Maternal vitamin B₁₂ in mice positively regulates bone, but not muscle mass and strength in post-weaning and mature offspring

Vitamin B₁₂ deficiency has been shown to affect bone mass in rodents and negatively impact bone formation in humans. In this study using mouse models, we define the effect of B₁₂ supplementation in the wild-type mother and B₁₂ deficiency in a mouse genetic model (Gif^-/- mice) during gestation on bone and muscle architecture and mechanical properties in the offspring. Analysis of bones from 4-wk-old offspring of the wild-type mother following vehicle or B₁₂ supplementation during gestation (from embryonic day 0.5 to 20.5) showed an increase in bone mass caused by an isolated increase in bone formation in the B₁₂-supplemented group compared with vehicle controls. Analysis of the effect of B₁₂ deficiency in the mother in a mouse genetic model (Gif^-/- mice) on the long bone architecture of the offspring showed a compromised cortical and trabecular bone mass, which was completely prevented by a single injection of B₁₂ in the B₁₂-deficient Gif^-/- mothers. Biomechanical analysis of long bones of the offspring born from B₁₂-supplemented wild-type mothers showed an increase in bone strength, and conversely, offspring born from B₁₂-deficient Gif^-/- mothers revealed a compromised bone strength, which could be rescued by a single injection of B₁₂ in the B₁₂-deficient Gif^-/- mother. Muscle structure and function analysis however revealed no significant effect on muscle mass, structure, and grip strength of B₁₂ deficiency or supplementation in Gif^-/- mice compared with littermate controls. Together, these results demonstrate the beneficial effect of maternally derived B₁₂ in the regulation of bone structure and function in the offspring.