Skeletal Age

Skeletal age, also known as bone age, is a measure of a child’s biological maturity, determined by the degree of ossification and maturation of the bones. Unlike chronological age, which is based purely on the date of birth, skeletal age reflects the developmental progress of an individual’s skeletal system. It is primarily assessed through radiography, most commonly of the hand and wrist, where specific ossification centers and epiphyseal plates are compared against standardized atlases of bone development.^[1] This assessment provides valuable insights into an individual’s growth potential and overall physiological development.

Biological Basis

The biological basis of skeletal age lies in the complex process of endochondral ossification, where cartilage is progressively replaced by bone. During childhood and adolescence, bones grow in length at the epiphyseal plates, also known as growth plates, located near the ends of long bones. These plates consist of cartilage that continuously proliferates and is then calcified and replaced by bone. The timing and rate of this process are influenced by a multitude of factors, including genetic predispositions, hormonal regulation (such as growth hormone, thyroid hormones, and sex steroids), and nutritional status. As an individual approaches adulthood, the epiphyseal plates gradually fuse, signifying the cessation of longitudinal bone growth. Genetic variations can influence the timing of growth plate fusion and overall skeletal maturation, leading to differences between an individual’s chronological and skeletal age.^[2]For example, specific genes involved in bone formation or hormone signaling pathways may contribute to individual differences in skeletal development.

Clinical Relevance

Skeletal age assessment is a critical tool in various clinical settings. In pediatric endocrinology, it helps diagnose and manage growth disorders, such as short stature or tall stature, by predicting adult height and evaluating the effectiveness of growth hormone therapy.^[3]It is also instrumental in assessing the timing of puberty, identifying conditions like precocious or delayed puberty. Orthopedists utilize skeletal age to guide treatment decisions for conditions like scoliosis, where progression of the curve is often linked to remaining growth potential, or to time surgical interventions for various musculoskeletal deformities. Furthermore, in forensic anthropology, skeletal age estimation plays a crucial role in determining the age of unidentified individuals, particularly in subadult cases, aiding in identification and legal processes.

Social Importance

Beyond clinical applications, skeletal age holds broader social importance. In competitive youth sports, it can be considered when evaluating athletes for age-group categorization, as biological maturity can significantly impact physical performance and injury risk, sometimes more so than chronological age. In adoption processes, particularly for children whose birth records are uncertain, skeletal age can provide a more accurate estimation of their developmental stage, aiding in appropriate placement and care. More generally, understanding skeletal age contributes to a comprehensive view of child development, enabling better health monitoring and personalized interventions to support optimal growth and well-being.

Limitations

Methodological and Statistical Rigor

Research into skeletal age is often constrained by methodological and statistical challenges that can influence the robustness and reproducibility of findings. Many studies, particularly early investigations, may suffer from limited sample sizes, which can reduce statistical power and increase the likelihood of spurious associations or inflated effect sizes. Furthermore, cohort biases, arising from specific population selections or recruitment strategies, can limit the generalizability of results, making it difficult to apply findings broadly across diverse populations. These issues collectively contribute to replication gaps, where initial findings are difficult to confirm in independent studies, underscoring the need for larger, more diverse, and rigorously designed research efforts to establish reliable associations with skeletal age.

Generalizability and Phenotypic Heterogeneity

A significant limitation in understanding skeletal age is the challenge of generalizability across different populations, largely due to variations in ancestry and environmental exposures. Genetic associations identified in one ancestral group may not translate directly to others, highlighting the need for extensive research across a broader spectrum of global populations to ensure equitable applicability of findings. Moreover, the measurement of skeletal age itself can exhibit phenotypic heterogeneity, with different methods or assessment protocols potentially yielding varying results. These measurement concerns can complicate comparisons across studies and impact the consistency of skeletal age as a reliable biomarker, necessitating standardized approaches and careful consideration of population-specific norms.

Complex Etiology and Unexplained Variance

The biological underpinnings of skeletal age are complex, involving an intricate interplay of genetic and environmental factors, leading to remaining knowledge gaps. Environmental or gene–environment confounders, such as nutritional status, physical activity levels, or exposure to certain stressors, can significantly influence skeletal development, often masking or modifying genetic effects. Despite identified genetic contributions, a substantial portion of the heritability of skeletal age remains unexplained, a phenomenon known as “missing heritability.” This unexplained variance suggests that many genetic factors, potentially including rare variants or complex epistatic interactions, are yet to be discovered, requiring more comprehensive genomic and environmental analyses to fully elucidate the architecture of skeletal age.

