Ahmadi et al., 2017 [1515. Ahmadi R, Hajialilo M, Ghorbanihaghjo A, Mota A, Raeisi S, Bargahi N, et al. FGF-23, Klotho and vitamin D levels in scleroderma. Iran J Public Health. 2017;46(4):530–6.] |
Cross-sectional |
15 ± 4.7 (60) |
27.2 ± 8.7 (30) |
|
|
Serum Klotho and vitamin D lower in SSc patients (p < 0.001). Higher intact PTH in SSc patients (p < 0.001). |
Arnson et al., 2011 [1616. Arnson Y, Amital H, Agmon-Levin N, Alon D, Sanchez-Castanon M, Lopez-Hoyos M, et al. Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev. 2011;10(8):490–4. https://doi.org/10.1016/j.autrev.2011.02.002. https://doi.org/10.1016/j.autrev.2011.02...
] |
Cross-sectional |
13.5±9 (327) |
21.6 ± 9.7 (141) |
|
|
Lower vitamin D levels in SSc patients (p< 0.001). Association with lower DLCO (p < 0.02). Inverse association with skin extent (mRSS> 10; p = 0.02) and RF expression (p < 0.001). |
Atteritano et al., 2013 [1414. Atteritano M, Lasco A, Mazzaferro S, Macri I, Catalano A, Santangelo A, et al. Bone mineral density, quantitative ultrasound parameters and bone metabolism in postmenopausal women with depression. Intern Emerg Med. 2013;8(6):485–91. https://doi.org/10.1007/s11739-011-0628-1. https://doi.org/10.1007/s11739-011-0628-...
] |
Cross-sectional |
18.3 ± 4.1 (54) |
39.6 ± 7.5 (54) |
|
|
Lower vitamin D levels in SSc patients (p< 0.001). Association with PTH (p= 0.001), osteocalcin (p< 0.05), deoxypyridinoline (p < 0.05) and BMD on lumbar spine and femur (p < 0.05). |
Atteritano et al., 2016 [1717. Atteritano M, Santoro D, Corallo G, Visalli E, Buemi M, Catalano A, et al. Skin involvement and pulmonary hypertension are associated with vitamin D insufficiency in scleroderma. Int J Mol Sci. 2016;17(12).] |
Cross-sectional |
25.8 ± 12.8 (40) |
35.1 ± 9.1 (40) |
0 (0) |
20 (50) |
Lower vitamin D levels in SSc patients (p = 0.0003). Association with skin extent (mRSS> 10; p = 0.02) and PASP> 35 mmHg (p = 0.02). No association with subtype and autoantibodies. |
Belloli et al., 2011 [1818. Belloli L, Ughi N, Marasini B. Vitamin D in systemic sclerosis. Clin Rheumatol. 2011;30(1):145–6. https://doi.org/10.1007/s10067-010-1564-6. https://doi.org/10.1007/s10067-010-1564-...
] |
Cross-sectional |
18.1 ± 15.2 (43) |
17.3 ± 12 (99 - OA) |
15 (34.8) |
37 (86) |
No significantly difference in insufficiency or deficiency between groups, regardless of disease duration, subtype and autoantibodies. |
Braun-Moscovici et al., 2008 [1919. Braun-Moscovici Y, Furst DE, Markovits D, Rozin A, Clements PJ, Nahir AM, et al. Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol. 2008;35(11):2201–5. https://doi.org/10.3899/jrheum.071171. https://doi.org/10.3899/jrheum.071171...
] |
Cross-sectional |
(60) |
|
26(46) |
|
High PTH associated with vitamin D deficiency (p = 0.01), calcinosis (p = 0.009), and acrosteolysis (p = 0.015). No significant correlation between supplementation and vitamin D levels. |
Caimmi et al., 2019 [2020. Caimmi C, Bertoldo E, Pozza A, Caramaschi P, Orsolini G, Gatti D, et al. Vitamin D serum levels and the risk of digital ulcers in systemic sclerosis: a longitudinal study. Int J Rheum Dis. 2019;22(6):1041–5. https://doi.org/10.1111/1756-185X.13554. https://doi.org/10.1111/1756-185X.13554...
