Advertisement

Calcified Tissue International

, Volume 106, Issue 1, pp 88–93 | Cite as

The Latest Evidence from Vitamin D Intervention Trials for Skeletal and Non-skeletal Outcomes

  • Arvind Sami
  • Bo AbrahamsenEmail author
Review

Abstract

Vitamin D has long been considered a central part of the treatment paradigm for osteoporosis. Initial studies in high-risk populations with widespread vitamin D deficiency found a reduction of both vertebral and non-vertebral fractures. Subsequent studies in the general population have yielded mixed but mostly disappointing results both for skeletal and especially non-skeletal outcomes. Recent sequential trial meta-analyses suggest that future studies are likely to be futile given the overall disappointing result. However, mega-trials are still in progress, and additional results have been released. This narrative review aims to evaluate new literature to determine if there has been any substantial change in the message. In conclusion, there is no longer a strong case for initiating vitamin D alone trials in the general adult population, irrespective of age and gender, for significant health outcomes such as fractures, cardiovascular disease and cancer. New studies should focus on risk groups and take directions from the Heaney criteria for evaluation of threshold nutrients. Indeed, real benefits may still be reaped by directing vitamin D supplementation to persons with proven or likely vitamin D deficiency. Further, the role of dietary calcium as a critical co-nutrient remains controversial and could contribute to the discrepancy between studies in terms of cancer outcomes and possibly falls and fractures.

Keywords

Vitamin D Outcomes Fracture Falls Cancer Cardiac 

Notes

Conflict of interest

Mr Sami reports no conflicts of interest. Dr. Abrahamsen reports institutional research contracts and personal speakers fees from UCB, institutional research contracts from Novartis, personal speakers fees from Eli Lily and from Amgen, outside the submitted work.

References

  1. 1.
    Bolland MJ, Grey A, Avenell A (2018) Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol 6:847–858.  https://doi.org/10.1016/S2213-8587(18)30265-1 CrossRefPubMedGoogle Scholar
  2. 2.
    Zhao JG, Zeng XT, Wang J, Liu L (2017) Association between calcium or Vitamin D supplementation and fracture incidence in community-dwelling older adults a systematic review and meta-analysis. JAMA 318:2466–2482.  https://doi.org/10.1001/jama.2017.19344 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bolland MJ, Grey A, Gamble GD, Reid IR (2014) The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol 2:307–320.  https://doi.org/10.1016/S2213-8587(13)70212-2 CrossRefPubMedGoogle Scholar
  4. 4.
    Ross AC, Taylor CL, Yaktine AL, Del Valle HB (2011) Dietary reference intakes for calcium and vitamin D. National Academies Press, Washington, DCGoogle Scholar
  5. 5.
    Heaney RP (2014) Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev 72:48–54.  https://doi.org/10.1111/nure.12090 CrossRefPubMedGoogle Scholar
  6. 6.
    Chapuy MC, Arlot ME, Duboeuf F et al (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327:1637–1642.  https://doi.org/10.1056/NEJM199212033272305 CrossRefPubMedGoogle Scholar
  7. 7.
    Freemantle N, Satram-Hoang S, Tang ET et al (2012) Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int 23:317–326.  https://doi.org/10.1007/s00198-011-1780-1 CrossRefPubMedGoogle Scholar
  8. 8.
    DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group (2010) Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340:b5463.  https://doi.org/10.1136/bmj.b5463
  9. 9.
    Gillespie LD, Gillespie WJ, Robertson MC et al (2001) Interventions for preventing falls in elderly people. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD000340 CrossRefPubMedGoogle Scholar
  10. 10.
    Robbins JA, Aragaki A, Crandall CJ et al (2014) Women’s Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy. Menopause 21:116–123.  https://doi.org/10.1097/GME.0b013e3182963901 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Khaw K-T, Stewart AW, Waayer D et al (2017) Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial. Lancet Diabetes Endocrinol 5:438–447.  https://doi.org/10.1016/S2213-8587(17)30103-1 CrossRefPubMedGoogle Scholar
  12. 12.
    Bislev LS, Langagergaard Rødbro L, Rolighed L et al (2018) Effects of vitamin D3 supplementation on muscle strength, mass, and physical performance in women with vitamin D insufficiency: a randomized placebo-controlled trial. Calcif Tissue Int 103:483–493.  https://doi.org/10.1007/s00223-018-0443-z CrossRefPubMedGoogle Scholar
  13. 13.
    Hin H, Tomson J, Newman C et al (2017) Optimum dose of vitamin D for disease prevention in older people: BEST-D trial of vitamin D in primary care. Osteoporos Int 28:841–851.  https://doi.org/10.1007/s00198-016-3833-y CrossRefPubMedGoogle Scholar
  14. 14.
    Aspray TJ, Chadwick T, Francis RM et al (2019) Randomized controlled trial of vitamin D supplementation in older people to optimize bone health. Am J Clin Nutr 109:207–217.  https://doi.org/10.1093/ajcn/nqy280 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Schnatz PF, Jiang X, Vila-Wright S et al (2014) Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women’s Health Initiative calcium/vitamin D randomized trial. Menopause 21:823–833.  https://doi.org/10.1097/GME.0000000000000188 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sollid ST, Hutchinson MYS, Fuskevag OM et al (2014) No effect of high-dose vitamin D supplementation on glycemic status or cardiovascular risk factors in subjects with prediabetes. Diabetes Care 37:2123–2131.  https://doi.org/10.2337/dc14-0218 CrossRefPubMedGoogle Scholar
  17. 17.
    Schnatz PF, Jiang X, Aragaki AK et al (2017) Effects of calcium, vitamin D, and hormone therapy on cardiovascular disease risk factors in the women’s health initiative: a randomized controlled trial. Obstet Gynecol 129:121–129.  https://doi.org/10.1097/AOG.0000000000001774 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lappe J, Watson P, Travers-Gustafson D et al (2017) Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. JAMA 317:1234–1243.  https://doi.org/10.1001/jama.2017.2115 CrossRefPubMedGoogle Scholar
  19. 19.
    Manson JE, Cook NR, Lee I-M et al (2019) Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 380:33–44.  https://doi.org/10.1056/NEJMoa1809944 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tomi-Pekka Tuomainen, Jyrki K Virtanen, Sari Voutilainen (2011) Finnish Vitamin D Trial (FIND). In: clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT01463813. Accessed 17 Aug 2019
  21. 21.
    Neale RE, Armstrong BK, Baxter C et al (2016) The D-health trial: a randomized trial of vitamin D for prevention of mortality and cancer. Contemp Clin Trials 48:83–90.  https://doi.org/10.1016/J.CCT.2016.04.005 CrossRefPubMedGoogle Scholar
  22. 22.
    Pittas AG, Dawson-Hughes B, Sheehan P et al (2019) Vitamin D supplementation and prevention of type 2 diabetes. N Engl J Med 381:520–530.  https://doi.org/10.1056/NEJMoa1900906 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK
  2. 2.Odense Patient Data Explorative Network, Institute of Clinical Research, Faculty of Health SciencesUniversity of Southern DenmarkOdenseDenmark
  3. 3.Department of MedicineHolbæk HospitalHolbækDenmark

Personalised recommendations