25-Hydroxyvitamin-D3 levels are positively related to subsequent cortical bone development in childhood: findings from a large prospective cohort study

In exploring relationships between vitamin D status in childhood and cortical bone, little relationship was observed with plasma concentrations of 25-hydroxyvitamin-D-2 [25(OH)D-2], whereas 25-hydroxyvitamin-D-3 [25(OH)D-3] was positively related to cortical bone mineral content (BMCC) and cortical thickness, suggesting D-3 exerts a beneficial effect on cortical bone development in contrast to D-2. The study is aimed to determine whether vitamin D status in childhood is related to cortical bone development by examining prospective relationships between plasma concentrations of 25(OH)D-2 and 25(OH)D-3 at 7.6, 9.9 or 11.8 years and peripheral quantitative computed tomography (pQCT) measurements of the mid-tibia at age 15.5 years, in children from the Avon Longitudinal Study of Parents and Children. Relationships between vitamin D status and pQCT outcomes were analysed by bootstrap linear regression, adjusted for age, sex, body composition, socioeconomic position and physical activity, in 2,247 subjects in whom all covariates were available. 25(OH)D-3 was also adjusted for season and 25(OH)D-2, and 25(OH)D-2 for 25(OH)D-3. 25(OH)D-3 was positively related to BMCC [0.066(0.009,0.122), P = 0.02], whereas no association was seen with 25(OH)D-2 [-0.008(-0.044,0.027), P = 0.7] [beta (with 95% CI) represents SD changes per doubling of vitamin D], P = 0.03 for difference in associations of 25(OH)D-2 and 25(OH)D-3 with BMCC. There were also differences in associations with cortical geometry, since 25(OH)D-3 was positively related to cortical thickness [0.11(0.04, 0.19), P = 0.002], whereas no association was seen with 25(OH)D-2 [-0.04(-0.08,0.009), P = 0.1], P = 0.0005 for difference. These relationships translated into differences in biomechanical strength as reflected by buckling ratio, which was positively related to 25(OH)D-2 [0.06(0.01,0.11), P = 0.02] indicating less resistance to buckling, but inversely related to 25(OH)D-3 [-0.1(-0.19,-0.02), P = 0.03], P = 0.001 for difference. In contrast to 25(OH)D-2, 25(OH)D-3 was positively related to subsequent cortical bone mass and predicted strength. In vitamin D-deficient children in whom supplementation is being considered, our results suggest that D-3 should be used in preference to D-2.