title: Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO).
abstract: BACKGROUND
  Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects.
  
  
  OBJECTIVE
  Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have reviewed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases, providing recommendations and guidelines for future studies in this field.
  
  
  CONCLUSIONS
  Robust mechanistic evidence is available from in vitro studies and in vivo animal studies, usually employing cholecalciferol, calcidiol or calcitriol in pharmacologic rather than physiologic doses. Although many cross-sectional and prospective association studies in humans have shown that low 25-hydroxyvitamin D levels (i.e., <50 nmol/L) are consistently associated with chronic diseases, further strengthened by a dose-response relationship, several meta-analyses of clinical trials have shown contradictory results. Overall, large randomized controlled trials with sufficient doses of vitamin D are missing, and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels >50 nmol/L, did not simultaneously assess multiple outcomes, and did not report overall safety (e.g., falls). Thus, no recommendations can be made to date for the use of vitamin D supplementation in general, parental compounds, or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases. Moreover, attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health cannot be recommended based on current evidence, since safety has yet to be confirmed. Finally, the promising findings from mechanistic studies, large cohort studies, and small clinical trials obtained for autoimmune diseases (including type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus), cardiovascular disorders, and overall reduction in mortality require further confirmation.
authors.affiliation: Bone Metabolic Diseases Unit, Department of Surgery and Translational Medicine, University Hospital of Florence and University of Florence, Florence, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Cianferotti
authors.affiliation: Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoldo
authors.affiliation: Department of Geriatrics and Aging Research, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
authors.forename: Heike A
authors.initials: HA
authors.lastname: Bischoff-Ferrari
authors.affiliation: Epidemiology and Public Health, University of Liege, CHU Sart Tilman, Liege, 4000, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bruyere
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, Hants, UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genoa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
authors.affiliation: Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK.|Institute for Health and Aging, Catholic University of Australia, Melbourne, VIC, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Kanis
authors.affiliation: Department of Endocrinology and Unit for Osteoporosis and Metabolic Bone Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Kaufman
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart-Tilman, Liège, Belgium.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.affiliation: Service of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Rene
authors.initials: R
authors.lastname: Rizzoli
authors.affiliation: Bone Metabolic Diseases Unit, Department of Surgery and Translational Medicine, University Hospital of Florence and University of Florence, Florence, Italy. marialuisa.brandi@unifi.it.
authors.forename: Maria Luisa
authors.identifier: http://orcid.org/0000-0002-8741-0592
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000517:prevention & control*; D019587:Dietary Supplements; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000517:prevention & control*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000517:prevention & control*; D014807:Vitamin D / Q000627:therapeutic use*
chemical_list: D014807:Vitamin D
keywords: Autoimmune diseases; Cancer; Cardiovascular diseases; Cholecalciferol; Diabetes; Mortality