1. 2018;21;121-145Is Vitamin D Supplementation Effective for Low Back Pain? A Systematic Review and Meta-Analysis
   Systematic Review
   Joshua Zadro, BAppSc, Debra Shirley, PhD, Manuela Ferreira, PhD, Ana Paula Carvalho Silva, MSc, Sarah E. Lamb, PhD, Cyrus Cooper, PhD, and Paulo H. Ferreira, PhD.

BACKGROUND: Low back pain (LBP) is the leading cause of years lived with disability worldwide. Current intervention strategies are failing to reduce the enormous global burden of LBP and are prompting researchers to investigate alternative management strategies, such as vitamin D supplementation. Vitamin D supplementation appears to down regulate pro-inflammatory cytokines which lead to pain and up regulate anti-inflammatory cytokines that reduce inflammation. These mechanisms might explain the increasing interest in the use of vitamin D supplementation for LBP.

OBJECTIVES: To determine whether vitamin D supplementation improves pain more than a control intervention for individuals with LBP.

STUDY DESIGN: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

METHODS: We performed searches in numerous electronic databases combining key words relating to “vitamin D” and “LBP” until March 2017. Studies were included if they investigated vitamin D supplementation in participants with LBP, provided there was a comparison intervention. There was no restriction on the type of LBP, the intervention parameters investigated, or the type of clinical trial (e.g., randomized, non-randomized). Two reviewers independently performed the selection of studies, extracted data, rated the methodological quality of the included studies, and evaluated the overall quality of the evidence using the Grading of Recommendations Assessment, Delevopment, and Evaulation (GRADE) approach.

RESULTS: After screening 3,534 articles, 8 clinical trials were included in this systematic review. There is very low quality evidence (based on the GRADE approach) that vitamin D supplementation is not more effective than any intervention (including placebo, no intervention, and other conservative/pharmacological interventions) (continuous pain measures [0–100]: mean difference [MD] = -2.65, 95% confidence interval [CI]: -10.42 to 5.12, P = 0.504, n = 5; self-reported reduction in pain: pooled odds ratio [OR] = 1.07, 95% CI: 0.35 to 3.26, P = 0.906, n = 5) or placebo/no intervention for individuals with LBP (continuous pain measures: MD = 1.29, 95% CI: -3.81 to 6.39, P = 0.620, n = 4; self-reported reduction in pain: pooled OR = 1.53, 95% CI: 0.38 to 6.20, P = 0.550, n = 4), where ‘n’ is the number of studies included in the meta-analysis. These results did not change when we stratified the meta-analyses by the type of vitamin supplementation (vitamin D3 vs. alfacalcidol) or the type of LBP (non-specific vs. LBP resulting from osteoporosis or vertebral fractures).

LIMITATIONS: The overall quality of evidence was “very low” due to the poor methodological quality and small sample sizes of the included studies.

CONCLUSIONS: Vitamin D supplementation is not more effective than placebo, no intervention, or other conservative/pharmacological interventions for LBP (based on very low quality evidence). These results are consistent, regardless of the type of LBP or vitamin D supplementation. Until well-designed and adequately powered clinical trials suggest otherwise, the prescription of vitamin D for LBP cannot be recommended.

PROSPERO Registration No: CRD42016046874. www.crd.york.ac.uk/PROSPERO/display_record.asp?ID = CRD42016046874

KEY WORDS: Vitamin D, low back pain, chronic low back pain, alfacalcidol, osteoporosis, vertebral fractures, serum 25-hydroxyvitamin D, systematic review