A fter a period of growth inhibition, the linear growth rate usually exceeds the normal range. This phenomenon, known as catch-up growth, was first described more than 40 years ago by Prader et al. It has been observed in humans and other mammals, after a wide variety of growth-inhibiting conditions, including malnutrition, Cushing syndrome, hypothyroidism, growth hormone deficiency, and many other systemic diseases. Tanner proposed the hypothesis that catch-up growth is regulated by a central nervous system mechanism that compares the individual’s actual body size to an age-appropriate set point and then adjusts the growth rate accordingly. However, this hypothesis is not supported by observations that transient growth inhibition within a single growth plate is followed by local catchup growth in rabbits. This local catch-up growth suggests a mechanism intrinsic to the growth plate. Evidence fromanimal studies suggests that catch-up growth is due, in large part, to a delay in growth plate senescence.Growth plate senescence refers to the normal, programmed changes that occur in the growth plate over time. With increasing age, there is a decrease in the linear growth rate, the chondrocyte proliferation rate, the height of the growth plate, and the number of cells in each growth plate zone. Animal studies suggest that growth plate senescence is not a function of time per se, but of cell proliferation. In particular, growth plate chondrocytes may have a finite proliferative capacity that is gradually exhausted, causing growth to slow and eventually to stop. Conditions that suppress growth plate chondrocyte proliferation conserve the proliferative capacity of the chondrocytes, thus slowing senescence. Consequently, after transient growth inhibition, growth plates retain a greater proliferative capacity, are less senescent, and, hence, show a greater growth rate than expected for age, resulting in catch-up growth. However, the relationship between catch-up growth and delayed growth plate senescence has only been studied in rabbits and rats. Thus it is not known whether catch-up growth is caused by delayed growth plate senescence in humans. Testing this hypothesis in humans is more difficult because most of the known hallmarks of growth plate senescence require microscopic examination of the growth plate. In children, we are restricted to indirect measures of growth plate senescence, including bone age and linear growth rate. Bone age assesses the degree to which the embryonic cartilaginous skeleton has been transformed into the adult bony skeleton. Bone age has been used as a surrogate marker for growth plate senescence on the basis of 2 lines of evidence. First, the determination of bone age is based partly on the thickness of the radiolucent bands between the epiphyses and metaphyses, and thus bone age depends in part on growth plate height, a structural marker of senescence. Second, bone age is inversely associated with the remaining linear growth potential. This association is the basis for most height prediction methods. Thus bone age is associated with a functional marker of senescence, the decline in growth potential of the growth plates. If catch-up growth in humans is indeed due to delayed growth plate senescence, and if bone age is a marker for growth plate senescence, then catch-up growth should be associated with delayed bone age. Abundant clinical data support this association. A delayed bone age is observed in essentially all conditions that impair growth, including nutritional, endocrine, rheumatologic, gastrointestinal, heart, lung, and kidney disease. Thus multiple conditions, which span the breadth of pediatric medicine, are all associated with growth inhibition, bone age delay, and, if the condition resolves, catch-up growth. This broad
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Open Access
Jan 8, 2006
Andrea Cristiane Michelan + 5
