Osteoporosis International

, Volume 20, Issue 3, pp 427–433 | Cite as

Vitamin D deficiency in patients with active systemic lupus erythematosus

  • V. Z. C. Borba
  • J. G. H. Vieira
  • T. Kasamatsu
  • S. C. Radominski
  • E. I. Sato
  • M. Lazaretti-Castro
Original Article

Abstract

Summary

We investigated the effects of disease activity on bone metabolism in 36 patients with systemic lupus erythematosus (SLE). Changes in bone remodeling were not explained by corticosteroid use. A high prevalence of 25OHD deficiency in SLE patients indicates the need for vitamin D replacement, mainly during high disease activity periods.

Introduction

We investigated the effects of SLE disease activity on bone metabolism, their relation to inflammatory cytokines and vitamin D levels.

Methods

We performed a cross-sectional analysis of 36 SLE patients classified according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in high activity (group I: 12 patients, mean age 29.6 years) or in minimal activity (group II: 24 patients, mean age 30.0 years), and compared them to normal controls (group III: 26 women, 32.8 years). Serum calcium, phosphorus, parathyroid and sex hormones, bone remodeling markers, interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), IL-1, tumor necrosis factor-α (TNF), 25-hydroxivitamin D (25OHD), and 1,25-dihydroxyvitamin D3 were measured, plus bone mineral density.

Results

All cytokines were significantly higher in SLE groups; IL-6 could differentiate SLE patients from controls. In group I, 25OHD levels were lower (P < 0.05), which was related to the SLEDAI (R = -0.65, P < 0.001). In multiple regression analysis, the 25OHD level was associated with SLEDAI, osteocalcin and bone-specific alkaline phosphatase. The SLEDAI score was positively correlated with all measured cytokines and especially TNF (R = 0.75, P < 0.001).

Conclusions

SLE patients demonstrated changes in bone remodeling strongly related to disease activity. A high prevalence of 25OHD deficiency was observed in SLE patients, indicating the need for vitamin D replacement.

Keywords

Bone markers Bone metabolism Cytokines Osteoporosis Systemic lupus erythematosus Vitamin D 

