Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation potential of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon adequate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are depleted, proliferative chondrocyte numbers decrease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and vascularized, the growth plate is closed, and longitudinal bone growth is complete. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further elucidation of these mechanisms will enable the development of new therapeutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.

Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation potential of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon adequate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are depleted, proliferative chondrocyte numbers decrease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and vascularized, the growth plate is closed, and longitudinal bone growth is complete. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further elucidation of these mechanisms will enable the development of new therapeutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.

Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation potential of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon adequate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are depleted, proliferative chondrocyte numbers decrease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and vascularized, the growth plate is closed, and longitudinal bone growth is complete. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further elucidation of these mechanisms will enable the development of new therapeutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.

Height gains result from longitudinal bone growth, which is largely dependent on chondrocyte differentiation and proliferation within the growth plates of long bones. The growth plate, that is, the epiphyseal plate, is divided into resting, proliferative, and hypertrophic zones according to chondrocyte characteristics. The differentiation potential of progenitor cells in the resting zone, continuous capacity for chondrocyte differentiation and proliferation within the proliferative zone, timely replacement by osteocytes, and calcification in the hypertrophic zone are the 3 main factors controlling longitudinal bone growth. Upon adequate longitudinal bone growth, growth plate senescence limits human body height. During growth plate senescence, progenitor cells within the resting zone are depleted, proliferative chondrocyte numbers decrease, and hypertrophic chondrocyte number and size decrease. After senescence, hypertrophic chondrocytes are replaced by osteocytes, the extracellular matrix is calcified and vascularized, the growth plate is closed, and longitudinal bone growth is complete. To date, gonadotropin-releasing hormone analogs, aromatase inhibitors, C-type natriuretic peptide analogs, and fibroblast growth factor receptor 3 inhibitors have been studied or used as therapeutic interventions to delay growth plate closure. Complex networks of cellular, genetic, paracrine, and endocrine signals are involved in growth plate closure. However, the detailed mechanisms of this process remain unclear. Further elucidation of these mechanisms will enable the development of new therapeutic modalities for the treatment of short stature, precocious puberty, and skeletal dysplasia.

The principles of treatment for diabetes in children and adolescents cannot simply be derived from care routinely provided to adults with diabetes. The major consideration is that the epidemiology, pathophysiology, developmental considerations, and response to treatment of pediatric diabetes are often different from those of adult diabetes. Second, recommended treatments for children and adolescents with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and other pediatric conditions such as monogenic diabetes (neonatal diabetes and MODY [maturity-onset diabetes of the young]) also differ. HbA1c goals in T1DM and T2DM must be individualized and reassessed over time. A HbA1c < 7% is appropriate for many children and adolescents with T1DM. In a case with hypoglycemia, hypoglycemic unawareness, lack of access to analog insulins, advanced insulin delivery technology and/or continuous glucose monitoring, a less stringent HbA1c < 7.5% will be required. A reasonable HbA1c goal for T2DM is < 7%. If possible, a strict HbA1c target of < 6.5% can be implemented. Metformin is the first-line treatment of choice in T2DM. In a case with ketosis or HbA1c > 8.5%, insulin will be required with once daily basal insulin (0.25~0.5 IU/kg). If the glycemic goal is not attained, the addition of a second agent is considered in adult patients but might not be applicable or safe in pediatric cases. Therefore, the efficacy and safety of these drugs used in adult patients, including glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors, should be evaluated in pediatric patients worldwide.

The principles of treatment for diabetes in children and adolescents cannot simply be derived from care routinely provided to adults with diabetes. The major consideration is that the epidemiology, pathophysiology, developmental considerations, and response to treatment of pediatric diabetes are often different from those of adult diabetes. Second, recommended treatments for children and adolescents with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and other pediatric conditions such as monogenic diabetes (neonatal diabetes and MODY [maturity-onset diabetes of the young]) also differ. HbA1c goals in T1DM and T2DM must be individualized and reassessed over time. A HbA1c < 7% is appropriate for many children and adolescents with T1DM. In a case with hypoglycemia, hypoglycemic unawareness, lack of access to analog insulins, advanced insulin delivery technology and/or continuous glucose monitoring, a less stringent HbA1c < 7.5% will be required. A reasonable HbA1c goal for T2DM is < 7%. If possible, a strict HbA1c target of < 6.5% can be implemented. Metformin is the first-line treatment of choice in T2DM. In a case with ketosis or HbA1c > 8.5%, insulin will be required with once daily basal insulin (0.25~0.5 IU/kg). If the glycemic goal is not attained, the addition of a second agent is considered in adult patients but might not be applicable or safe in pediatric cases. Therefore, the efficacy and safety of these drugs used in adult patients, including glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors, should be evaluated in pediatric patients worldwide.