During breastfeeding, calcium for the infant is supplied by resorption of the maternal skeleton; this bone is restored during weaning, a process reported to be independent of calcitriol. However, that evidence was from 1-α-hydroxylase or Vitamin D receptor (VDR) null mice fed a calcium-enriched “rescue” diet to prevent rickets. Here we assess whether skeletal recovery from lactation-induced bone loss is calcitriol-independent on a normal diet.
Wild type and VDR null mice were fed the rescue diet from birth to end lactation and switched to a normal diet at weaning. Bones were collected at baseline, day 18.5 of pregnancy, 21 days of lactation, and 28 days post-weaning (recovery). Bones were also collected from non-mated mice of both genotypes given the same diets at the same ages; these showed no bone loss compared to controls.
Cortical thickness and maximal bone strength were both significantly reduced by 25% in lactating wild type mice compared to baseline and age-matched controls and were both completely restored post-weaning. In contrast, VDR null mice had a similar 25% reduction in cortical thickness and maximal strength with lactation, but neither were restored post-weaning. VDR null femora at 28 days post-weaning exhibited high cortical porosity and abundant very low-density bone on the endocortical surface.
Low-, mid-, and high-density measurements revealed that wild types lost and restored high-density bone. However, while VDR null mice lost high density bone in lactation, they formed only low-density bone post-weaning, to 3x normal levels. Histology revealed abnormally thick seams of unmineralised osteoid and significantly greater extent of osteoblast and osteoid on both endocortical and intracortical surfaces.
We conclude that calcitriol is required for recovery from lactation-induced bone loss on a normal diet, and that while bone matrix production during recovery is calcitriol-independent, it lacks mineral likely due to insufficient dietary calcium and phosphate supply.