The association between vitamin D concentration and pain: a systematic review and meta-analysis

Abstract

Objective: Pain-related conditions, such as chronic widespread pain and fibromyalgia, are major burdens for individuals and the health system. Evidence from previous research on the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and pain is conflicting. Thus, we aimed to determine if there is an association between mean 25(OH)D concentration (primary aim), or proportion of hypovitaminosis D (secondary aim), and pain conditions in observational studies.

Design: Published observational research on 25(OH)D concentration and pain-related conditions was systematically searched for in electronic sources (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) and a random-effects meta-analysis was conducted on included studies.

Results: Eighty-one observational studies with a total of 50 834 participants were identified. Compared with controls, mean 25(OH)D concentration was significantly lower in patients with arthritis (mean difference (MD): -12·34 nmol/l; P<0·001), muscle pain (MD: -8·97 nmol/l; P=0·003) and chronic widespread pain (MD: -7·77 nmol/l; P<0·001), but not in patients with headache or migraine (MD: -2·53 nmol/l; P=0·06). The odds of vitamin D deficiency was increased for arthritis, muscle pain and chronic widespread pain, but not for headache or migraine, compared with controls. Sensitivity analyses revealed similar results.

Conclusions: A significantly lower 25(OH)D concentration was observed in patients with arthritis, muscle pain and chronic widespread pain, compared with those without. These results suggest that low 25(OH)D concentrations may be associated with pain conditions.

Keywords: Meta-analysis; Observational studies; Pain; Systematic review; Vitamin D.

Fig. 1

(colour online) PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram of study selection

Fig. 2

(colour online) Meta-analysis of the difference in mean serum vitamin D concentration (nmol/l) between participants with and without pain-related conditions. The study-specific mean difference (MD) and 95 % CI are represented by the square and horizontal line, respectively; the centre of the diamond represents the pooled MD and its width represents the pooled 95 % CI. IV denotes inverse variance; random denotes random-effects model

Fig. 3

(colour online) Meta-analysis of the difference in the proportion of vitamin D deficiency between participants with and without pain-related conditions. The study-specific OR and 95 % CI are represented by the square and horizontal line, respectively; the centre of the diamond represents the pooled OR and its width represents the pooled 95 % CI. M-H denotes Mantel–Haenszel; random denotes random-effects model