References

  1. 1.
    Borba VZC, Matos PG, Viana PRS, Fernandes A, Sato EI, Lazaretti-Castro M (2005) High prevalence of vertebral deformity in premenopausal systemic lupus erythematosus patients and its correlation with bone mineral density. Lupus 14:529–533PubMedCrossRefGoogle Scholar
  2. 2.
    Bultinik IEM, Lems WF, Kostense PJ, Dijkmans BAC, Voskuyl AE (2005) Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erithematosus. Arthritis Rheum 54:2044–2050CrossRefGoogle Scholar
  3. 3.
    Yee C-S, Crabtree N, Skan J, Bowman S, Situnayake D, Gordon C (2005) Prevalence and predictors of fractures in systemic lupus erythematosus. Ann Rheum Dis 64:11–113CrossRefGoogle Scholar
  4. 4.
    Houssiau FA, Lefebre C, Depresseux G, Lambert M, Devogelaer JP, Deuxchaisnes CN (1996) Trabecular and cortical bone loss in systemic lupus erythematosus. Br J Rheumatol 35:244–247PubMedCrossRefGoogle Scholar
  5. 5.
    Kalla AA, Fataar AB, Jessop SJ, Bewerunge L (1993) Loss of trabecular bone mineral density in systemic lupus erythematosus. S Afr Med J 36:1726–1734Google Scholar
  6. 6.
    Sels F, Dequeker J, Verwilghen, Mbuyi-Muamba J (1996) SLE and osteoporosis: dependence and/or independence on glucocorticoids. Lupus 5:89–92PubMedCrossRefGoogle Scholar
  7. 7.
    Cunnane G, Lane NE (2000) Steroid-induced osteoporosis in systemic lupus erythematosus. Rheum Dis Clin North Am 26:311–329PubMedCrossRefGoogle Scholar
  8. 8.
    Sen D, Keen RW (2001) Osteoporosis in systemic lupus erythematosus: prevention and treatment. Lupus 10:227–232PubMedCrossRefGoogle Scholar
  9. 9.
    Müller K, Kriegbaum NJ, Baslund B, Sorensen OH, Thymann M, Bentzen K (1995) Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus. Clin Rheumatol 14:397PubMedCrossRefGoogle Scholar
  10. 10.
    Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS (2006) Vitamin D deficiency in systemic lupus erythematosus. Autoimmunity Rev 5:114–117CrossRefGoogle Scholar
  11. 11.
    Aringer M, Smolen JS (2004) Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention. Lupus 13:344–347PubMedCrossRefGoogle Scholar
  12. 12.
    Gabay C, Cakir N, Moral F, Roux-Lombard P, Meyer O, Dayer JM, Vischer T et al (1997) Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol 24:303–308PubMedGoogle Scholar
  13. 13.
    Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRefGoogle Scholar
  14. 14.
    Saraiva GL, Cendoroglo MS, Ramos LR, Araujo LMQ, Vieira JGH, Kunii I, Hayashi LF, Correa MP, Marise Lazaretti-Castro M (2005) Influence of ultraviolet radiation on the production of 25 hydroxyvitamin D in the elderly population in the city of Sa˜o Paulo (23 o 34’S), Brazil. Osteoporos Int 16:1649–1654PubMedCrossRefGoogle Scholar
  15. 15.
    Bombardier C, Gladman DD, Urowitz M, Caron D, Chang CH (1992) Derivation of SLEDAI. A disease activity index for lupus patients. Arthritis Rheum 35:630–640PubMedCrossRefGoogle Scholar
  16. 16.
    Bowers GN Jr, Rains TC (1988) Measurement of total calcium in biological fluids: flame atomic absorption spectrometry. Methods Enzymol 158:302–319PubMedCrossRefGoogle Scholar
  17. 17.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281PubMedCrossRefGoogle Scholar
  18. 18.
    Vieira JG, Nishida SK, Kasamatsu T (1994) Development and clinical application of an immunofluorometric assay for intact parathyroid hormone. Brazilian J Med Biol Res 27:2379–2382Google Scholar
  19. 19.
    Zonana-Nacach A, Barr SG, Magder LS, Petri M (2000) Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum 43:1801–1808PubMedCrossRefGoogle Scholar
  20. 20.
    Lee C, Almagor O, Dunlop DD, Manzi S, Spies S, Chadha AB, Ramsey-Goldman R (2006) Disease damage and low bone mineral density: an analysis of women with systemic lupus erythematosus ever and never receiving corticosteroids. Rheumatology 45:53–60PubMedCrossRefGoogle Scholar
  21. 21.
    Pineau CA, Urowitz MB, Fortin PJ, Ibanez D, Gladman DD (2004) Osteoporosis in systemic lupus erythematosus: factors associated with referral for bone mineral density studies, prevalence of osteoporosis and factors associated with reduced bone density. Lupus 13:436–441PubMedCrossRefGoogle Scholar
  22. 22.
    Romas E, Martin TJ (1997) Cytokines in the pathogenesis of osteoporosis. Osteop Int 7(Suppl 3):S47–S53Google Scholar
  23. 23.
    Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21(2):115–137, AprPubMedCrossRefGoogle Scholar
  24. 24.
    Spronk P, Borg E, Limburg P, Kallenberg C (1992) Plasma concentrations of Il-6 in systemic lupus erythematosus; an indicator of disease activity. Clin Exp Immunol 90:106–110PubMedGoogle Scholar
  25. 25.
    Maury CPJ, Teppo A (1989) Tumor necrosis factor in the serum of patients with systemic lupus erythematosus. Arthritis Rheum 32:146–150PubMedCrossRefGoogle Scholar
  26. 26.
    Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR (1991) Elevated levels of IL-6 in systemic lupus erythematosus. J Immunol 147:117–123PubMedGoogle Scholar
