Rheumatology International

, Volume 32, Issue 11, pp 3365–3372 | Cite as

Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases

  • Pier Paolo SainaghiEmail author
  • Mattia Bellan
  • Stefano Carda
  • Chiara Cerutti
  • Daniele Sola
  • Alessandra Nerviani
  • Rossella Molinari
  • Carlo Cisari
  • Gian Carlo Avanzi
Original Article


Recent reports suggest a role of hypovitaminosis D in the pathogenesis of inflammatory autoimmune diseases (ARD); we investigated 25(OH)vitamin D plasma level before and after supplementation in ARD and NARD (non-ARD: osteoporosis and/or OA) patients. We retrospectively evaluated 572 consecutive clinical records of adult patients at immuno-rheumatology and rehabilitative units of our institution from January 2006 to October 2009. We excluded patients with vitamin D supplementation or renal failure, primary hyperparathyroidism, liver failure. We recorded 25(OH)vitamin D plasma concentration of 245 patients together with other clinical data. We then evaluated 25(OH)vitamin D plasma concentration of 100 (43 ARD and 57 NARD) patients previously included who underwent 750–1,000 UI/die 25(OH)vitamin D supplementation for at least 6 months. Appropriate statistical analysis was performed. The median 25(OH)vitamin D concentration was not significantly different between 119 ARD [33.4 (IQR 22.5–54.9) nmol/l] and 126 NARD patients 32.9 (IQR 18.7–50.2). In stepwise logistic regression, female sex (F:13.7), winter-spring season (F:5.6) and older age (F:5.3), but not ARD, predicted plasma 25(OH)vitamin D <75 nmol/l. Cholecalciferol supplementation increased 25(OH)vitamin D plasma concentration equally in both ARD and NARD; however, only 29/100 patients reached a plasma level ≥75 nmol/l without differences between ARD and NARD (χ2 = n.s.). Hypovitaminosis D is common in rheumatic patients. Sex and age but not ARD are risk factors for this condition. 750–1,000 UI/die of cholecalciferol is not sufficient to normalize plasma level in these patients. Increase of plasma 25(OH)vitamin D after treatment is not influenced by the presence of an inflammatory autoimmune disease.


Hypovitaminosis D 25(OH)vitamin D supplementation Inflammatory autoimmune diseases Osteoarthritis 



