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Unlabelled: We wanted to improve detection of low bone mineral density in preterm infants by combining serum measurements of total alkaline phosphatase, its bone-type isoenzyme and serum inorganic phosphate in a prospective design. The subjects were 43 preterm infants. Total and bone isoenzyme activity of alkaline phosphatase was determined at 3 wk chronological age and at 3 and 6 mo corrected age. The main outcome measure, apparent bone mineral density (BMAD) at the distal forearm and forearm shaft, was assessed by dual energy X-ray absorptiometry at 3 and 6 mo corrected age. An apparent density below 95 mg/cm3 at 3 mo corrected age was considered to indicate bone disease, based on the distribution of BMAD values of children with non-complicated courses of prematurity. At 3 mo corrected age, total alkaline phosphatase activities exceeding 900 IU/l revealed low bone mineral density with 88% sensitivity and 71% specificity. Measurements of bone isoenzyme activity did not improve diagnostic performance. Serum inorganic phosphate levels below 1.8 mmol/l reflected low bone density with high specificity (96%), but the sensitivity was only 50%., Conclusion: A combination of the criteria "serum total alkaline phosphatase activity above 900 IU/l" and "serum inorganic phosphate concentrations below 1.8 mmol/l" yielded a sensitivity of 100% at a specificity of 70%. This was the best available screening method for low bone mineral density in preterms.

Metabolic bone disease is recognized with increasing frequency in very-low-birth-weight infants. Radiological changes characteristic of rickets have been found in 55% of infants with a birth weight of less than 1000 g and in 23% of infants weighing less than 1500 g at birth. Twenty-four per cent of infants with a birth weight of less than 1500 g have fractures. The main aetiological factor is insufficient phosphorus supplementation. The aetiology is, however, multifactorial and also includes calcium deficiency, vitamin D deficiency, certain drugs, aluminium loading and immobilisation. The method of choice in detecting subclinical mineral bone disease of prematurity is measurement of bone mineral density, but there is as yet no single good diagnostic method available for premature infants. The optimal mineral and vitamin D requirement of the premature infant must be established so that proper recommendations can be given. The current recommended vitamin D dose in Europe (ESPGAN 800-1000 IU/day) is probably too high when extra minerals are supplied. Moreover, the duration of mineral supplementation may need to be continued until the infant has reached a body weight of 3.5 kg. This article deals with the aetiology, pathogenesis, diagnosis and future prospects of metabolic bone disease of prematurity.