Bone structure and volumetric density in young adults born prematurely: a peripheral quantitative computed tomography study.

Prematurity is known to be associated with reduced bone mineral density (BMD) in childhood, but whether this condition has long-term detrimental consequences on adult bone structure is not known. In this study, we measured with peripheral quantitative computed tomography (pQCT) the total bone cross-sectional area, cortical area and wall thickness, cortical and trabecular density, and a density-weighed polar section modulus as a bone strength index (BSI) at distal and shaft sites of right radius and tibia in a group of 40 prematurely born, otherwise normally developed and healthy young adults (17 women and 23 men, aged 18 to 27 years) and compared their data to corresponding data obtained from a group of 42 control subjects born term (20 women and 22 men, aged 18 to 28 years). Body height and weight were similar in both groups, but the preterm group had significantly lower BSI values at distal sites of tibia (approximately -16%) and radius (approximately -13%) and at tibial shaft (approximately -11%) as compared to control group. In the weight-bearing tibia, BMC was lower and the lower BSI values were mainly due to smaller total bone cross-sectional area. For unknown reason, this prematurity-associated detrimental effect seemed to concern more men than women. In contrast, prematurity was not associated with volumetric trabecular and cortical densities at any measured bone site while the typical sex differences in bone density were observed. We conclude that prematurity is associated with somewhat smaller cross-sectional bone dimensions in terms of body size in young adulthood. Due to the cross-sectional design, this study could not reveal specific reasons but they may pertain to nutrition during the neonatal period and living habits in general.

Genetic determinants of bone mineral content in premature infants.

Genetic determinants of bone mineral content in prematurely born children at 3 months and 9-11 years of age were studied. The findings suggest that multiple genes are involved in the regulation of site specific bone mass accumulation during childhood.

Enamel defects in primary and permanent teeth of children born prematurely.

The objective of this study was to determine the prevalence of enamel defects in both primary and permanent dentitions of the same preterm children, and to elucidate the role of early dietary mineral and vitamin D intake in the etiology of the enamel defects. The status of the primary and permanent teeth was evaluated in 32 preterm children and in 64 control children. The prevalence of enamel defects in children born preterm was clearly higher as compared with controls in both the primary (78% vs 20%, P<0.001) and permanent (83% vs 36%, P<0.001) dentitions. Neither the mineral supplementation used nor a vitamin D dose of 1000 IU/day, as compared with a lower dose of 500 IU/day, reduced the prevalence of enamel defects in the primary or permanent dentitions. Further studies are needed to clarify whether achieving near optimum intra-uterine mineral retention would lower the prevalence of subsequent enamel defects in infants born prematurely.

Maturation of primary and permanent teeth in preterm infants.

AIMS: To elucidate the development of primary and permanent teeth and to interpret the effect of different calcium, phosphorus, and vitamin D supplementation in the neonatal period on dental maturation in preterm children. METHODS: Preterm infants were randomised to four groups to receive a vitamin D dose of 500 or 1000 IU/day and calcium and phosphorus supplemented or unsupplemented breast milk. The maturity of the primary and permanent teeth was recorded in 30 preterm children. Sixty children aged 2 years and 60 children aged 9-11 years served as controls. Bone mineral content/density was assessed in the preterm infants. RESULTS: The median (range) corrected teething age was 7 (2-16) months in preterm infants and 6 (2-12) months in controls (p = 0.43). The median (range) number of erupted teeth at 2 years of age was 16 (11-19) in preterm infants and 16 (12-20) in controls (p = 0.16). Maturation of the permanent teeth in the preterm infants was not delayed compared with the controls (mean Demirjian SDS 0.16 v 0.49, p = 0.14). Early dietary intake of either mineral or vitamin D did not affect maturation of the primary dentition in preterm children. Children receiving the higher vitamin D dose in the neonatal period had more mature permanent dentition than those receiving the lower dose, but mineral intake did not affect maturation of the permanent teeth. Dental maturation did not correlate with bone mineral status. CONCLUSIONS: This is the first longitudinal study to follow primary and permanent tooth maturation in the same preterm children. Premature birth has no appreciable late sequelae in tooth maturation.

Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity.

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.

The long-term effect of early mineral, vitamin D, and breast milk intake on bone mineral status in 9- to 11-year-old children born prematurely.

