Clinical Rheumatology

, Volume 36, Issue 5, pp 1201–1208 | Cite as

Does vitamin D supplementation alleviate chronic nonspecific musculoskeletal pain? A systematic review and meta-analysis

  • M. Gaikwad
  • S. Vanlint
  • M. Mittinity
  • G. L. Moseley
  • N. Stocks
Letter to the Editor


Chronic nonspecific musculoskeletal pain (CNMP) is an idiopathic condition often seen in general practice and rheumatology clinics, the aetiology of which may include vitamin D deficiency. The objective of the present study is to evaluate the effectiveness of vitamin D supplementation in the management of CNMP through a systematic review and meta-analysis. According to PRISMA guidelines, PubMed, Embase, Web of Science, Cochrane and Scopus electronic databases were searched for randomised controlled trials comparing vitamin D supplementation to a control or placebo in CNMP patients; the search was not limited by language or date. Meta-analysis was performed using the mean and standardised mean difference which was computed with 95 % confidence intervals, and overall effect size was calculated. Both fixed and random effects models were used in meta-analysis to account for heterogeneity in the studies. The initial search identified 107 studies, of which 10 were potentially relevant, with 7 studies excluded because they did not meet selection criteria. Three studies were included in the meta-analysis. We found no effect of vitamin D supplementation (standardised mean difference (SMD) 0.004; 95 % confidence interval (CI) −0.248 to 0.256) on pain in CNMP patients. Forest plot is used to present the results from meta-analysis. Contrary to a widespread clinical view, there is a moderate level of evidence that vitamin D supplementation is not helpful for treating CNMP patients.


Chronic nonspecific musculoskeletal pain Meta-analysis Systematic review Vitamin D Vitamin D supplementation 


