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Editor’s Spotlight/Take 5—Early Maturity as the New Normal

A Century-long Study of Bone Age

Leopold, Seth S., MD

Clinical Orthopaedics and Related Research®: November 2018 - Volume 476 - Issue 11 - p 2108–2111
doi: 10.1097/CORR.0000000000000481
REGULAR FEATURES

S. S. Leopold, Editor-In-Chief, Clinical Orthopaedics and Related Research®, Philadelphia, PA, USA

S. S. Leopold MD, Clinical Orthopaedics and Related Research®, 1600 Spruce Street, Philadelphia, PA 19013 USA, Email: sleopold@clinorthop.org

A note from the Editor-In-Chief: In “Editor’s Spotlight,” one of our editors provides brief commentary on a paper we believe is especially important and worthy of general interest. Following the explanation of our choice, we present “Take Five,” in which the editor goes behind the discovery with a one-on-one interview with an author of the article featured in “Editor’s Spotlight.”

The author certifies that neither he, nor any members of his immediate family, have any commercial associations (such as consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

The opinions expressed are those of the writer, and do not reflect the opinion or policy of CORR® or The Association of Bone and Joint Surgeons®.

This comment refers to the article available at: DOI: 10.1097/CORR.0000000000000446.

Received August 13, 2018

Accepted August 16, 2018

It certainly seems as though our children are growing up faster. Twenty years ago, the public-policy think tank Manhattan Institute said so, lamenting—among other social ills—the fact that cosmetics were being marketed to 12-year-olds [11]. Then again, nearly 100 years before that, psychologist Granville Stanley Hall wrote in his book The Psychology of Adolescence: “Never has youth been exposed to such dangers of both perversion and arrest as in our own land and day. Increasing urban life with its temptations, prematurities … and passive stimuli just when an active life is most needed …” [8].

They both were right, and it’s not getting any easier. The question is this: If 70 is the new 50 [12], is 12 also the new 16?

The answer may be yes in terms of menarche [1] and something close to yes for several other important physiological milestones, including skeletal development [9, 10]. In this month’s Clinical Orthopaedics and Related Research®, Dana L. Duren PhD, and her team at the University of Missouri demonstrate that during the last century or so, the timing of epiphyseal fusion in the hand and wrist gradually has shifted to occur earlier—by nearly 10 months in girls, and nearly 7 months in boys [2].

Their finding, which follows up on earlier work Dr. Duren’s team also published in CORR® [4], calls for a reassessment of the radiograph-based assessment tools that pediatric orthopaedic surgeons use to guide the timing of interventions for leg-length inequalities, scoliosis, and other problems related to skeletal development. In particular, their observations are substantially out of sync with the Greulich-Pyle standards [5], which is considered a valid approach to guide the timing of limb-lengthening surgery, growth-modulation procedures in the extremities, and spinal fusions [15]. Studies like Dr. Duren’s [2], which are drawn from particular (and sometimes rather homogeneous [16]) patient populations remind us that we need more information about how to make decisions on patients whose racial or ethnic backgrounds differ from the populations from which the normative standards are derived, and that this kind of information often is not easy to come by [9].

In addition to calling into question our standard approaches to gauging skeletal maturity [5], Dr. Duren’s findings should cause us to ask why the observed developmental changes are occurring. Specifically, it seems relevant to ask what harms might arise alongside accelerated skeletal maturation in children. Dr. Duren and her team [2] posited that estrogen exposure (through obesity, dietary exposure, and earlier puberty) may have caused the skeletal findings they observed. Others have associated those same exposures with a host of other health problems both in girls [6] and boys [3, 7], including serious emotional fallout that may occur when physical maturity occurs so much earlier than psychological maturity [13, 14].

Please join me in the Take 5 interview with Dr. Duren, senior author of “Early Maturity as the New Normal: A Century-long Study of Bone Age,” to get the answers to these and other questions that are important regardless of whether you treat children in your practice, have them at home, or know anyone who does.

Take Five Interview with Dana L. Duren, PhD senior author of “Early Maturity as the New Normal: A Century-long Study of Bone Age”

Seth S. Leopold MD: Congratulations on this ground-breaking work. Please share with our readers what sparked your interest in this somewhat-unusual topic, and why you think the Fels Longitudinal Study [16] was the right setting for this work?

