Tuba Tulay KOCA, Burhan Fatih KOÇYİĞİT, Ahmet Akyol

The relationship between vitamin D level and disease activity and focal erosion in rheumatoid arthritis

Aim: Bone loss,fragility,and fractures are well-described complications that affect quality of life, morbidity, and health care costs during the course of rheumatoid arthritis (RA). Besides its well-known role in bone metabolism, vitamin D is also an important immune modulator, meant to affect the disease activity of rheumatic disorders. However, conflicting results have been demonstrated about the relationship between levels of vitamin D and disease activity in RA. Primary aim of was to compare vitamin D levels and Bone Mineral Density (BMD) values between RA and control groups.The secondary aim was to assess the correlations between vitamin D and disease activity and radiologic damage in RA.Material and Methods: A total of 41 RA patients and 40 healthy controls were included in this study. The patient and control groups were between the ages of 18 and 65. Disease activity score 28 (DAS-28) was used to determine the severity of disease.Sharp/van der Heijde method was performed to evaluate the radiologic changes.Dual energy X-ray absorptiometry (DEXA) was performed to measure Bone Mineral Density (BMD).Enzyme-Linked Immunosorbent Assay (ELISA) method was used to measure serum D vitamin concentrations.Results: Vitamin D levels, the BMD-lumbar spine, BMD-femur total and BMD-femur neck values were significantly lower in the patient group (p = 0.012, p < 0.001, p < 0.001 and p < 0.001). No significant correlations were detected between vitamin D levels and BMD values, disease activity, and radiologic damage scores (p > 0.05). DAS-28 was significantly and negatively correlated with BMD values (p < 0.05).Conclusion: Our study suggests that RA patients have lower vitamin D levels, BMD-lumbar spine, BMD-femur total and BMD-femur neck values. Higher disease activity increases bone loss in RA. Vitamin D levels and BMD values should be monitored for the risk of osteoporosis and fracture in RA.

PDF

___

1. Cojocaru M, Cojocaru IM, Silosi I, et al. Extra-articular Manifestations in Rheumatoid Arthritis.Maedica (Buchar) 2010;5:286-91.
2. Khurana R, Berney SM. Clinical aspects of rheumatoid arthritis. Pathophysiology 2005;12:153-65.
3. Malmström V, Catrina AI, Klareskog L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting.Nat Rev Immunol 2017;17:60-75.
4. Güler-Yüksel M, Bijsterbosch J, Goekoop-Ruiterman YP, et al. Bone mineral density in patients with recently diagnosed, active rheumatoid arthritis. Ann Rheum Dis 2007;66:1508-12.
5. Haugeberg G, Orstavik RE, Uhlig T, Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 2002;46:1720-8.
6. Colin EM, Asmawidjaja PS, van Hamburg JP, et al. 1,25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis. Arthritis Rheum 2010;62:132-42.
7. Tetlow LC, Smith SJ, Mawer EB, et al. Vitamin D receptors in the rheumatoid lesion: Expression by chondrocytes, macrophages, and synoviocytes. Ann Rheum Dis 1999;58:118-21.
8. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 2007;66:1137-42.
9. Yang J, Liu L, Zhang Q, et al. Effect of vitamin D on the recurrence rate of rheumatoid arthritis. ExpTher Med 2015;10:1812-6.
10. Cutolo M. Vitamin D or hormone D deficiency in autoimmune rheumatic diseases, including undifferentiated connective tissue disease. Arthritis Res Ther 2008;10:123.
11. Rossini M, Bagnato G, Frediani B, et al. Relationship of focal erosions, bone mineral density, and parathyroid hormone in rheumatoid arthritis. J Rheumatol 2011;38:997-1002.
12. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569-81.
13. van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000;27:261-3.
14. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc 2010;85:752-7.
15. Cutillos Marco E, Morales-Suarez-Varela M, Marquina-Vila A, et al. Serum 25-hydroxyvitamin D levels in patients with cutaneous lupus erythematosus in a Mediterranean region. Lupus 2010;19:810-4.
16. Lequerre´ T, Richez C. Pathophysiology of rheumatoid arthritis. Rev Prat 2012;62:1085-93.
17. Holick MF. Vitamin D: Extraskeletal health. Rheum Dis Clin North Am 2012;38:141-60.
18. Baykal T, Senel K, Alp F, et al. Is there an association between serum 25-hydroxyvitamin D concentrations and disease activity in rheumatoid arthritis? Bratisl Lek Listy 2012;113:610-1.
19. Rossini M, Maddali Bongi S, La Montagna G, et al. Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability. Arthritis Res Ther 2010;12:R216.
20. Kostoglou-Athanassiou I, Athanassiou P, Lyraki A, Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab 2012;3:181-7.
21. Kroger H, Penttila IM, Alhava EM. Low serum vitamin D metabolities in women with rheumatoid arthritis. Scand J Rheumatol 1993;22:172-7.
22. Nielen MM, van Schaardenburg D, Lems WF, et al. Vitamin D deficiency does not increase the risk of rheumatoid arthritis: comment on the article by Merlino et al. Arthritis Rheum 2006;54:3719-20.
23. Cutolo M, Otsa K, Laas K, et al. Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 2006;24:702-4.
24. Turhanoglu AD, Güler H, Yönden Z, et al. The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis. Rheumatol Int 2011;31:911-4.
25. Gopinath K, Danda D. Supplementation of 1,25dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: a randomised controlled trial. Int J Rheum Dis 2011;14:332-9.
26. Baker JF, Baker DG, Toedter G, et al. Associations between vitamin D, disease activity, and clinical response to therapy in rheumatoid arthritis. Clin Exp Rheumatol 2012;30:658-64.
27. Haga HJ, Schmedes A, Naderi Y, et al. Severe deficiency of 25-hydroxyvitamin D(3) (25-OH-D (3)) is associated with high disease activity of rheumatoid arthritis. ClinRheumatol 2013;32:629-33.
28. Song GG, Bae SC, Lee YH. Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin Rheumatol 2012;31:1733-9.
29. Craig SM, Yu F, Curtis JR, et al. Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis. J Rheumatol 2010;37:275-81.
30. van Staa TP1, Geusens P, Bijlsma JW, et al. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:3104-12.
31. Kröger H, Honkanen R, Saarikoski S, et al. Decreased axial bone mineral density in perimenopausal women with rheumatoid arthritis-a population based study. Ann Rheum Dis 1994;53:18-23.
32. Ladder MC, de Jong Z, Kostense PJ, et al. Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density. Ann Rheum Dis 2004;63:1576-80.
33. Laan RF, van Riel PL, van de Putte LB. Bone mass in patient with rheumatoid arthritis. Ann Rheum Dis 1992;51:826-32.
34. Shibuya K, Hagino H, Morio Y, et al. Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis. Clin Rheumatol 2002;21:150-8.
35. Peng J, Gong Y, Zhang Y, et al. Bone Mineral Density in Patients With Rheumatoid Arthritis and 4-Year Follow-up Results. J Clin Rheumatol 2016;22:71-4.
36. Sivas F, Barça N, Önder M, et al. The relation between joint erosion and generalized osteoporosis and disease activity in patients with rheumatoid arthritis. Rheumatol Int 2006;26:896-9.
37. Braun T, Zwerina J. Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther 2011;13:235.
38. Ding C, Parameswaran V, Udayan R, et al. Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab 2008;93:1952-8.