Preterm infants are at significant risk of reduced bone mineral content and subsequent bone disease, variably termed osteopenia of prematurity or neonatal rickets. The prevalence varies depending on gestation, occurs up to 30% of Korean extremely low birth weight infants (ELBW). The etiology is multifactoreal: inadequate nutrient intake, prolonged parenteral nutrition, chronic co-morbidities and immobilization. In Korean ELBW infants, rickets of prematurity was significantly increased by 18 times with severe parenteral nutrition associated cholestasis, and by 3 times with moderate/severe bronchopulmonary dysplasia. Prolonged hospitalization with ventilator care could lead to lack of physical activity and muscle contraction against resistance in preterm infants, which may increase bone resorption and demineralization, resulting in osteopenia. Low serum P and high alkaline phosphatase (ALP) are suggestive of metabolic bone disease. In Korean ELBW infants, increased serum ALP (>495 IU) at the age of 5 weeks has a 81% of sensitivity and 87% of specificity for radiographic rickets. An early nutritional intervention can reduce both the prevalence and the severity of osteopenia. Provision of adequate nutrition including energy, protein and minerals, and passive physical exercise during first weeks of life may prevent abnormal bone remodeling activity in preterm infants. Early detection by vigorous monitoring of bone homeostasis and prompt treatment of osteopenia are warranted in these high-risk infants. This review is to focus on the recent advances in the understanding of bone metabolism in preterm infants and on the therapeutic approach to prevent and to treat metabolic bone disease of prematurity.