Dana L. Duren PhD: Thank you for inviting me to participate in the Take Five interview. Changes in skeletal form have been a focus of my research for many years. The childhood and adolescent changes that bring a young person to adulthood are fascinating, and the range of variation in the form and timing of skeletal change is important, particularly in light of accelerated maturation in other somatic and psychological phenotypes. As you noted, trends for earlier skeletal maturation are becoming evident across the globe. We wanted to know if particular aspects of maturation that are likely driving “bone age” could be examined independently for such trends. The Fels Longitudinal Study is a unique source for examining changes in human biology over the past century. Unlike the other growth studies of the 20th Century (Bolton-Brush, Berkeley, Harvard, and Denver growth studies), the Fels Longitudinal Study continued to see participants long after others had closed up shop mid-century, making it the world’s only century-long study of human growth and development. Because this community-based study continued for such a long period of time using radiography throughout its existence, we can track things like skeletal maturation and fusion events across this population and across time. It really is an exciting use of this resource.

Dr. Leopold: Your work raises some important questions that apply to how we acquire normative data; it seems that almost every study that sets population norms must make compromises between data density and generalizability. Your source (again, the Fels study [16]) is extremely rich in terms of the detail it provides, but it provides it on a single, relatively homogeneous population. It’s inconceivable that we will ever get data like this on a population as diverse as that of the United States. How, then, is a provider to make clinical decisions on these important topics?

Dr. Duren: You are absolutely correct. It is important to acknowledge the bias inherent in any “normative” data we use in research and for clinical decision-making. This is particularly salient in skeletal maturation, where variation in ancestral heritage in American children is associated with the timing and/or tempo of maturation, yet the most commonly used methods for assessing skeletal maturity (Greulich-Pyle [5] and Fels [16]) are currently based on reference populations that are out of date and not representative of the diversity within the United States. Clinical use of these standards is necessary in order to gauge the developmental status of patients, and an awareness of expected variation should be appreciated. Despite the limitations of current methods, they do provide the clinician with useful information regarding maturity. And fortunately, tracking changes in a single patient is reliable for identifying accelerations or delays in that child.

Dr. Leopold: Related to that, how important is it that the commonly used metrics of bone age—such as Greulich-Pyle [5]—be revised considering your findings, or is more confirmatory work needed before that should happen? If more work is needed, where is it likely to come from? You know better than anyone else how difficult these data are to come by.

Dr. Duren: Greulich-Pyle is a valuable tool for orthopaedists to evaluate maturation. However, I hope that we can acknowledge that it is out of date and certainly has room for improvement. It is based on a small reference sample of white children born in the early part of the 20th Century. The changes in epiphyseal fusion initiation and completion in whites that we have observed over the past century highlight, at minimum, the need for updated reference samples. This time-trend analysis does not address the meaningful variation in skeletal maturation traits observed among nonwhite children, which plays an equally important role in our interpretations of a child’s biological maturity status. The good news is that efforts are underway to update the reference population upon which maturity standards are based. I have an ongoing grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to update these standards, incorporating contemporary children of different ancestries and ethnicities, as well as streamlining the number of indicators to be assessed in a method like Fels to make it more clinically palatable. We hope to release this new method in 2019.

Dr. Leopold: Others have written extensively on what appear to be serious psychological and behavioral problems associated with the dissociation of physical maturity (menarche, puberty), which seems to be occurring earlier and earlier, from emotional maturity, which comes much later [13, 14]. While your work does not bear directly on this, I have no doubt that you’ve given it considerable thought. How should we—as parents, physicians, and policymakers—address these concerns to best protect our children?

Dr. Duren: These studies are fascinating and incredibly important as we raise children and treat patients. I feel that there has yet to be a definitive analysis on cause and effect and covariation on psychosocial issues and physical maturation. Behavioral and psychological phenotypes are not my primary expertise, but it seems that physical maturation and these nonphysical phenotypes are likely to have a common set of factors influencing variation. Speaking as a parent on this topic, I work hard to identify what I feel is best for my daughter. I use my training to make decisions and I talk to her about those decisions. I think that may work for physicians and policymakers as well.

Dr. Leopold: Others also have written extensively about the physical harms that seem to be associated with accelerated physical maturation (menarche, puberty), including differential risks of cancer, heart disease, and diabetes. Must we accept this as “a new normal,” as your title suggests, or do we have any hope to mitigate at least the environmental causes that may be contributing to these changes in how our children seem to be developing?