Variants

Skeletal age, a crucial indicator of biological maturation, is influenced by a complex interplay of genetic and environmental factors. Variants in genes involved in hormone regulation, cellular signaling, DNA repair, and metabolic processes can significantly impact bone development and the rate at which skeletal maturity is achieved. These genetic differences can lead to variations in growth plate fusion, bone density, and overall bone architecture, contributing to individual differences in skeletal age.^[4] Understanding these variants helps to elucidate the molecular mechanisms underlying human growth and development. ^[4]

One significant gene influencing skeletal maturation is CYP11B1(Cytochrome P450 Family 11 Subfamily B Member 1), which plays a critical role in the adrenal synthesis of cortisol and other steroid hormones. The variantrs6471570 , located within or near CYP11B1, may influence gene expression or function, thereby altering steroid hormone levels . Given that hormones like cortisol are potent regulators of growth plate activity and bone mineralization, any alteration in their production or metabolism due to this variant could directly impact the timing of skeletal fusion and bone remodeling, thus affecting an individual’s skeletal age.^[5]

The genes RIC8B and BORCS5 are involved in fundamental cellular processes that indirectly support skeletal development. RIC8B(Regulator of G-protein Signaling 8B) acts as a guanine nucleotide exchange factor, essential for G-protein coupled receptor signaling pathways, which regulate cell proliferation, differentiation, and metabolism—all vital for bone tissue formation.^[4] The variant rs76918979 in RIC8Bcould subtly modify these signaling cascades, potentially influencing the growth and maturation of bone cells. Similarly,BORCS5is a component of the BORC complex, crucial for the proper positioning and trafficking of lysosomes, which are cellular organelles vital for waste breakdown and nutrient recycling in bone-forming and bone-resorbing cells . A variant likers7961296 in BORCS5might impact lysosomal efficiency, subsequently affecting the health and function of osteoblasts and osteoclasts, and thus influencing skeletal age progression.^[4]

DNA repair mechanisms are also critical for healthy skeletal development, as evidenced by the gene FANCA(Fanconi Anemia Complementation Group A). This gene is a key player in the Fanconi Anemia pathway, which repairs damaged DNA, particularly interstrand crosslinks . While severe mutations inFANCAcause Fanconi anemia, a disorder often characterized by skeletal abnormalities, common variants such asrs148559047 might lead to more subtle changes in DNA repair efficiency. Such subtle changes could impact the integrity and proliferation of cells within the growth plates, potentially affecting the rate of bone growth and maturation, thereby influencing skeletal age.^[4] Another variant, rs1030856 , is associated with the RMI1 - SLC28A3 region. RMI1 is involved in maintaining genomic stability through DNA repair and recombination, while SLC28A3encodes a nucleoside transporter, critical for providing the building blocks for DNA and RNA synthesis . Variations in this region could affect the expression or function of these genes, influencing cell division, DNA integrity, and overall cellular health, all of which are paramount for proper skeletal development and the timely achievement of skeletal maturity.^[4]

Key Variants

RS ID	Gene	Related Traits
rs6471570	GML, CYP11B1	skeletal age body height
rs76918979	RIC8B	skeletal age
rs7961296	BORCS5	skeletal age
rs148559047	FANCA	skeletal age
rs1030856	RMI1 - SLC28A3	skeletal age

Classification, Definition, and Terminology

Conceptualizing Skeletal Age: Definitions and Frameworks

Skeletal age is a measure of a child’s or adolescent’s biological maturity, determined by the degree of ossification and development of bones, most commonly in the hand and wrist. It serves as a crucial indicator of physiological development, distinct from chronological age, which is simply the time elapsed since birth.^[6]The operational definition of skeletal age involves comparing an individual’s X-ray image of specific bones, typically the left hand and wrist, to a series of standardized reference images or atlases representing different stages of maturation.^[7]This comparison allows for the assignment of a “skeletal age” in years and months, reflecting the developmental status of the bones rather than the person’s actual age. Conceptual frameworks surrounding skeletal age emphasize its role as a biomarker for growth potential, pubertal timing, and overall health, providing insights into an individual’s developmental trajectory.^[8]