The study was supported by “Università del Piemonte Orientale Ricerca Locale” research grants.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Holick MF (2006) Resurrection of vitamin D deficiency and rickets. J Clin Invest 116:2062–2072PubMedCrossRefGoogle Scholar
  2. 2.
    Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporos Int 16:713–716PubMedCrossRefGoogle Scholar
  3. 3.
    Sunyecz JA (2008) The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag 4:827–836PubMedGoogle Scholar
  4. 4.
    Lemire JM (1992) Immunomodulatory role of 1, 25-dihydroxyvitamin D3. J Cell Biochem 49:26–31PubMedCrossRefGoogle Scholar
  5. 5.
    Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R (2000) Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun 270:701–708PubMedCrossRefGoogle Scholar
  6. 6.
    Helming L, Böse J, Ehrchen J, Schiebe S, Frahm T, Geffers R et al (2005) 1alpha, 25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation. Blood 106:4351–4358PubMedCrossRefGoogle Scholar
  7. 7.
    van Etten E, Mathieu C (2005) Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101PubMedCrossRefGoogle Scholar
  8. 8.
    Holick MF (2008) The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med 29:361–368PubMedCrossRefGoogle Scholar
  9. 9.
    Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG (2004) Iowa Women’s Health Study. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 50:72–77PubMedCrossRefGoogle Scholar
  10. 10.
    Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D (2007) Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 56:2143–2149PubMedCrossRefGoogle Scholar
  11. 11.
    Cutolo M, Otsa K, Laas K, Yprus M, Lehtme R, Secchi ME et al (2006) Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 24:702–704PubMedGoogle Scholar
  12. 12.
    Houston DK, Cesari M, Ferrucci L, Cherubini A, Maggio D, Bartali B et al (2007) Association between vitamin D status and physical performance: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 62:440–446PubMedCrossRefGoogle Scholar
  13. 13.
    Gerdhem P, Ringsberg KA, Obrant KJ, Akesson K (2005) Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women. Osteoporos Int 16:1425–1431PubMedCrossRefGoogle Scholar
  14. 14.
    Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28PubMedGoogle Scholar
  15. 15.
    Cutolo M (2009) Vitamin D and autoimmune rheumatic diseases. Rheumatology (Oxford) 48:210–212CrossRefGoogle Scholar
  16. 16.
    Lips P (2007) Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol 103:620–625PubMedCrossRefGoogle Scholar
  17. 17.
    Isaia G, Giorgino R, Rini GB, Bevilacqua M, Maugeri D, Adami S (2003) Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Osteoporos Int 14:577–582PubMedCrossRefGoogle Scholar
  18. 18.
    Mouyis M, Ostor AJ, Crisp AJ, Ginawi A, Halsall DJ, Shenker N et al (2008) Hypovitaminosis D among rheumatology outpatients in clinical practice. Rheumatology (Oxford) 47:1348–1351CrossRefGoogle Scholar
  19. 19.
    Costenbader KH, Feskanich D, Holmes M, Karlson EW, Benito-Garcia E (2008) Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women. Ann Rheum Dis 67:530–535PubMedCrossRefGoogle Scholar
  20. 20.
    Nielen MM, van Schaardenburg D, Lems WF, van de Stadt RJ, de Koning MH, Reesink HW et al (2006) Vitamin D deficiency does not increase the risk of rheumatoid arthritis: comment on the article by Merlino et al. Arthritis Rheum 54:3719–3720PubMedCrossRefGoogle Scholar
  21. 21.
    Craig SM, Yu F, Curtis JR, Alarcón GS, Conn DL, Jonas B et al (2010) Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis. J Rheumatol 37:275–281PubMedCrossRefGoogle Scholar
  22. 22.
    Talwar SA, Aloia JF, Pollack S, Yeh JK (2007) Dose response to vitamin D supplementation among post-menopausal African American women. Am J Clin Nutr 86:1657–1662PubMedGoogle Scholar
  23. 23.
    von Restorff C, Bischoff-Ferrari HA, Theiler R (2009) High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency. Bone 45:747–749CrossRefGoogle Scholar
  24. 24.
    Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D’Erasmo E et al (2008) Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab 93:3015–3020PubMedCrossRefGoogle Scholar
  25. 25.
    Romagnoli E, Caravella P, Scarnecchia L, Martinez P, Minisola S (1999) Hypovitaminosis D in an Italian population of healthy subjects and hospitalized patients. Br J Nutr 81:133–137PubMedCrossRefGoogle Scholar
  26. 26.
    Reuch J, Ackermann H, Badenhoop K (2009) Cyclic changes of vitamin D and pth are primarily regulated by solar radiation: 5-year analysis of German (50 degrees N) population. Horm Metab Res 41:402–407CrossRefGoogle Scholar
  27. 27.
    Jacques PF, Felson DT, Tucker KL, Mahnken B, Wilson PW, Rosenberg IH et al (1997) Plasma 25-hydroxyvitamin D and its determinants in an elderly population sample. Am J Clin Nutr 66:929–936PubMedGoogle Scholar
  28. 28.
    Lanske B, Razzaque MS (2007) Vitamin D and aging: old concepts and new insights. J Nutr Biochem 18:771–777PubMedCrossRefGoogle Scholar
  29. 29.
    MacLaughlin J, Holick MF (1985) Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 76:1536–1538PubMedCrossRefGoogle Scholar
  30. 30.
    Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA (2010) Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 69:20–28PubMedCrossRefGoogle Scholar
  31. 31.
    Carnevale V, Modoni S, Pileri M, Di Giorgio A, Chiodini I, Minisola S et al (2001) Longitudinal evaluation of vitamin D status in healthy subjects from southern Italy: seasonal and gender differences. Osteoporos Int 12:1026–1030PubMedCrossRefGoogle Scholar
  32. 32.
    Rockell JE, Skeaff CM, Williams SM, Green TJ (2006) Serum 25-hydroxy vitamin D concentrations of New Zealanders aged 15 years and older. Osteoporos Int 17:1382–1389PubMedCrossRefGoogle Scholar
  33. 33.
    Saintonge S, Bang H, Gerber LM (2009) Implications of a new definition of vitamin D deficiency in a multiracial US adolescent population: the national health and nutrition examination survey III. Pediatrics 123:797–803PubMedCrossRefGoogle Scholar
  34. 34.
    Atkins GJ, Anderson PH, Findlay DM, Welldon KJ, Vincent C, Zannettino AC et al (2007) Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha, 25-dihydroxyvitamin D3. Bone 40:1517–1528PubMedCrossRefGoogle Scholar
  35. 35.
    Hewison M (2010) Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin N Am 39:365–379CrossRefGoogle Scholar
  36. 36.
    Edfeldt K, Liu PT, Chun R, Fabri M, Schenk M, Wheelwright M et al (2010) T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc Natl Acad Sci USA 107:22593–22598PubMedCrossRefGoogle Scholar
  37. 37.
    Oelzner P, Müller A, Deschner F, Hüller M, Abendroth K, Hein G et al (1998) Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tiss Int 62:193–198CrossRefGoogle Scholar
  38. 38.
    Lange U, Jung O, Teichmann J, Neeck G (2001) Relationship between disease activity and serum levels of vitamin D metabolites and parathyroid hormone in ankylosing spondylitis. Osteoporos Int 12:1031–1035PubMedCrossRefGoogle Scholar
  39. 39.
    Ebert R, Jovanovic M, Ulmer M, Schneider D, Meissner-Weigl J, Adamski J et al (2004) Down-regulation by nuclear factor kappaB of human 25-hydroxy vitamin D3 1alpha-hydroxylase promoter. Mol Endocrinol 18:2440–2450PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Pier Paolo Sainaghi
    • 1
    • 2
    Email author
  • Mattia Bellan
    • 1
  • Stefano Carda
    • 3
  • Chiara Cerutti
    • 1
  • Daniele Sola
    • 1
  • Alessandra Nerviani
    • 1
  • Rossella Molinari
    • 1
  • Carlo Cisari
    • 3
  • Gian Carlo Avanzi
    • 1
    • 2
  1. 1.Immuno-Rheumatology UnitDMCS Università del Piemonte Orientale “A. Avogadro” and AOU “Maggiore della Carità”NovaraItaly
  2. 2.IRCAD (Interdisciplinary Research Center of Autoimmune Diseases)NovaraItaly
  3. 3.Physical and Rehabilitative MedicineDMCS Università del Piemonte Orientale “A. Avogadro” and AOU “Maggiore della Carità”NovaraItaly

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