  27. 27.
    Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH (2007) Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 27:461–466PubMedCrossRefGoogle Scholar
  28. 28.
    Formiga F, Moga I, Navarro MA, Nolla JM, Bonnin R, Roig-Escofet D, Pujol R (1996) Bone mineral density in female patients with systemic lupus erythematosus treated with high glucocorticoid doses. Rev Clin Esp 196:747–750PubMedGoogle Scholar
  29. 29.
    Hearth-Holmes M, Elder C, Wolf RE (1993) Bone Mineral Density (BMD) in Patients with Systemic Lupus Erythematosus (SLE). Arthritis Rheum 36:S229Google Scholar
  30. 30.
    Conti A, Sartorio A, Ferrero S, Ferrario S, Ambrosi B (1996) Modifications of biochemical markers of bone and collagen turnover during corticosteroid therapy. J Endocrinol Invest 19:127–130PubMedGoogle Scholar
  31. 31.
    Hauache OM, Amarante EC, Vieira JG, Faresin SM, Fernandes AL, Jardim JR, Lazaretti-Castro M (1999) Evaluation of bone metabolism after the use of an inhaled glucocorticoid (flunisolide) in patients with moderate asthma. Clin Endocrinol 51:35–39CrossRefGoogle Scholar
  32. 32.
    Reed A, Haugen M, Pachman LM, Langman CB (1990) Abnormalities in serum osteocalcin values in children with chronic rheumatic diseases. J Pediatr 116:574–580PubMedCrossRefGoogle Scholar
  33. 33.
    Hansen M, Halberg P, Kollerup G, Pedersen-Zbinden B, Horslev-Petersen K, Hyldstrup L, Lorenzen I (1998) Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment. Scand J Rheumatol 27:197–206PubMedCrossRefGoogle Scholar
  34. 34.
    Kipen Y, Will R, Strauss BJ, Morand EF (1998) Urinary excretion of the pyridinium cross-links of collagen in systemic lupus erythematosus patients. Clin Rheumatol 17:271–276PubMedCrossRefGoogle Scholar
  35. 35.
    Lee C, Almagor O, Dunlop DD, Manzi S, Spies S, Ramsey-Goldman R (2007) Self-reported fractures and associated factors in women with systemic lupus erythematosus. J Rheumatol 34:2018–2023PubMedGoogle Scholar
  36. 36.
    Holick MF (1995) Vitamin D: photobiology, metabolism, and clinical applications. In: DeGroot LJ, Besser M, Burger HG et al (eds) Endocrinology, 3rd edn. WB Saunders Company, Philadelphia, pp 990–1014Google Scholar
  37. 37.
    Bouillon R, Okamura WH, Norman AW (1995) Structure-function relationships in the vitamin D endocrine system. Endocr Rev 20:22–45Google Scholar
  38. 38.
    Lemire JM, Ince A, Takashima M (1992) 1,25-Dihydroxivitamin D3 attenuates the expression of experimental murine lupus of MRL/1 mice. Autoimmunity 12:143–148PubMedCrossRefGoogle Scholar
  39. 39.
    Vaisberg MW, Kameno R, Franco MF, Mendes NF (2000) Influence of cholecalciferol (vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice. J Clin Lab Anal 14:91–96PubMedCrossRefGoogle Scholar
  40. 40.
    Linker-Israeli M, Elstner E, Klinenberg JR, Wallace DJ, Koeffler HP (2001) Vitamin D and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC. Clin Immunol 99:2–93CrossRefGoogle Scholar
  41. 41.
    Becker A, Fischer R, Schneider M (2001) Bone density and 25-OH vitamin D serum level in patients with systemic lupus erythematosus. Z Rheumatol 60:352–358PubMedCrossRefGoogle Scholar
  42. 42.
    Huisman AM, White KP, Algra A, Harth M, Vieth R, Jacobs JW, Bijlsma JW, Bell DA (2001) Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol 28:2535–2539PubMedGoogle Scholar
  43. 43.
    O’Regan S, Chesney RW, Hamstra A, Eisman JA, O’Gorman AM, Deluca HF (1979) Reduced serum 1,25(OH)2vitamin D3 levels in prednisone treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand 68:109–111PubMedCrossRefGoogle Scholar
  44. 44.
    Redlich K, Ziegler S, Kiener HP, Spitzauer S, Stohlawetz P, Bernecker P, Kainberger F et al (2000) Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus. Ann Rheum Dis 59:308–310PubMedCrossRefGoogle Scholar
  45. 45.
    Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC et al (1998) Hypovitaminosis D in medical inpatients. N Engl J Med 338:773–777CrossRefGoogle Scholar
  46. 46.
    Carvalho JF, Blank M, Kiss E, Tarr T, Amital H, Shoenfeld Y (2007) Anti-vitamin D, vitamin D in SLE: preliminary results. Ann N Y Acad Sci 1109:550–557, AugPubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • V. Z. C. Borba
    • 1
    • 2
    • 4
  • J. G. H. Vieira
    • 1
  • T. Kasamatsu
    • 1
  • S. C. Radominski
    • 3
  • E. I. Sato
    • 5
  • M. Lazaretti-Castro
    • 1
  1. 1.Division of EndocrinologyUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Division of EndocrinologyServiço de Endocrinologia da Universidade Federal do Paraná (SEMPR), Universidade Federal do ParanáCuritibaBrazil
  3. 3.Division of RheumatologyUniversidade Federal do ParanáCuritibaBrazil
  4. 4.CuritibaBrazil
  5. 5.Division of RheumatologyUniversidade Federal de São PauloSão PauloBrazil

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