{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:56:09Z","timestamp":1781052969411,"version":"3.54.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Int"],"DOI":"10.1007\/s00296-025-06045-5","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T06:27:57Z","timestamp":1765175277000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Methotrexate osteopathy in rheumatoid arthritis"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2437-4420","authenticated-orcid":false,"given":"Olga Dorota","family":"Lotkowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4194-9146","authenticated-orcid":false,"given":"Sabine","family":"Adler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5724-1604","authenticated-orcid":false,"given":"Armin","family":"Zgraggen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"6045_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1136\/ard-2022-223356","volume":"82","author":"JS Smolen","year":"2023","unstructured":"Smolen JS, Landew\u00e9 RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D et al (2023) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 82:3\u201318. https:\/\/doi.org\/10.1136\/ard-2022-223356","journal-title":"Ann Rheum Dis"},{"key":"6045_CR2","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1136\/ard-2024-225531","volume":"83","author":"L Gossec","year":"2024","unstructured":"Gossec L, Kerschbaumer A, Ferreira RJO, Aletaha D, Baraliakos X, Bertheussen H et al (2024) EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis 83:706\u201319. https:\/\/doi.org\/10.1136\/ard-2024-225531","journal-title":"Ann Rheum Dis"},{"key":"6045_CR3","first-page":"S95","volume":"28","author":"K Albrecht","year":"2010","unstructured":"Albrecht K, M\u00fcller-Ladner U (2010) Side effects and management of side effects of methotrexate in rheumatoid arthritis. Clin Exp Rheumatol Italy 28:S95\u2013101","journal-title":"Clin Exp Rheumatol Italy"},{"key":"6045_CR4","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/1097-0142(197003)25:3<580::AID-CNCR2820250313>3.0.CO;2-M","volume":"25","author":"AH Ragab","year":"1970","unstructured":"Ragab AH, Frech RS, Vietti TJ (1970) Osteoporotic fractures secondary to methotrexate therapy of acute leukemia in remission. Cancer 25:580\u2013585.","journal-title":"Cancer"},{"key":"6045_CR5","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.3899\/jrheum.100385","volume":"37","author":"L Meier","year":"2010","unstructured":"Meier L, van Tuyll van Sersooskerken A-M, Liberton E, Kleijn L, Westgeest T, Polak M et al (2010) Fractures of the proximal tibia associated with longterm use of methotrexate: 3 case reports and a review of literature. J Rheumatol Can 37:2434\u20132438. https:\/\/doi.org\/10.3899\/jrheum.100385","journal-title":"J Rheumatol Can"},{"key":"6045_CR6","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00198-020-05664-x","volume":"32","author":"F Robin","year":"2021","unstructured":"Robin F, Cadiou S, Albert J-D, Bart G, Coiffier G, Guggenbuhl P (2021) Methotrexate osteopathy: five cases and systematic literature review. Osteoporos Int 32:225\u201332. https:\/\/doi.org\/10.1007\/s00198-020-05664-x","journal-title":"Osteoporos Int"},{"key":"6045_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s00223-020-00765-5","volume":"108","author":"T Rolvien","year":"2021","unstructured":"Rolvien T, Jandl NM, St\u00fcrznickel J, Beil FT, K\u00f6tter I, Oheim R et al (2021) Clinical and radiological characterization of patients with immobilizing and progressive stress fractures in methotrexate osteopathy. Calcif Tissue Int 108:219\u201330. https:\/\/doi.org\/10.1007\/s00223-020-00765-5","journal-title":"Calcif Tissue Int"},{"key":"6045_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2022.151952","volume":"52","author":"N Ruffer","year":"2022","unstructured":"Ruffer N, Krusche M, Beil FT, Amling M, K\u00f6tter I, Rolvien T (2022) Clinical features of methotrexate osteopathy in rheumatic musculoskeletal disease: a systematic review. Semin Arthritis Rheum 52:151952. https:\/\/doi.org\/10.1016\/j.semarthrit.2022.151952","journal-title":"Semin Arthritis Rheum"},{"key":"6045_CR9","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S1297-319X(03)00024-1","volume":"70","author":"M Soubrier","year":"2003","unstructured":"Soubrier M, Dubost J-J, Boisgard S, Sauvezie B, Gaillard P, Michel JL et al (2003) Insufficiency fracture. A survey of 60 cases and review of the literature. Joint Bone Spine 70:209\u2013218. https:\/\/doi.org\/10.1016\/S1297-319X(03)00024-1","journal-title":"Joint Bone Spine"},{"key":"6045_CR10","first-page":"77","volume":"20","author":"HM