Bone Abstracts

Background: Preclinical model studies suggest early life vitamin D depletion reduces bone’s response to mechanical loading. The MAVIDOS trial (randomised placebo controlled trial of vitamin D supplementation in pregnancy) reported winter-born infants of mothers receiving vitamin D supplementation had higher bone mass; the earlier Southampton Princess Ann Cohort study linked pregnancy blood vitamin D levels to later bone mass and size. We showed previously that bone responds quickly to short periods of mechanical stimulation. This study aimed to determine whether antenatal vitamin D supplementation alters postnatal bone formation in response to mechanical stimulation.

Methods: Thirty-one children (4–5 years age) born to mothers who participated in MAVIDOS during pregnancy and received placebo [n=19] or Cholecalciferol 1000IU/day [n=12] were recruited. Children received whole body vibration (WBV; LivMd vibrating platform) for 10 minutes (4×2.5 minutes interspersed with 30 seconds rest) on 5 consecutive days. Fasting blood samples for bone homeostasis, including 25-hydroxyvitamin D (25OHD) and parathormone (PTH), and turnover markers (P1NP, CTX) were collected pre-WBV and on D8.

Results: Bone profile including serum 25OHD and PTH were normal in the entire cohort; there were no significant differences between groups. Median (25th/75th centiles) P1NP (ng/mL) at baseline within placebo and vitamin D-supplementation groups were 587.1(518.2,801.7) and 552.2(512.3,678.6). Mean changes (Δ) in P1NP (ng/ml) between baseline and D8 in the supplementation and placebo groups respectively were 40.6 and −92.6; between group difference in ΔP1NP 133.2 ng/mL [95% CI 0.4,266.0; P=0.049]. Median (25th/75th centiles) for CTX (ng/mL) at baseline within the placebo and supplementation groups were 1.59(1.3,1.81) and 1.52(1.29,1.81) respectively. The mean changes in CTX (ng/ml) between baseline and D8 in the supplementation and placebo groups respectively were −0.034 and −0.084 ng/ml; between group difference in ΔCTX 0.05 ng/ml (95% CI=−0.159,0.26 ng/mL; P=0.62).

Conclusion: Following vitamin D supplementation in pregnancy, P1NP increased significantly more in response to WBV compared to children whose mothers had received placebo. This implies early life vitamin D supplementation increases the anabolic response of bone to mechanical loading in children; given the limited sample size, confirmation in a larger cohort is needed, along with prospective data collection on fractures.

Disclosure: NJB consults for Alexion, Mereo, UCB and Amgen, and receives grant support for clinical studies from Alexion and Amgen.