Randomized Trial of Varying Mineral Intake on Total Body Bone Mineral Accretion During the First Year of Life

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Abstract
Objective. The effect of varying mineral intakes on total body bone mass accretion during the first year of life in healthy full-term infants is unknown. The purpose of this study was to determine whether total body bone mass accretion during the first year of life was influenced by the calcium and phosphorus intake of an infant and whether early differences in bone accretion persist through 1 year of age. Design. This prospective, randomized trial was conducted in two phases. In phase I, 67 infants were randomized within the first 2 weeks of life into either a low (439 mg of calcium per liter and 240 mg of phosphorus per liter) or moderate (510 mg of calcium per liter and 390 mg of phosphorus per liter) mineral-containing formula feeding group. An additional group of 34 human milk–fed (low mineral) infants also was enrolled. Phase II involved an additional randomization of all infants at 6 months of age into moderate-mineral formula (see above), high-mineral formula (1350 mg of calcium per liter and 900 mg of phosphorus per liter), or cow milk (1230 mg of calcium per liter and 960 mg of phosphorus per liter) feeding group. Anthropometric measurements, nutrient intake, and total body bone mineral content (BMC) by dual-energy x-ray absorptiometry were measured at 1, 3, 6, 9, and 12 months. Results. During the first 6 months, the moderate-mineral group had a greater increase in weight (3.42 ± 0.62 kg) compared with the human milk group (2.93 ± 0.56 kg); the low-mineral group (3.19 ± 0.62 kg) was intermediate. Bone mass accretion differed in a similar direction, with the moderate-mineral feeding group having a greater increase than the human milk group and the low-mineral group being intermediate of the two. Including weight, length, and bone area as covariates, both the low-mineral formula– and human milk–fed groups had similar BMC, which was lower than that of the moderate-mineral group at 3 and 6 months of age. Adjusted mean BMC values for the moderate-mineral formula–fed group compared with the low-mineral formula– and human milk–fed groups were 127.8 ± 1.5 (SEM) g vs 119.2 ± 1.5 and 122.1 ± 1.4 g, respectively, at 3 months of age and 168.7 ± 2.5 g vs 157.6 ± 2.5 and 158.7 ± 2.4 g, respectively, at 6 months of age. The BMC at 6 months of age among the formula-fed infants was correlated with both average dietary phosphorus intake (r = .592) and average daily calcium intake (r = .620) during the first 6 months. The relationships between BMC and these minerals remained significant even after controlling for caloric intake. It was not possible to determine the independent effects of dietary calcium and phosphorus on BMC because of the strong correlation of these minerals with each other. Despite significant differences in both calcium and phosphorus intakes during the second 6 months of life, there were no differences in growth parameters or bone mass accretion. Means for BMC, adjusted for body weight, length, and bone area, were not significantly different among feeding groups at either 9 or 12 months of age. Adjusted means were 199 ± 2 (SEM) and 237 ± 3 g at 9 and 12 months of age for infants receiving moderate-mineral formula; 198 ± 2 and 236 ± 3 g at 9 and 12 months of age for infants receiving the high-mineral formulas and 202 ± 5 and 233 ± 5 g at 9 and 12 months of age for infants receiving cow milk. The gain in bone mass during the second 6 months differed by the first 6-month feeding group; mean changes in BMC between 6 and 12 months, adjusted for changes in weight, length, and bone area, were greater in human milk–fed infants than in either the low- or moderate-mineral–containing formula groups: 81 ± 16 g in human milk–fed infants and 73 ± 15 and 71 ± 15 g in the low- and moderate-mineral formula groups, respectively. Infants fed whole cow milk during the second 6 months were excluded from this analysis because of the small number of infants completing the study. By 12 months of age there were no differences in BMC in either the early or late feeding groups. Conclusion. These results indicate that during the first 6 months, bone mass accretion is less in infants fed human or low-mineral formula compared with infants fed moderate-mineral formula. Infants fed human milk during the first 6 months had greater bone mass accretion during the second 6 months compared with formula-fed infants. By 12 months of age there were no differences in bone mass among the different feeding groups. bone, growth, infant feeding.

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