{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T06:44:37Z","timestamp":1777877077976,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP16ek0109024"],"award-info":[{"award-number":["JP16ek0109024"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is a major underlying disease of glucocorticoid-associated osteonecrosis of the femoral head (ONFH). Despite its clinical significance, no prophylactic treatment has been established to prevent ONFH in patients receiving systemic glucocorticoid therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To investigate the efficacy and safety of a three-drug combination therapy consisting of clopidogrel sulfate, pitavastatin calcium hydrate, and tocopherol acetate, administered concurrently with initial glucocorticoid therapy to prevent ONFH in patients with SLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A multicenter, single-arm, interventional clinical trial conducted as an advanced medical treatment approved by the Ministry of Health, Labor and Welfare of Japan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This study was conducted at 12 sites in Japan between August 2014 and March 2024. Patients with SLE who required initial glucocorticoid therapy (\u2a7e0.5\u2009mg\/kg\/day of prednisolone) received the three study drugs concurrently with glucocorticoids for 90\u2009days. Magnetic resonance imaging of both hip joints was performed 180\u2009days after initiation of glucocorticoid therapy to determine ONFH occurrence. The primary endpoint was ONFH incidence, and safety and potential risk factors were also evaluated using logistic regression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Of the 50 enrolled patients, 43 completed the 90-day regimen. ONFH was identified in 8 of 43 patients (18.6%), which was below the threshold incidence of 25% based on the historical control, suggesting a potential signal of reduced incidence (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.1664). Treatment-emergent adverse events were observed in 19 patients; the only severe adverse event was a drug eruption in one patient. The exploratory analysis identified the period of drinking as a significant risk factor for ONFH occurrence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The findings demonstrate the feasibility and acceptable safety of this three-drug combination therapy. Although the results should be regarded as preliminary and hypothesis-generating, they suggest a potential signal that warrants further investigation in adequately powered randomized controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>\n                      Clinical trial for the control of osteonecrosis of the femoral head secondary to the initial corticosteroid treatment in patients with systemic lupus erythematosus (UMIN000008230;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/center6.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000009636\">https:\/\/center6.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000009636<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x261423841","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T09:01:26Z","timestamp":1771837286000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Three-drug combination therapy to prevent glucocorticoid-associated osteonecrosis in patients with systemic lupus erythematosus: a proof-of-concept study"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-8202","authenticated-orcid":false,"given":"Goro","family":"Motomura","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yojiro","family":"Arinobu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Niiro","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuoto","family":"Hiramoto","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Takeyama","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Kyoto University 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