M\u00e4enp\u00e4\u00e4","year":"2002","unstructured":"M\u00e4enp\u00e4\u00e4 HM, Soini I, Lehto MUK, Belt EA (2002) Insufficiency fractures in patients with chronic inflammatory joint diseases. Clin Exp Rheumatol 20:77\u201379","journal-title":"Clin Exp Rheumatol"},{"key":"6045_CR11","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.3899\/jrheum.220758","volume":"50","author":"B Buehring","year":"2023","unstructured":"Buehring B, Al-Azem N, Kiltz U, Fruth M, Andreica I, Kiefer D et al (2023) High prevalence of foot insufficiency fractures in patients with inflammatory rheumatic musculoskeletal diseases. J Rheumatol 50:1071\u20131077. https:\/\/doi.org\/10.3899\/jrheum.220758","journal-title":"J Rheumatol"},{"key":"6045_CR12","unstructured":"Fiehn C, Bauhammer J. Methotrexat-osteopathie: analyse von 7 F\u00e4llen einer oft \u00fcbersehenen Komplikation der rheumatologischen Therapie [Internet]. https:\/\/rheuma-badenbaden.de\/wp-content\/uploads\/2021\/09\/MTX-OsteopathiePoster27-8-21Final.pdf"},{"key":"6045_CR13","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.ard.2025.01.047","volume":"84","author":"B Hauser","year":"2025","unstructured":"Hauser B, Merriman A, Foley J, Golla J, McRorie E, Ralston SH (2025) Methotrexate continuation increases fracture risk in patients who sustained lower limb insufficiency fractures. Ann Rheum Dis 84:554\u2013561. https:\/\/doi.org\/10.1016\/j.ard.2025.01.047","journal-title":"Ann Rheum Dis"},{"key":"6045_CR14","doi-asserted-by":"publisher","first-page":"602","DOI":"10.2106\/00004623-198466040-00016","volume":"66","author":"GE Friedlaender","year":"1984","unstructured":"Friedlaender GE, Tross RB, Doganis AC, Kirkwood JM, Baron R (1984) Effects of chemotherapeutic agents on bone. I. Short-term methotrexate and doxorubicin (adriamycin) treatment in a rat model. J Bone Joint Surg Am 66:602\u2013607","journal-title":"J Bone Joint Surg Am"},{"key":"6045_CR15","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1093\/rheumatology\/35.4.342","volume":"35","author":"MJ Van Der Veen","year":"1996","unstructured":"Van Der Veen MJ, Scheven BAA, Van Roy JLAM, Damen CA, Lafeber FPJG, Bijlsma JWJ (1996) In vitro effects of methotrexate on human articular cartilage and bone-derived osteoblasts. Rheumatology 35:342\u20139. https:\/\/doi.org\/10.1093\/rheumatology\/35.4.342","journal-title":"Rheumatology"},{"key":"6045_CR16","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1093\/rheumatology\/41.7.735","volume":"41","author":"NJ Minaur","year":"2002","unstructured":"Minaur NJ (2002) Methotrexate in the treatment of rheumatoid arthritis. I. In vitro effects on cells of the osteoblast lineage. Rheumatology 41:735\u2013740. https:\/\/doi.org\/10.1093\/rheumatology\/41.7.735","journal-title":"Rheumatology"},{"key":"6045_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/ar4444","volume":"16","author":"NJ Olsen","year":"2014","unstructured":"Olsen NJ, Spurlock CF 3rd, Aune TM (2014) Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther 16:R17. https:\/\/doi.org\/10.1186\/ar4444","journal-title":"Arthritis Res Ther"},{"key":"6045_CR18","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s00296-012-2375-7","volume":"33","author":"MH Abdel Meguid","year":"2013","unstructured":"Abdel Meguid MH, Hamad YH, Swilam RS, Barakat MS (2013) Relation of interleukin-6 in rheumatoid arthritis patients to systemic bone loss and structural bone damage. Rheumatol Int 33:697\u2013703. https:\/\/doi.org\/10.1007\/s00296-012-2375-7","journal-title":"Rheumatol Int"},{"key":"6045_CR19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ajpath.2012.03.037","volume":"181","author":"TJ King","year":"2012","unstructured":"King TJ, Georgiou KR, Cool JC, Scherer MA, Ang ESM, Foster BK et al (2012) Methotrexate chemotherapy promotes osteoclast formation in the long bone of rats via increased pro-inflammatory cytokines and enhanced NF-\u03baB activation. Am J Pathol 181:121\u20139. https:\/\/doi.org\/10.1016\/j.ajpath.2012.03.037","journal-title":"Am J Pathol"},{"key":"6045_CR20","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.semarthrit.2008.04.004","volume":"39","author":"C Barnabe","year":"2009","unstructured":"Barnabe C, Hanley DA (2009) Effect of tumor necrosis factor alpha inhibition on bone density and turnover markers in patients with rheumatoid arthritis and spondyloarthropathy. Semin Arthritis Rheum 39:116\u201322. https:\/\/doi.org\/10.1016\/j.semarthrit.2008.04.004","journal-title":"Semin Arthritis Rheum"},{"key":"6045_CR21","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.bone.2017.10.020","volume":"107","author":"S