Fig. 1. The many plausible target tissues and effects of the vitamin D endocrine system.

The potential skeletal and extra-skeletal target tissues and effects of the vitamin D endocrine system (vitamin D and vitamin D receptor) as based on preclinical and observational studies, Mendelian randomization studies and randomized controlled trials (RCTs). In vitro studies have identified many molecular and genetic targets of vitamin D action. Animal models have confirmed a variety of skeletal and extra-skeletal actions. Human observational data are largely in line with preclinical data. However, Mendelian randomization studies and RCTs have not confirmed such a widespread action profile in vitamin D-replete adults. Therefore, the health consequences of poor vitamin D status remain controversial. The strength of the relationship between the vitamin D endocrine system and health effects are indicated by the arrow thickness. FGF23, fibroblast growth factor 23; PTH, parathyroid hormone.