BACKGROUND: Although the short-term benefits of mineral supplementation in preterm infants has been established, the long-term benefits are less clear. The purpose of the study was to evaluate effects of early-life mineral, vitamin D, and breast milk intake on bone mineral status in children 9 to 11 years of age who were born prematurely. METHODS: Seventy preterm infants born 1985 through 1987 were randomized into four groups: to receive a vitamin D dose of 500 or 1000 IU/day and calcium- and phosphorus-supplemented or unsupplemented breast milk. At 3 months of age, radial bone mineral content was determined by single-photon absorptiometry and vitamin D metabolites were assessed. At 9 to 11 years of age, the bone mineral status of the radius and lumbar spine was assessed using dual energy x-ray absorptiometry. RESULTS: At the age of 3 months, the preterm infants with diets supplemented with minerals had 36% higher bone mineral content than the preterm infants whose diet was not supplemented with minerals. At the age of 9 to 11 years, in contrast, bone mineral status was comparable among the groups, irrespective of different mineral supplementation during the neonatal period. Interestingly, the lumbar bone mineral apparent density was positively related to lactation in mineral-supplemented children. There was neither short-term nor long-term benefit to bone mineral status of a vitamin D dose of 1000 IU/day compared with 500 IU/day. CONCLUSIONS: The short-term benefit to bone mineral density in preterm infants of mineral supplementation of the early diet is obvious, but, in the long term, the effects seem to disappear. The results also imply that a relatively long period of breast-feeding may be needed to optimize long-term bone mineral acquisition in the lumbar spine.

Randomised controlled trial of vitamin D supplementation on bone density and biochemical indices in preterm infants.

AIMS: To test the hypothesis that a vitamin D dose of 200 IU/kg, maximum 400 IU/day, given to preterm infants will maintain normal vitamin D status and will result in as high a bone mineral density as that attained with the recommended dose of 960 IU/day. METHODS: Thirty nine infants of fewer than 33 weeks of gestational age were randomly allocated to receive vitamin D 200 IU/kg of body weight/day up to a maximum of 400 IU/day or 960 IU/day until 3 months old. Vitamin D metabolites, bone mineral content and density were determined by dual energy x-ray absorptiometry, and plasma ionised calcium, plasma alkaline phosphatase, and intact parahormone measurements were used to evaluate outcomes. RESULTS: The 25 hydroxy vitamin D concentrations tended to be higher in infants receiving 960 IU/day, but the differences did not reach significance at any age. There was no difference between the infants receiving low or high vitamin D dose in bone mineral content nor in bone mineral density at 3 and 6 months corrected age, even after taking potential risk factors into account. CONCLUSIONS: A vitamin D dose of 200 IU/kg of body weight/day up to a maximum of 400 IU/day maintains normal vitamin D status and as good a bone mineral accretion as the previously recommended higher dose of 960 IU/day. Vitamin D is a potent hormone which affects organs other than bone and should not be given in excess to preterm infants.

Dual energy x-ray absorptiometry of the forearm in preterm and term infants: evaluation of the methodology.

The objective of this study was to evaluate the performance of dual energy x-ray absorptiometry (DXA) in forearm measurements of preterm and newborn term infants. The accuracy and linearity of DXA in measuring low mineral content levels (ranging from 30 to 300 mg) was assessed using bone-simulating K2HPO4 phantoms. For in vivo precision, DXA was performed twice on left forearms of four new-born term babies, 21 preterm infants at corrected age 3 mo, and 20 at corrected age 6 mo. Bone mineral content (BMC in mg) and areal bone mineral density (BMD in mg/cm2) at distal forearm and forearm shaft were measured. A special software program allowing a free adjustment of the bone detection threshold was used in the analysis of the scan data. The threshold level affected the overall ability of analysis to detect bone tissue and altered significantly the BMC and BMD values too. Given absolute success in detecting low amounts of bone mineral (BMC > 100 mg), the lowest bone detection threshold evaluated (0.040 g/cm2) became the preferable choice. The relationships between the actual and measured data were highly linear (r was 0.94 for BMC and 0.97 for BMD) but showed underestimation (corresponding slopes were 0.66 and 0.64). In vivo precision expressed as 95% limits of agreement was approximately +/-45 mg for BMC and +/-16 mg/cm2 for BMD. We conclude that DXA provides adequate reliability for in vivo determinations of BMC and areal BMD in the distal and shaft sites of forearm in term and preterm infants and thus strongly supports the clinical utility of DXA in the diagnosis and monitoring of metabolic disease of prematurity. Movements during scanning are typical of pediatric measurements and may decrease the precision considerably. Therefore, every effort must be made to prevent movement artefacts. In addition, special attention must be paid to keeping the analysis procedures consistent.

Metabolic bone disease of prematurity.

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.