The effect sizes that we observed were similar in magnitude to that of other important external influences

on skeletal development such as fat mass, which we have previously reported to influence cortical bone development [14]. In further analyses, based on the same study sample, we found that a doubling in fat mass was associated with a 0.13 SD increase in cortical thickness (analyses adjusted for age and height), which was similar to that seen for 25(OH)D3, of which a doubling was associated with a 0.11 SD increase in cortical thickness. Identification of 25(OH)D concentrations in childhood associated with optimal outcomes for bone and other health outcomes, and how these might translate into #Selleck Captisol randurls[1|1|,|CHEM1|]# public health recommendations, is a matter of controversy [26]. Arguably, the finding that a doubling in 25(OH)D3 is

associated with a 0.11 SD increase in cortical thickness is not a strong enough effect to justify widespread vitamin H 89 mw D supplementation in childhood. Since >25% of our study population had insufficient total 25(OH)D based on the 20 ng ml-1 cutoff [26], this conclusion is likely to apply to other, predominantly Caucasian, populations with a similarly high prevalence of vitamin D insufficiency based on this definition. This may represent a contrast with early life exposure in utero, when vitamin D status has been suggested to have major long-term influences on subsequent bone development including periosteal growth [27, 28]. On the other hand, 25(OH)D3 may have a stronger association with cortical outcomes in certain subgroups, in whom supplementation may be more justifiable. For example, beta coefficients were generally higher in boys, in

whom a doubling in 25(OH)D3 was associated with a 0.18 SD increase in CT. Moreover, the magnitude of effects that we observed may have been tempered by aspects of the study design (see ‘Limitations’ below). Furthermore, whereas observational studies of this Rebamipide nature provide some information as to the likely benefits of vitamin D supplementation in childhood, evidence from randomized controlled trials is required before definitive conclusions can be drawn. In those children in whom vitamin D supplementation is being considered, an important question which follows is which form of vitamin D is the most effective. In contrast to the positive associations between 25(OH)D3 and cortical bone outcomes described above, relationships with 25(OH)D2 were null in the case of BMCC and cortical thickness. Whereas a weak positive association was present between 25(OH)D2 and periosteal circumference, there was a weak inverse association with BMDC, as well as a weak positive association with buckling ratio suggesting reduced resistance to buckling.