Recovery of the maternal skeleton after lactation is impaired by advanced maternal age but not by reduced IGF availability in the mouse

PLoS One. 2021 Sep 1;16(9):e0256906. doi: 10.1371/journal.pone.0256906. eCollection 2021.

Abstract

Background: Lactation results in substantial maternal bone loss that is recovered following weaning. However, the mechanisms underlying this recovery, and in particular the role of insulin-like growth factor 1 (IGF-I), is not clear. Furthermore, there is little data regarding whether recovery is affected by advanced maternal age.

Methods: Using micro-computed tomography, we studied bone recovery following lactation in mice at 2, 5 and 7 months of age. We also investigated the effects of reduced IGF-I availability using mice lacking PAPP-A2, a protease of insulin-like growth factor binding protein 5 (IGFBP-5).

Results: In 2 month old mice, lactation affected femoral trabecular and cortical bone, but only cortical bone showed recovery 3 weeks after weaning. This recovery was not affected by deletion of the Pappa2 gene. The amount of trabecular bone was reduced in 5 and 7 month old mice, and was not further reduced by lactation. However, the recovery of cortical bone was impaired at 5 and 7 months compared with at 2 months.

Conclusions: Recovery of the maternal skeleton after lactation is impaired in moderately-aged mice compared with younger mice. Our results may be relevant to the long-term effects of breastfeeding on the maternal skeleton in humans, particularly given the increasing median maternal age at childbearing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Bone Density / physiology
  • Bone Diseases, Metabolic / genetics
  • Bone Diseases, Metabolic / physiopathology*
  • Cancellous Bone / diagnostic imaging
  • Cancellous Bone / physiopathology
  • Carrier Proteins / blood
  • Carrier Proteins / metabolism
  • Cortical Bone / diagnostic imaging
  • Cortical Bone / physiopathology
  • Disease Models, Animal
  • Female
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism
  • Lactation / metabolism*
  • Maternal Age*
  • Mice
  • Mice, Knockout
  • Osteogenesis / physiology*
  • Pregnancy
  • Pregnancy-Associated Plasma Protein-A / genetics
  • Pregnancy-Associated Plasma Protein-A / metabolism
  • X-Ray Microtomography

Substances

  • Carrier Proteins
  • IGFBP5-interacting protein, mouse
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I
  • PAPPA2 protein, mouse
  • Pregnancy-Associated Plasma Protein-A

Grants and funding

This study was funded by a Natural Sciences and Engineering Research Council of Canada Discovery Grant (JKC; grant number RGPIN-2016-04047) and an NSERC Undergraduate Student Research Award (NB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.