] |
Cohort |
(65) |
|
|
|
Lower vitamin D levels in patients with incident DU in relation to patients with no incident DU over 5 years (- 17.4 vs 13.0, p=0,018). |
Calzolari et al., 2009 [2121. Calzolari G, Data V, Carignola R, Angeli A. Hypovitaminosis D in systemic sclerosis. J Rheumatol. 2009;36(12):2844 author reply 5.] |
Cross-sectional |
23(3–92) (18)(60) |
39(14–138) (60) |
4 (6.7) |
38 (63.4) |
Lower vitamin D levels in SSc patients (p<0.001). No association with disease subtype, cutaneous ulcers, skin extent, gastrointestinal and joint involvement. |
Caramaschi et al., 2010 [2222. Caramaschi P, Dalla Gassa A, Ruzzenente O, Volpe A, Ravagnani V, Tinazzi I, et al. Very low levels of vitamin D in systemic sclerosis patients. Clin Rheumatol. 2010;29(12):1419–25. https://doi.org/10.1007/s10067-010-1478-3. https://doi.org/10.1007/s10067-010-1478-...
] |
Cross-sectional |
15.8 ± 9.1 (65) |
|
19 (29.2) |
62 (95.4) |
Association with lung disease (p = 0.009),longer disease duration (p = 0.026), lower DLCO (p= 0.014), and higher PASP (p = 0.037), ESR (p = 0.001) and CRP (p = 0.004). |
Carmel et al., 2015 [2323. Carmel NN, Rotman-Pikielny P, Lavrov A, Levy Y. Vitamin D antibodies in systemic sclerosis patients: findings and clinical correlations. Isr Med Assoc J. 2015;17(2):80–4.] |
Cross-sectional |
(54) |
(41) |
|
39 (82.1) |
Anti-25(OH) D IgM antibodies more frequent in SSc patients and in a higher level (p=0.002). No correlation with severity, other autoantibodies and target organ damage. |
Corrado et al., 2015 [1212. Corrado A, Colia R, Mele A, Di Bello V, Trotta A, Neve A, et al. Relationship between body mass composition, bone mineral density, skin fibrosis and 25(OH) vitamin D serum levels in systemic sclerosis. PLoS One. 2015;10(9): e0137912. https://doi.org/10.1371/journal.pone.0137912. https://doi.org/10.1371/journal.pone.013...
] |
Cross-sectional |
15.7 ± 10.2 (64) |
22.9 ± 9.1 (35) |
|
|
Lower vitamin D levels in patients, especially in diffuse cutaneous SSc (p<0.001). Negative correlation with mRSS (p<0.05). No association with any internal organ involvement. |
Cruz-Domínguez et al., 2017 [2424. Cruz-Dominguez MP, Garcia-Collinot G, Saavedra MA, Medina G, Carranza- Muleiro RA, Vera-Lastra OL, et al. Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis. Clin Rheumatol. 2017;36(1):111–7. https://doi.org/10.1007/s10067-016-3412-9. https://doi.org/10.1007/s10067-016-3412-...
] |
Cohort |
(109) |
|
|
|
Lower vitamin D levels in SSc patients with and without calcinosis (19.1 vs. 13.1; p = 0.56). |
Di Liberto et al., 2019 [2525. Di Liberto D, Scazzone C, La Rocca G, Cipriani P, Lo Pizzo M, Ruscitti P, et al. Vitamin D increases the production of IL-10 by regulatory T cells in patients with systemic sclerosis. Clin Exp Rheumatol. 2019;37(Suppl 119(4)):76–81.] |
Cross-sectional |
22.1 ± 9.7 (45) |
|
|
|
Low vitamin D levels in SSc patients. Similar percentage of regulatory T-cells (Tregs) in SSc patients and control group, with higher percentage in SSc patients taking cholecalciferol. Impaired Tregs capability to suppress T cell proliferation in SSc patients. Increase in IL-10 in vitro production of patients Tregs after treatment with (1,25(OH)2D3). |
Gambichler et al., 2011 [2626. Gambichler T, Chrobok I, Hoxtermann S, Kreuter A. Significantly decreased serum 25-hydroxyvitamin d levels in a large german systemic sclerosis cohort. J Rheumatol. 2011;38(11):2492–3 author reply 4.] |
Cross-sectional |
13.1(4–48) (133) |
|
49 (35.8) |
123 (89.8) |
No association with disease subtype, BMI, lung fibrosis, renal involvement, GERD, digital ulcers, mRSS, autoantibodies and therapy. |
Giuggioli et al., 2017 [2727. Giuggioli D, Colaci M, Cassone G, Fallahi P, Lumetti F, Spinella A, et al. Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature. Clin Rheumatol. 2017;36(3):583–90. https://doi.org/10.1007/s10067-016-3535-z. https://doi.org/10.1007/s10067-016-3535-...
