Temporal milestones during childhood : identification of a maturational spurt

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The transition of the human skeleton from immature to mature is characterized by a series of predictable milestones in both growth (e.g., peak height velocity) and development (e.g., ossification of the adductor sesamoid). As such, the treatment of many skeletal growth and/or developmental disorders often includes a detailed skeletal assessment to predict the attainment of future milestones; however, differences in actual growth and development and those predicted from prior assessments are often less precise then that required for positive patient outcomes. A lack of estimate precision may be related to the 'Linear Paradigm'--a long-held assumption that skeletal maturation should progress linearly throughout childhood and adolescence (a detailed discussion can be found in Chapter One). Thus, the complex characterization of skeletal maturation, including the identification of a maturational 'spurt', akin to the pubertal growth spurt, may provide greater prognostic value than that which is provided under the Linear Paradigm. Chapters Two, Three, and Four (i.e., Aim 1) aimed to characterize longitudinal assessments of skeletal maturation throughout childhood and adolescence by leveraging existing data from the Fels Longitudinal Study. Chapter Two highlights the strengths and weakness of distinct statistical methodologies for milestone estimates of height and also provides the statistical justification for the longitudinal methodologies used in throughout the remainder of this dissertation. Chapter Three explores the longitudinal relationship, particularly related to the tempo of skeletal maturation, between chronological age and skeletal age throughout childhood and adolescence. This chapter provides a comprehensive characterization of the maturational spurt, which includes the identification of three discrete longitudinal maturational trajectories (i.e., childhood only maturational spurt, adolescent only maturational spurt, and both a childhood and adolescent maturational spurt). Chapter Four explores the clinical significance of modeling longitudinal changes in the tempo of skeletal maturation with two distinct higher order polynomial models. Aim 2 (i.e., Chapter Five) focuses on refining existing skeletal maturity phenotypes associated with relevant ontogenetic milestones of the maturational spurt. This chapter highlights the skeletal phenotypes associated with peak maturational velocity in participants that exhibited a maturational spurt in adolescence only and also establishes multivariate statistical models that can be used by pediatric practitioners to predict the timing of peak maturational velocity. Because the tempo of skeletal maturation is influenced by racial and/or ethnic background, Aim 3 (i.e., Chapter 6) characterizes relevant ontogenetic milestones associated with the maturational spurt in participants of African American, Asian American, and Hispanic descent from the Bone Mineral and Density in Childhood Study. Taken together, the data presented herein highlight the non-linear nature of normal skeletal maturation, which provides robust evidence toward a shift in the maturational paradigm. Additionally, these data provide pediatric clinicians with a more detailed understanding of the progression of skeletal maturation, particularly during adolescence, which will increase patient-specific treatment resulting in improved patient outcomes and quality of life for those suffering from skeletal growth and/or developmental disorders