Chapter 73 - Vitamin D and its Metabolites and Analogs in the Management of Osteoporosis

Abstract

Rickets is an old disease that was first clearly described in the medical literature in the 17th century as PhD thesis equivalents by Daniel Whistler (Leiden) and Francis Glisson (London). The discovery of the dual origin of vitamin D in the beginning of the 20th century gradually resulted in the virtual elimination of rickets in the western world. Vitamin D is now probably drug number one in the world with regards to the number of people who are exposed to regular intake of a pharmaceutical product. It took about one century to understand the function of vitamin D better: from its photosynthesis, transport, and metabolism into a very large number of metabolites, including the tightly regulated vitamin D hormone, 1α,25(OH)2D3. Although intestinal calcium absorption was rapidly suspected to be a key target action of vitamin D and thus of intestinal calcium balance (absorption minus excretion), the effects of vitamin D for the kidney and bone calcium and phosphate balance was much more speculative and is even now not yet finally understood. The wider spectrum of activities of vitamin D metabolites and vitamin D receptor (VDR) was only recognized more recently based on mouse genetic studies (especially but not limited to VDR and 25-OH-1α-hydroxylase-deficient mice) and on human observational studies. These possible noncalcemic actions include the barrier function of the skin, hair growth, the innate and acquired immune system, cell proliferation, cardiovascular and metabolic effects, and neuromuscular function.