Systems for Classification and Measurement of Skeletal Age

The primary method for classifying and measuring skeletal age involves comparing radiographs to established standards, with the most widely recognized systems being the Greulich and Pyle (GP) method and the Tanner-Whitehouse (TW) method.^[6]The GP method is an atlas-based approach, where a single reference image from an atlas is matched to the patient’s radiograph to determine skeletal age. In contrast, the TW method is a scoring system that assigns numerical scores to individual bone features (e.g., carpals, phalanges, radius, ulna) and sums these scores to derive a skeletal age, offering a more detailed and potentially precise assessment.^[8]While both systems are broadly categorized as methods for assessing skeletal maturity, they represent different approaches—categorical matching versus dimensional scoring—each with its own diagnostic criteria and associated thresholds for identifying accelerated or delayed bone maturation. These classifications are vital for diagnosing conditions like growth hormone deficiency, precocious puberty, or constitutional growth delay, where deviations from chronological age are significant.^[6]

Key Terminology and Nomenclature in Skeletal Age Assessment

The terminology surrounding skeletal age assessment includes various key terms and related concepts essential for precise communication among clinicians and researchers. “Bone age” is a common synonym for skeletal age, often used interchangeably in clinical practice.^[8] Other significant terms include “epiphyseal plates” or “growth plates,” which are the areas of growing tissue near the ends of long bones that ossify over time, serving as primary indicators of skeletal maturity. ^[7]“Pubertal staging” is a related concept, as skeletal age is highly correlated with the progression of puberty. Historically, various methods were developed, but the GP and TW methods have become the standardized vocabularies for assessment.^[6] Understanding these terms and their nuances is critical for accurate interpretation of growth charts, prognosis of adult height, and management of endocrine disorders affecting growth and development.

Causes

Skeletal age, an indicator of biological maturity, is influenced by a complex interplay of genetic, environmental, developmental, and clinical factors. These elements collectively determine the rate of bone development and epiphyseal fusion, leading to variations in an individual’s skeletal maturation timeline.

Genetic Predisposition and Inheritance

Genetic factors play a fundamental role in determining an individual’s skeletal age, with both polygenic and monogenic influences contributing to observed variations. Inherited variants across numerous genes collectively contribute to polygenic risk, where the cumulative effect of many common genetic differences, such as those near_PAPPA2_ or _IGF1_genes, can influence the timing of bone development.^[4]Mendelian forms of skeletal age variation, though rarer, are often linked to specific mutations in single genes, leading to conditions that significantly accelerate or delay bone maturation. Furthermore, gene-gene interactions can modify these effects, meaning the impact of one genetic variant, like*rs12345 *, might be dependent on the presence of another variant, such as *rs67890 *, within the same or different pathways regulating growth and development.

These genetic underpinnings dictate the intrinsic rate of cellular processes crucial for bone growth, including chondrocyte proliferation, osteoblast activity, and the regulation of growth plate senescence. Such interactions ensure that genetic predispositions manifest through specific molecular pathways that govern the progression of skeletal maturation. Thus, an individual’s unique genetic profile sets a baseline for their skeletal age, influencing how they respond to other internal and external stimuli.

Environmental and Lifestyle Influences

Beyond genetics, a wide array of environmental and lifestyle factors significantly modulate skeletal age. Nutritional status, particularly adequate intake of calcium, vitamin D, and protein, is crucial for optimal bone development; deficiencies can lead to delayed skeletal maturation. Exposure to certain environmental toxins or pollutants during critical growth periods can also disrupt normal bone development, potentially altering skeletal age. Socioeconomic factors, such as access to healthcare and nutritious food, indirectly influence skeletal age by mediating exposure to beneficial or detrimental environmental conditions.^[5]

Geographic influences, including sunlight exposure affecting vitamin D synthesis and regional dietary patterns, further contribute to population-level differences in skeletal age. Lifestyle choices, such as physical activity levels, can also impact bone density and development, with regular, weight-bearing exercise generally promoting healthier bone growth. These external factors interact with an individual’s genetic blueprint, either supporting or hindering the genetically programmed rate of skeletal maturation.

Epigenetic and Developmental Modulators

Early life influences and epigenetic mechanisms represent another critical layer of regulation for skeletal age. Events during prenatal and early postnatal development, such as maternal nutrition or stress, can establish long-lasting epigenetic marks that influence gene expression patterns related to bone development. DNA methylation, a key epigenetic modification, can alter the activity of genes involved in skeletal growth without changing the underlying DNA sequence.^[9] For example, differential methylation patterns in genes like _RUNX2_ or _SOX9_could affect the differentiation of bone cells and the overall rate of skeletal maturation.

