{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:06:59Z","timestamp":1790809619984,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-\u03baB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.<\/jats:p>","DOI":"10.3390\/jcm10061241","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T11:48:22Z","timestamp":1615981702000},"page":"1241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-7139","authenticated-orcid":false,"given":"Yoshiya","family":"Tanaka","sequence":"first","affiliation":[{"name":"The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Kitakyushu 807-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"8","author":"Smolen","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41232-020-00133-8","article-title":"Rheumatoid arthritis","volume":"40","author":"Tanaka","year":"2020","journal-title":"Inflamm. Regen."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1016\/S0140-6736(17)31472-1","article-title":"Pathogenetic insights from the treatment of rheumatoid arthritis","volume":"389","author":"McInnes","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16069","DOI":"10.1038\/nrdp.2016.69","article-title":"Postmenopausal osteoporosis","volume":"2","author":"Eastell","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/nrrheum.2015.48","article-title":"A look behind the scenes: The risk and pathogenesis of primary osteoporosis","volume":"11","author":"Hendrickx","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrd3669","article-title":"Inflammatory bone loss: Pathogenesis and therapeutic intervention","volume":"11","author":"Redlich","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1152\/physrev.00011.2015","article-title":"Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy","volume":"96","author":"Hartmann","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.rdc.2015.08.005","article-title":"Glucocorticoid-induced Osteoporosis","volume":"42","author":"Whittier","year":"2016","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1056\/NEJMcp1800214","article-title":"Glucocorticoid-Induced Osteoporosis","volume":"379","author":"Buckley","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00774-018-0965-5","article-title":"Clinical immunity in bone and joints","volume":"37","author":"Tanaka","year":"2019","journal-title":"J. Bone Miner. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nrrheum.2009.217","article-title":"Osteoimmunology and the effects of the immune system on bone","volume":"5","author":"Takayanagi","year":"2009","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/01.bor.0000231912.24740.a5","article-title":"Osteoclasts, rheumatoid arthritis, and osteoimmunology","volume":"18","author":"Sato","year":"2006","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3389\/fimmu.2019.00505","article-title":"What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Various Inflammatory Diseases Associated with Bone Loss?","volume":"10","author":"Kamradt","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3109\/14397595.2016.1153449","article-title":"Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice","volume":"26","author":"Hirata","year":"2016","journal-title":"Mod. Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1136\/annrheumdis-2012-202850","article-title":"Osteitis and synovitis, but not bone erosion, is associated with proteoglycan loss and microstructure damage in the cartilage of patients with rheumatoid arthritis","volume":"73","author":"Herz","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nrrheum.2012.153","article-title":"Bone erosion in rheumatoid arthritis: Mechanisms, diagnosis and treatment","volume":"8","author":"Schett","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1136\/ard.2010.135061","article-title":"From bone biology to clinical outcome: State of the art and future perspectives","volume":"69","author":"Schett","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/BOR.0000000000000007","article-title":"Arthritis and bone loss: A hen and egg story","volume":"26","author":"Kleyer","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrrheum.2016.200","article-title":"Mechanisms leading from systemic autoimmunity to joint-specific disease in rheumatoid arthritis","volume":"13","author":"Catrina","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2174\/1568010054022015","article-title":"Osteoblasts and Osteoclasts in Bone Remodeling and Inflammation","volume":"4","author":"Nakayamada","year":"2005","journal-title":"Curr. Drug Target-Inflammation Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115616","DOI":"10.1016\/j.bone.2020.115616","article-title":"Human dendritic cell-derived osteoclasts with high bone resorption capacity and T cell stimulation ability","volume":"142","author":"Narisawa","year":"2020","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1136\/ard.2009.126532","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs","volume":"69","author":"Smolen","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1136\/ard.2011.149765","article-title":"American College of Rheumatology\/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials","volume":"70","author":"Felson","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4158\/GL-2020-0524SUPPL","article-title":"American Association of Clinical Endocrinologists\/American College of Endocri-nology clinical practice guideline for the diagnosis and treatment of post-menopausal osteoporosis-2020 update","volume":"26","author":"Camacho","year":"2020","journal-title":"Endocr. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1056\/NEJMcp1513724","article-title":"Clinical Practice. Postmenopausal Osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: Recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1080\/14656566.2020.1787381","article-title":"Osteoporosis in patients with rheumatoid arthritis: An update in epidemiology, pathogenesis, and fracture prevention","volume":"21","author":"Raterman","year":"2020","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_32","first-page":"713","article-title":"Trends and Determinants of Osteoporosis Treatment and Screening in Patients With Rheumatoid Arthritis Compared to Osteoarthritis","volume":"70","author":"Ozen","year":"2018","journal-title":"Arthritis Antirheum."