Endocr Rev. 2018 Oct 12. doi: 10.1210/er.2018-00126. [Epub ahead of print]
Skeletal and extra-skeletal actions of vitamin D: Current evidence and outstanding questions
Bouillon R1, Marcocci C2, Carmeliet G1, Bikle D3, White JH4, Dawson-Hughes B5, Lips P6, Munns CF7, Lazaretti-Castro M8, Giustina A9, Bilezikian J10.
Author information:
1. Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Belgium.
2. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
3. University of California San Francisco and VA Medical Center, CA, USA.
4. Department of Physiology, McGill University, Montreal Qc, Canada.
5. Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
6. Department of Internal Medicine, Endocrine Section, VU University Medical Center, Amsterdam, The Netherlands.
7. The Children's Hospital at Westmead, Sydney, Australia. Sydney Medical School, University of Sydney, Sydney, Australia.
8. Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil.
9. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
10. Department of Endocrinology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Abstract
The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate is primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25OHD < 50 nmol/l) accelerates bone turnover, bone loss and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D deficient elderly subjects.The VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular and animal studies strongly suggest that vitamin D signaling has many extra-skeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need of continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health.Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.