  1. 1.
    Kumar A, Gopal H, Khamkar K et al (2012) Vitamin D deficiency as the primary cause of musculoskeletal complaints in patients referred to rheumatology clinic: a clinical study. Indian J Rheumatol 7:199–203CrossRefGoogle Scholar
  2. 2.
    O’Sullivan P, Beales D, Jensen L, Murray K, Myers T (2011) Characteristics of chronic non-specific musculoskeletal pain in children and adolescents attending a rheumatology outpatients clinic: a cross-sectional study. Pediatr Rheumatol Online J 9:3CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    de Vries HJ, Reneman MF, Groothoff JW, Geertzen JHB, Brouwer S (2012) Factors promoting staying at work in people with chronic nonspecific musculoskeletal pain: a systematic review. Disabil Rehabil 34:443–58CrossRefPubMedGoogle Scholar
  4. 4.
    Konijnenberg AY, Uiterwaal CS, Kimpen JL, van der Hoeven J, Buitelaar JK, Graeff-Meeder ER (2005) Children with unexplained chronic pain: substantial impairment in everyday life. Arch Dis Child 90:680–6CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Guite J, Logan D, Sherry D, Rose J (2007) Adolescent self-perception: associations with chronic musculoskeletal pain and functional disability. J Pain 8:379–86CrossRefPubMedGoogle Scholar
  6. 6.
    de Vries HJ, Reneman MF, Groothoff JW, Geertzen JH, Brouwer S (2013) Self-reported work ability and work performance in workers with chronic nonspecific musculoskeletal pain. J Occup Rehabil 23:1–10CrossRefPubMedGoogle Scholar
  7. 7.
    Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC (2007) The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull 133:581–624CrossRefPubMedGoogle Scholar
  8. 8.
    Perquin C, Hunfeld J, Hazeborek-Kampschreur A et al (2003) The natural course of chronic benign pain in childhood and adolescence: a two-year population-based follow-up study. Eur J Pain 7:551–9CrossRefPubMedGoogle Scholar
  9. 9.
    Perquin C, Hunfeld J, Hazeborek-kampschreur A et al (2001) Insights in the use of health care services in chronic benign pain in childhood and adolescence. Pain 94:205–13CrossRefPubMedGoogle Scholar
  10. 10.
    El-Metwally A, Salminen JJ, Auvinen A, Kautiainen H, Mikkelsson M (2004) Prognosis of non-specific musculoskeletal pain in preadolescents: a prospective 4-year follow-up study till adolescence. Pain 110:550–9CrossRefPubMedGoogle Scholar
  11. 11.
    Plotnikoff GA, Quigley JM (2003) Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 73:1463–70CrossRefGoogle Scholar
  12. 12.
    Tague SE, Clarke GL, Winter MK, McCarson KE, Wright DE, Smith PG (2011) Vitamin D deficiency promotes skeletal muscle hypersensitivity and sensory hyperinnervation. J Neurosci 31:13728–38CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lai Y-H, Fang T-C (2013) The pleiotropic effect of vitamin D. ISRN Nephrol Article ID 898125Google Scholar
  14. 14.
    Zittermann A (2003) Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 89:552–72CrossRefPubMedGoogle Scholar
  15. 15.
    Lyman D (2005) Undiagnosed vitamin D deficiency in the hospitalized patient. Am Fam Physician 71:299–304PubMedGoogle Scholar
  16. 16.
    Body JJ, Bergmann P, Boonen S et al (2012) Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications. Osteoporos Int 23(Suppl 1):S1–23CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Chaudhary WA, Arshad SH, Waqas S et al (2013) Vitamin D supplement as an adjuvant in the management of chronic musculoskeletal pain. Anaesth Pain Intensive Care 17:296–300Google Scholar
  18. 18.
    Knutsen KV, Brekke M, Gjelstad S, Lagerløv P (2010) Vitamin D status in patients with musculoskeletal pain, fatigue and headache: a cross-sectional descriptive study in a multi-ethnic general practice in Norway. Scand J Prim Health Care 28:166–71CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Straube S, Derry S, Straube C, Moore RA (2015) Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst RevGoogle Scholar
  20. 20.
    Guyatt G, Gutterman D, Baumann MH et al (2006) Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians Task Force. Chest 129:174–81CrossRefPubMedGoogle Scholar
  21. 21.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Group TP (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. PloS 6Google Scholar
  22. 22.
    Jadad AR, Moore A, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12CrossRefPubMedGoogle Scholar
  23. 23.
    Cohen J (2013) Statistical power analysis for the behavioral sciences. Academic PressGoogle Scholar
  24. 24.
    Glass GV (1976) Primary, secondary, and meta-analysis of research. Educ Res 5:3–8CrossRefGoogle Scholar
