It is widely believed that osteoporosis prevention may be best accomplished during childhood and adolescence, when bones are growing rapidly and are most sensitive to environmental influences, such as diet and physical activity. For children with chronic diseases, a variety of factors may influence normal bone mineralization, including altered growth, delayed maturation, inflammation, malabsorption, reduced physical activity, glucocorticoid exposure, and poor dietary intake. In healthy children, maintaining adequate levels of calcium intake, serum vitamin D, and weightbearing physical activity may be sufficient to prevent osteoporosis later in life. Far less is known about effective prevention and treatment of poor bone mineralization in children with chronic illness, such as CF or CD. Osteoporosis prevention and intervention measures during childhood are limited by the paucity of reference data on bone mineralization. Although it is widely recognized that puberty, skeletal maturation, and body size influence BMC and bone density, no reference data for bone mineralization are scaled to these important measures. In children with chronic disease with delayed growth and maturation, the creation of such reference data is of paramount importance. In addition, the dynamic changes that occur during growth and maturation in the structural characteristics of trabecular and cortical bone and the development of the bone-muscle unit may influence current and future fracture risk. Further research is needed to characterize these changes and their use in the assessment of bone health and fracture risk in children. Only then can the impact of treatment strategies be appreciated fully.