{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:37:22Z","timestamp":1788327442268,"version":"build-2803163510"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics\/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, <jats:italic>P<\/jats:italic> &lt; 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg\/day, <jats:italic>P<\/jats:italic> = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL\/min\/1.73m<jats:sup>2<\/jats:sup>, <jats:italic>P<\/jats:italic> = 0.02) than those without supplementation. Disease-related SDI (0.73 \u00b1 1.12 vs 0.73 \u00b1 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age \u2265 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0270569","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T17:28:45Z","timestamp":1656523725000},"page":"e0270569","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Real-world data on vitamin D supplementation and its impacts in systemic lupus erythematosus: Cross-sectional analysis of a lupus registry of nationwide institutions (LUNA)"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2935-6284","authenticated-orcid":true,"given":"Keigo","family":"Hayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-Ei","family":"Sada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshia","family":"Miyawaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7837-086X","authenticated-orcid":true,"given":"Haruki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Katsuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Narazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-3962","authenticated-orcid":true,"given":"Nobuyuki","family":"Yajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusuke","family":"Yoshimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Shimojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kajiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Ichinose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzo","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"pone.0270569.ref001","first-page":"218","article-title":"Vitamin D in lupus\u2014new kid on the block?","volume":"68","author":"DL Kamen","year":"2010","journal-title":"Bull NYU Hosp Jt Dis"},{"key":"pone.0270569.ref002","doi-asserted-by":"crossref","first-page":"42","DOI":"10.5001\/omj.2013.10","article-title":"Vitamin d deficiency in patients with systemic lupus erythematosus","volume":"28","author":"SM Attar","year":"2013","journal-title":"Oman Med J"},{"key":"pone.0270569.ref003","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.4049\/jimmunol.164.5.2405","article-title":"1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation","volume":"164","author":"G Penna","year":"2000","journal-title":"J Immunol"},{"key":"pone.0270569.ref004","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.4049\/jimmunol.179.3.1634","article-title":"Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation","volume":"179","author":"S Chen","year":"2007","journal-title":"J Immunol"},{"key":"pone.0270569.ref005","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jaut.2004.06.004","article-title":"1alpha,25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis","volume":"23","author":"AG van Halteren","year":"2004","journal-title":"J Autoimmun"},{"key":"pone.0270569.ref006","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1097\/00002030-200105250-00004","article-title":"Differential disappearance of inhibitory natural killer cell receptors during HAART and possible impairment of HIV-1-specific CD8 cytotoxic T lymphocytes","volume":"15","author":"P Costa","year":"2001","journal-title":"AIDS"},{"key":"pone.0270569.ref007","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/1756-185X.12289","article-title":"Differential expression of natural killer activating and inhibitory receptors in patients with newly diagnosed systemic lupus erythematosus","volume":"19","author":"Z Ye","year":"2016","journal-title":"Int J Rheum Dis"},{"key":"pone.0270569.ref008","doi-asserted-by":"crossref","first-page":"e0186223","DOI":"10.1371\/journal.pone.0186223","article-title":"Activating and inhibitory receptors on natural killer cells in patients with systemic lupus erythematosis-regulation with interleukin-15","volume":"12","author":"SJ Lin","year":"2017","journal-title":"PLoS One"},{"key":"pone.0270569.ref009","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.3390\/ijms22084288","article-title":"Vitamin D and Microbiota: Is There a Link with Allergies?","volume":"22","author":"G Murdaca","year":"2021","journal-title":"Int J Mol Sci"},{"key":"pone.0270569.ref010","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1177\/0961203311422094","article-title":"Vitamin D deficiency as marker for disease activity and damage in systemic lupus erythematosus: a comparison with anti-dsDNA and anti-C1q","volume":"21","author":"CC Mok","year":"2012","journal-title":"Lupus"},{"key":"pone.0270569.ref011","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1136\/ard.2009.120329","article-title":"Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D?","volume":"69","author":"H