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Biochemical, Molecular, and Genetic Mechanisms

Infant Formula Promotes Bone Growth in Neonatal Piglets by Enhancing Osteoblastogenesis through Bone Morphogenic Protein Signaling^1–3,

⁴ Arkansas Children's Nutrition Center, ⁵ Departments of Pediatrics, ⁶ Physiology and Biophysics, and ⁷ Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202

Relatively few studies have examined the effects of formula feeding relative to breast-feeding on bone in the neonate. Using peripheral quantitative CT scan and histomorphometric analysis, we demonstrated that neonatal piglets fed with soy-based formula (SF) and cow milk-based formula (MF) for 21 or 35 d had greater bone mineral density and content than breast-fed piglets (BF) (P < 0.05). Osteoblast numbers and bone formation rate at postnatal d 35 were greater in SF compared with other groups (P < 0.05), whereas osteoclast numbers were lower in both MF and SF groups than in the BF group (P < 0.05). Osteoblastogenesis was greater in ex vivo bone marrow cell cultures from SF than in MF or BF piglets (P < 0.05). Bone formation markers in serum were greater, whereas bone resorption markers were lower in the MF- and SF-fed groups than in the BF group (P < 0.05). Bone morphogenic protein (BMP) 2 and alkaline phosphatase mRNAs were upregulated in the MF and SF groups compared with the BF group (P < 0.05), whereas receptor activator of NF-B ligand was downregulated (P < 0.05). Extracellular signal-regulated kinase, p38, Smad1/5/8 phosphorylation, and runt-related transcription factor 2 expression were greater in bone from the MF and SF groups compared with the BF group (P < 0.05). In vitro studies showed that 2.5% serum from SF- or MF-fed piglets was able to stimulate osteoblast differentiation but not in the presence of the BMP blocker noggin. Therefore, formula feeding promoted bone growth compared with BF. SF piglets had the highest bone volume over tissue volume. This suggests that SF-fed piglets may have the best quality bone. The anabolic effects of SF on bone appear to be mediated through enhanced BMP signaling.

^* To whom correspondence should be addressed. E-mail: ronismartinj{at}uams.edu and chenjin-ran{at}uams.edu.

Manuscript received 20 April 2009. Initial review completed 15 May 2009. Revision accepted 4 August 2009.

Published online 26 August 2009.