of epiphyses at the growth plates and the physical examination of the secondary sexual characteristics have been employed to define BA. We then discuss some practical issues related to skeletal age (SA) assessment, using the well described Greulich and Pyle and the Tanner Whitehouse methods before moving to some of the newer, but less validated methods of SA assessment using magnetic resonance imaging, computed tomography, ultrasound and dual x-ray assessment techniques. We close with a short discussion of modern methods for the estimation of BA noting that these biological methods depend on multi 'omics and DNA methylation, but are more suited to the prediction of adult morbidities than they are to the determination of BA of an individual child at the time of evaluation-the precise parameter of interest at that time.