Amital","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"pone.0270569.ref012","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/rheumatology\/ker212","article-title":"Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis","volume":"51","author":"CC Mok","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"pone.0270569.ref013","doi-asserted-by":"crossref","first-page":"e000064","DOI":"10.1136\/lupus-2014-000064","article-title":"Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort","volume":"2","author":"KS Yap","year":"2015","journal-title":"Lupus Sci Med"},{"key":"pone.0270569.ref014","first-page":"1","article-title":"Role of vitamin D deficiency in systemic lupus erythematosus incidence and aggravation","volume":"9","author":"T Hassanalilou","year":"2017","journal-title":"Auto Immun Highlights"},{"key":"pone.0270569.ref015","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/annrheumdis-2019-215089","article-title":"2019 update of the EULAR recommendations for the management of systemic lupus erythematosus","volume":"78","author":"A Fanouriakis","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"pone.0270569.ref016","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/acr.21664","article-title":"American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis","volume":"64","author":"BH Hahn","year":"2012","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"pone.0270569.ref017","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1136\/annrheumdis-2018-213512","article-title":"First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)","volume":"77","author":"BA Pons-Estel","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"pone.0270569.ref018","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/rheumatology\/kex286","article-title":"The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults","volume":"57","author":"C Gordon","year":"2018","journal-title":"Rheumatology (Oxford)"},{"key":"pone.0270569.ref019","first-page":"1955","article-title":"Accrual of organ damage over time in patients with systemic lupus erythematosus","volume":"30","author":"DD Gladman","year":"2003","journal-title":"J Rheumatol"},{"key":"pone.0270569.ref020","article-title":"Impact of disease activity on organ damage progression in systemic lupus erythematosus: University of Toronto Lupus Clinic Cohort","author":"MB Urowitz","year":"2020","journal-title":"J Rheumatol"},{"key":"pone.0270569.ref021","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1136\/annrheumdis-2013-204620","article-title":"The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort","volume":"74","author":"MF Ugarte-Gil","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"pone.0270569.ref022","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.semarthrit.2011.11.002","article-title":"Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s","volume":"41","author":"A Mak","year":"2012","journal-title":"Semin Arthritis Rheum"},{"key":"pone.0270569.ref023","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1177\/0961203317693096","article-title":"Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years","volume":"26","author":"M Taraborelli","year":"2017","journal-title":"Lupus"},{"key":"pone.0270569.ref024","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/art.1780350606","article-title":"Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE","volume":"35","author":"C Bombardier","year":"1992","journal-title":"Arthritis Rheum"},{"key":"pone.0270569.ref025","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/art.1780390303","article-title":"The development and initial validation of the Systemic Lupus International Collaborating Clinics\/American College of Rheumatology damage index for systemic lupus erythematosus","volume":"39","author":"D Gladman","year":"1996","journal-title":"Arthritis Rheum"},{"key":"pone.0270569.ref026","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/ki.2010.483","article-title":"The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report","volume":"80","author":"AS Levey","year":"2011","journal-title":"Kidney Int"},{"key":"pone.0270569.ref027","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1093\/rheumatology\/keu148","article-title":"Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus","volume":"53","author":"I Ruiz-Arruza","year":"2014","journal-title":"Rheumatology (Oxford)"},{"key":"pone.0270569.ref028","doi-asserted-by":"crossref","first-page":"e000157","DOI":"10.1136\/lupus-2016-000157","article-title":"Independent association of glucocorticoids with damage accrual in SLE","volume":"3","author":"D Apostolopoulos","year":"2016","journal-title":"Lupus Sci Med"},{"key":"pone.0270569.ref029","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1007\/s00296-019-04407-4","article-title":"High bisphosphonate treatment rates and the prevalence of atypical femoral fractures in patients with systematic lupus erythematosus: a single-center retrospective study performed in Japan","volume":"39","author":"H