  25. 25.
    Hedges LV, Olkin I (2014) Statistical method for meta-analysis. Academic pressGoogle Scholar
  26. 26.
    Higgins PT, Green S (2008) Cochrane handbook for systematic reviews of interventions. Wiley-Blackwell, Chichester, EnglandCrossRefGoogle Scholar
  27. 27.
    StataCorp (2011) Stata Statistical Software: Release 12. StataCorp LP, TXGoogle Scholar
  28. 28.
    Bailey KR (1987) Inter-study differences: how should they influence the interpretation and analysis of results. Stat Med 6:351–60CrossRefPubMedGoogle Scholar
  29. 29.
    Sakalli H, Arslan D, Yucel AE (2012) The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatol Int 32:2279–83CrossRefPubMedGoogle Scholar
  30. 30.
    Schreuder F, Bernsen RM, van der Wouden JC (2012) Vitamin D supplementation for nonspecific musculoskeletal pain in non-western immigrants: a randomized controlled trial. Ann Fam Med 10:547–55CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Warner AE, Arnspiger SA (2008) Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol 14Google Scholar
  32. 32.
    Gendelman O, Itzhaki D, Makarov S, Bennun M, Amital H (2015) A randomized double-blind placebo-controlled study adding high dose vitamin D to analgesic regimens in patients with musculoskeletal pain. Lupus 24:483–9CrossRefPubMedGoogle Scholar
  33. 33.
    Guyatt G, Oxman AD, Vist GE et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Br Med J 336:924CrossRefGoogle Scholar
  34. 34.
    Grace PM, Hutchinson MR, Maier SF, Watkins LR (2014) Pathological pain and the neuroimmune interface. Nat Rev Immunol 14:217–31CrossRefPubMedGoogle Scholar
  35. 35.
    Woolf CJ (2014) What to call the amplification of nociceptive signals in the central nervous system that contribute to widespread pain? Pain 155:1911–2CrossRefPubMedGoogle Scholar
  36. 36.
    Moseley GL, Vlaeyen JWS (2015) Beyond nociception: the imprecision hypothesis of chronic pain. Pain 156:35–8CrossRefPubMedGoogle Scholar
  37. 37.
    Vlaeyen JWS, Linton SJ (2012) Fear-avoidance model of chronic musculoskeletal pain: 12 years on. Pain 153:1144–7CrossRefPubMedGoogle Scholar
  38. 38.
    Moseley GL, Butler DS (2015) Fifteen years of explaining pain: the past, present, and future. J Pain 16:807–13CrossRefPubMedGoogle Scholar
  39. 39.
    Butler DS, Moseley GL (2013) Explain pain, 2nd edn. Noigroup Publications, AdelaideGoogle Scholar
  40. 40.
    Meulders A, Harvie DS, Bowering JK, Caragianis S, Vlaeyen JW, Moseley GL (2014) Contingency learning deficits and generalization in chronic unilateral hand pain patients. J Pain 15:1046–56CrossRefPubMedGoogle Scholar
  41. 41.
    Ryan PJ (2007) Vitamin D therapy in clinical practice. One dose does not fit all. Int J Clin Pract 61:1894–9CrossRefPubMedGoogle Scholar
  42. 42.
    Moseley GL (2006) Do training diaries affect and reflect adherence to home programs? Arthritis Rheum 55:662–4CrossRefPubMedGoogle Scholar
  43. 43.
    Abbasi M, Hashemipour S, Hajmanuchehri F, Kazemifar AM (2013) Is vitamin D deficiency associated with non specific musculoskeletal pain? Glob J Health Sci 5Google Scholar
  44. 44.
    O’Connell NE, Moseley GL, McAuley JH, Wand BM, Herbert RD (2015) Interpreting effectiveness evidence in pain: short tour of contemporary issues. Phys Ther 95:1087–94CrossRefPubMedGoogle Scholar
  45. 45.
    Pop LC, Shapses SA, Chang B, Sun W, Wang X (2015) Vitamin D-binding protein in healthy pre- and postmenopausal women: relationship with estradiol concentrations. Endocr Pract 21:936–42CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kanwar G, Sharma N, Shekhawat M, Sharma P, Hada R, Chandel CS (2015) Comparison of vitamin D levels in pre and post menopausal type 2 diabetic females. IOSR-JDMS 14:70–3Google Scholar
  47. 47.
    Kendall JM (2003) Designing a research project: randomised controlled trials and their principles. Emerg Med J 20:164–8CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Sim J, Reid N (1999) Statistical inference by confidence intervals: issues of interpretation and utilization. Phys Ther 79:186–95PubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2016

Authors and Affiliations

  • M. Gaikwad
    • 1
  • S. Vanlint
    • 1
  • M. Mittinity
    • 2
  • G. L. Moseley
    • 3
  • N. Stocks
    • 1
  1. 1.Discipline of General Practice, School of MedicineUniversity of AdelaideAdelaideAustralia
  2. 2.School of Public HealthUniversity of AdelaideAdelaideAustralia
  3. 3.Sansom Institute for Health ResearchUniversity of South AustraliaAdelaideAustralia

Personalised recommendations