Bone Abstracts

Classical vitamin D biology relates the active hormone, 1,25-dihydroxvitamin D₃, to promotion of calcium homeostasis through actions on the intestine and bone, and regulation of parathyroid hormone production and release. Added to this classical action of vitamin D is the up-regulation of FGF23 production and release by osteocytes as a means of regulation of circulating levels of vitamin D by reducing kidney synthesis of 1,25-dihydroxvitamin D₃ and increasing catabolism peripherally of substrate 25-hydroxyvitamin D₃ and of 1,25-dihydroxvitamin D₃. A review of mechanism of action in producing rickets related to altered classical pathway vitamin D metabolism will be presented, including FGF23 disorders.

However, non-canonical pathways of vitamin D actions are recognized increasingly, and involve both substrate 25-hydroxyvitamin D, as well as active hormone. An important pathway in this regard includes control of the vasculature and the cardiovascular system. Vitamin D insufficiency is recognized as being associated with myocardial infarction, incident hypertension, cerebrovascular accidents, and peripheral arterial disease. Further, as vitamin D alters inflammation, and insufficiency is recognized as being associated with elevations of highly-sensitive C-reactive protein. Further, vitamin D replenishment may improve the deleterious effects on the microvasculature as studied in humans. Thus, vitamin D becomes an important regulator of the endothelium. The pathogenesis of vitamin D related endothelial dysfunction will be presented and reviewed for human disease.

A newer area of vitamin D biology relates to definitions of normal levels, especially as parsed by patient ancestry/ethnicity. Currently, adequacy of vitamin D are defined by blood levels of total 25-hydroxyvitamin D₃, while only ‘free’ (unbound) hormone is felt to be biologically active. Data will be reviewed for the meanings of the algorithms for free vitamin D and newer studies that challenge them.