] |
Cross-sectional |
9.8 ± 4.1 (140) |
|
40/91 (44) |
91/91 (100) |
Lower vitamin D levels in not supplemented patients (9.8 ± 4.1 vs. 26 ± 8.1; p < 0.0001), but only 15/49 (31%) supplemented patients reached the normal range of vitamin D. |
Groseanu et al., 2016 [88. Groseanu L, Bojinca V, Gudu T, Saulescu I, Predeteanu D, Balanescu A, et al. Low vitamin D status in systemic sclerosis and the impact on disease phenotype. Eur J Rheumatol. 2016;3(2):50–5. https://doi.org/10.5152/eurjrheum.2015.0065. https://doi.org/10.5152/eurjrheum.2015.0...
] |
Cross-sectional |
17.1 ± 9.1 (51) |
|
12 (23.5) |
46 (90.2) |
Positive correlation with DLCO (p = 0.019). Negative correlation of vitamin D with diastolic dysfunction, digital contractures and muscle weakness. No correlation with autoantibodies or skin extent. Higher vitamin D levels in patients with usual supplementation (25.5%), but the difference between groups failed to reach statistical significance (p = 0.488). |
Gupta et al., 2018 [2828. Gupta S, Mahajan VK, Yadav RS, Mehta KS, Bhushan S, Chauhan PS, et al. Evaluation of serum vitamin D levels in patients with systemic sclerosis and healthy controls: results of a pilot study. Indian Dermatol Online J. 2018;9(4): 250–5. https://doi.org/10.4103/idoj.IDOJ_328_17. https://doi.org/10.4103/idoj.IDOJ_328_17...
] |
Cross-sectional |
19.5 ± 77.8 (38) |
100± 31.3 (38) |
13 (34.2) |
23 (60.5) |
Lower vitamin D levels in SSc patients (p = 0.001). Inverse correlationwith mRSS. No correlation with age, disease duration, autoantibodies, digital ulcers, or systemic involvement. |
Hajialilo et al., 2017 [2929. Hajialilo M, Noorabadi P, Tahsini Tekantapeh S, Malek MA. Endothelin-1, alphaKlotho, 25(OH) Vit D levels and severity of disease in scleroderma patients. Rheumatol Int. 2017;37(10):1651–7. https://doi.org/10.1007/s00296-017-3797-z. https://doi.org/10.1007/s00296-017-3797-...
] |
Cross-sectional |
14.9 ± 4.6 (60) |
30.4 ± 7.9 (60) |
|
|
Serum ET-1 higher in SSc patients (p=0.001). Serum α-Klotho and vitamin D lower in SSc patients (p=0.001). Association of vitamin D with gastrointestinal involvement on Medsger severity scale (p = 0.003). |
Hax et al., 2020 [3030. Hax V, Gasparin AA, Schneider L, Monticielo OA, Soares HMF, Streit MDA, et al. Vitamin D and cytokine profiles in patients with systemic sclerosis. J Clin Rheumatol. 2020;26(7):289–94. https://doi.org/10.1097/RHU.0000000000001112. https://doi.org/10.1097/RHU.000000000000...
] |
Cross-sectional |
23.9 ± 8.5 (50) |
30.2 ± 6.2 (35) |
2 (4%) |
36 (72%) |
Lower vitamin D levels in SSc patients compared to control group and lower vitamin D levels in SSc patients not taking vitamin D supplementation. No associations between vitamin D and cytokine levels or between vitamind D levels and disease duration. |
Ibn-Yacoub et al., 2012 [1313. Ibn Yacoub Y, Amine B, Laatiris A, Wafki F, Znat F, Hajjaj-Hassouni N. Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status. Rheumatol Int. 2012; 32(10):3143–8. https://doi.org/10.1007/s00296-011-2150-1. https://doi.org/10.1007/s00296-011-2150-...
] |
Cross-sectional |
10.9 ± 2.7 (30) |
57.4 ± 4.2 (30) |
8 (26.7) |
30 (100) |
Lower vitamin D levels in SSc patients (p=0.001). Association with number of painful (p = 0.006) and swollen joints (p = 0.013) and anti-Scl70 (p = 0.027). Association of vitamin D with BMD |
Kamal et al., 2016 [3131. Kamal A, Gamal SM, Elgengehy FT, Alkemary AK, Siam I. Association of VDR ApaI and TaqI gene polymorphisms with the risk of scleroderma and Behcet's disease. Immunol Investig. 2016;45(6):531–42. https://doi.org/10.1080/08820139.2016.1180302. https://doi.org/10.1080/08820139.2016.11...