Dr. Duren: If the changes we and others see in the pediatric skeleton and in physical maturation, puberty, and menarche are heavily influenced by modifiable changes to our environment, then we do not have to accept this as “the new normal.” Growth and development, however, are so tightly intertwined with our diet and exposures (including psychological exposure) that identifying cause and effect is difficult. It is further complicated by the realization that the factors influencing one population may be different than those affecting another population. The challenge of identifying the mechanisms leading to changes in child health is not straightforward. The answer will require an integrative multifactorial approach that includes examination of factors including transgenerational (genetic and epigenetic) and environmental (diet, behavior, external chemical contact) perturbations to the developing child.

Dana L. Duren PhD

Dana L. Duren PhD

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Acknowledgments

The author thanks Matthew B. Dobbs MD, for his thoughtful suggestions that improved the Editor’s Spotlight commentary.

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References

1. Bellis MA, Downing J, Ashton JR. Adults at 12? Trends in puberty and their public health consequences. J Epidemiol Community Health. 2006;60:910–911.
2. Boeyer ME, Sherwood RJ, Deroche CB, Duren DL. Early maturity as the new normal: A century-long study of bone age. Clin Orthop Relat Res. [Published online ahead of print]. DOI: 10.1097/CORR.0000000000000446.
3. Bonilla C, Lewis SJ, Martin RM, Donovan JL, Hamdy FC, Neal DE, Eeles R, Easton D, Kote-Jarai Z, Al Olama AA, Benlloch S, Muir K, Giles GG, Wiklund F, Gronberg H, Duren D, Nahhas R, Sherwood R. Do secular trends in skeletal maturity occur equally in both sexes? Clin Orthop Relat Res. 2015;473:2559–2567.
4. Duren D, Nahhas R, Sherwood R. Do secular trends in skeletal maturity occur equally in both sexes? Clin Orthop Relat Res. 2015;473:2559–2567.
5. Greulich W, Pyle S. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford, CA, USA: Stanford University Press; 1959.
6. Grunnet LG, Hansen S, Hjort L, Madsen CM, Kampmann FB, Thuesen ACB, Granstrømi C, Strøm M, Maslova E, Frikke-Schmidt R, Damm P, Chavarro JE, Hu FB, Olsen SF, Vaag A. Adiposity, dysmetabolic traits, and earlier onset of female puberty in adolescent offspring of women with gestational diabetes mellitus: A clinical study within the Danish national birth cohort. Diabetes Care. 2017;40:1746–1755.
7. Haiman CA, Schleutker J, Nordestgaard BG, Travis RC, Pashayan N, Khaw KT, Stanford JL, Blot WJ, Thibodeau S, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Brenner H, Park J, Kaneva R, Batra J, Teixeira MR, Pandha H, Lathrop M, Davey Smith G; PRACTICAL consortium. Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort. BMC Med. 2016;14:66.
8. Hall GS. The Psychology of Adolescence. New York, NY: D Appleton and Company; 1904.
9. Hawley N, Rousham E, Norris S, Pettifor J, Cameron N. Secular trends in skeletal maturity in South Africa: 1962-2001. Ann Hum Biol. 2009;36:584–594.
10. Herman-Giddens ME. Recent data on pubertal milestones in United States children: The secular trend toward earlier development. Int J Androl. 2006;29:241–246.
11. Hymowitz KS. Kids today are growing up way too fast. Available at: https://www.manhattan-institute.org/html/kids-today-are-growing-way-too-fast-0528.html. Accessed on July 24, 2018.
12. Knapton S. Old age does not begin until 74, researchers suggest in a new report which looks at the real impact of an ageing population. Available at: https://www.telegraph.co.uk/science/2016/03/15/old-age-does-not-begin-until-74-researchers-suggest-in-a-new-rep/. Accessed on July 24, 2018.
13. Mathias CW, Charles NE, Liang Y, Acheson A, Lake SL, Ryan SR, Olvera RL, Dougherty DM. Pubertal maturation compression and behavioral impulsivity among boys at increased risk for substance use. Addict Disord Their Treat. 2016;15:61–73.
14. Mendle J, Ryan RM, McKone KMP. Age at menarche, depression, and antisocial behavior in adulthood. Pediatrics. 2018;141:e20171703.
15. Park KW, Kim JH, Sung S, Lee MY, Song HR. Assessment of skeletal age in multiple epiphyseal dysplasia. J Pediatr Orthop. 2014;34:738–742.
16. Roche A. Growth, Maturation, and Body Composition: The Fels Longitudinal Study 1929-1991. New York, NY: Cambridge University Press; 1992.
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