Bone Abstracts

Fractures in children are common; prospective cohort studies suggest narrower bones predispose to fracture. Early life events can influence later growth and development. Observational studies suggest children born to mothers with lower vitamin D levels during pregnancy have narrower bones. We investigated the effects of maternal vitamin D deficiency on offspring’s bones’ response to mechanical loading in a model system.

C57BL/6 female mice (n=13) were maintained on a vitamin D replete (n=7) or deficient diet for 6 weeks, mated and maintained on their respective diets until offspring weaning. Following birth drinking water was supplemented with 2 mM Ca²⁺. Weaned female pups then received a vitamin D replete diet. At both 8 and 16 weeks mice underwent non-invasive tibial axial loading with a peak 11N dynamic load applied to the left tibiae 3x weekly for 2 weeks. Mice were sacrificed at 18 weeks. Trabecular and cortical morphometry of fixed tibiae were quantified using a SkyScan 1172 desktop microCT machine. Results show the difference between loaded and contralateral non-loaded tibias by animal, comparing group means±SD.

Tibial loading increased cortical bone volume (BV), bone fraction BV/TV and cortical thickness (Ct.Th) in both groups of mice. Offspring of antenatally vitamin D sufficient as opposed to vitamin D deficient dams showed an increase in BV: 32.3±4.7% vs 23.6±5.4% (P=0.01); BV/TV 9.33%±3.6% vs 4.5±2.8% and in Ct.Th: 26.5±3.9% vs 20.56±4.0% (P=0.02) and trends to increased cortical porosity: 64.3±12.1% vs 46.5±20.0% (P=0.09), and tissue volume: 25.4±4.1% vs 19.8±6.6% (P=0.1)

Trabecular bone parameters significantly increased in both groups in response to tibial loading; however there were no significant differences between the two groups.

MicroCT demonstrates non-invasive tibial loading induces an osteogenic response in both cortical and trabecular bone in mice exposed to normal or deficient vitamin D levels in utero. However, mice exposed to vitamin D deficiency in utero showed a reduced response to post-natal mechanical loading, with reduced bone volume and thinner cortices. Such bones would be at increased risk of fracture; we speculate that ensuring vitamin D sufficiency during pregnancy could contribute to fracture risk reduction during childhood and later life.

Disclosure: The authors declared no competing interests.