Osteopenia of prematurity is a metabolic bone disease of premature infants with birth weight < 1500 g and gestational age < 32 weeks. Sub-optimal bone matrix, poor skeletal support and an increased risk of fractures characterized the disease. Its importance is determined by relatively high frequency--between 30-70% of infants at risk, multifactorial etiology and impact on early and late morbidity of the newborns. The prevention and treatment of bone disorders are important aspects of the care of preterm babies.To identify of the risk factors, to determine early diagnostic criteria and to create a prevention program for osteopenia in infants with very low and extremely low birth weight.The prospective study includes 39 preterm babies with birth weight below 1500 gr. and < 32 g. w who were admitted to the NICU from September 2011-January 2012. Bone metabolism was monitored by calcium, phosphate and alkaline phosphatise at 2-weeks intervals. Vitamin D levels of the neonates were registered at birth, and at 8th week. PTH was measured at the second and the 8th weeks.The following biochemical abnormalities were found. Hypophosphatemia in two weeks (P < 1,6 mmol/l), a gradual increase in phosphorus levels and normalization at eight weeks of age. There was a significant positive correlation between 25OHD/phosphorus at eight weeks/r = 0.353/. Significantly elevated levels of parathyroid hormone in eight weeks, correlating with low levels of vitamin D (negative correlation between 25OHD/parathormone r = -0.581). Blood levels of calcium and alkaline phosphatase were in normal limits.Risk factors for osteopenia are: the low gestational age and low levels of vitamin D at birth. Biochemical markers of osteopenia are: changes in levels of parathyroid hormone, phosphorus and vitamin D at eight weeks of age. Prevention includes: early supplementation of vitamin D in the risk neonates with individual dose adjustment. Upon biochemical evidence of osteopenia treatment should begin in the second week of life with supplementation of phosphorus, and vitamin D 1320 IU/daily and appropriate physiotherapy.