Author(s): Alberto Falchetti, Elisa Rossi, Roberta Cosso, A. Buffa, Stefania Corvaglia, Nazzarena Malavolta
The vitamin D3 molecule, or cholecalciferol, is now considered a hormone that acts on multiple homeostatic fronts, either skeletal or extra-skeletal. After 100 years since from its identification as a protective and curative factor of rickets, during the last decade the interest in vitamin D among scientists and general public increased substantially and the use of vitamin D supplements has increased nearly exponentially in many countries. The aim of the present review is to clarify the mechanisms of action of vitamin D compounds on bone health through well-known concepts identified, and readily available, in the scientific literature. Taking advantage of our multi-year and consolidated experience in the pathophysiology of bone and mineral metabolism, we aim to briefly describe those few “hot” topics that we have perceived not to be easy to understand both for health professionals engaged on metabolic bone disorders and for those that are non-experts in this field and who should approach it. We describe, through basic pathophysiology concepts, the relationships between vitamin D and skeletal health: the main sources of vitamin D in humans, the vitamin D metabolites, evaluation of vitamin D status, tissue distribution of vitamin D, natural factors affecting the half-life of vitamin D3, the effects of cholecalciferol on calcium homeostasis and bone tissue, the relationship between vitamin D3 and bone cells and physical performance in the elderly, the effects of low vitamin D3 levels on bone loss and increased risk of fracture. Although currently different international institutional-academic positions exist about which is the best threshold value of serum vitamin D to be considered as adequate, it is important to bring out and lay a solid foundation supporting at least the crucial role played by it in the pathophysiology of skeletal tissue, despite the difficulties arising from the current lack of the specific molecular basis that clearly explain the balance between bone formation, mineralization and skeletal resorption. Finally, it should be also taken into consideration also the numerous reports, more recently identifiable in PubMed, in which, even in presence of very high levels of circulating values of 25OHD, clinically and biochemically observable toxic effects are not reported.
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