] |
Cross-sectional |
(30) |
(60) |
|
|
on lumbar spine (p = 0.002) and femoral neck (p = 0.032). No association between VDR polymorphisms (ApaI and TaqI) and SSc susceptibility. Significant association between ApaI and diffuse cutaneous SSc. |
Matsuoka et al., 1991 [3232. Matsuoka LY, Dannenberg MJ, Wortsman J, Hollis BW, Jimenez SA, Varga J. Cutaneous vitamin D3 formation in progressive systemic sclerosis. J Rheumatol. 1991;18(8):1196–8.] |
Cross-sectional |
28 ± 3 (19) |
29±3 (19) |
|
|
Hypovitaminosis D common in SSc patients and healthy controls. No correlation with skin extent. |
Montabone et al., 2016 [3333. Montabone E, Data V, Carignola R. Vitamin D status and quality of life in systemic sclerosis patients. J Clin Rheumatol. 2016;22(4):229–30. https://doi.org/10.1097/RHU.0000000000000406. https://doi.org/10.1097/RHU.000000000000...
] |
Cross-sectional |
18.5(7.5–37) (35) |
|
4 (11) |
30 (85) |
Association with a worse physical component on SF-36 and physical function (p < 0.04). No association with gastrointestinal, kidney and cardiopulmonary involvement. |
Orbach et al., 2007 [3434. Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007;1109(1): 385–400. https://doi.org/10.1196/annals.1398.044. https://doi.org/10.1196/annals.1398.044...
] |
Cross-sectional |
11 ± 5.8 (229) |
|
|
|
Lower vitamin D levels in different autoimmune diseases (SSc, SLE, PM, DM, APS, and RA). |
Park et al., 2017 [3535. Park EK, Park JH, Kweon SM, Kim GT, Lee SG. Vitamin D deficiency is associated with digital ulcer but not with atherosclerosis or arterial stiffness in patients with systemic sclerosis: a pilot study. Clin Rheumatol. 2017;36(6): 1325–33. https://doi.org/10.1007/s10067-017-3622-9. https://doi.org/10.1007/s10067-017-3622-...
] |
Cross-sectional |
43.7(25–68) (40) |
57.5(40–81) (80) |
2 (5) |
12 (30) |
Association with digital ulcers (p = 0.012). No association with arterial stiffness, atherosclerosis, autoantibodies, mRSS, lung disease, PASP, ESR and CRP. |
Rios Fernández et al., 2010 [3636. Rios Fernandez R, Fernandez Roldan C, Callejas Rubio JL, Ortego CN. Vitamin D deficiency in a cohort of patients with systemic scleroderma from the south of Spain. J Rheumatol. 2010;37(6):1355; author reply 6. https://doi.org/10.3899/jrheum.091143. https://doi.org/10.3899/jrheum.091143...
] |
Cross-sectional |
(48) |
|
5 (9.5) |
39 (81) |
No significant vitamin D correlation with PASP or lung fibrosis. Hypovitaminosis D was common, despite 60.4% of patients were taking usual supplementation. |
Rios Fernández et al., 2012 [3737. Rios-Fernandez R, Callejas-Rubio JL, Fernandez-Roldan C, Simeon-Aznar CP, Garcia-Hernandez F, Castillo-Garcia MJ, et al. Bone mass and vitamin D in patients with systemic sclerosis from two Spanish regions. Clin Exp Rheumatol. 2012;30(6):905–11.] |
Cross-sectional |
(90) |
|
10 (11) |
69 (76.7) |
Association of vitamin D with calcinosis (p<0.034), heart involvement (p < 0.012), DLCO (p < 0.006) and positive ANA (p < 0.017). Hypovitaminosis D was common, despite 58.9% of patients were taking usual supplementation. Vitamin D deficiency was not different between groups (52% vs. 66.7%). |
Sampaio-Barros et al., 2016 [1010. Sampaio-Barros MM, Takayama L, Sampaio-Barros PD, Bonfa E, Pereira RM. Low vitamin D serum levels in diffuse systemic sclerosis: a correlation with worst quality of life and severe capillaroscopic findings. Rev Bras Reumatol Engl Ed. 2016;56(4):337–44. https://doi.org/10.1016/j.rbre.2016.05.006. https://doi.org/10.1016/j.rbre.2016.05.0...
] |
Cross-sectional |
20.7 ± 8.2 (38) |
|
4 (11) |
33 (87) |
Vitamin D positive correlation with anti-Scl70 (p = 0.039) and some SF-36 domains (vitality, social function, emotional role and mental health). Negative correlation with HAQ-reach and HAQ-grip strength. Positive correlation of vitamin D with BMI (p = 0.038) and femur BMD (p = 0.037). |
Seriolo et al., 2011 [3838. Seriolo B, Molfetta L, Cutolo M. Seasonal variations in serum levels of 25- hydroxyvitamin D in patients with systemic sclerosis. Clin Rheumatol. 2011; 30(3):445–6. https://doi.org/10.1007/s10067-011-1684-7. https://doi.org/10.1007/s10067-011-1684-...
