The antifracture efficacy of vitamin D in adults - are we assessing it reliably? A systematic review.

Introduction: The antifracture efficacy of vitamin D is still controversial. The aim of this systematic review was to examine if the vitamin D trials were designed adequately to reliably assess its antifracture activity.

Material and methods: The electronic databases PubMed, Medline, Embase, Web of Science, and Cochrane Library were searched to identify clinical trials evaluating the antifracture efficacy of vitamin D in adults. We compared the protocols of the trials against the opinions of the American Society for Bone and Mineral Research (ASBMR), International Society for Clinical Densitometry (ISCD), National Osteoporosis Foundation (NOF), European Medicines Agency (EMEA) experts, and the consensus statement from the 2nd International Conference on Controversies in Vitamin D, and against the protocols of the trials of the medications with proven antifracture efficacy (bisphosphonates, teriparatide, abaloparatide, raloxifene, denosumab, romosozumab). We assessed the prospective character, study design, group description, number of patients, study duration, and vitamin D (serum examination and dosage) supplementation. A description of the desired characteristics of the study protocol was presented.

Results: Thirteen eligible trials were identified. All but 2 were conducted in the elderly population only. Nine trials were included in the final analysis. Serum 25-hydroxy vitamin D (25OHD) was not measured in a representative number of subjects before (except in 2 studies), during, or after treatment in any study.

Conclusions: The analysed studies did not conclusively assess the vitamin D antifracture efficacy in patients with prestudy low serum vitamin levels, due to the lack of assessment of whether sufficient doses of vitamin D were used. They informed about the relevant doses and preparations of vitamin D in particular groups (specific fracture risk, age, place of residence) only.