},{"key":"ref_33","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":"Buckley","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10393","DOI":"10.1002\/jbm4.10393","article-title":"The Association of Methotrexate, Sulfasalazine, and Hydroxychloroquine Use with Fracture in Postmenopausal Women with Rheumatoid Arthritis: Findings from the Women\u2019s Health Initiative","volume":"4","author":"Carbone","year":"2020","journal-title":"JBMR Plus"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00223-018-0401-9","article-title":"Osteoporosis in Rheumatic Diseases: Anti-rheumatic Drugs and the Skeleton","volume":"102","author":"Dubrovsky","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1002\/acr.22519","article-title":"Meta-Analysis of Tumor Necrosis Factor Inhibitors and Glucocorticoids on Bone Density in Rheumatoid Arthritis and Ankylosing Spondylitis Trials","volume":"67","author":"Siu","year":"2015","journal-title":"Arthritis Rheum."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"i70","DOI":"10.1136\/annrheumdis-2011-200595","article-title":"In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis","volume":"71","author":"Tanaka","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"ii111","DOI":"10.1136\/annrheumdis-2012-202576","article-title":"Janus kinase inhibitors in autoimmune diseases","volume":"72","author":"Kontzias","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s40259-016-0190-5","article-title":"Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid Arthritis","volume":"30","author":"Nakayamada","year":"2016","journal-title":"BioDrugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1093\/rheumatology\/key280","article-title":"The JAK inhibitors: Do they bring a paradigm shift for the management of rheumatic diseases?","volume":"58","author":"Tanaka","year":"2019","journal-title":"Rheumatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1056\/NEJMoa1608345","article-title":"Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis","volume":"376","author":"Taylor","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1016\/S0140-6736(19)30419-2","article-title":"Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): A randomised, placebo-controlled, double-blind phase 3 study","volume":"393","author":"Smolen","year":"2019","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1002\/art.34329","article-title":"A JAK inhibitor tofacitinib regulates synovitis through inhibition of IFN-g and IL-17 production by human CD4+ T cells","volume":"64","author":"Maeshima","year":"2012","journal-title":"Arthritis Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1002\/art.10408","article-title":"Bone loss in patients with rheumatoid arthritis: Results from a population-based cohort of 366 patients followed up for two years","volume":"46","author":"Haugeberg","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41584-020-0370-z","article-title":"Views on glucocorticoid therapy in rheumatology: The age of convergence","volume":"16","author":"Buttgereit","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1007\/s00774-015-0709-8","article-title":"Analysis of bone metabolism during early stage and clinical benefits of early intervention with alendronate in patients with systemic rheumatic diseases treated with high dose glucocorticoid. Early DIagnosis and Treatment of OsteopoRosis in Japan (EDITOR-J) Study","volume":"34","author":"Tanaka","year":"2016","journal-title":"J. Bone Miner Metabolism."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.tem.2017.10.010","article-title":"Therapeutic Mechanisms of Glucocorticoids","volume":"29","author":"Vandewalle","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nri.2017.1","article-title":"Immune regulation by glucocorticoids","volume":"17","author":"Cain","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bone.2013.11.016","article-title":"Differing effects of denosumab and alendronate on cortical and trabecular bone","volume":"59","author":"Zebaze","year":"2014","journal-title":"Bone"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.bone.2010.11.020","article-title":"Denosumab and bisphosphonates: Different mechanisms of action and effects","volume":"48","author":"Baron","year":"2011","journal-title":"Bone"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S2213-8587(17)30138-9","article-title":"10 years of denosumab treatment in postmenopausal women with osteoporosis: Results from the phase 3 randomised FREEDOM trial and open-label extension","volume":"5","author":"Bone","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s00774-020-01159-1","article-title":"RANKL as a therapeutic target of rheumatoid arthritis","volume":"39","author":"Tanaka","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/14397595.2017.1369491","article-title":"RANKL: A therapeutic target for bone destruction in rheumatoid arthritis","volume":"28","author":"Tanaka","year":"2017","journal-title":"Mod. Rheumatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1136\/annrheumdis-2015-208052","article-title":"Effect of denosumab on Japanese patients with rheumatoid arthritis: A dose\u2013response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)\u2014A 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial","volume":"75","author":"Takeuchi","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1136\/annrheumdis-2018-214827","article-title":"Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"78","author":"Takeuchi","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.coph.2018.03.006","article-title":"Mechanisms and therapeutic targets for bone damage in rheumatoid arthritis, in particular the RANK-RANKL system","volume":"40","author":"Tanaka","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1056\/NEJMoa1305224","article-title":"Romosozumab in Postmenopausal Women with Low Bone Mineral Density","volume":"370","author":"McClung","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/6\/1241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:37:01Z","timestamp":1760161021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/6\/1241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":59,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["jcm10061241"],"URL":"https:\/\/doi.org\/10.3390\/jcm10061241","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,17]]}}}