Inhibitors of osteoblastogenesis in early human milk and maternal serum: evidence for protective properties of mother's milk on bone

J Matern Fetal Neonatal Med. 2020 Apr;33(7):1095-1099. doi: 10.1080/14767058.2018.1514383. Epub 2018 Sep 10.

Abstract

Objective: Lactation is associated with a dramatic increase of maternal bone turnover, leading to a reversible bone loss. Early life nutrition may influence later osteoporosis risk. Proteins synthesized by the group of wingless (Wnt) genes are key mediators of osteoblastogenesis and bone formation. We aimed to investigate maternal milk and serum concentrations of the inhibitors of the Wnt signaling pathway, Dickkopf-1 (DKK-1) and sclerostin.Material and methods: In 80 women, maternal milk and serum concentrations of DKK-1 and sclerostin were determined by ELISA on the 3rd-4th day postpartum. Concentrations were associated with various maternal, gestational and neonatal characteristics.Results: DKK-1 and sclerostin were detectable in early milk [mean ± SD: 817.17 ± 259.61 pg/mL, median (range) 258.04 (2452.40-53.17) pg/mL, respectively] at significantly lower concentrations than in maternal serum [mean ± SD: 3375.36 ± 416.75 pg/mL, median (range) 16 200.54 (58 832.00-3012.60) pg/mL, respectively], (p < .000). Maternal milk sclerostin concentrations positively correlated with respective serum ones (r = 0.599, p = .000). Maternal serum and milk sclerostin concentrations positively correlated with maternal body mass index (r = 0.37, p = .001 and r =0.38, p = .000, respectively), while maternal serum sclerostin concentrations were higher in primiparas (p = .002).Conclusion: DKK-1 and sclerostin are present in early human milk at significantly lower concentrations, compared with maternal serum, probably contributing to the short- and long-term benefits of mother's milk for bone health. Moreover, the large amounts of both substances in maternal serum may represent disruption of the Wnt cascade, contributing to the well-known lactation-associated bone loss, which seems to be greater in primiparas and obese mothers.

Keywords: Bone formation; DKK1; Wnt signaling pathway; breast milk; maternal blood; sclerostin.

MeSH terms

  • Adaptor Proteins, Signal Transducing / blood*
  • Adult
  • Female
  • Humans
  • Infant, Newborn
  • Intercellular Signaling Peptides and Proteins / blood*
  • Male
  • Milk, Human / chemistry*
  • Osteogenesis*
  • Prospective Studies
  • Wnt Signaling Pathway*
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • SOST protein, human