Vitamin D and Bone Health: Basic and Clinical Aspects

Vitamin D is a calciotropic hormone with essential roles in postnatal skeletal development as well as mineral homeostasis in the elderly. Severe vitamin D deficiency or genetic defects in vitamin D actions may result in rickets (before epiphyseal growth plate closure) or osteomalacia. Vitamin D is mainly synthesized in the epidermis from cholesterol precursors by ultraviolet B light exposure, followed by conversion to 25-hydroxyvitamin D in liver by CYP2R1 and other cytochrome P450 enzymes. The definition of vitamin D deficiency as well as the role of free vitamin D not bound to vitamin D-binding protein (GC globulin) remains controversial. In the kidney, CYP27B1 converts the 25-hydrovitamin D prohormone to the active metabolite 1,25-dihydroxyvitamin D which acts upon the vitamin D receptor to regulate transcription in target cells. The beneficial skeletal effects of vitamin D are mainly determined by its stimulation of intestinal calcium absorption, prevention of secondary hyperparathyroidism and subsequent increases in bone turnover, as well as reducing the risk of falls in vitamin D-deficient elderly. Remarkably low doses are however needed for these beneficial effects, while very high dose vitamin D supplements may stimulate bone resorption, suppress mineralization, and increase the risk of falls. This chapter will critically discuss basic and clinical aspects of vitamin D related to bone health across the lifespan.