Sato","year":"2019","journal-title":"Rheumatol Int"},{"key":"pone.0270569.ref030","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1002\/acr.20186","article-title":"Changes in vitamin D levels in patients with systemic lupus erythematosus: Effects on fatigue, disease activity, and damage","volume":"62","author":"G Ruiz-Irastorza","year":"2010","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"pone.0270569.ref031","doi-asserted-by":"crossref","first-page":"R221","DOI":"10.1186\/ar4060","article-title":"Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation","volume":"14","author":"B Terrier","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"pone.0270569.ref032","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s12026-016-8829-3","article-title":"Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+\/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort","volume":"65","author":"A Marinho","year":"2017","journal-title":"Immunol Res"},{"key":"pone.0270569.ref033","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1002\/art.37953","article-title":"Vitamin D in systemic lupus erythematosus: modest association with disease activity and the urine protein-to-creatinine ratio","volume":"65","author":"M Petri","year":"2013","journal-title":"Arthritis Rheum"},{"key":"pone.0270569.ref034","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/acr.22621","article-title":"Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"68","author":"GL Lima","year":"2016","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"pone.0270569.ref035","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s00198-009-1119-3","article-title":"Benefit-risk assessment of vitamin D supplementation","volume":"21","author":"HA Bischoff-Ferrari","year":"2010","journal-title":"Osteoporos Int"},{"key":"pone.0270569.ref036","first-page":"230","article-title":"Homocysteine, bone mineral density, and fracture risk over 2 years of followup in women with and without systemic lupus erythematosus","volume":"35","author":"EY Rhew","year":"2008","journal-title":"J Rheumatol"},{"key":"pone.0270569.ref037","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00198-008-0676-1","article-title":"Vitamin D deficiency in patients with active systemic lupus erythematosus","volume":"20","author":"VZ Borba","year":"2009","journal-title":"Osteoporos Int"},{"key":"pone.0270569.ref038","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1002\/art.40137","article-title":"2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis","volume":"69","author":"L Buckley","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"pone.0270569.ref039","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/acr.20150","article-title":"Osteoporosis screening, prevention, and treatment in systemic lupus erythematosus: application of the systemic lupus erythematosus quality indicators","volume":"62","author":"G Schmajuk","year":"2010","journal-title":"Arthritis Care & Research"},{"key":"pone.0270569.ref040","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/rheumatology\/kem105","article-title":"Prevalence and risk factors of osteoporosis in female SLE patients-extended report","volume":"46","author":"K Almehed","year":"2007","journal-title":"Rheumatology (Oxford)"},{"key":"pone.0270569.ref041","first-page":"2018","article-title":"Self-reported fractures and associated factors in women with systemic lupus erythematosus","volume":"34","author":"C Lee","year":"2007","journal-title":"J Rheumatol"},{"key":"pone.0270569.ref042","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1002\/art.39108","article-title":"Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus","volume":"67","author":"C Aranow","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"pone.0270569.ref043","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11657-018-0443-7","article-title":"Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review","volume":"13","author":"S Fujiwara","year":"2018","journal-title":"Arch Osteoporos"},{"key":"pone.0270569.ref044","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1007\/s00296-021-04898-0","article-title":"Barriers to medication adherence and degree of nonadherence in a systemic lupus erythematosus (SLE) outpatient population","volume":"41","author":"C Hardy","year":"2021","journal-title":"Rheumatol Int"},{"key":"pone.0270569.ref045","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3390\/nu12030743","article-title":"Vitamin D Status in Japanese Adults: Relationship of Serum 25-Hydroxyvitamin D with Simultaneously Measured Dietary Vitamin D Intake and Ultraviolet Ray Exposure","volume":"12","author":"K Asakura","year":"2020","journal-title":"Nutrients"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270569","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T17:29:24Z","timestamp":1656523764000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270569"}},"subtitle":[],"editor":[{"given":"Masataka","family":"Kuwana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0270569","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]}}}