EF is a primary trait used by pediatric orthopaedists when assessing the skeletal maturity status of a child, particularly when developing treatment plans for skeletal growth and/or developmental disorders. However, the current gold standard methods for determining skeletal maturity, including the ages at which EF should be achieved, are based on populations of children born 60 to 80 years in the past, and century-long population shifts in the timing of maturation have likely influenced the age at which EF occurs. The present study aimed to quantify changes in EF timing by leveraging a large-scale longitudinal sample that ranges in birth years from 1915 to 2006 and provides clinicians with a sense of the “new normal” for EF-I and EF-C in the bones of the hand and wrist. Our results suggest that children born more recently experience EF-I and EF-C at earlier ages than when compared with those born in the early part of the 20th century and used to develop the gold standard methods. For example, EF-I in the third metacarpal is reached approximately 6.7 months earlier in males born in 1995 than those born in 1935. Our findings are critical for clinical assessments of skeletal maturity because EF-I and EF-C are occurring at substantially younger ages in normally developing children than previously thought.
This study has limitations related to the geographic and familial heritage of the study participants. The participants in this study accurately represent the greater Fels Longitudinal Study (Fig. 1), most of whom are white and from southwest Ohio. Documented differences in the timing of maturation in nonwhite children may limit the generalizability of our results to children of different ethnic groups and possibly even white children from other regions within the United States. Extrapolating these results to other groups or populations should be done with caution. However, detecting trends over time in traits such as EF timing requires longitudinal data that span many decades in a single population. Dense longitudinal data of this kind are rare, and the Fels Longitudinal Study is an important resource for tracking such trends. Nevertheless, the patterns of earlier age at EF observed in this study may be similar to those experienced by children in other geographic areas. Additional studies are needed to confirm if these trends hold true for other ethnic groups. Examination of historic radiographic records of such groups would be essential for this type of confirmation. Another minor limitation of this study is the frequency of radiographic assessments. Fels Longitudinal Study participants were examined at 6-month intervals, thereby limiting the resolution of the exact timing of specific EF events. However, the 6-month interval used by the Fels Longitudinal Study is both consistent with clinical followup assessments and is narrower than many other longitudinal studies that assess participants on a yearly basis [7, 24, 37].
We previously reported a trend toward earlier skeletal maturity in US children born after 1965, including accelerated EF . The present study examined EF-I and EF-C as separate events across continuous birth years, showing that the timing of EF has shifted in contemporary males and females. Assuming shifts in the timing of EF are truly independent of progression in other indicators of maturation such as shape changes, projections, and radiopaque densities, as shown previously , then maturity assessments that do not grade fusion separately (including Gruelich-Pyle ) may mask the influence of EF on bone age, particularly EF-I. The Fels  and Sanders  methods are more sensitive to EF events and should be utilized more readily in contexts in which linear growth is most important.
The changes in EF timing we observed over the past century have happened gradually and are consistent with trends toward earlier maturation in puberty and menarche [13, 19, 21]. The typical age of menarche, for example, has decreased by approximately 3 months in white females [15, 21] and 6 months in black females [15, 20, 21] between the early 1960s and the late 1990s in the United States. Similar trends have occurred worldwide (see Euling et al.  for a full review). It is not surprising that maturation in other systems such as the skeleton would follow and also exhibit advancement. In addition to trends identified in Fels Longitudinal Study participants, contemporary children from other studies in the United States also exhibit advanced skeletal maturation between 4 and 10 months when compared with Greulich-Pyle standards . In South Africa, children born in 1990 showed advanced skeletal maturation relative to children born in the 1960s with South African blacks exhibiting an advancement of approximately 12 months on average and South African whites exhibiting an advancement of approximately 3 months . These previous studies, however, do not report the timing of fusion separately, but rather overall skeletal age.
The mechanism underlying fusion events at earlier chronological ages may be systemic and related to the secular changes in puberty noted previously. Maturation of the skeleton is influenced by sex hormones, which itself can be influenced by adipose tissue. The Fels Longitudinal Study has documented a trend in the age of onset for puberty and menarche  and a modest increase in body mass index , contributing to earlier exposure to these hormones. Because estrogen, in particular, is critical for EF-I and EF-C during adolescence [8, 14, 25], active estrogen receptors on growth plate chondrocytes may underlie the noted trend toward advanced EF. Because estrogen accelerates the senescent decline of chondrocytes in the hypertrophic zone , earlier introduction to estrogen through environmental and dietary exposure may, therefore, lead to an earlier reduction in growth plate cartilage thickness in both males and females, contributing to growth plate closure. Although the exact mechanism behind the observed advancement in the timing of EF milestones remains unknown, it is essential to consider the sources of potential factors influencing EF timing when examining individual growth trajectories for diagnosis and the development of treatment plans. Earlier natural fusion of the physes in contemporary children alters the expectations of clinical observations compared with skeletal maturity standards. When monitoring a patient for anticipated growth-related manipulation, earlier interventions may be warranted.
A trend toward a more rapidly maturing skeleton in contemporary cohorts suggests that the timing of EF is likely changing; thus, the windows of treatment timing such as deformity correction or physeal manipulation may also be affected. Using nearly a century of longitudinal data, we showed a moderate shift toward earlier ages of EF-I and EF-C in 13 of 29 (45%) traits in males and in 19 of 29 (66%) traits in females. In general, EF-I traits exhibited greater changes in age than did EF-C traits with the magnitude of the observed trends appearing to be larger in females than in males. As the contemporary population shifts the timing of maturational milestones, expectations regarding the average age of occurrence for a maturational milestone, including EF, must shift as well.
We thank the participants of the Fels Longitudinal Study for their lifelong dedication to research. Thank you to the anonymous reviewers and the various faculty and staff involved in the Fels Study over the years, specifically Beverly Barry, Carol Cottom, Kimberly Lever, and Sharon Lawrence for data collection and Christina Holzhauser and Nicole Odom for assistance in skeletal phenotyping.
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