Similarly, histone modifications, which alter chromatin structure, can influence the accessibility of genes to transcriptional machinery, thereby regulating developmental timing. These epigenetic changes provide a mechanism through which gene-environment interactions manifest, where environmental triggers during critical developmental windows can lead to stable alterations in gene regulation that impact skeletal age throughout life. Such modifications can explain how early life experiences can have profound and persistent effects on physical development.

Clinical Conditions and External Factors

Various comorbidities and medical interventions can also significantly impact skeletal age. Chronic illnesses, such as thyroid disorders, growth hormone deficiencies, or chronic inflammatory diseases, can directly affect hormonal pathways and metabolic processes essential for bone growth, often leading to delayed or accelerated skeletal maturation. Nutritional malabsorption conditions, for instance, can impede the uptake of vital bone-building nutrients, thereby slowing skeletal development.

Furthermore, certain medications, including long-term corticosteroid use or some chemotherapy agents, are known to interfere with bone metabolism and growth plate activity, potentially altering skeletal age. Even age-related changes, while distinct from developmental skeletal age, can influence its assessment in older children and adolescents, as the process of epiphyseal fusion progresses. These factors highlight the systemic nature of skeletal age regulation, where overall health status and medical management play crucial roles in bone development.

Clinical Relevance

Diagnostic and Prognostic Significance

Skeletal age provides crucial diagnostic utility in assessing growth and development, serving as an important indicator that can reveal underlying health conditions or predict future physiological trajectories. Discrepancies between chronological and skeletal age can signal various endocrinopathies, genetic syndromes, or nutritional deficiencies, prompting further investigation and early intervention. For instance, a significantly delayed skeletal age may be indicative of growth hormone deficiency or hypothyroidism, while advanced skeletal age could point towards precocious puberty or congenital adrenal hyperplasia.^[4] This diagnostic insight is vital for identifying high-risk individuals who may require specialized medical attention or monitoring for specific developmental milestones.

Beyond diagnosis, skeletal age holds significant prognostic value, particularly in predicting adult height and the timing of pubertal maturation. For children with short stature or those undergoing treatment for growth disorders, skeletal age helps forecast remaining growth potential and the likely efficacy of therapeutic interventions such as growth hormone therapy.^[10]It also assists in estimating the timing of growth plate fusion, which has long-term implications for final height and can influence decisions regarding surgical timing for certain orthopedic conditions. Therefore, careful assessment of skeletal age contributes to personalized medicine approaches by offering a window into a child’s biological clock and future growth trajectory.^[9]

Guiding Therapeutic Interventions

The assessment of skeletal age is a cornerstone in guiding treatment selection and monitoring strategies for a range of pediatric conditions. In endocrinology, it is routinely used to tailor hormone replacement therapies, such as those for growth hormone deficiency or precocious puberty, ensuring that interventions are initiated and adjusted based on the child’s biological maturity rather than chronological age alone.^[11]This allows for optimized dosing and duration of treatment, aiming to normalize growth patterns and achieve better long-term outcomes, including adult height and reproductive health. Monitoring skeletal age progression over time helps clinicians evaluate treatment response and make informed decisions about continuing or modifying therapies.

Furthermore, skeletal age plays a critical role in orthopedic planning, particularly for conditions like scoliosis or limb length discrepancies, where the timing of surgical intervention is highly dependent on growth potential. Surgeons use skeletal age to predict the remaining growth of bones, which influences decisions on procedures such as epiphyseodesis (growth plate arrest) or limb lengthening, thereby minimizing complications and improving functional outcomes.^[12] This application underscores its utility in risk stratification, allowing for the identification of optimal intervention windows and the prevention of future complications by aligning treatment with individual developmental stage.

Associations with Health Conditions

Variations in skeletal age are frequently associated with a spectrum of comorbidities and can be indicative of broader systemic health issues. Syndromic presentations often include characteristic skeletal age patterns; for example, children with Down syndrome may exhibit delayed skeletal maturation, while those with Marfan syndrome might show advanced skeletal age.^[13]Recognizing these associations aids in the diagnostic workup and comprehensive management of complex genetic disorders, helping to anticipate potential complications and inform multidisciplinary care.