Uster","year":"2018","unstructured":"Uster S, Coelho FM, Aeberli D, Stein JV, Hofstetter W, Engelhardt B et al (2018) TNF\u03b1 blockade mediates bone protection in antigen-induced arthritis by reducing osteoclast precursor supply. Bone 107:56\u201365. https:\/\/doi.org\/10.1016\/j.bone.2017.10.020","journal-title":"Bone"},{"key":"6045_CR22","first-page":"1489","volume":"24","author":"LM Buckley","year":"1997","unstructured":"Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM (1997) Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 24:1489\u20131494","journal-title":"J Rheumatol"},{"key":"6045_CR23","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1007\/s002239900585","volume":"64","author":"LD Carbone","year":"1999","unstructured":"Carbone LD, Kaeley G, McKown KM, Cremer M, Palmieri G, Kaplan S (1999) Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis. Calcif Tissue Int 64:100\u20131. https:\/\/doi.org\/10.1007\/s002239900585","journal-title":"Calcif Tissue Int"},{"key":"6045_CR24","first-page":"327","volume":"18","author":"M Mazzantini","year":"2000","unstructured":"Mazzantini M, Di Munno O, Incerti-Vecchi L, Pasero G (2000) Vertebral bone mineral density changes in female rheumatoid arthritis patients treated with low-dose methotrexate. Clin Exp Rheumatol 18:327\u201331","journal-title":"Clin Exp Rheumatol"},{"key":"6045_CR25","first-page":"2395","volume":"28","author":"AB Cranney","year":"2001","unstructured":"Cranney AB, McKendry RJ, Wells GA, Ooi DS, Kanigsberg ND, Kraag GR et al (2001) The effect of low dose methotrexate on bone density. J Rheumatol 28:2395\u20132399","journal-title":"J Rheumatol"},{"key":"6045_CR26","first-page":"1305","volume":"31","author":"O di Munno","year":"2004","unstructured":"di Munno O, Mazzantini M, Sinigaglia L, Bianchi G, Minisola G, Muratore M et al (2004) Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study. J Rheumatol Can 31:1305\u20131309","journal-title":"J Rheumatol Can"},{"key":"6045_CR27","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1093\/rheumatology\/41.7.741","volume":"41","author":"NJ Minaur","year":"2002","unstructured":"Minaur NJ, Kounali D, Vedi S, Compston JE, Beresford JN, Bhalla AK (2002) Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density. Rheumatology (Oxford, England) 41:741\u2013749. https:\/\/doi.org\/10.1093\/rheumatology\/41.7.741","journal-title":"Rheumatology (Oxford, England)"},{"key":"6045_CR28","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1007\/s00296-023-05286-6","volume":"43","author":"A Palmowski","year":"2023","unstructured":"Palmowski A, Akahoshi M, Muche B, Boyadzhieva Z, Hermann S, Terao C et al (2023) No association between methotrexate and impaired bone mineral density in a cohort of patients with polymyalgia rheumatica, giant cell arteritis, granulomatosis with polyangiitis and other vasculitides-a cross-sectional analysis with dose-response analyses. Rheumatol Int 43:903\u20139. https:\/\/doi.org\/10.1007\/s00296-023-05286-6","journal-title":"Rheumatol Int"},{"key":"6045_CR29","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10393","volume":"4","author":"L Carbone","year":"2020","unstructured":"Carbone L, Vasan S, Elam R, Gupta S, Tolaymat O, Crandall C et al (2020) The association of methotrexate, sulfasalazine, and hydroxychloroquine use with fracture in postmenopausal women with rheumatoid arthritis: findings from the Women\u2019s Health Initiative. JBMR Plus 4:e10393. https:\/\/doi.org\/10.1002\/jbm4.10393","journal-title":"JBMR Plus"}],"container-title":["Rheumatology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-025-06045-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00296-025-06045-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-025-06045-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T15:13:57Z","timestamp":1771427637000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00296-025-06045-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["6045"],"URL":"https:\/\/doi.org\/10.1007\/s00296-025-06045-5","relation":{},"ISSN":["1437-160X"],"issn-type":[{"value":"1437-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,8]]},"assertion":[{"value":"27 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All patient data included in this review were collected in accordance with the institutional ethical standards of Kantonsspital Aarau and national regulations. Written general consent for the analysis and processing of their data was obtained from all patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and\u00a0informed consent"}}],"article-number":"8"}}