] |
Cross-sectional |
21.7 ± 13.4 (53) |
39.4 ± 15.4 (35) |
13 (24) |
47 (88) |
Seasonal variation in patients and controls (highest values in summer, p<0.01). Significantly lower levels in SSc patients in all seasons. |
Shinjo et al., 2011 [3939. Shinjo SK, Bonfa E, de Falco CV, Pereira RM. Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency. Rheumatol Int. 2011;31(8):1075–80. https://doi.org/10.1007/s00296-010-1421-6. https://doi.org/10.1007/s00296-010-1421-...
] |
Cross-sectional |
18.1 ± 6.4 (10) |
25.1 ± 6.6 (10) |
|
|
Lower vitamin D levels in juvenile SSc patients (p = 0.04). Positive correlation with femur BMD (p = 0.02). |
Taylan et al., 2019 [4040. Taylan A, Birlik M, Kenar G, Toprak B, Gundogdu B, Gurler O, et al. Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis, skin fibrosis, and vasculopathy in systemic sclerosis: a potential multifaceted relationship between OPG/RANKL/TRAIL and Wnt inhibitors. Mod Rheumatol. 2019;29(4):619–24. https://doi.org/10.1080/14397595.2018.1500736. https://doi.org/10.1080/14397595.2018.15...
] |
Cross-sectional |
8.7(4.5–18) (46) |
16.5(9–21) (30) |
|
|
Lower serum vitamin D levels in SSc patients (p=0.02). No correlation with mRSS. |
Trombetta et al., 2017 [4141. Trombetta AC, Smith V, Gotelli E, Ghio M, Paolino S, Pizzorni C, et al. Vitamin D deficiency and clinical correlations in systemic sclerosis patients: a retrospective analysis for possible future developments. PLoS One. 2017; 12(6):e0179062. https://doi.org/10.1371/journal.pone.0179062. https://doi.org/10.1371/journal.pone.017...
] |
Cross-sectional |
18.7±9 (154) |
|
|
124 (80.5) |
Association of vitamin D with pulmonary fibrotic changes (p = 0.04). Correlation with some domains of Medsger severity scale (peripheral vascular, renal and gastrointestinal involvement). Vitamin D levels not influenced by usual supplementation (p = 0.81). |
Ursini et al., 2017 [4242. Ursini F, D’Angelo S, Padula A, Leccese P, Abignano G, Mennillo GA, et al. Vitamin D deficiency in systemic sclerosis: a possible role of subclinical liver fibrosis? Retrospective analysis from an Italian cohort. Clin Rheumatol. 2017; 36(12):2871–2. https://doi.org/10.1007/s10067-017-3709-3. https://doi.org/10.1007/s10067-017-3709-...
] |
Cohort |
15.4(8–25) (124) |
|
|
13 (89.5) |
Inverse correlation with mRSS (p = 0.03) and subclinical liver fibrosis (evaluated using the aspartate aminotransferase-to-platelet ratio index; p = 0.02). No correlation with age and disease duration. |
Vacca et al., 2009 [99. Vacca A, Cormier C, Piras M, Mathieu A, Kahan A, Allanore Y. Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with systemic sclerosis. J Rheumatol. 2009;36(9):1924–9. https://doi.org/10.3899/jrheum.081287. https://doi.org/10.3899/jrheum.081287...
] |
Cross-sectional |
19 ± 11 (156) |
|
44 (28) |
131 (84) |
Association of vitamin D with higher PASP (p = 0.004), lung fibrosis (p=0.04), anticentromere (p=0.04) and ESR (p = 0.008). No association with calcinosis, HAQ, or Medsger severity score. Negative correlation with EDAS (p=0.04). Vitamin D levels not influenced by usual supplementation (p = 0.1). |
Zhang et al., 2017 [4343. Zhang L, Duan Y, Zhang TP, Huang XL, Li BZ, Ye DQ, et al. Association between the serum level of vitamin D and systemic sclerosis in a Chinese population: a case control study. Int J Rheum Dis. 2017;20(8):1002–8. https://doi.org/10.1111/1756-185X.12794. https://doi.org/10.1111/1756-185X.12794...
] |
Cross-sectional |
26.5 ± 6.3 (60) |
36.3 ± 14.2 (60) |
|
45 (75) |
Lower vitamin D levels in SSc patients (p<0.001). More frequent lung involvement, but without significance (p = 0.08). No difference in joint involvement, autoantibodies, ESR and CRP. |