, Volume 56, Issue 2, pp 245–261 | Cite as

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)

  • Luisella Cianferotti
  • Francesco Bertoldo
  • Heike A. Bischoff-Ferrari
  • Olivier Bruyere
  • Cyrus Cooper
  • Maurizio Cutolo
  • John A. Kanis
  • Jean-Marc Kaufman
  • Jean-Yves Reginster
  • Rene Rizzoli
  • Maria Luisa BrandiEmail author
Position statement/Guideline



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.

Purpose and Methods

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.

Results and 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.


Cholecalciferol Cancer Diabetes Mortality Cardiovascular diseases Autoimmune diseases 



This paper was derived from a Working Group meeting supported by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

Conflict of interest

H.A.B.F. contributed as invitated speaker and on advisory boards for Roche, Pfizer, Sanofi, DSM Nutritional Products, Nestlé and WILD. She received investigator initiated and independent funding from DSM Nutritional Products, Roche Diagnostics, Pfizer and Nestlé. O.B. has disclosed that he has received grant support from IBSA, MSD, Nutraveris, Novartis, Pfizer, Rottapharm, Servier, and Theramex; lecture fees from IBSA, Rottapharm, Meda, Servier, and SMB. C.C. has received consultancy fees and honoraria from Amgen, Danone, Eli Lilly, GSK, Medtronic, Merck, Nestlé, Novartis, Pfizer, Roche, Servier, Shire, Takeda and UCB. J.A.K. reports grants from Amgen, grants from Lilly, non-financial support from Medimaps, non-financial support from Asahi, grants from Radius Health, other from AgNovos, outside the submitted work; and Dr Kanis is the architect of FRAX but has no financial interest. J.M.K. has received consultancy fees rom Amgen and Eli Lilly. J-Y.R. has received consultancy fees or paid advisory boards from Servier, IBSA-Genevrier, UCB, Asahi, Radius Health, Meda, Pierre Fabre; he has received lecture fees from Merck Sharp & Dohme, IBSA-Genevrier, Servier, Danone, Pharmevo Cniel, Meda, Dairy Research Council (DRC); he has received grant support from Merck Sharp & Dohme, Amgen, Lilly, Sevier Pfizer, Danone, Meda, Cniel, IBSA-Genevrier. R.R.: Speaker Bureau of Companies in the Mineral Metabolism Field (Amgen, Danone, Takeda); member of Scientific Advisory Boards of Amgen, Danone, Labatec, Nestlé, Radius Health. M.L.B. has received consultancy fees and grant support from: Alexion, Abiogen, Amgen, Eli Lilly and Shire. The remaining authors declare that they have no conflict of interest.


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© Springer Science+Business Media New York 2017

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Luisella Cianferotti
    • 1
  • Francesco Bertoldo
    • 2
  • Heike A. Bischoff-Ferrari
    • 3
  • Olivier Bruyere
    • 4
  • Cyrus Cooper
    • 5
  • Maurizio Cutolo
    • 6
  • John A. Kanis
    • 7
    • 8
  • Jean-Marc Kaufman
    • 9
  • Jean-Yves Reginster
    • 10
  • Rene Rizzoli
    • 11
  • Maria Luisa Brandi
    • 1
    Email author
  1. 1.Bone Metabolic Diseases Unit, Department of Surgery and Translational MedicineUniversity Hospital of Florence and University of FlorenceFlorenceItaly
  2. 2.Department of MedicineUniversity of VeronaVeronaItaly
  3. 3.Department of Geriatrics and Aging ResearchUniversity Hospital Zurich and University of ZurichZurichSwitzerland
  4. 4.Epidemiology and Public HealthUniversity of Liege, CHU Sart TilmanLiegeBelgium
  5. 5.MRC Lifecourse Epidemiology UnitUniversity of SouthamptonSouthamptonUK
  6. 6.Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal MedicineUniversity of GenovaGenoaItaly
  7. 7.Centre for Metabolic Bone DiseasesUniversity of Sheffield Medical SchoolSheffieldUK
  8. 8.Institute for Health and AgingCatholic University of AustraliaMelbourneAustralia
  9. 9.Department of Endocrinology and Unit for Osteoporosis and Metabolic Bone DiseasesGhent University HospitalGhentBelgium
  10. 10.Department of Public Health, Epidemiology and Health EconomicsUniversity of Liège, CHU Sart-TilmanLiègeBelgium
  11. 11.Service of Bone DiseasesGeneva University Hospitals and Faculty of MedicineGenevaSwitzerland

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