Very premature infants are at an increased risk for metabolic bone disease because they forego the last trimester of pregnancy, the period of greatest mineral accretion. Most of these infants cannot tolerate full enteral feedings within the first postnatal days or weeks, and nutrients including calcium and phosphorus need to be delivered by parenteral nutrition. The ongoing challenges for bone nutrition in preterm infants involve not only guaranteeing high concentrations of calcium and phosphorus in parenteral nutrition admixtures while maintaining their compatibility but also achieving an optimal skeletal mineralization with the large amounts of minerals delivered. The main factors promoting calcium and phosphorus compatibility in parenteral nutrition admixtures include low final pH and temperature to produce more monobasic phosphate, use of organic calcium and P salts, and final high amino acid concentration with the inclusion of cysteine. © Springer Science+Business Media New York 2015.