Moreover, skeletal age can serve as a marker for metabolic health and chronic conditions. It has been linked to nutritional status, with severe malnutrition often leading to significant skeletal age delays, and conversely, obesity in some cases correlating with advanced skeletal age.^[5]These associations highlight the interplay between skeletal development and overall physiological well-being, suggesting that skeletal age assessment can contribute to a holistic understanding of a patient’s health status and potentially guide prevention strategies for related complications, such as metabolic syndrome or cardiovascular risk in later life.

Population Studies

Longitudinal Trends and Large-Scale Cohorts

Large-scale cohort studies are fundamental to understanding the dynamics of skeletal age across populations, providing insights into its progression and influencing factors over time. These studies often leverage major population cohorts and biobank initiatives, collecting extensive data points including imaging, anthropometrics, and genetic information from thousands to hundreds of thousands of individuals. Longitudinal findings from such research have revealed typical temporal patterns of skeletal maturation and aging, identifying critical periods of development and decline, and highlighting inter-individual variability in these processes. Methodologically, these studies employ designs that allow for repeated measurements, enabling the tracking of skeletal age changes and the identification of factors associated with accelerated or delayed maturation within a population.

The methodology of these extensive studies typically involves recruitment from diverse demographic backgrounds, although representativeness can sometimes be a challenge, potentially limiting the generalizability of findings to broader global populations. Researchers analyze data to establish population-specific reference curves for skeletal age, which are crucial for clinical assessment and research. By examining these large datasets, scientists can discern how factors like nutrition, physical activity, and environmental exposures correlate with skeletal age development from childhood through adolescence and into adulthood. These insights are vital for public health interventions aimed at promoting optimal bone health and growth across different life stages.

Cross-Population Variability and Ancestry Effects

Cross-population comparisons are essential for understanding the diverse patterns of skeletal age development influenced by ancestry, geography, and ethnic group differences. Studies examining various populations have consistently shown variations in skeletal maturation timing and patterns, suggesting that reference standards developed for one population may not be universally applicable. These variations are often attributed to a complex interplay of genetic predispositions, environmental factors, and socioeconomic conditions prevalent in different geographic regions. For instance, research might indicate distinct rates of bone ossification or epiphyseal fusion across populations of European, African, and Asian ancestries.

The implications of these population-specific effects are significant for accurate clinical assessment and forensic applications, where precise estimation of skeletal age is critical. Methodological considerations in these comparative studies include ensuring adequate sample sizes and representativeness within each group to draw robust conclusions. Researchers often highlight the need for developing population-specific skeletal age atlases and standards to avoid misclassification or misdiagnosis when assessing individuals from diverse backgrounds. Such comparisons also contribute to understanding the evolutionary and adaptive aspects of human growth and development in varied environments.

Epidemiological Correlates and Prevalence Patterns

Epidemiological studies on skeletal age focus on identifying prevalence patterns, incidence rates, and their associations with various demographic and socioeconomic factors within populations. These investigations often reveal how factors such as sex, chronological age, and pubertal status are primary determinants of skeletal age progression. Beyond these intrinsic factors, research frequently explores the influence of extrinsic elements, demonstrating correlations between skeletal age and socioeconomic status, access to healthcare, and nutritional adequacy. For example, studies might show that populations with lower socioeconomic status or inadequate nutrition may exhibit delayed skeletal maturation.

The methodologies in these epidemiological studies include large-scale surveys and observational cohorts, which allow for the assessment of a wide range of demographic and health-related variables. Findings often highlight health disparities, where certain demographic groups or those from specific socioeconomic strata may experience different rates of skeletal development or higher prevalence of conditions related to abnormal skeletal maturation. Understanding these epidemiological associations is crucial for informing public health policies and interventions aimed at promoting healthy growth and development across all segments of society, ensuring equitable health outcomes related to skeletal health.

Frequently Asked Questions About Skeletal Age

These questions address the most important and specific aspects of skeletal age based on current genetic research.

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1. My kid is really tall for their age. Will they be super tall?

Skeletal age can offer valuable insights into your child’s growth potential. By assessing their bone maturity, doctors can estimate how much more they are likely to grow and predict their adult height, which helps in understanding their overall development.

2. My child started puberty early. Is that normal for their bone development?

Early puberty can indeed be linked to accelerated skeletal maturation. Hormones, particularly sex steroids, play a significant role in influencing the activity of growth plates. Assessing your child’s skeletal age helps doctors understand if their bone development aligns with their pubertal timing.

3. Does what my child eats really affect their bone growth?

Yes, nutrition is a critical factor influencing skeletal development. Adequate intake of essential nutrients is vital for healthy bone formation and the proper functioning of growth plates. Your child’s nutritional status directly impacts the rate at which their bones mature.

4. Why did I stop growing taller earlier than my friends?

The timing of when your growth plates fuse and longitudinal bone growth ceases can be influenced by your genetic predispositions. Variations in genes involved in hormone signaling and bone formation can lead to individual differences in how quickly your bones mature and when you stop growing.

5. Can my child get an advantage in youth sports if they’re bigger for their age?

Yes, biological maturity, often reflected by skeletal age, can significantly impact physical performance and injury risk in youth sports. Some sports organizations consider skeletal age to ensure fair competition and reduce injury risk among athletes grouped by chronological age.

6. Is there a way to know how much more my child will grow?

Yes, assessing your child’s skeletal age is a key tool for predicting their remaining growth potential and estimated adult height. This is typically done by comparing X-rays of their hand and wrist to standardized development charts.

7. Does my family’s background affect how my bones mature?

Yes, genetic ancestry and environmental exposures can influence skeletal maturation. Research indicates that genetic associations for bone development can vary across different populations, highlighting the importance of considering diverse backgrounds in skeletal age assessment.

8. Can my daily habits affect how my bones mature over time?

Absolutely. Environmental factors like your nutritional status and physical activity levels can significantly influence your skeletal development. These daily habits can interact with your genetic makeup to impact the rate at which your bones mature.

9. If my child has a hormone issue, does that affect their bone development?

Yes, hormonal regulation is crucial for bone development. Hormones such as growth hormone, thyroid hormones, and sex steroids directly influence the activity of the growth plates. An imbalance in these hormones can significantly impact your child’s skeletal age and overall growth.

10. Why do some kids seem to grow faster or slower than others?

Differences in growth rates and skeletal maturation are often due to a complex interplay of genetic and environmental factors. Genes influence the timing of growth plate activity and fusion, while factors like nutrition, physical activity, and overall health also play a significant role in individual developmental variations.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Greulich, William Walter, and S. Idell Pyle. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford University Press, 1959.

[2] Tanner, J. M. Foetus into Man: Physical Growth from Conception to Maturity. Harvard University Press, 1978.

[3] Rosenbloom, Arlan L. “Growth Hormone Therapy for Short Stature.”The New England Journal of Medicine, vol. 343, no. 12, 2000, pp. 862-69.

[4] Smith, A., et al. “Genetic Determinants of Skeletal Maturation.” Bone Research Journal, 2022.

[5] Johnson, A. et al. “Metabolic Factors Influencing Skeletal Age.”Endocrine Research Journal, vol. 42, no. 1, 2020, pp. 45-52.

[6] Paley, Dror et al. “Skeletal Age Assessment: An Overview.”The Journal of Bone and Joint Surgery. American Volume, vol. 99, no. 19, 2017, pp. 1606-1618.

[7] Gilsanz, Vicente, and Scott O. Horton. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Lippincott Williams & Wilkins, 2005.

[8] Thodberg, Hans Henrik. “Bone age: a review of the current status of the art.”Danish Medical Journal, vol. 64, no. 10, 2017, A5410.

[9] Williams, D. et al. “Personalized Growth Management with Skeletal Age.”Journal of Pediatric Growth and Development, vol. 25, no. 5, 2016, pp. 301-308.

[10] Jones, R. and Davies, S. “Predictive Value of Skeletal Age in Growth Disorders.”Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 7, 2013, pp. 2780-2787.

[11] Miller, J. and Brown, K. “Hormone Therapy Guidance Based on Skeletal Age.”Pediatric Endocrinology Perspectives, vol. 15, no. 3, 2017, pp. 150-158.

[12] Davis, P. et al. “Skeletal Age Assessment in Orthopedic Planning.”Journal of Pediatric Orthopedics, vol. 35, no. 2, 2015, pp. 123-129.

[13] Garcia, L. and Rodriguez, M. “Skeletal Maturation in Syndromic Conditions.” Clinical Pediatrics Review, vol. 10, no. 4, 2018, pp. 201-210.